spalde-v3-lexical
stringlengths 4.95k
41.3k
| _id
stringlengths 4
9
| text
stringlengths 174
10k
| title
stringlengths 2
300
|
|---|---|---|---|
{"1014": 0.15526613593101501, "1019": 0.45994341373443604, "1020": 0.17759032547473907, "1021": 0.16607704758644104, "1042": 0.018384648486971855, "1999": 0.1485546976327896, "2003": 0.23556606471538544, "2004": 0.01934296265244484, "2006": 0.1064341589808464, "2012": 0.01934296265244484, "2029": 0.09050461649894714, "2034": 0.3601844012737274, "2043": 0.10555581003427505, "2044": 0.7737906575202942, "2051": 0.4437839686870575, "2054": 0.15023678541183472, "2076": 0.10203468054533005, "2079": 0.2652147710323334, "2080": 0.18978065252304077, "2090": 0.35128939151763916, "2109": 0.2881702482700348, "2129": 0.056018441915512085, "2139": 0.28082266449928284, "2146": 0.6548244953155518, "2152": 0.08782484382390976, "2154": 0.6096806526184082, "2172": 0.21922965347766876, "2184": 0.7942996621131897, "2202": 0.043007105588912964, "2206": 0.24248650670051575, "2213": 0.43434104323387146, "2217": 0.056018441915512085, "2220": 0.018384648486971855, "2260": 0.09406650811433792, "2265": 0.026976587250828743, "2274": 0.27564704418182373, "2283": 0.06795065850019455, "2291": 0.3012613356113434, "2309": 0.5336109399795532, "2322": 0.8433839678764343, "2335": 0.08064348995685577, "2339": 0.08782484382390976, "2340": 0.4337083101272583, "2350": 0.20102575421333313, "2363": 0.27786844968795776, "2367": 0.04860413447022438, "2378": 0.48670899868011475, "2382": 0.7692760229110718, "2420": 0.5995445251464844, "2425": 0.011650617234408855, "2429": 0.19782574474811554, "2484": 0.495672345161438, "2504": 0.7191727757453918, "2515": 0.13414156436920166, "2584": 0.25088030099868774, "2638": 0.6312094330787659, "2659": 0.15442965924739838, "2668": 0.7782850861549377, "2689": 0.1011524572968483, "2702": 0.5893046259880066, "2714": 0.4914994537830353, "2756": 0.05694137513637543, "2765": 0.007782140281051397, "2812": 0.040196798741817474, "2817": 0.30558720231056213, "2846": 0.18167030811309814, "2847": 0.4067663550376892, "2851": 0.7710843086242676, "2871": 0.503966212272644, "2895": 0.6950984001159668, "2904": 0.040196798741817474, "2913": 0.27934664487838745, "2920": 0.06154331564903259, "3083": 0.22001366317272186, "3085": 0.29328158497810364, "3141": 0.4891071021556854, "3170": 0.21135559678077698, "3174": 0.4330752193927765, "3207": 0.3034266233444214, "3231": 0.5016035437583923, "3273": 0.17020416259765625, "3276": 0.006812678650021553, "3278": 0.03360854089260101, "3284": 0.401551216840744, "3322": 0.07612881064414978, "3327": 0.007782140281051397, "3350": 0.674915611743927, "3362": 0.1677299439907074, "3375": 0.6926587820053101, "3378": 0.25239890813827515, "3424": 0.45437926054000854, "3426": 0.09406650811433792, "3431": 0.45623743534088135, "3433": 0.1913948506116867, "3435": 0.12038381397724152, "3445": 0.5696102976799011, "3447": 0.9944084882736206, "3463": 0.1734936386346817, "3466": 0.37974658608436584, "3491": 0.10203468054533005, "3619": 0.46117570996284485, "3623": 0.49982786178588867, "3643": 0.2852376699447632, "3659": 0.058784693479537964, "3671": 0.030771657824516296, "3679": 0.11256109178066254, "3695": 0.14179791510105133, "3798": 0.8109301924705505, "3893": 0.1401015669107437, "3896": 0.35950297117233276, "3949": 0.4770587682723999, "3988": 0.10555581003427505, "4106": 0.13243216276168823, "4143": 0.6075552701950073, "4146": 0.06246116757392883, "4167": 0.3930181860923767, "4180": 0.6301699280738831, "4200": 0.11604541540145874, "4228": 0.4855078160762787, "4295": 0.1212492436170578, "4319": 0.6291293501853943, "4340": 0.2667117714881897, "4376": 0.19862671196460724, "4414": 0.17431432008743286, "4453": 0.2837681770324707, "4496": 0.5051454305648804, "4502": 0.7276995778083801, "4506": 0.304147332906723, "4555": 0.05970508232712746, "4621": 0.05417001247406006, "4632": 0.020300358533859253, "4651": 0.11343330889940262, "4663": 0.08961215615272522, "4668": 0.04767346754670143, "4672": 0.1751343309879303, "4812": 0.09050461649894714, "4852": 0.0174254160374403, "4921": 0.47584590315818787, "4971": 0.1946154683828354, "5022": 0.2763880789279938, "5067": 0.535327672958374, "5072": 0.3757305145263672, "5127": 1.034073829650879, "5159": 0.49030399322509766, "5177": 0.36290550231933594, "5267": 0.07068414986133575, "5300": 0.4431571960449219, "5320": 0.2160874605178833, "5333": 0.03360854089260101, "5360": 0.5133614540100098, "5468": 0.255429208278656, "5531": 0.011650617234408855, "5604": 0.3084607720375061, "5643": 0.040196798741817474, "5646": 0.25088030099868774, "5761": 0.02792670577764511, "5769": 0.2719337046146393, "5776": 0.2223619967699051, "5845": 0.11343330889940262, "5850": 0.6613984704017639, "5852": 0.24859806895256042, "5911": 0.1930064558982849, "5920": 0.004870930220931768, "5997": 0.0913962796330452, "6022": 0.07431721687316895, "6049": 0.07884006202220917, "6064": 0.020300358533859253, "6177": 0.037378571927547455, "6199": 0.20421554148197174, "6245": 1.495358943939209, "6337": 0.1401015669107437, "6370": 0.1946154683828354, "6444": 0.35060185194015503, "6459": 0.13414156436920166, "6494": 0.7028654217720032, "6517": 0.18978065252304077, "6561": 0.18004031479358673, "6612": 0.15526613593101501, "6693": 0.17267228662967682, "6709": 0.3903779089450836, "6726": 0.906871497631073, "6825": 0.20977331697940826, "6832": 0.10379679501056671, "6844": 0.2160874605178833, "6845": 0.2637155055999756, "6888": 1.0144377946853638, "6897": 0.27342069149017334, "6911": 0.11430477350950241, "6937": 0.5651806592941284, "6939": 0.16359257698059082, "7099": 0.5045560002326965, "7127": 0.018384648486971855, "7242": 0.14518201351165771, "7290": 0.4752389192581177, "7337": 0.7389566898345947, "7356": 0.7445381283760071, "7366": 0.10993985831737518, "7438": 0.151916041970253, "7457": 0.39367714524269104, "7461": 0.4974553883075714, "7485": 0.8649974465370178, "7551": 0.10026945173740387, "7594": 0.1751343309879303, "7629": 0.026976587250828743, "7637": 0.06154331564903259, "7718": 0.347847044467926, "7747": 0.436867892742157, "7766": 0.09495500475168228, "7885": 0.056018441915512085, "7891": 0.35403475165367126, "8023": 0.15526613593101501, "8030": 0.1229778528213501, "8137": 0.31560876965522766, "8168": 0.6634125709533691, "8281": 0.17020416259765625, "8290": 0.7067264318466187, "8317": 0.21765978634357452, "8319": 0.3743882179260254, "8358": 0.12986256182193756, "8386": 0.4190443754196167, "8417": 0.2696990668773651, "8458": 0.3027053773403168, "8552": 0.043007105588912964, "8564": 0.861702561378479, "8625": 0.07793712615966797, "8700": 0.6327666640281677, "8761": 0.7286425232887268, "8776": 0.861702561378479, "8943": 0.2881702482700348, "9063": 0.1619328260421753, "9113": 0.4002431631088257, "9181": 0.5074998140335083, "9351": 0.23015019297599792, "9365": 0.05046287178993225, "9367": 0.2990913391113281, "9556": 0.09761575609445572, "9671": 0.1485546976327896, "9885": 0.5010119676589966, "9908": 0.15943801403045654, "9997": 0.009718249551951885, "9998": 0.6563454270362854, "10089": 0.48970574140548706, "10266": 0.4873090982437134, "10279": 0.030771657824516296, "10358": 0.040196798741817474, "10426": 0.021256839856505394, "10450": 0.0019512200960889459, "10509": 0.013579257763922215, "10548": 0.6857960224151611, "10595": 0.43244171142578125, "10610": 0.030771657824516296, "10788": 0.46486347913742065, "10790": 0.24248650670051575, "10840": 0.5290185213088989, "10847": 0.255429208278656, "10976": 0.7454653382301331, "11129": 0.7537717819213867, "11156": 0.7370892763137817, "11233": 0.7863243818283081, "11234": 0.013579257763922215, "11265": 0.40285754203796387, "11375": 0.18573370575904846, "11460": 0.659380316734314, "11467": 0.5957841277122498, "11477": 0.6664261221885681, "11487": 0.823009729385376, "11585": 0.006812678650021553, "11628": 0.03925827145576477, "11636": 0.9650808572769165, "11709": 1.0695481300354004, "11835": 0.6181373596191406, "11860": 0.6808650493621826, "11949": 0.11691460013389587, "12123": 1.1647365093231201, "12141": 0.28670501708984375, "12248": 0.04860413447022438, "12259": 0.004870930220931768, "12381": 0.03831886500120163, "12407": 0.09050461649894714, "12435": 0.11778303235769272, "12719": 0.2674594223499298, "12740": 0.10731173306703568, "12863": 0.5209306478500366, "12928": 0.055094651877880096, "13004": 0.5596157908439636, "13109": 0.015504186972975731, "13228": 0.6492279767990112, "13293": 0.9084475636482239, "13331": 0.09228714555501938, "13341": 0.34370049834251404, "13441": 0.12814582884311676, "13461": 0.9115922451019287, "13531": 0.20977331697940826, "13691": 0.06429435312747955, "13699": 0.5990082025527954, "13808": 0.2160874605178833, "13833": 0.0797421783208847, "13978": 0.14686977863311768, "14061": 0.1229778528213501, "14080": 0.08244366943836212, "14262": 0.9893379211425781, "14396": 0.12038381397724152, "14412": 0.16442140936851501, "14623": 0.06520967930555344, "14667": 0.5827828645706177, "14777": 0.9348671436309814, "14847": 0.026976587250828743, "14956": 0.12814582884311676, "14963": 0.10379679501056671, "15113": 0.0029254043474793434, "15115": 0.15526613593101501, "15158": 0.16690383851528168, "15420": 0.04487626627087593, "15698": 0.17922431230545044, "15704": 0.083342544734478, "15725": 0.5116065740585327, "15869": 0.8091925978660583, "15965": 1.1051015853881836, "16012": 0.7153595685958862, "16020": 0.17020416259765625, "16076": 0.14095009863376617, "16103": 0.32764431834220886, "16233": 0.7314660549163818, "16381": 0.8699195384979248, "16463": 0.13157635927200317, "16515": 0.08154398202896118, "16705": 1.0073304176330566, "16731": 0.21372433006763458, "16902": 0.09495500475168228, "17245": 0.01934296265244484, "17253": 0.05694137513637543, "17442": 0.026025565341114998, "17785": 0.06154331564903259, "17879": 0.014542185701429844, "17913": 0.42353010177612305, "18037": 0.7454653382301331, "18224": 0.22782009840011597, "18479": 0.7258110046386719, "18595": 0.23247487843036652, "18684": 0.03266380727291107, "18714": 0.36967599391937256, "18891": 0.1510767638683319, "18925": 0.021256839856505394, "19037": 0.4337083101272583, "19229": 0.08692999184131622, "19265": 0.07159364968538284, "19470": 0.6155022978782654, "19818": 0.3499138653278351, "19857": 1.2477279901504517, "19915": 0.1751343309879303, "19960": 0.08154398202896118, "20110": 0.9194108247756958, "20155": 0.0842406153678894, "20194": 0.36900100111961365, "20310": 0.0029254043474793434, "20409": 0.058784693479537964, "20523": 0.1011524572968483, "20624": 1.1255888938903809, "20752": 0.3027053773403168, "20896": 0.5307431221008301, "20992": 0.4093637466430664, "21150": 0.19381128251552582, "21254": 0.12038381397724152, "21453": 0.022212404757738113, "21461": 0.06154331564903259, "21497": 0.49626702070236206, "21656": 0.45499902963638306, "21670": 0.38441169261932373, "22071": 0.09584271162748337, "22419": 0.05417001247406006, "22500": 0.06154331564903259, "22552": 0.4580921530723572, "22799": 1.1592369079589844, "22930": 1.2781087160110474, "23150": 0.25239890813827515, "23310": 0.0029254043474793434, "23389": 0.037378571927547455, "23624": 0.09317722171545029, "23820": 0.02412080205976963, "23900": 0.12642613053321838, "24054": 0.4067663550376892, "24081": 0.27786844968795776, "24110": 0.012615402229130268, "24128": 0.19541899859905243, "24229": 0.03925827145576477, "24442": 0.3443928062915802, "24848": 0.24631060659885406, "24901": 0.02316705882549286, "25456": 0.3388410806655884, "25481": 0.8649974465370178, "25862": 1.2894693613052368, "25952": 0.040196798741817474, "26014": 0.8633513450622559, "26094": 0.21372433006763458, "26445": 0.10379679501056671, "26455": 0.8813109993934631, "26721": 0.04953393340110779, "27144": 0.03831886500120163, "27354": 0.12642613053321838, "27484": 0.8641747236251831, "27790": 0.09050461649894714, "27824": 0.26146242022514343, "28329": 0.0038986403960734606, "28436": 0.42990362644195557, "28518": 0.0009760859538801014, "28685": 0.129004567861557, "28828": 0.8559102416038513, "28868": 0.12470348179340363, "28965": 0.30917787551879883, "29398": 0.27342069149017334, "29441": 0.5461324453353882, "29477": 0.029824240133166313} | 12039953 | Depression is a mood disorder characterized by complex alterations of neurotransmitters such as serotonin, norepinephrine, and dopamine. In particular, there is substantial evidence of abnormalities in serotonin neurotransmission. Peripheral parameters of serotoninergic transmission, such as the 5-hydroxytryptamine content of plasma and platelets, have been used to identify biochemical alterations related to depression. In recent years, these parameters have also been used to examine the mechanism of action of antidepressive drugs such as the selective serotonin reuptake inhibitors. This study investigated the interaction between the plasma and platelet levels of fluoxetine and serotonin after fluoxetine administration to depressed patients. Twelve patients affected by major depression (according to the DSM-IV criteria) received a single oral dose of fluoxetine in the morning: 5 mg in the first 5 days, 10 mg from day 6 to day 10, and 20 mg from day 11 to day 40. Blood samples were collected at 0, 7, 10, and 24 hours after drug administration on the day 1 of fluoxetine 5 mg and on the 1st and the 30th day of fluoxetine 20 mg (days 11 and 40 of treatment, respectively). Plasma fluoxetine and serotonin levels increased after drug administration, reaching the highest levels on the 30th day of fluoxetine 20 mg. Fluoxetine levels were also detectable in platelets, with a time variation similar to plasma values. Platelet serotonin levels decreased after drug administration, and the lowest values were observed on the 30th day of fluoxetine 20 mg. | Serotonin and fluoxetine levels in plasma and platelets after fluoxetine treatment in depressive patients. |
{"1011": 0.04394211992621422, "1041": 0.5734702348709106, "1044": 0.24018502235412598, "1059": 0.22782009840011597, "2005": 0.08782484382390976, "2007": 0.151916041970253, "2008": 0.034552380442619324, "2010": 0.8100618124008179, "2011": 0.1693800985813141, "2029": 0.2786078155040741, "2031": 0.05139094591140747, "2038": 0.004870930220931768, "2058": 0.1873544454574585, "2064": 0.05139094591140747, "2076": 0.020300358533859253, "2079": 0.11778303235769272, "2119": 0.1905880719423294, "2239": 0.37371641397476196, "2243": 0.04674193635582924, "2278": 1.1185935735702515, "2290": 0.43244171142578125, "2377": 0.2145126610994339, "2407": 0.0058422754518687725, "2439": 0.3381449282169342, "2458": 0.5220900774002075, "2490": 0.07431721687316895, "2509": 0.4487839937210083, "2515": 0.1718502640724182, "2535": 0.6654226183891296, "2546": 0.9621002674102783, "2549": 0.35745587944984436, "2590": 0.009718249551951885, "2629": 0.5255602598190308, "2632": 0.5021947622299194, "2638": 0.4709797203540802, "2734": 0.05046287178993225, "2838": 0.6838265657424927, "2891": 0.5244048833847046, "2897": 0.3339579105377197, "2920": 0.259204238653183, "2944": 0.04487626627087593, "2969": 1.1431772708892822, "3145": 0.4002431631088257, "3209": 0.42161011695861816, "3223": 0.37102460861206055, "3248": 0.4067663550376892, "3252": 0.004870930220931768, "3258": 0.22392450273036957, "3279": 0.5438674688339233, "3370": 0.5489565134048462, "3375": 0.35677260160446167, "3378": 0.06337817758321762, "3395": 0.7647408246994019, "3433": 0.6244332790374756, "3444": 0.6543170213699341, "3449": 0.24401791393756866, "3457": 0.14264501631259918, "3491": 0.1221139207482338, "3526": 0.9598589539527893, "3539": 0.7482418417930603, "3569": 0.08513788133859634, "3625": 0.22001366317272186, "3670": 0.7182208299636841, "3723": 0.40806588530540466, "3853": 0.3615458607673645, "3930": 0.043007105588912964, "3968": 0.23556606471538544, "3972": 0.5607312321662903, "3974": 0.18654440343379974, "4022": 0.8013357520103455, "4072": 0.20739519596099854, "4106": 0.32341301441192627, "4167": 0.02412080205976963, "4195": 0.10555581003427505, "4245": 0.0842406153678894, "4372": 0.2822965085506439, "4395": 0.5393219590187073, "4442": 1.0907690525054932, "4558": 0.6619023680686951, "4563": 0.7647408246994019, "4637": 0.11168810725212097, "4758": 0.37907835841178894, "4765": 0.7987030148506165, "4958": 0.659380316734314, "4962": 0.9005423784255981, "4972": 0.2881702482700348, "5224": 0.5489565134048462, "5228": 0.31845372915267944, "5284": 0.06612417846918106, "5377": 0.05786345899105072, "5387": 0.6369074583053589, "5441": 0.7863243818283081, "5521": 0.8517522215843201, "5524": 0.9317949414253235, "5537": 0.5551415085792542, "5591": 0.010684899985790253, "5644": 0.18978065252304077, "5668": 0.025073638185858727, "5739": 0.42161011695861816, "5876": 0.5990082025527954, "5901": 0.42225050926208496, "5915": 0.669430673122406, "5918": 0.012615402229130268, "5942": 0.03360854089260101, "6032": 0.8161250352859497, "6064": 0.4041621685028076, "6125": 0.19622190296649933, "6169": 1.094698429107666, "6177": 0.04953393340110779, "6377": 0.23556606471538544, "6409": 0.16276304423809052, "6459": 0.4437839686870575, "6540": 0.17020416259765625, "6576": 0.1064341589808464, "6593": 0.3127557039260864, "6622": 0.2881702482700348, "6753": 0.016465263441205025, "6822": 0.4041621685028076, "6827": 0.45994341373443604, "6869": 0.259204238653183, "6887": 0.401551216840744, "6895": 0.46608972549438477, "6922": 0.22079704701900482, "6970": 0.7995813488960266, "7040": 0.06429435312747955, "7096": 0.8715548515319824, "7337": 0.2026219218969345, "7356": 0.28743788599967957, "7366": 0.2576959431171417, "7403": 0.6430866718292236, "7461": 0.01934296265244484, "7578": 0.6848117709159851, "7591": 0.043007105588912964, "7645": 0.3443928062915802, "7711": 0.23015019297599792, "7730": 0.669430673122406, "7755": 0.2622140049934387, "7816": 0.9769153594970703, "7872": 1.3843393325805664, "7906": 0.05970508232712746, "8153": 0.22937409579753876, "8281": 0.5990082025527954, "8328": 0.053244512528181076, "8360": 0.08064348995685577, "8462": 0.5209306478500366, "8498": 0.5427330136299133, "8586": 0.10203468054533005, "8663": 0.8349450826644897, "8713": 0.960606575012207, "8733": 0.10203468054533005, "8840": 0.6461620330810547, "8878": 0.13755162060260773, "8906": 0.18816383183002472, "8991": 0.151916041970253, "9006": 0.021256839856505394, "9007": 0.5209306478500366, "9078": 1.0023250579833984, "9090": 0.45499902963638306, "9099": 0.08244366943836212, "9100": 0.37304413318634033, "9114": 0.05046287178993225, "9165": 0.9394577741622925, "9175": 0.24859806895256042, "9230": 0.07884006202220917, "9279": 0.09761575609445572, "9319": 0.7258110046386719, "9413": 0.08603433519601822, "9468": 0.469759464263916, "9496": 0.9052929878234863, "9587": 1.1994705200195312, "9686": 1.498855471611023, "9702": 0.4318077862262726, "9706": 0.6369074583053589, "9897": 0.8109301924705505, "10071": 0.11430477350950241, "10288": 0.4932899475097656, "10343": 0.12384103983640671, "10381": 0.2667117714881897, "10580": 0.14433705806732178, "10595": 0.02792670577764511, "10673": 0.0606246218085289, "10708": 0.08782484382390976, "10738": 0.9754437208175659, "10960": 0.23402166366577148, "11008": 0.9463045597076416, "11115": 0.5540198087692261, "11187": 0.034552380442619324, "11423": 0.26146242022514343, "11548": 0.09495500475168228, "11601": 0.4248080551624298, "11619": 0.7987030148506165, "11637": 0.00875066313892603, "11772": 0.009718249551951885, "11916": 0.6476961374282837, "12115": 0.2247048318386078, "12222": 0.8074519634246826, "12247": 0.0009760859538801014, "12386": 0.36697331070899963, "12402": 0.6578640341758728, "12562": 0.1384023278951645, "12944": 0.13670019805431366, "12955": 0.08513788133859634, "12987": 0.304147332906723, "13024": 0.6451379656791687, "13070": 0.11256109178066254, "13248": 0.2741633653640747, "13323": 0.680370569229126, "13458": 0.6492279767990112, "13502": 0.007782140281051397, "13532": 0.3982778787612915, "13595": 0.05694137513637543, "13626": 0.8057082891464233, "13712": 0.6813592314720154, "13791": 0.3963087201118469, "13833": 0.21293537318706512, "13874": 0.4158279001712799, "13908": 0.8500841856002808, "13909": 0.8949713706970215, "14048": 0.1358480453491211, "14120": 0.41647201776504517, "14193": 1.0326838493347168, "14357": 0.4679262638092041, "14471": 0.10906458646059036, "14494": 0.19381128251552582, "14524": 1.005902886390686, "14800": 0.04767346754670143, "14828": 0.23402166366577148, "14863": 0.53589928150177, "15053": 0.15442965924739838, "15176": 0.6471850275993347, "15527": 0.1734936386346817, "15543": 0.5272908806800842, "15680": 0.9531047344207764, "16081": 0.6950984001159668, "16091": 0.4228905141353607, "16221": 0.3170322775840759, "16285": 0.06795065850019455, "16341": 0.5381823778152466, "16387": 0.10818854719400406, "16515": 0.6441128253936768, "16530": 0.669430673122406, "16691": 0.10731173306703568, "16706": 0.2830325961112976, "16984": 0.045809537172317505, "17441": 0.015504186972975731, "17785": 0.02316705882549286, "17824": 0.06703783571720123, "17908": 0.011650617234408855, "18260": 0.9178520441055298, "19220": 0.22079704701900482, "19293": 0.055094651877880096, "19476": 0.6296497583389282, "19539": 0.1510767638683319, "19653": 0.19381128251552582, "19701": 0.953857421875, "19723": 0.33953672647476196, "20045": 0.45994341373443604, "20110": 0.5612884759902954, "20125": 0.021256839856505394, "20228": 0.7134475708007812, "20232": 0.15693697333335876, "20350": 0.3683255612850189, "20363": 0.7898768186569214, "20582": 1.1281205415725708, "20624": 0.7389566898345947, "20655": 0.5220900774002075, "20687": 0.8195732831954956, "21032": 0.3005385100841522, "21101": 0.7220231294631958, "21150": 0.045809537172317505, "21312": 0.04767346754670143, "21575": 0.5734702348709106, "21618": 1.1337933540344238, "21647": 0.14095009863376617, "21716": 0.7201237678527832, "21890": 0.42990362644195557, "21903": 0.27712854743003845, "21906": 0.07793712615966797, "22026": 0.04767346754670143, "22170": 0.07341018319129944, "22239": 0.21293537318706512, "22422": 0.2105647772550583, "22747": 0.8600510358810425, "23216": 0.04860413447022438, "23391": 0.7863243818283081, "23586": 0.004870930220931768, "23737": 0.306306391954422, "23767": 0.04953393340110779, "24012": 0.3526630103588104, "24051": 0.6338034868240356, "24054": 0.1994270235300064, "24140": 0.8600510358810425, "24374": 0.4679262638092041, "24558": 0.7827593088150024, "24848": 0.07341018319129944, "25003": 1.0382318496704102, "25194": 0.09317722171545029, "25562": 0.026025565341114998, "25644": 1.0207915306091309, "25714": 0.12814582884311676, "25761": 0.13243216276168823, "25778": 0.07250232994556427, "26305": 0.08064348995685577, "26402": 0.3916989266872406, "26512": 0.42608439922332764, "26520": 0.11604541540145874, "26534": 0.18573370575904846, "26651": 0.18573370575904846, "26741": 0.026025565341114998, "26773": 0.6512666940689087, "26775": 0.08782484382390976, "27094": 0.347847044467926, "28086": 1.3640767335891724, "28327": 0.9568626880645752, "28405": 0.39367714524269104, "28517": 0.05417001247406006, "28613": 0.7995813488960266, "28691": 0.0606246218085289, "28788": 0.1905880719423294, "28991": 1.049919843673706, "29206": 1.0641717910766602, "29217": 0.04860413447022438} | 12040627 | Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs. | The histone acetyltransferase MOF is a key regulator of the embryonic stem cell core transcriptional network. |
{"1009": 0.2531573474407196, "1011": 0.3910386264324188, "1014": 0.1905880719423294, "1015": 0.43053874373435974, "1018": 0.43434104323387146, "1019": 0.12642613053321838, "1020": 0.27342069149017334, "1023": 0.12038381397724152, "1039": 1.0236024856567383, "1048": 0.2089812457561493, "1060": 0.4228905141353607, "1996": 0.18816383183002472, "1999": 0.08782484382390976, "2005": 0.02792670577764511, "2007": 0.34370049834251404, "2011": 0.31845372915267944, "2015": 0.16607704758644104, "2028": 0.11343330889940262, "2029": 0.26146242022514343, "2046": 0.450652539730072, "2063": 0.02316705882549286, "2073": 0.20977331697940826, "2076": 0.40285754203796387, "2083": 0.004870930220931768, "2089": 0.030771657824516296, "2112": 0.04207121208310127, "2176": 0.1229778528213501, "2179": 0.10467668622732162, "2188": 0.4337083101272583, "2206": 0.20818853378295898, "2207": 0.8349450826644897, "2229": 0.12038381397724152, "2247": 0.08782484382390976, "2278": 0.7925328612327576, "2339": 0.0770333781838417, "2349": 0.045809537172317505, "2358": 0.4132472574710846, "2362": 0.09317722171545029, "2377": 0.006812678650021553, "2389": 0.49030399322509766, "2416": 0.014542185701429844, "2430": 0.6425731778144836, "2475": 0.46424978971481323, "2487": 0.3930181860923767, "2513": 0.4158279001712799, "2515": 0.1332872211933136, "2535": 0.6704301834106445, "2537": 0.7067264318466187, "2546": 0.6512666940689087, "2549": 0.8315495252609253, "2550": 0.48850810527801514, "2595": 1.187628984451294, "2599": 0.011650617234408855, "2609": 0.5984715819358826, "2659": 0.16276304423809052, "2666": 0.3923587501049042, "2668": 0.6160298585891724, "2693": 0.12038381397724152, "2709": 0.8143964409828186, "2713": 0.9240728616714478, "2765": 0.2409527748823166, "2865": 0.6654226183891296, "2895": 0.026025565341114998, "2920": 0.7163142561912537, "2981": 0.06246116757392883, "2993": 0.33115679025650024, "3078": 0.679875910282135, "3117": 0.4891071021556854, "3248": 0.24325250089168549, "3276": 0.043007105588912964, "3295": 0.0019512200960889459, "3378": 0.637939989566803, "3429": 0.603290855884552, "3433": 0.304147332906723, "3463": 0.3676496744155884, "3466": 0.6086184978485107, "3491": 0.11430477350950241, "3525": 0.08244366943836212, "3526": 0.5033760666847229, "3550": 0.4041621685028076, "3560": 0.14264501631259918, "3595": 0.0038986403960734606, "3597": 0.1889725625514984, "3623": 0.020300358533859253, "3625": 0.2145126610994339, "3665": 0.10731173306703568, "3670": 0.7134475708007812, "3796": 0.5139457583427429, "3798": 0.0058422754518687725, "3853": 0.25995752215385437, "3893": 0.02792670577764511, "3896": 0.46853771805763245, "3952": 0.129004567861557, "3965": 0.4311734735965729, "3989": 0.42990362644195557, "4023": 0.02792670577764511, "4078": 0.7286425232887268, "4090": 0.684319257736206, "4187": 0.5573811531066895, "4192": 0.5244048833847046, "4195": 0.1011524572968483, "4263": 0.5640701055526733, "4359": 0.007782140281051397, "4371": 0.42416930198669434, "4395": 0.5255602598190308, "4442": 0.7592713832855225, "4456": 0.24554696679115295, "4539": 0.07793712615966797, "4563": 0.05139094591140747, "4573": 0.5045560002326965, "4588": 0.2659635543823242, "4668": 0.21922965347766876, "4697": 0.13243216276168823, "4742": 0.3777405619621277, "4745": 0.1677299439907074, "4812": 0.26146242022514343, "4904": 0.9409833550453186, "4939": 0.8349450826644897, "4962": 0.03266380727291107, "4975": 0.09850110858678818, "5072": 0.05046287178993225, "5155": 0.2674594223499298, "5173": 1.02149498462677, "5228": 0.3560888469219208, "5250": 0.004870930220931768, "5302": 0.319873183965683, "5360": 0.0058422754518687725, "5387": 0.8212929964065552, "5393": 0.029824240133166313, "5402": 0.08154398202896118, "5403": 0.04207121208310127, "5428": 0.011650617234408855, "5589": 0.44753631949424744, "5651": 0.5104349255561829, "5769": 0.15693697333335876, "5812": 0.20660123229026794, "5876": 0.6107416749000549, "5901": 0.1685553640127182, "5915": 0.5668440461158752, "5923": 1.0030416250228882, "5944": 0.5506471395492554, "5991": 0.32764431834220886, "5994": 0.020300358533859253, "6026": 0.6902132034301758, "6132": 0.6482070088386536, "6169": 0.20660123229026794, "6178": 0.04674193635582924, "6187": 0.13071982562541962, "6190": 0.27342069149017334, "6370": 0.022212404757738113, "6377": 0.11081436276435852, "6459": 0.5640701055526733, "6562": 0.906871497631073, "6577": 0.0354953333735466, "6591": 0.49030399322509766, "6592": 0.18329764902591705, "6624": 0.2470736801624298, "6648": 0.11256109178066254, "6774": 0.32199856638908386, "6873": 0.8004589080810547, "6968": 0.34508460760116577, "6999": 0.2409527748823166, "7017": 0.1685553640127182, "7037": 0.09672962874174118, "7085": 0.7592713832855225, "7137": 0.3191637098789215, "7242": 0.2637155055999756, "7336": 0.12470348179340363, "7337": 0.7737906575202942, "7356": 0.0797421783208847, "7457": 0.052318159490823746, "7461": 0.32058215141296387, "7485": 0.24171993136405945, "7570": 0.6960725784301758, "7591": 0.037378571927547455, "7645": 0.5209306478500366, "7711": 0.14433705806732178, "7755": 0.33115679025650024, "7790": 0.8039615154266357, "7872": 0.9783848524093628, "7978": 0.3923587501049042, "8039": 0.0354953333735466, "8116": 0.13499516248703003, "8123": 1.264413595199585, "8153": 0.04394211992621422, "8278": 0.03831886500120163, "8281": 0.3870677351951599, "8287": 0.4837033152580261, "8290": 0.9591107368469238, "8292": 0.21687394380569458, "8418": 0.1718502640724182, "8528": 0.2478361576795578, "8556": 0.055094651877880096, "8586": 0.13157635927200317, "8699": 0.920189380645752, "8878": 0.6764062643051147, "8920": 0.013579257763922215, "9007": 0.5051454305648804, "9048": 0.20580662786960602, "9113": 0.015504186972975731, "9125": 0.19862671196460724, "9141": 0.9248477816581726, "9276": 0.46117570996284485, "9279": 0.1677299439907074, "9355": 0.055094651877880096, "9358": 0.03266380727291107, "9412": 0.19381128251552582, "9468": 0.11081436276435852, "9496": 0.04767346754670143, "9597": 0.11168810725212097, "9869": 0.10026945173740387, "9885": 0.5151132941246033, "9998": 0.014542185701429844, "10057": 0.06520967930555344, "10266": 0.9379299283027649, "10381": 0.1913948506116867, "10448": 0.31560876965522766, "10507": 0.13414156436920166, "10509": 0.14179791510105133, "10548": 0.5952457785606384, "10556": 0.07341018319129944, "10572": 0.846739649772644, "10595": 0.6828403472900391, "10610": 0.6704301834106445, "10624": 0.4500300884246826, "10671": 0.6476961374282837, "10744": 0.08513788133859634, "10769": 0.7827593088150024, "10847": 0.4574742913246155, "10851": 0.6734226942062378, "11211": 0.13670019805431366, "11240": 0.9263957738876343, "11254": 0.02887592278420925, "11265": 0.7710843086242676, "11311": 0.4126010537147522, "11382": 0.1510767638683319, "11423": 0.16524957120418549, "11835": 0.7144040465354919, "12123": 0.21922965347766876, "12153": 0.06612417846918106, "12247": 0.09938567131757736, "12402": 0.3297532796859741, "12530": 0.15526613593101501, "12732": 0.18492233753204346, "12745": 0.10026945173740387, "12823": 0.14518201351165771, "13004": 0.08064348995685577, "13330": 0.06154331564903259, "13341": 0.40741631388664246, "13461": 0.29255300760269165, "13523": 0.7881022095680237, "13531": 0.012615402229130268, "13791": 0.9724938273429871, "13833": 0.8004589080810547, "13853": 1.2158164978027344, "13922": 0.1011524572968483, "14074": 0.14686977863311768, "14126": 0.007782140281051397, "14828": 0.7746911644935608, "15115": 0.1734936386346817, "15166": 0.10026945173740387, "15439": 0.1734936386346817, "15680": 0.04674193635582924, "15946": 0.19622190296649933, "16285": 0.09672962874174118, "16480": 0.22626367211341858, "16483": 0.006812678650021553, "16691": 0.0058422754518687725, "16730": 0.14686977863311768, "16910": 0.07250232994556427, "17250": 0.49864232540130615, "17257": 0.29255300760269165, "17371": 1.0478670597076416, "17379": 0.34922540187835693, "17441": 0.4494072198867798, "17629": 0.026976587250828743, "17698": 0.04767346754670143, "17820": 0.04860413447022438, "17913": 0.4487839937210083, "18037": 0.08513788133859634, "18044": 0.33325836062431335, "18133": 0.18167030811309814, "18178": 1.2813677787780762, "18349": 0.2105647772550583, "18547": 0.3423145115375519, "18622": 0.8264343738555908, "18684": 0.1718502640724182, "18714": 0.30558720231056213, "18715": 0.043007105588912964, "18924": 0.7047978043556213, "18981": 0.8682814836502075, "19251": 1.19829261302948, "19335": 0.846739649772644, "19466": 1.0144377946853638, "19589": 0.6244332790374756, "19610": 0.567397952079773, "19612": 0.22157983481884003, "19653": 0.680370569229126, "19780": 0.0029254043474793434, "19872": 0.32341301441192627, "20125": 0.5707147121429443, "20156": 0.04487626627087593, "20187": 1.0409941673278809, "20194": 0.015504186972975731, "20415": 0.2674594223499298, "20464": 0.09584271162748337, "20523": 1.0172666311264038, "20544": 0.7229714393615723, "20752": 0.13071982562541962, "20817": 0.083342544734478, "20858": 0.10379679501056671, "21083": 0.037378571927547455, "21117": 1.0389231443405151, "21150": 0.08154398202896118, "21197": 0.7827593088150024, "21471": 0.026025565341114998, "21618": 0.10555581003427505, "21656": 0.34715715050697327, "21716": 0.8861536383628845, "21733": 0.6989894509315491, "21735": 0.0009760859538801014, "21758": 0.06977381557226181, "21770": 0.854249119758606, "21823": 0.151916041970253, "21903": 0.3485364317893982, "21919": 0.46608972549438477, "21935": 0.3723714053630829, "21967": 0.03831886500120163, "22022": 0.043007105588912964, "22260": 0.06520967930555344, "22291": 0.35745587944984436, "22458": 0.7009293437004089, "22931": 0.956112265586853, "23041": 0.34922540187835693, "23216": 0.21135559678077698, "23586": 0.14264501631259918, "23616": 0.1710275560617447, "23900": 0.16524957120418549, "24004": 0.036437395960092545, "24054": 0.3339579105377197, "24269": 1.0423725843429565, "24335": 0.777387797832489, "24848": 0.12384103983640671, "24960": 1.538210391998291, "25090": 0.77198725938797, "25194": 0.28597161173820496, "25456": 0.06612417846918106, "25468": 0.5301685929298401, "25580": 1.0285027027130127, "25608": 0.3325583338737488, "25610": 0.15610189735889435, "25714": 0.5461324453353882, "26243": 0.1011524572968483, "26402": 0.20580662786960602, "26435": 0.06886265426874161, "26721": 0.0009760859538801014, "26773": 0.0913962796330452, "26775": 1.162295937538147, "26819": 0.02887592278420925, "27144": 0.9658246636390686, "27295": 0.12556517124176025, "27526": 0.4248080551624298, "27781": 1.0030416250228882, "27854": 0.906871497631073, "28309": 1.013020396232605, "28696": 0.9108069539070129, "28788": 0.6317287683486938, "28873": 0.34577593207359314, "29248": 0.08244366943836212, "29290": 0.32058215141296387, "29490": 0.08154398202896118, "29592": 0.13157635927200317} | 12058271 | The bone marrow is the primary site for neutrophil production and release into the circulation. Because the CXC chemokine receptor-4/stromal derived factor-1 (CXCR4/SDF-1) axis plays a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether reciprocal CXCR4-dependent mechanisms might be involved in neutrophil release and subsequent return to the marrow following circulation. Neutralizing antibody to CXCR4 reduced marrow retention of infused neutrophils (45.7% +/- 0.5% to 6.9% +/- 0.5%) and was found to mobilize neutrophils from marrow (34.4% +/- 4.4%). Neutrophil CXCR4 expression and SDF-1-induced calcium flux decreased with maturation and activation of the cells, corresponding to the decreased marrow homing associated with these characteristics in vivo. Infusion of the inflammatory mediator and CXCR2 ligand KC led to mobilization of neutrophils from marrow by itself and was augmented 3-fold by low doses of CXCR4-blocking antibody that otherwise had no mobilizing effect. Examination of KC and SDF-1 calcium signaling demonstrated that the effect of KC may, in part, be due to heterologous desensitization to SDF-1. These results suggest that the CXCR4/SDF-1 axis is critical in circulating neutrophil homeostasis and that it may participate in the rapid release of neutrophils from the marrow during inflammation through a novel interaction with inflammatory CXC chemokines. | Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. |
{"1011": 0.025073638185858727, "1014": 0.22548456490039825, "1026": 0.04394211992621422, "1040": 1.261651873588562, "1044": 0.04394211992621422, "1048": 0.043007105588912964, "1052": 0.21530038118362427, "1998": 0.06612417846918106, "2022": 0.04674193635582924, "2064": 0.02887592278420925, "2078": 0.10993985831737518, "2084": 0.21214580535888672, "2090": 0.0354953333735466, "2094": 0.09850110858678818, "2116": 0.22937409579753876, "2120": 0.2607102394104004, "2124": 0.14179791510105133, "2152": 0.22626367211341858, "2154": 0.6233867406845093, "2172": 0.49030399322509766, "2199": 0.022212404757738113, "2202": 0.12728634476661682, "2204": 0.21687394380569458, "2217": 0.02887592278420925, "2240": 0.6011518239974976, "2270": 0.40546512603759766, "2323": 0.21687394380569458, "2378": 0.04394211992621422, "2389": 0.23864774405956268, "2391": 0.53589928150177, "2410": 0.4190443754196167, "2411": 0.11430477350950241, "2420": 0.0038986403960734606, "2422": 0.37707099318504333, "2423": 1.0087559223175049, "2431": 0.7028654217720032, "2445": 0.02412080205976963, "2470": 0.1808556467294693, "2504": 0.27564704418182373, "2511": 0.47827014327049255, "2515": 0.02316705882549286, "2531": 0.5751199722290039, "2566": 0.20977331697940826, "2579": 0.07341018319129944, "2599": 0.16690383851528168, "2601": 0.06154331564903259, "2625": 0.04674193635582924, "2635": 0.026025565341114998, "2659": 0.09495500475168228, "2671": 0.35813871026039124, "2677": 0.2674594223499298, "2685": 0.022212404757738113, "2692": 0.05417001247406006, "2734": 0.28890204429626465, "2740": 0.4425300657749176, "2753": 0.6578640341758728, "2779": 0.09938567131757736, "2817": 0.42735910415649414, "2825": 0.0842406153678894, "2846": 0.4450363218784332, "2895": 0.6223390698432922, "2896": 0.4794800877571106, "2913": 0.5238267183303833, "2914": 0.777387797832489, "2951": 0.0019512200960889459, "2992": 0.21214580535888672, "3020": 0.1734936386346817, "3070": 0.8925741910934448, "3100": 0.018384648486971855, "3103": 0.7276995778083801, "3120": 0.02316705882549286, "3141": 0.20818853378295898, "3197": 0.011650617234408855, "3210": 0.4286321699619293, "3223": 0.0009760859538801014, "3273": 0.34922540187835693, "3276": 0.6931471824645996, "3356": 0.574020504951477, "3378": 0.7809720039367676, "3382": 0.0019512200960889459, "3426": 0.15442965924739838, "3433": 1.0073304176330566, "3445": 0.31489628553390503, "3446": 0.1873544454574585, "3452": 0.33605360984802246, "3463": 0.18978065252304077, "3466": 0.0797421783208847, "3497": 0.025073638185858727, "3512": 0.0009760859538801014, "3517": 0.06977381557226181, "3609": 0.5086748600006104, "3623": 0.44753631949424744, "3634": 0.12556517124176025, "3643": 0.5080875158309937, "3647": 0.9650808572769165, "3653": 0.47402387857437134, "3671": 0.23710809648036957, "3679": 0.6096806526184082, "3798": 0.20818853378295898, "3808": 0.4568560719490051, "3815": 0.20421554148197174, "3867": 0.13499516248703003, "3891": 0.9643365740776062, "3896": 0.28082266449928284, "3943": 0.5762182474136353, "3979": 0.10993985831737518, "3991": 0.49864232540130615, "4045": 0.07068414986133575, "4102": 0.6793810129165649, "4106": 0.06337817758321762, "4118": 0.2976420819759369, "4163": 0.32553088665008545, "4179": 0.28743788599967957, "4180": 0.10906458646059036, "4270": 0.11343330889940262, "4281": 0.7210738658905029, "4293": 0.043007105588912964, "4295": 0.013579257763922215, "4308": 0.11778303235769272, "4340": 0.2659635543823242, "4431": 0.46363574266433716, "4456": 1.138809084892273, "4506": 0.011650617234408855, "4521": 0.06886265426874161, "4595": 0.6064908504486084, "4621": 0.14686977863311768, "4652": 0.08513788133859634, "4668": 0.39762192964553833, "4725": 0.37640097737312317, "4788": 0.004870930220931768, "4795": 0.45994341373443604, "4849": 0.27342069149017334, "4971": 0.31560876965522766, "5012": 0.15693697333335876, "5043": 0.09406650811433792, "5300": 0.5584990978240967, "5302": 0.18411032855510712, "5333": 0.6338034868240356, "5436": 0.007782140281051397, "5443": 0.12384103983640671, "5473": 0.06520967930555344, "5531": 0.25239890813827515, "5547": 0.05417001247406006, "5790": 0.045809537172317505, "5799": 0.1619328260421753, "5816": 0.04113444685935974, "5838": 0.3027053773403168, "5983": 0.10906458646059036, "6022": 0.0019512200960889459, "6038": 0.5979346632957458, "6086": 0.5990082025527954, "6165": 0.20022670924663544, "6274": 0.3547199070453644, "6302": 0.5756692886352539, "6388": 0.04953393340110779, "6431": 0.27564704418182373, "6444": 0.07431721687316895, "6445": 0.05139094591140747, "6463": 0.9929623603820801, "6529": 0.015504186972975731, "6540": 0.18654440343379974, "6640": 0.0038986403960734606, "6693": 0.7782850861549377, "6694": 0.8973627090454102, "6749": 0.14518201351165771, "6812": 0.22548456490039825, "6869": 0.6218147873878479, "7012": 0.2637155055999756, "7017": 0.3870677351951599, "7091": 0.4318077862262726, "7189": 0.27044451236724854, "7290": 0.083342544734478, "7386": 0.1212492436170578, "7399": 0.9915141463279724, "7457": 0.18248429894447327, "7461": 0.09050461649894714, "7524": 0.9340999722480774, "7591": 0.3262358605861664, "7629": 0.0009760859538801014, "7691": 0.17922431230545044, "7718": 0.04860413447022438, "7730": 0.12814582884311676, "7760": 0.7592713832855225, "7831": 0.736154317855835, "7965": 0.36697331070899963, "7978": 0.2689530849456787, "8089": 0.7086513638496399, "8123": 0.0009760859538801014, "8249": 0.09584271162748337, "8279": 0.03925827145576477, "8290": 0.02887592278420925, "8319": 0.13499516248703003, "8381": 0.45870962738990784, "8483": 0.021256839856505394, "8700": 0.8600510358810425, "8729": 0.04113444685935974, "8738": 0.27044451236724854, "9032": 0.6038249135017395, "9063": 0.009718249551951885, "9280": 0.13499516248703003, "9325": 1.0788878202438354, "9336": 0.2034190446138382, "9367": 0.5272908806800842, "9420": 0.176772341132164, "9469": 0.03925827145576477, "9556": 0.1718502640724182, "9592": 0.0174254160374403, "9597": 0.1677299439907074, "9608": 0.11430477350950241, "9609": 0.5838727951049805, "9626": 0.02316705882549286, "9689": 0.3554046154022217, "9718": 0.009718249551951885, "9723": 0.06703783571720123, "9874": 1.0628231763839722, "9938": 0.04953393340110779, "9998": 0.9092346429824829, "10020": 0.5773153901100159, "10074": 0.02792670577764511, "10174": 0.05139094591140747, "10238": 1.243794322013855, "10509": 0.35128939151763916, "10611": 0.056018441915512085, "10744": 0.11865071207284927, "10754": 0.7028654217720032, "10831": 0.6327666640281677, "10847": 0.06612417846918106, "10960": 0.3388410806655884, "11326": 0.18167030811309814, "11441": 0.33953672647476196, "11460": 0.23787821829319, "11616": 0.31132611632347107, "11695": 0.23092569410800934, "11704": 0.1808556467294693, "11706": 0.24248650670051575, "11765": 0.29255300760269165, "11852": 0.015504186972975731, "12123": 0.2659635543823242, "12171": 0.2223619967699051, "12353": 0.0009760859538801014, "12418": 0.09584271162748337, "12435": 0.3656192123889923, "12448": 0.2689530849456787, "12596": 0.12384103983640671, "12765": 0.056018441915512085, "12826": 0.4752389192581177, "12878": 0.5947071313858032, "13004": 0.9553611874580383, "13070": 0.11343330889940262, "13105": 0.09850110858678818, "13275": 0.11517547070980072, "13331": 0.2231435477733612, "13509": 0.0058422754518687725, "13599": 0.5876781344413757, "13656": 0.2763880789279938, "13726": 0.43053874373435974, "13822": 0.841701865196228, "13827": 0.09495500475168228, "13845": 0.007782140281051397, "13986": 0.09938567131757736, "13990": 0.18573370575904846, "14061": 0.5562619566917419, "14120": 0.5893046259880066, "14267": 0.12556517124176025, "14451": 0.2983669638633728, "14639": 0.29328158497810364, "14708": 0.36426326632499695, "14710": 0.7134475708007812, "14944": 0.00875066313892603, "15306": 0.6754127144813538, "15316": 0.03831886500120163, "15502": 0.12470348179340363, "15559": 0.16442140936851501, "16007": 0.22157983481884003, "16134": 0.32058215141296387, "16211": 0.040196798741817474, "16412": 0.10731173306703568, "16519": 0.055094651877880096, "16643": 0.010684899985790253, "16678": 0.1693800985813141, "16731": 0.4132472574710846, "16844": 1.0458102226257324, "16902": 0.5162794589996338, "17503": 0.05417001247406006, "17631": 0.3903779089450836, "17663": 1.4487555027008057, "17686": 0.0009760859538801014, "17760": 0.07612881064414978, "17788": 0.41647201776504517, "17886": 0.0842406153678894, "17922": 0.5415972471237183, "17978": 1.0855059623718262, "18037": 0.8400169610977173, "18178": 0.09317722171545029, "18479": 0.9092346429824829, "18539": 0.18654440343379974, "18622": 0.12038381397724152, "18949": 0.9769153594970703, "19064": 0.18248429894447327, "19126": 0.20818853378295898, "19188": 0.4041621685028076, "19300": 0.04674193635582924, "19352": 0.1332872211933136, "19425": 0.06795065850019455, "19824": 0.26446542143821716, "19875": 0.7510106563568115, "20014": 0.022212404757738113, "20194": 0.9531047344207764, "20435": 0.306306391954422, "20647": 0.27712854743003845, "20994": 0.09406650811433792, "21081": 0.5865923762321472, "21150": 0.12986256182193756, "21434": 0.175953671336174, "21447": 0.3269403576850891, "21656": 0.567951500415802, "21879": 0.6838265657424927, "22423": 0.015504186972975731, "22471": 1.1337933540344238, "22963": 0.4093637466430664, "23444": 0.14602625370025635, "23579": 0.043007105588912964, "23691": 0.04767346754670143, "23900": 0.4412745535373688, "24410": 0.053244512528181076, "24759": 0.06429435312747955, "24868": 0.034552380442619324, "25078": 0.7934166193008423, "25086": 0.04860413447022438, "25135": 0.24631060659885406, "25409": 0.7220231294631958, "25613": 0.07341018319129944, "25654": 0.15023678541183472, "25732": 0.8022117614746094, "25775": 0.12642613053321838, "26163": 0.11081436276435852, "26237": 0.11517547070980072, "26651": 0.5540198087692261, "26745": 0.5668440461158752, "26780": 0.2674594223499298, "27347": 0.40806588530540466, "28207": 0.02887592278420925, "28268": 0.1930064558982849, "28403": 0.9447870850563049, "28667": 0.030771657824516296, "29371": 0.010684899985790253} | 12074066 | BACKGROUND Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence rates of colorectal cancer, but the dose-response relationship has not been adequately studied. METHODS Dose-response gradients from observational studies of Vitamin D intake and serum 25-hydroxyvitamin D were plotted as trend lines. The point on each linear trend line corresponding to an odds ratio of 0.50 provided the prediagnostic Vitamin D intake or 25-hydroxyvitamin D concentration associated with 50% lower risk compared to <100IU/day Vitamin D or <13ng/ml serum 25-hydroxyvitamin D. Medians of these values were determined. RESULTS Overall, individuals with >or=1000IU/day oral Vitamin D (p<0.0001) or >or=33ng/ml (82nmol/l) serum 25-hydroxyvitamin D (p<0.01) had 50% lower incidence of colorectal cancer compared to reference values. CONCLUSIONS Intake of 1000IU/day of Vitamin D, half the safe upper intake established by the National Academy of Sciences, was associated with 50% lower risk. Serum 25-hydroxyvitamin D of 33ng/ml, which is known to be safe, also was associated with 50% lower risk. Prompt public health action is needed to increase intake of Vitamin D(3) to 1000IU/day, and to raise 25-hydroxyvitamin D by encouraging a modest duration of sunlight exposure. | Vitamin D and prevention of colorectal cancer. |
{"1011": 0.10379679501056671, "1042": 0.5887627601623535, "1054": 0.11168810725212097, "1997": 0.053244512528181076, "2004": 0.8349450826644897, "2008": 0.04113444685935974, "2010": 0.7473171949386597, "2011": 0.31845372915267944, "2024": 0.014542185701429844, "2025": 0.27044451236724854, "2029": 0.13414156436920166, "2049": 0.0317181795835495, "2079": 0.22859740257263184, "2092": 0.3676496744155884, "2094": 0.3897167444229126, "2128": 0.27044451236724854, "2129": 0.055094651877880096, "2152": 0.20977331697940826, "2164": 0.053244512528181076, "2193": 0.4914994537830353, "2339": 0.1332872211933136, "2350": 0.5540198087692261, "2407": 0.4337083101272583, "2408": 0.3949938118457794, "2421": 0.1332872211933136, "2439": 0.12642613053321838, "2442": 0.3870677351951599, "2443": 0.02792670577764511, "2487": 0.6086184978485107, "2491": 0.5707147121429443, "2506": 0.176772341132164, "2515": 0.3325583338737488, "2532": 1.2432310581207275, "2546": 0.5278670787811279, "2556": 0.034552380442619324, "2599": 0.2539152204990387, "2647": 0.3601844012737274, "2649": 0.05139094591140747, "2669": 0.06520967930555344, "2828": 0.009718249551951885, "2832": 0.4734157919883728, "2885": 0.3615458607673645, "2921": 0.040196798741817474, "2950": 0.1064341589808464, "2951": 0.32553088665008545, "2981": 0.8973627090454102, "3064": 0.03266380727291107, "3117": 0.5290185213088989, "3161": 0.4318077862262726, "3223": 0.5104349255561829, "3252": 0.20022670924663544, "3257": 0.42416930198669434, "3279": 0.6853039860725403, "3338": 0.7182208299636841, "3378": 0.026025565341114998, "3491": 0.10467668622732162, "3508": 0.7172679901123047, "3512": 0.41065993905067444, "3526": 0.4248080551624298, "3560": 0.4512746334075928, "3563": 0.0174254160374403, "3568": 0.08244366943836212, "3605": 0.7124901413917542, "3616": 0.3070250153541565, "3631": 0.08513788133859634, "3668": 0.41195443272590637, "3670": 0.17759032547473907, "3674": 0.4311734735965729, "3685": 0.2689530849456787, "3698": 0.3084607720375061, "3714": 0.22001366317272186, "3768": 0.22704219818115234, "3774": 0.014542185701429844, "3775": 0.5455666780471802, "3787": 0.7528522610664368, "3796": 0.37907835841178894, "3811": 0.8100618124008179, "3904": 0.46608972549438477, "3943": 0.07612881064414978, "4039": 0.07612881064414978, "4072": 0.2516399025917053, "4081": 0.1693800985813141, "4225": 0.1510767638683319, "4227": 0.3269403576850891, "4423": 0.5903874635696411, "4442": 0.33953672647476196, "4453": 0.35128939151763916, "4541": 0.016465263441205025, "4558": 0.2447827309370041, "4588": 0.3560888469219208, "4679": 0.1011524572968483, "4720": 0.43875885009765625, "4758": 0.47827014327049255, "4809": 0.5074998140335083, "4842": 0.8813109993934631, "4863": 0.3588210940361023, "4911": 0.34715715050697327, "4935": 1.2894693613052368, "4962": 0.5512100458145142, "5082": 0.5220900774002075, "5114": 0.8567397594451904, "5153": 0.03266380727291107, "5158": 0.5127768516540527, "5186": 0.043007105588912964, "5224": 0.7898768186569214, "5250": 0.6064908504486084, "5258": 0.5313173532485962, "5260": 0.27786844968795776, "5320": 0.04207121208310127, "5331": 0.12642613053321838, "5354": 0.16359257698059082, "5358": 0.3464667797088623, "5441": 0.6471850275993347, "5449": 0.2837681770324707, "5450": 0.5162794589996338, "5478": 0.680370569229126, "5512": 0.4132472574710846, "5524": 0.7987030148506165, "5537": 0.6244332790374756, "5549": 0.7610978484153748, "5567": 1.0023250579833984, "5643": 0.7978238463401794, "5719": 0.1064341589808464, "5769": 0.037378571927547455, "5783": 0.6867793202400208, "5867": 0.8740028142929077, "5908": 0.43053874373435974, "5942": 0.5045560002326965, "5991": 0.22626367211341858, "6025": 0.16607704758644104, "6032": 0.38308101892471313, "6064": 1.3118107318878174, "6075": 0.20977331697940826, "6083": 0.29473719000816345, "6100": 0.5979346632957458, "6194": 0.1946154683828354, "6228": 0.06612417846918106, "6409": 0.32553088665008545, "6459": 0.16607704758644104, "6483": 0.5773153901100159, "6540": 0.025073638185858727, "6555": 1.0560526847839355, "6592": 0.40546512603759766, "6635": 0.18329764902591705, "6673": 0.75193190574646, "6681": 0.11168810725212097, "7065": 0.025073638185858727, "7077": 0.2696990668773651, "7229": 0.07612881064414978, "7327": 1.1102628707885742, "7337": 1.0695481300354004, "7347": 0.272677481174469, "7356": 0.18167030811309814, "7366": 0.3615458607673645, "7403": 0.5876781344413757, "7539": 0.043007105588912964, "7607": 0.07431721687316895, "7645": 0.22626367211341858, "7677": 0.4203280806541443, "7711": 0.49030399322509766, "7730": 0.7463917136192322, "7790": 1.076228141784668, "7807": 0.5584990978240967, "7816": 0.6139179468154907, "7818": 0.8989537954330444, "7949": 0.3622259199619293, "8077": 0.14349138736724854, "8171": 0.6512666940689087, "8281": 0.016465263441205025, "8303": 0.012615402229130268, "8335": 0.07250232994556427, "8385": 0.33953672647476196, "8402": 0.006812678650021553, "8498": 0.3163207769393921, "8525": 0.4831010699272156, "8534": 0.020300358533859253, "8676": 0.1485546976327896, "8878": 0.1221139207482338, "8991": 0.8022117614746094, "9007": 0.23402166366577148, "9034": 0.35128939151763916, "9041": 0.24554696679115295, "9104": 0.013579257763922215, "9165": 0.38905516266822815, "9174": 0.42608439922332764, "9186": 0.4974553883075714, "9279": 0.272677481174469, "9285": 0.3077431619167328, "9292": 0.8298473954200745, "9319": 0.6149744987487793, "9330": 0.3106105625629425, "9377": 1.207676887512207, "9530": 0.33675122261047363, "9601": 0.4158279001712799, "9756": 0.18573370575904846, "9885": 0.5701626539230347, "10066": 0.14179791510105133, "10071": 0.5767669677734375, "10210": 0.08782484382390976, "10327": 0.1751343309879303, "10335": 0.47463157773017883, "10341": 0.007782140281051397, "10394": 0.757441520690918, "10480": 0.9363996982574463, "10548": 0.46363574266433716, "10572": 0.9256220459938049, "10595": 0.997294545173645, "10694": 0.2837681770324707, "10738": 0.4891071021556854, "10744": 0.1710275560617447, "10785": 0.15526613593101501, "10851": 0.5272908806800842, "10867": 0.1384023278951645, "10889": 0.46302130818367004, "10958": 1.0775588750839233, "11043": 0.009718249551951885, "11115": 0.5461324453353882, "11158": 0.5925496220588684, "11160": 0.23247487843036652, "11508": 0.011650617234408855, "11539": 0.129004567861557, "11583": 0.45437926054000854, "11644": 0.5220900774002075, "11649": 0.7370892763137817, "11718": 0.34922540187835693, "12014": 0.35813871026039124, "12154": 0.5215105414390564, "12222": 1.031988263130188, "12328": 0.0038986403960734606, "12530": 0.6358738541603088, "12540": 0.4437839686870575, "12702": 0.0752234235405922, "12732": 0.5127768516540527, "12789": 0.27786844968795776, "12823": 0.04953393340110779, "12987": 0.5651806592941284, "13070": 0.08064348995685577, "13458": 0.5573811531066895, "13595": 0.8074519634246826, "14080": 0.18573370575904846, "14087": 0.20501139760017395, "14127": 0.7969439625740051, "14163": 0.15610189735889435, "14193": 0.24248650670051575, "14471": 0.24171993136405945, "14494": 0.8517522215843201, "14627": 0.21293537318706512, "14632": 0.05786345899105072, "14800": 0.33675122261047363, "14967": 0.27342069149017334, "14996": 0.2637155055999756, "15059": 0.637939989566803, "15122": 0.04487626627087593, "15176": 0.5092619061470032, "15192": 1.0560526847839355, "15200": 0.0038986403960734606, "15289": 0.09406650811433792, "15445": 0.14095009863376617, "15527": 0.7239188551902771, "15543": 0.013579257763922215, "15712": 0.1685553640127182, "15770": 0.0009760859538801014, "15775": 0.8829278349876404, "15778": 0.0019512200960889459, "15826": 0.34370049834251404, "15946": 0.20102575421333313, "16021": 0.7426811456680298, "16086": 0.26446542143821716, "16221": 0.9621002674102783, "16226": 0.10818854719400406, "16238": 0.2711893916130066, "16360": 0.5220900774002075, "16428": 1.3525274991989136, "16429": 0.7728893756866455, "16599": 0.0770333781838417, "16643": 0.6016870141029358, "16706": 0.8340972661972046, "16803": 0.036437395960092545, "16840": 0.2145126610994339, "16910": 0.35745587944984436, "16922": 0.0317181795835495, "16961": 0.25995752215385437, "17215": 0.13243216276168823, "17341": 0.11430477350950241, "17366": 0.18654440343379974, "17431": 0.02792670577764511, "17785": 0.011650617234408855, "17913": 0.3903779089450836, "17959": 0.03831886500120163, "17993": 1.2204381227493286, "18234": 0.0029254043474793434, "18562": 0.9340999722480774, "18642": 0.10555581003427505, "19304": 0.21530038118362427, "19395": 1.167778730392456, "19500": 0.04674193635582924, "19611": 0.11778303235769272, "19653": 0.817850649356842, "19723": 0.10379679501056671, "19872": 0.20501139760017395, "19896": 0.3241194784641266, "20125": 0.03925827145576477, "20250": 0.21135559678077698, "20299": 0.1358480453491211, "20307": 0.0058422754518687725, "20396": 1.1337933540344238, "20419": 0.6517757177352905, "20487": 0.06520967930555344, "20519": 0.09317722171545029, "21104": 0.7473171949386597, "21114": 1.104454517364502, "21144": 0.13071982562541962, "21197": 0.7629209756851196, "21376": 0.1358480453491211, "21486": 0.29981520771980286, "21557": 0.29400965571403503, "21575": 0.23556606471538544, "21618": 0.2852376699447632, "21647": 1.3300546407699585, "21716": 0.11865071207284927, "21821": 0.4412745535373688, "21903": 0.058784693479537964, "21957": 1.3274686336517334, "22026": 0.9900637865066528, "22203": 1.0855059623718262, "22207": 0.0038986403960734606, "22275": 0.4709797203540802, "22422": 0.04207121208310127, "22625": 0.6704301834106445, "22932": 0.0029254043474793434, "23079": 0.25467249751091003, "23087": 0.10026945173740387, "23277": 0.025073638185858727, "23318": 0.7314660549163818, "23563": 1.1864371299743652, "23750": 0.40089741349220276, "23892": 0.7067264318466187, "24004": 0.956112265586853, "24394": 0.16690383851528168, "24473": 0.41001203656196594, "24545": 0.2493593990802765, "24558": 0.036437395960092545, "24731": 0.5145297050476074, "24854": 0.05046287178993225, "25206": 0.02412080205976963, "25269": 0.36697331070899963, "25338": 0.20022670924663544, "25499": 0.8315495252609253, "25524": 0.40546512603759766, "25644": 0.036437395960092545, "25746": 1.1153976917266846, "26224": 0.17267228662967682, "26402": 0.00875066313892603, "26601": 0.11517547070980072, "26773": 0.5145297050476074, "26874": 0.46363574266433716, "26976": 0.25088030099868774, "27009": 0.5267143249511719, "27559": 0.12986256182193756, "27598": 0.2918238639831543, "27642": 1.0423725843429565, "27814": 0.4938860833644867, "27846": 0.04207121208310127, "28024": 0.7951818704605103, "28079": 0.006812678650021553, "28154": 1.202409029006958, "28297": 0.014542185701429844, "28311": 0.07068414986133575, "28424": 0.3464667797088623, "28667": 0.9710156321525574, "28774": 0.0606246218085289, "28911": 0.06337817758321762, "29129": 0.5069117546081543, "29264": 0.3163207769393921, "29290": 0.40089741349220276, "29300": 0.30989447236061096, "29722": 0.0009760859538801014} | 12086599 | Major eukaryotic genomic elements, including the ribosomal DNA (rDNA), are composed of repeated sequences with well-defined copy numbers that must be maintained by regulated recombination. Although mechanisms that instigate rDNA recombination have been identified, none are directional and they therefore cannot explain precise repeat number control. Here, we show that yeast lacking histone chaperone Asf1 undergo reproducible rDNA repeat expansions. These expansions do not require the replication fork blocking protein Fob1 and are therefore independent of known rDNA expansion mechanisms. We propose the existence of a regulated rDNA repeat gain pathway that becomes constitutively active in asf1Δ mutants. Cells lacking ASF1 accumulate rDNA repeats with high fidelity in a processive manner across multiple cell divisions. The mechanism of repeat gain is dependent on highly repetitive sequence but, surprisingly, is independent of the homologous recombination proteins Rad52, Rad51 and Rad59. The expansion mechanism is compromised by mutations that decrease the processivity of DNA replication, which leads to progressive loss of rDNA repeats. Our data suggest that a novel mode of break-induced replication occurs in repetitive DNA that is dependent on high homology but does not require the canonical homologous recombination machinery. | Repeat expansion in the budding yeast ribosomal DNA can occur independently of the canonical homologous recombination machinery |
{"1019": 0.09406650811433792, "1039": 0.5506471395492554, "1041": 0.37907835841178894, "1043": 0.5278670787811279, "1996": 0.11430477350950241, "1999": 0.10906458646059036, "2002": 0.5381823778152466, "2008": 0.04207121208310127, "2011": 0.010684899985790253, "2025": 0.05139094591140747, "2029": 0.1905880719423294, "2053": 0.058784693479537964, "2058": 0.18978065252304077, "2066": 0.11517547070980072, "2075": 0.4067663550376892, "2078": 0.47584590315818787, "2083": 0.11951763927936554, "2089": 0.034552380442619324, "2098": 0.4556184411048889, "2099": 0.3824150264263153, "2116": 0.04394211992621422, "2135": 0.48008447885513306, "2159": 0.176772341132164, "2179": 0.17759032547473907, "2182": 0.20421554148197174, "2207": 0.3916989266872406, "2229": 0.31560876965522766, "2239": 0.30989447236061096, "2257": 0.1485546976327896, "2260": 0.007782140281051397, "2274": 0.3995884954929352, "2334": 0.5640701055526733, "2339": 0.00875066313892603, "2358": 0.17840765416622162, "2368": 0.2026219218969345, "2377": 0.14179791510105133, "2378": 0.906871497631073, "2382": 0.36967599391937256, "2389": 0.4938860833644867, "2410": 0.15777134895324707, "2426": 0.3241194784641266, "2474": 0.5370414853096008, "2515": 0.1602703034877777, "2529": 0.3662964701652527, "2535": 0.45623743534088135, "2550": 0.08603433519601822, "2555": 0.4624064862728119, "2556": 0.08692999184131622, "2638": 0.4788752794265747, "2696": 0.5838727951049805, "2713": 0.4673144817352295, "2714": 0.46608972549438477, "2891": 0.5255602598190308, "2920": 0.1510767638683319, "3117": 0.6275664567947388, "3145": 0.48850810527801514, "3170": 0.35950297117233276, "3226": 0.3949938118457794, "3239": 0.37035053968429565, "3248": 0.1485546976327896, "3252": 0.14518201351165771, "3258": 0.7537717819213867, "3279": 0.30486753582954407, "3372": 0.3248254358768463, "3378": 0.15777134895324707, "3393": 0.029824240133166313, "3491": 0.09317722171545029, "3526": 0.6704301834106445, "3550": 0.7067264318466187, "3563": 0.6639154553413391, "3590": 0.45870962738990784, "3595": 1.039613962173462, "3597": 0.6223390698432922, "3605": 0.058784693479537964, "3625": 0.04394211992621422, "3630": 0.35745587944984436, "3670": 0.5267143249511719, "3672": 0.2659635543823242, "3674": 0.5381823778152466, "3701": 0.14518201351165771, "3755": 0.19622190296649933, "3774": 0.46486347913742065, "3811": 0.6327666640281677, "3853": 0.5427330136299133, "3867": 0.01934296265244484, "3899": 0.10906458646059036, "3930": 0.09228714555501938, "3952": 0.5584990978240967, "3981": 0.6296497583389282, "3989": 0.16110190749168396, "4115": 0.6128603219985962, "4135": 0.4873090982437134, "4160": 0.6338034868240356, "4167": 0.7047978043556213, "4195": 0.06337817758321762, "4242": 0.4926934838294983, "4286": 0.2231435477733612, "4321": 0.056018441915512085, "4372": 0.5307431221008301, "4395": 0.3883931338787079, "4442": 0.8707374930381775, "4453": 0.3127557039260864, "4469": 0.848413348197937, "4471": 0.4537591338157654, "4522": 0.6471850275993347, "4653": 0.4041621685028076, "4654": 0.8829278349876404, "4655": 0.5104349255561829, "4659": 0.004870930220931768, "4671": 0.12642613053321838, "4697": 0.043007105588912964, "4728": 0.04394211992621422, "4742": 0.20660123229026794, "4767": 0.7665573358535767, "4895": 0.7047978043556213, "4921": 0.5635144114494324, "4949": 0.3750596046447754, "4958": 0.3949938118457794, "4962": 0.8450632095336914, "4972": 0.38441169261932373, "5072": 0.11865071207284927, "5084": 0.24248650670051575, "5228": 0.7229714393615723, "5243": 0.129004567861557, "5250": 0.757441520690918, "5258": 0.04394211992621422, "5326": 0.6482070088386536, "5358": 0.25694093108177185, "5387": 0.8332487344741821, "5398": 0.10993985831737518, "5498": 0.7314660549163818, "5644": 0.6165571808815002, "5648": 0.3963087201118469, "5668": 0.020300358533859253, "5714": 0.42990362644195557, "5812": 0.33325836062431335, "5876": 0.906871497631073, "5939": 0.6327666640281677, "6024": 0.46486347913742065, "6026": 0.05786345899105072, "6064": 0.10467668622732162, "6282": 0.41195443272590637, "6296": 0.00875066313892603, "6309": 0.030771657824516296, "6459": 0.0842406153678894, "6593": 0.4617912769317627, "6709": 0.25694093108177185, "6887": 0.5773153901100159, "6913": 0.2223619967699051, "6974": 0.2969166338443756, "7017": 0.23710809648036957, "7076": 0.35334911942481995, "7085": 0.2674594223499298, "7246": 0.3012613356113434, "7327": 0.04767346754670143, "7337": 0.20739519596099854, "7341": 0.6107416749000549, "7352": 0.7951818704605103, "7356": 0.034552380442619324, "7366": 0.026976587250828743, "7403": 0.5156965255737305, "7645": 0.2689530849456787, "7694": 0.34715715050697327, "7696": 0.3824150264263153, "7704": 0.45994341373443604, "7755": 0.15943801403045654, "7934": 0.058784693479537964, "8031": 0.9029204845428467, "8123": 0.9287132620811462, "8153": 0.5723689198493958, "8163": 0.6512666940689087, "8171": 0.6960725784301758, "8176": 0.14433705806732178, "8285": 0.20102575421333313, "8327": 0.02792670577764511, "8331": 0.7258110046386719, "8360": 0.18411032855510712, "8458": 0.48430517315864563, "8496": 0.28963330388069153, "8525": 0.5381823778152466, "8569": 0.848413348197937, "8578": 0.4311734735965729, "8609": 0.0019512200960889459, "8676": 0.5838727951049805, "8681": 0.04767346754670143, "8720": 0.49626702070236206, "8777": 0.04487626627087593, "8834": 0.5882205963134766, "8865": 0.18816383183002472, "8878": 0.24018502235412598, "8902": 0.8450632095336914, "8909": 0.2317005842924118, "8939": 0.7809720039367676, "9007": 0.3743882179260254, "9113": 0.020300358533859253, "9147": 0.02887592278420925, "9152": 0.5751199722290039, "9165": 0.7656494975090027, "9197": 0.23787821829319, "9307": 0.41065993905067444, "9336": 0.8117979168891907, "9353": 0.8247235417366028, "9402": 0.4574742913246155, "9412": 0.5528968572616577, "9488": 0.030771657824516296, "9495": 0.08154398202896118, "9530": 0.47158926725387573, "9589": 0.7978238463401794, "9777": 0.3560888469219208, "9781": 1.0478670597076416, "9869": 0.129004567861557, "10057": 0.4487839937210083, "10085": 0.7934166193008423, "10210": 0.8057082891464233, "10253": 1.0986123085021973, "10415": 0.755608320236206, "10572": 0.18492233753204346, "10595": 0.08871890604496002, "10631": 0.777387797832489, "10637": 0.1751343309879303, "10737": 0.020300358533859253, "10769": 0.16607704758644104, "10788": 0.015504186972975731, "10857": 0.11691460013389587, "10882": 0.5376120805740356, "10924": 0.08513788133859634, "10956": 0.1994270235300064, "10976": 0.5450005531311035, "11156": 0.4145384132862091, "11265": 0.40806588530540466, "11467": 0.7710843086242676, "11487": 0.3070250153541565, "11498": 0.1994270235300064, "11585": 0.8442239761352539, "11595": 0.10906458646059036, "11598": 0.8764448165893555, "11867": 0.6563454270362854, "12151": 0.08692999184131622, "12228": 0.08513788133859634, "12274": 0.8298473954200745, "12319": 0.39762192964553833, "12375": 0.4574742913246155, "12604": 0.8135309815406799, "12732": 0.8298473954200745, "12737": 0.37974658608436584, "12987": 0.40220460295677185, "12996": 0.026025565341114998, "13096": 1.0101795196533203, "13100": 0.006812678650021553, "13186": 0.8004589080810547, "13490": 0.6634125709533691, "13776": 0.6892333030700684, "13791": 0.20102575421333313, "13833": 0.31845372915267944, "13853": 0.9769153594970703, "13922": 0.13925230503082275, "14026": 0.08064348995685577, "14049": 0.3163207769393921, "14067": 0.5690577030181885, "14084": 0.045809537172317505, "14095": 0.469759464263916, "14163": 0.3949938118457794, "14187": 0.4770587682723999, "14193": 0.1384023278951645, "14402": 0.567397952079773, "14573": 0.8323994874954224, "14778": 1.200058937072754, "14828": 0.6714286804199219, "14847": 0.022212404757738113, "14962": 0.0797421783208847, "15370": 0.014542185701429844, "15431": 0.09672962874174118, "15459": 0.7314660549163818, "15476": 1.1287524700164795, "15543": 0.1734936386346817, "15702": 0.0797421783208847, "15879": 0.7665573358535767, "16026": 0.18167030811309814, "16168": 0.8550800085067749, "16221": 0.02792670577764511, "16285": 0.058784693479537964, "16308": 0.7314660549163818, "16552": 0.11691460013389587, "16643": 0.804835319519043, "16690": 0.10555581003427505, "16691": 0.009718249551951885, "16783": 0.022212404757738113, "16882": 0.9621002674102783, "16910": 0.8238670229911804, "16983": 0.87237149477005, "17134": 0.841701865196228, "17441": 0.24859806895256042, "17715": 0.15023678541183472, "17771": 0.04207121208310127, "18714": 0.5180262327194214, "18749": 1.4293015003204346, "18969": 0.1710275560617447, "19220": 0.11604541540145874, "19335": 0.020300358533859253, "19362": 0.920189380645752, "19589": 0.436867892742157, "19601": 0.12986256182193756, "19653": 0.45994341373443604, "19872": 0.10818854719400406, "20026": 1.1786550283432007, "20194": 0.014542185701429844, "20226": 0.24248650670051575, "20250": 0.8433839678764343, "20350": 0.7942996621131897, "20544": 0.14518201351165771, "20582": 1.0927356481552124, "20679": 0.817850649356842, "20752": 0.42353010177612305, "20806": 0.22157983481884003, "20817": 0.7473171949386597, "20852": 0.16276304423809052, "20858": 0.5318912267684937, "20989": 0.1485546976327896, "21032": 0.5197699069976807, "21114": 0.9680526852607727, "21337": 0.9178520441055298, "21572": 0.49626702070236206, "21755": 0.45251765847206116, "21903": 0.11951763927936554, "21919": 0.34715715050697327, "21967": 0.18492233753204346, "22415": 0.472198486328125, "22471": 0.650757372379303, "22571": 0.7009293437004089, "22574": 0.22392450273036957, "22644": 1.013020396232605, "23079": 0.19541899859905243, "23150": 0.12038381397724152, "23216": 0.8699195384979248, "23245": 0.8649974465370178, "23340": 0.7500885725021362, "23737": 0.2026219218969345, "23924": 0.7951818704605103, "24171": 0.29109421372413635, "24278": 0.40871503949165344, "24345": 0.11951763927936554, "24374": 0.4286321699619293, "24412": 0.39762192964553833, "24587": 0.6446255445480347, "25117": 0.175953671336174, "25194": 0.8957691192626953, "25320": 0.9553611874580383, "25643": 0.8941729068756104, "25708": 1.018678069114685, "25714": 0.6603899002075195, "26243": 0.004870930220931768, "26279": 0.2659635543823242, "26308": 0.7925328612327576, "26402": 0.27342069149017334, "26512": 0.043007105588912964, "26642": 0.3615458607673645, "26692": 0.021256839856505394, "26773": 0.08154398202896118, "26775": 0.5849615335464478, "27295": 0.5517725944519043, "27777": 0.026976587250828743, "27854": 0.07159364968538284, "28667": 0.6338034868240356, "28691": 0.129004567861557, "28696": 0.19220098853111267, "28788": 0.05694137513637543, "28808": 0.7995813488960266, "28815": 0.00875066313892603, "28848": 0.5968599319458008, "29610": 0.6070231795310974} | 12086818 | Multiple extracellular factors are hypothesized to promote the differentiation of unstimulated and/or stimulated secretory pathways in exocrine secretory cells, but the identity of differentiation factors, particularly those organ-specific, remain largely unknown. Here, we report on the identification of a novel secreted glycoprotein, lacritin, that enhances exocrine secretion in overnight cultures of lacrimal acinar cells which otherwise display loss of secretory function. Lacritin mRNA and protein are highly expressed in human lacrimal gland, moderately in major and minor salivary glands and slightly in thyroid. No lacritin message or protein is detected elsewhere among more than 50 human tissues examined. Lacritin displays partial similarity to the glycosaminoglycan-binding region of brain-specific neuroglycan C (32 % identity over 102 amino acid residues) and to the possibly mucin-like amino globular region of fibulin-2 (30 % identity over 81 amino acid residues), and localizes primarily to secretory granules and secretory fluid. The lacritin gene consists of five exons, displays no alternative splicing and maps to 12q13. Recombinant lacritin augments unstimulated but not stimulated acinar cell secretion, promotes ductal cell proliferation, and stimulates signaling through tyrosine phosphorylation and release of calcium. It binds collagen IV, laminin-1, entactin/nidogen-1, fibronectin and vitronectin, but not collagen I, heparin or EGF. As an autocrine/paracrine enhancer of the lacrimal constitutive secretory pathway, ductal cell mitogen and stimulator of corneal epithelial cells, lacritin may play a key role in the function of the lacrimal gland-corneal axis. | cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland. |
{"1998": 0.0174254160374403, "2001": 0.1619328260421753, "2043": 0.21135559678077698, "2045": 0.3560888469219208, "2058": 0.18654440343379974, "2062": 0.13157635927200317, "2095": 0.2667117714881897, "2106": 0.22859740257263184, "2108": 0.14349138736724854, "2111": 0.4950772523880005, "2116": 0.5690577030181885, "2120": 0.4944818615913391, "2135": 0.1677299439907074, "2137": 0.10993985831737518, "2146": 0.2954642176628113, "2154": 0.0009760859538801014, "2155": 0.6853039860725403, "2168": 0.10291612148284912, "2177": 0.10731173306703568, "2188": 0.762009859085083, "2193": 0.46055975556373596, "2214": 0.5838727951049805, "2266": 0.6038249135017395, "2287": 0.9710156321525574, "2291": 0.12642613053321838, "2304": 0.9131608605384827, "2308": 0.1913948506116867, "2313": 0.6348392367362976, "2317": 0.3910386264324188, "2326": 0.3870677351951599, "2336": 0.04767346754670143, "2339": 0.2990913391113281, "2367": 0.5472630262374878, "2372": 0.5795059204101562, "2393": 0.06154331564903259, "2415": 0.056018441915512085, "2426": 0.5045560002326965, "2451": 0.11951763927936554, "2465": 0.06795065850019455, "2470": 0.39893341064453125, "2490": 0.27044451236724854, "2512": 0.5290185213088989, "2542": 0.11865071207284927, "2561": 0.5057345628738403, "2578": 0.47402387857437134, "2591": 0.21530038118362427, "2679": 1.1798561811447144, "2711": 0.09317722171545029, "2729": 1.1236859560012817, "2740": 0.3134697377681732, "2744": 1.0430610179901123, "2779": 0.0770333781838417, "2817": 0.45994341373443604, "2829": 0.004870930220931768, "2897": 0.8525851964950562, "2902": 0.15777134895324707, "2913": 0.5313173532485962, "2945": 0.34300774335861206, "2946": 0.33605360984802246, "2951": 0.4788752794265747, "2960": 0.6471850275993347, "2966": 0.029824240133166313, "2967": 0.02412080205976963, "3020": 0.3423145115375519, "3026": 0.7370892763137817, "3060": 0.8374842405319214, "3080": 0.7473171949386597, "3088": 0.11343330889940262, "3095": 0.09672962874174118, "3160": 0.1718502640724182, "3202": 0.22782009840011597, "3228": 0.05970508232712746, "3251": 0.04860413447022438, "3252": 0.6160298585891724, "3273": 0.17020416259765625, "3287": 0.10906458646059036, "3348": 0.20660123229026794, "3382": 0.0606246218085289, "3445": 0.04487626627087593, "3446": 0.022212404757738113, "3452": 0.3163207769393921, "3466": 0.04487626627087593, "3477": 0.32270604372024536, "3497": 0.4158279001712799, "3515": 0.6358738541603088, "3609": 0.3269403576850891, "3616": 0.18492233753204346, "3618": 0.04767346754670143, "3633": 0.26446542143821716, "3638": 0.1064341589808464, "3667": 0.04860413447022438, "3767": 0.11081436276435852, "3776": 0.13499516248703003, "3825": 0.6107416749000549, "3837": 0.8957691192626953, "3842": 0.02412080205976963, "3866": 0.05694137513637543, "3867": 0.18492233753204346, "3891": 0.0797421783208847, "3901": 0.06520967930555344, "3980": 0.1221139207482338, "4106": 0.14602625370025635, "4128": 0.1384023278951645, "4207": 0.04207121208310127, "4279": 0.14518201351165771, "4322": 0.026976587250828743, "4381": 0.04860413447022438, "4480": 0.009718249551951885, "4489": 0.5557019114494324, "4531": 0.08961215615272522, "4541": 0.31204116344451904, "4793": 0.14349138736724854, "4841": 0.3810817003250122, "4863": 0.31845372915267944, "5002": 0.8306987881660461, "5014": 0.7028654217720032, "5090": 0.31845372915267944, "5337": 0.08064348995685577, "5360": 0.1873544454574585, "5381": 0.42799583077430725, "5443": 0.17759032547473907, "5535": 0.3897167444229126, "5605": 0.09672962874174118, "5636": 0.820433497428894, "5762": 0.9929623603820801, "5776": 0.06612417846918106, "5779": 0.21372433006763458, "5856": 0.9256220459938049, "5873": 0.04953393340110779, "5876": 0.037378571927547455, "5907": 0.2719337046146393, "5921": 0.013579257763922215, "5966": 0.755608320236206, "5981": 0.0913962796330452, "6001": 0.22859740257263184, "6125": 0.672426164150238, "6165": 0.08513788133859634, "6234": 0.7276995778083801, "6299": 0.6522845029830933, "6319": 0.07612881064414978, "6397": 0.09938567131757736, "6401": 0.09495500475168228, "6422": 0.5238267183303833, "6431": 0.18167030811309814, "6469": 0.304147332906723, "6512": 0.39433568716049194, "6631": 0.053244512528181076, "6696": 0.18248429894447327, "6697": 0.10467668622732162, "6704": 0.018384648486971855, "6709": 0.1710275560617447, "6747": 0.5551415085792542, "6818": 0.14179791510105133, "6821": 0.46670228242874146, "6950": 0.05694137513637543, "6952": 0.1401015669107437, "7016": 0.04767346754670143, "7017": 0.4311734735965729, "7079": 0.176772341132164, "7080": 0.08961215615272522, "7162": 0.5244048833847046, "7197": 0.5506471395492554, "7396": 0.05786345899105072, "7402": 0.19541899859905243, "7403": 0.32764431834220886, "7461": 0.39893341064453125, "7565": 0.39893341064453125, "7578": 0.1913948506116867, "7607": 0.1229778528213501, "7809": 0.05139094591140747, "8137": 0.3070250153541565, "8192": 0.23633737862110138, "8315": 0.29619070887565613, "8318": 0.2652147710323334, "8329": 1.12938392162323, "8332": 0.2184450328350067, "8358": 0.1332872211933136, "8360": 0.7987030148506165, "8386": 0.23556606471538544, "8554": 0.1946154683828354, "8556": 0.0029254043474793434, "8725": 0.021256839856505394, "8781": 0.2741633653640747, "8832": 0.20501139760017395, "8906": 0.21922965347766876, "9053": 0.18573370575904846, "9064": 0.06977381557226181, "9147": 0.5512100458145142, "9426": 0.04767346754670143, "9556": 0.6461620330810547, "9582": 0.29400965571403503, "9592": 0.17020416259765625, "9671": 0.05046287178993225, "9723": 0.10906458646059036, "9750": 0.8731874823570251, "9776": 0.7791815400123596, "9783": 0.0770333781838417, "9871": 0.45499902963638306, "9879": 0.15943801403045654, "9945": 0.02412080205976963, "10238": 0.1734936386346817, "10571": 0.17922431230545044, "10662": 0.2976420819759369, "10802": 0.2969166338443756, "10823": 0.9485763907432556, "10826": 0.18816383183002472, "10847": 0.29255300760269165, "11036": 0.10026945173740387, "11234": 0.7942996621131897, "11500": 0.3864043951034546, "11543": 0.3353555500507355, "11573": 0.03360854089260101, "11670": 0.3034266233444214, "11900": 1.072225570678711, "11922": 0.5421652793884277, "11980": 0.6451379656791687, "11982": 0.24018502235412598, "12265": 0.7105726003646851, "12285": 0.04207121208310127, "12319": 0.10291612148284912, "12455": 0.016465263441205025, "12461": 0.4093637466430664, "12473": 0.058784693479537964, "12520": 0.28155985474586487, "12533": 0.01934296265244484, "12593": 0.0913962796330452, "12631": 0.10467668622732162, "12778": 0.10993985831737518, "12876": 0.41195443272590637, "12969": 0.15693697333335876, "12980": 0.1873544454574585, "13105": 0.0009760859538801014, "13376": 0.5074998140335083, "13531": 0.18978065252304077, "13597": 0.4002431631088257, "13827": 0.3027053773403168, "14028": 0.6598852276802063, "14048": 0.37102460861206055, "14240": 0.0354953333735466, "14302": 0.3777405619621277, "14336": 0.3269403576850891, "14398": 0.8100618124008179, "14542": 0.07159364968538284, "14592": 0.09406650811433792, "14977": 0.09672962874174118, "15157": 0.05046287178993225, "15571": 0.07793712615966797, "15822": 0.43053874373435974, "15919": 0.045809537172317505, "15982": 0.1401015669107437, "15995": 0.6989894509315491, "16022": 0.08782484382390976, "16302": 0.6410312056541443, "16440": 0.025073638185858727, "16578": 0.2539152204990387, "16593": 0.33115679025650024, "16660": 0.11951763927936554, "16680": 0.07793712615966797, "16824": 0.2763880789279938, "16939": 0.5930894017219543, "16965": 0.3027053773403168, "17522": 0.10906458646059036, "17600": 0.2741633653640747, "17676": 0.22626367211341858, "17837": 0.08692999184131622, "17908": 0.07884006202220917, "17959": 0.15943801403045654, "18076": 0.469759464263916, "18234": 0.8349450826644897, "18240": 0.8143964409828186, "18771": 0.2493593990802765, "19046": 0.09317722171545029, "19174": 0.06795065850019455, "19541": 0.37371641397476196, "20272": 0.34023189544677734, "20502": 0.0354953333735466, "21090": 0.1212492436170578, "21858": 0.5162794589996338, "21901": 0.1718502640724182, "22470": 0.06886265426874161, "22648": 0.23092569410800934, "23284": 0.27712854743003845, "23368": 0.5562619566917419, "23693": 0.1751343309879303, "23795": 0.9944084882736206, "23850": 1.210591435432434, "24004": 0.13925230503082275, "24382": 0.08603433519601822, "24835": 0.07250232994556427, "24904": 0.09228714555501938, "25094": 0.014542185701429844, "25172": 0.6833335757255554, "25352": 0.05046287178993225, "25737": 0.04767346754670143, "25835": 0.10467668622732162, "26319": 0.17922431230545044, "27166": 0.3297532796859741, "27322": 0.09406650811433792, "27615": 0.25995752215385437, "27694": 0.32764431834220886, "27891": 0.7656494975090027, "28321": 0.41065993905067444, "28436": 0.029824240133166313, "28767": 0.22937409579753876, "29213": 0.0174254160374403, "29258": 0.04207121208310127, "29277": 0.5232481360435486} | 12087063 | This study investigated whether there are race differences in the structure of informal caregiving networks. Data on 3,793 functionally impaired persons age 65 and over from the 1989 National Long-Term Care Survey were analyzed. The size of the total caregiver network and the unpaid network did not differ by race, but the likelihood of there being a non-immediate family member among unpaid caregivers was higher among disabled older blacks. These findings raise questions about whether race differences in nursing home utilization and paid long-term care services, documented in other studies, can be explained by differences in caregiving arrangements. | The structure of informal care: are there differences by race? |
{"1011": 0.1212492436170578, "1017": 0.3588210940361023, "1023": 0.2317005842924118, "1044": 0.5330380201339722, "1999": 0.06429435312747955, "2007": 0.32270604372024536, "2008": 0.05046287178993225, "2010": 0.8877626657485962, "2011": 0.38374659419059753, "2015": 0.38041436672210693, "2029": 0.42353010177612305, "2033": 0.7295845746994019, "2044": 0.06337817758321762, "2046": 0.4450363218784332, "2061": 0.7791815400123596, "2076": 0.603290855884552, "2093": 0.04207121208310127, "2119": 0.31132611632347107, "2124": 0.1693800985813141, "2128": 0.306306391954422, "2135": 0.2089812457561493, "2139": 0.3269403576850891, "2179": 0.27934664487838745, "2241": 0.26446542143821716, "2243": 0.77198725938797, "2275": 0.175953671336174, "2284": 0.4849066734313965, "2290": 0.4879087805747986, "2346": 0.9178520441055298, "2353": 0.13414156436920166, "2362": 0.19862671196460724, "2367": 0.20421554148197174, "2389": 0.3750596046447754, "2397": 0.9500881433486938, "2458": 0.39762192964553833, "2475": 0.2018241584300995, "2487": 0.22626367211341858, "2504": 0.11865071207284927, "2509": 0.8877626657485962, "2523": 0.27712854743003845, "2535": 0.4926934838294983, "2560": 0.06703783571720123, "2595": 1.09404456615448, "2609": 0.31132611632347107, "2683": 0.9958525896072388, "2689": 0.3622259199619293, "2695": 0.6527929902076721, "2707": 0.45499902963638306, "2719": 0.053244512528181076, "2724": 0.2223619967699051, "2777": 0.20660123229026794, "2818": 0.7845434546470642, "2824": 0.4914994537830353, "2832": 0.3601844012737274, "2839": 0.6223390698432922, "2898": 0.1734936386346817, "2904": 0.1229778528213501, "2920": 0.4190443754196167, "2927": 0.3027053773403168, "2928": 0.44753631949424744, "3161": 0.9724938273429871, "3217": 0.9687942266464233, "3225": 0.7028654217720032, "3295": 0.347847044467926, "3367": 0.28597161173820496, "3370": 0.8195732831954956, "3375": 0.025073638185858727, "3378": 0.5936289429664612, "3388": 0.33953672647476196, "3431": 0.4450363218784332, "3445": 0.31560876965522766, "3449": 0.1710275560617447, "3466": 0.18411032855510712, "3484": 0.058784693479537964, "3491": 0.06612417846918106, "3494": 0.2184450328350067, "3508": 0.4349733293056488, "3526": 0.7314660549163818, "3603": 0.1873544454574585, "3619": 0.4831010699272156, "3623": 0.40546512603759766, "3625": 0.055094651877880096, "3653": 0.7791815400123596, "3670": 0.3191637098789215, "3701": 0.3127557039260864, "3742": 0.6970458030700684, "3795": 1.094698429107666, "3796": 0.8161250352859497, "3798": 0.4196864068508148, "3853": 0.10379679501056671, "3858": 0.43434104323387146, "3921": 0.3084607720375061, "3936": 0.2918238639831543, "3952": 0.23556606471538544, "4023": 0.11778303235769272, "4081": 0.24631060659885406, "4102": 0.3784096837043762, "4106": 0.5010119676589966, "4162": 0.2918238639831543, "4167": 0.24171993136405945, "4168": 0.34508460760116577, "4195": 0.7067264318466187, "4245": 0.10818854719400406, "4321": 0.12470348179340363, "4353": 0.7500885725021362, "4395": 0.42926809191703796, "4417": 0.6931471824645996, "4442": 0.9271688461303711, "4453": 0.4425300657749176, "4487": 0.14602625370025635, "4520": 0.11430477350950241, "4531": 0.11256109178066254, "4539": 0.16110190749168396, "4573": 0.6950984001159668, "4627": 0.034552380442619324, "4758": 0.20102575421333313, "4765": 0.6902132034301758, "4958": 0.7610978484153748, "4962": 0.9425065517425537, "4972": 0.0038986403960734606, "5017": 0.011650617234408855, "5038": 0.3297532796859741, "5158": 0.011650617234408855, "5250": 0.7665573358535767, "5269": 0.2852376699447632, "5387": 0.7380234599113464, "5393": 0.0797421783208847, "5421": 0.05970508232712746, "5449": 1.0158531665802002, "5456": 0.10467668622732162, "5482": 0.2983669638633728, "5500": 0.4481603503227234, "5524": 0.9037119746208191, "5531": 0.045809537172317505, "5620": 0.053244512528181076, "5705": 0.25995752215385437, "5716": 0.03925827145576477, "5769": 0.17431432008743286, "5857": 0.11343330889940262, "5876": 0.5057345628738403, "5991": 0.6921701431274414, "5994": 0.11865071207284927, "6017": 0.8238670229911804, "6064": 0.46424978971481323, "6083": 0.3423145115375519, "6194": 0.1011524572968483, "6310": 0.7683706283569336, "6444": 0.030771657824516296, "6459": 0.0317181795835495, "6494": 0.5174443125724792, "6537": 0.0842406153678894, "6562": 0.7800771594047546, "6592": 0.5865923762321472, "6622": 0.04860413447022438, "6691": 0.4494072198867798, "6709": 0.3923587501049042, "6807": 0.49030399322509766, "7336": 0.5341835021972656, "7337": 0.32270604372024536, "7356": 0.22704219818115234, "7366": 0.13414156436920166, "7403": 0.6000806093215942, "7444": 0.03360854089260101, "7457": 0.4831010699272156, "7461": 0.2231435477733612, "7551": 0.021256839856505394, "7645": 0.42990362644195557, "7657": 0.11430477350950241, "7711": 0.12728634476661682, "7775": 0.3485364317893982, "7783": 1.0361549854278564, "7816": 0.49923527240753174, "7831": 0.03925827145576477, "7872": 1.2324692010879517, "7885": 0.10026945173740387, "8031": 0.6999598741531372, "8107": 0.2026219218969345, "8153": 0.08692999184131622, "8171": 0.6970458030700684, "8303": 1.0030416250228882, "8360": 0.06795065850019455, "8450": 0.034552380442619324, "8478": 0.5629584193229675, "8534": 0.27712854743003845, "8674": 0.18654440343379974, "8713": 0.9650808572769165, "8776": 0.42608439922332764, "8803": 0.12470348179340363, "8878": 0.5914691090583801, "8924": 0.09050461649894714, "8991": 0.1946154683828354, "9007": 0.48670899868011475, "9069": 0.09050461649894714, "9099": 0.22937409579753876, "9104": 0.39893341064453125, "9125": 0.3850763738155365, "9165": 1.02149498462677, "9197": 0.9643365740776062, "9228": 0.49626702070236206, "9259": 0.14433705806732178, "9412": 0.6011518239974976, "9416": 0.02792670577764511, "9468": 0.0019512200960889459, "9496": 0.9857001900672913, "9556": 0.6144463419914246, "10060": 0.3297532796859741, "10266": 0.04487626627087593, "10381": 0.5729197263717651, "10572": 1.0285027027130127, "10580": 0.25467249751091003, "10595": 0.07884006202220917, "10624": 0.6011518239974976, "10708": 0.38574060797691345, "10738": 0.36358460783958435, "10744": 0.12986256182193756, "10814": 1.0655186176300049, "10851": 0.5133614540100098, "10882": 0.42735910415649414, "11008": 1.0409941673278809, "11020": 1.2187074422836304, "11115": 0.5893046259880066, "11156": 0.09050461649894714, "11234": 0.0038986403960734606, "11393": 0.812664806842804, "11477": 0.1808556467294693, "11598": 0.8583967685699463, "11601": 0.0842406153678894, "11835": 0.13243216276168823, "11916": 0.8383291959762573, "12222": 0.8433839678764343, "12248": 0.04113444685935974, "12346": 0.28082266449928284, "12402": 0.4248080551624298, "12435": 0.04953393340110779, "12618": 0.854249119758606, "12644": 0.8600510358810425, "12719": 1.0030416250228882, "12837": 0.6476961374282837, "12987": 0.32270604372024536, "12990": 0.736154317855835, "12997": 1.2985725402832031, "13070": 0.08154398202896118, "13113": 1.1923824548721313, "13458": 0.7683706283569336, "13490": 0.006812678650021553, "13502": 0.09050461649894714, "13595": 0.14939609169960022, "13599": 0.02412080205976963, "13685": 0.12986256182193756, "13791": 0.8933739066123962, "13833": 0.12470348179340363, "13887": 0.8600510358810425, "13908": 0.8949713706970215, "13922": 0.07431721687316895, "14080": 0.9515975713729858, "14137": 0.007782140281051397, "14187": 0.5455666780471802, "14193": 1.133164644241333, "14313": 0.022212404757738113, "14471": 0.11168810725212097, "14494": 0.1485546976327896, "14531": 1.018678069114685, "14600": 0.469759464263916, "14622": 0.3615458607673645, "14828": 0.06886265426874161, "14847": 0.02412080205976963, "15053": 0.1401015669107437, "15115": 0.15610189735889435, "15176": 0.6931471824645996, "15266": 0.1401015669107437, "15501": 0.6583697199821472, "15527": 0.2667117714881897, "15543": 0.21372433006763458, "15663": 0.39762192964553833, "15946": 0.3615458607673645, "16119": 0.3615458607673645, "16134": 0.010684899985790253, "16221": 0.27044451236724854, "16285": 0.21372433006763458, "16341": 0.0038986403960734606, "16360": 1.250528335571289, "16389": 0.06154331564903259, "16452": 0.6118015646934509, "16515": 0.02412080205976963, "16530": 0.6563454270362854, "16552": 0.21135559678077698, "16691": 0.18492233753204346, "16705": 0.25995752215385437, "16706": 0.35403475165367126, "16745": 0.18816383183002472, "16840": 0.4926934838294983, "17118": 0.9485763907432556, "17324": 1.1971133947372437, "17367": 0.6244332790374756, "17379": 0.2105647772550583, "17439": 0.18411032855510712, "17441": 0.4067663550376892, "17463": 0.06246116757392883, "17666": 0.004870930220931768, "17678": 0.02792670577764511, "17702": 0.41840189695358276, "17890": 0.0606246218085289, "17908": 0.28670501708984375, "18322": 0.6634125709533691, "18939": 0.9131608605384827, "19199": 0.07159364968538284, "19612": 0.011650617234408855, "19653": 0.7500885725021362, "19723": 0.18248429894447327, "19933": 0.14686977863311768, "20155": 0.9302552938461304, "20226": 0.22157983481884003, "20228": 0.8845420479774475, "20363": 1.1031591892242432, "20492": 0.9076598286628723, "20544": 0.5557019114494324, "20567": 0.6882523894309998, "20611": 0.14095009863376617, "20817": 0.8357921838760376, "21047": 0.20421554148197174, "21112": 0.4228905141353607, "21150": 0.32905077934265137, "21573": 0.5568217039108276, "21575": 0.21765978634357452, "21618": 0.15275461971759796, "21716": 1.0229004621505737, "21770": 1.0546929836273193, "21823": 0.0606246218085289, "21903": 0.6808650493621826, "22415": 0.42990362644195557, "22422": 0.38441169261932373, "22595": 0.7352184057235718, "22694": 0.0038986403960734606, "22931": 0.015504186972975731, "22963": 0.09228714555501938, "23150": 0.07159364968538284, "23191": 0.29328158497810364, "23216": 0.045809537172317505, "23467": 0.969535231590271, "23586": 0.9878844022750854, "23737": 0.1401015669107437, "23767": 0.10818854719400406, "23892": 0.011650617234408855, "23900": 0.25239890813827515, "24004": 0.12384103983640671, "24051": 0.20739519596099854, "24054": 0.7737906575202942, "24110": 0.41195443272590637, "24269": 0.011650617234408855, "24370": 0.083342544734478, "25003": 1.2336074113845825, "25136": 0.02412080205976963, "25194": 0.0019512200960889459, "25202": 0.7305257320404053, "25416": 0.11691460013389587, "25456": 0.5979346632957458, "25458": 0.495672345161438, "25502": 0.12728634476661682, "25644": 0.040196798741817474, "25761": 0.04953393340110779, "25932": 0.28082266449928284, "26356": 0.854249119758606, "26402": 1.0298984050750732, "26512": 0.00875066313892603, "26520": 0.16110190749168396, "26534": 0.007782140281051397, "26563": 0.2409527748823166, "26773": 0.6389714479446411, "26775": 0.20102575421333313, "26874": 0.011650617234408855, "27226": 0.6338034868240356, "27709": 0.9754437208175659, "27854": 0.151916041970253, "28086": 1.202995777130127, "28405": 0.14349138736724854, "28424": 0.026025565341114998, "28522": 0.9724938273429871, "28667": 0.02792670577764511, "28691": 0.08871890604496002, "28699": 0.6389714479446411, "28991": 1.175042748451233, "29206": 1.0030416250228882, "29226": 0.2954642176628113, "29237": 0.10026945173740387, "29290": 0.4512746334075928, "29458": 0.04860413447022438, "29721": 0.48068851232528687} | 12100854 | Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) involves a marked reorganization of chromatin. To identify post-translational histone modifications that change in global abundance during this process, we have applied a quantitative mass-spectrometry-based approach. We found that iPSCs, compared with both the starting fibroblasts and a late reprogramming intermediate (pre-iPSCs), are enriched for histone modifications associated with active chromatin, and depleted for marks of transcriptional elongation and a subset of repressive modifications including H3K9me2/me3. Dissecting the contribution of H3K9 methylation to reprogramming, we show that the H3K9 methyltransferases Ehmt1, Ehmt2 and Setdb1 regulate global H3K9me2/me3 levels and that their depletion increases iPSC formation from both fibroblasts and pre-iPSCs. Similarly, we find that inhibition of heterochromatin protein-1γ (Cbx3), a protein known to recognize H3K9 methylation, enhances reprogramming. Genome-wide location analysis revealed that Cbx3 predominantly binds active genes in both pre-iPSCs and pluripotent cells but with a strikingly different distribution: in pre-iPSCs, but not in embryonic stem cells, Cbx3 associates with active transcriptional start sites, suggesting a developmentally regulated role for Cbx3 in transcriptional activation. Despite largely non-overlapping functions and the predominant association of Cbx3 with active transcription, the H3K9 methyltransferases and Cbx3 both inhibit reprogramming by repressing the pluripotency factor Nanog. Together, our findings demonstrate that Cbx3 and H3K9 methylation restrict late reprogramming events, and suggest that a marked change in global chromatin character constitutes an epigenetic roadblock for reprogramming. | Proteomic and genomic approaches reveal critical functions of H3K9 methylation and Heterochromatin Protein-1γ in reprogramming to pluripotency |
{"1011": 0.08064348995685577, "1021": 0.11604541540145874, "1022": 0.6461620330810547, "1037": 0.5162794589996338, "1039": 0.052318159490823746, "1041": 0.5795059204101562, "1056": 1.133164644241333, "2011": 0.45251765847206116, "2013": 0.4145384132862091, "2029": 0.02316705882549286, "2034": 0.22626367211341858, "2041": 0.31845372915267944, "2046": 0.26296505331993103, "2058": 0.75193190574646, "2073": 0.0842406153678894, "2075": 0.026976587250828743, "2076": 0.14686977863311768, "2079": 0.32553088665008545, "2099": 0.6016870141029358, "2102": 0.7182208299636841, "2109": 0.037378571927547455, "2114": 0.2881702482700348, "2121": 0.6634125709533691, "2125": 0.1011524572968483, "2135": 0.6369074583053589, "2179": 0.14095009863376617, "2185": 0.08961215615272522, "2206": 0.09850110858678818, "2233": 0.06154331564903259, "2240": 0.35677260160446167, "2278": 0.1693800985813141, "2339": 0.11256109178066254, "2491": 0.20022670924663544, "2515": 0.2689530849456787, "2535": 0.4481603503227234, "2545": 0.2637155055999756, "2581": 1.0641717910766602, "2590": 0.09406650811433792, "2609": 0.7389566898345947, "2620": 1.2192846536636353, "2681": 0.08692999184131622, "2693": 0.31845372915267944, "2741": 0.022212404757738113, "2809": 0.3034266233444214, "2828": 0.04394211992621422, "2891": 0.20660123229026794, "2906": 0.15777134895324707, "2907": 0.04674193635582924, "2944": 0.4770587682723999, "2946": 0.22782009840011597, "2951": 0.04767346754670143, "2953": 1.2732000350952148, "2954": 0.06886265426874161, "2965": 0.08782484382390976, "2981": 0.08513788133859634, "3048": 0.043007105588912964, "3073": 0.15526613593101501, "3126": 0.7182208299636841, "3210": 0.01934296265244484, "3215": 0.41065993905067444, "3258": 0.21214580535888672, "3273": 0.0058422754518687725, "3283": 0.0038986403960734606, "3342": 0.4093637466430664, "3344": 0.09672962874174118, "3366": 0.055094651877880096, "3433": 0.5313173532485962, "3457": 0.15860503911972046, "3466": 1.197703242301941, "3526": 1.0648454427719116, "3563": 0.3995884954929352, "3593": 0.6813592314720154, "3603": 0.05786345899105072, "3604": 0.29981520771980286, "3638": 1.1300151348114014, "3639": 0.7124901413917542, "3640": 0.13755162060260773, "3659": 0.1710275560617447, "3665": 0.34922540187835693, "3718": 0.0058422754518687725, "3726": 0.6197150945663452, "3729": 0.9857001900672913, "3737": 0.41647201776504517, "3754": 0.015504186972975731, "3755": 0.04674193635582924, "3800": 0.2674594223499298, "3853": 0.6813592314720154, "3858": 0.43875885009765625, "3860": 0.08961215615272522, "3896": 0.6522845029830933, "3995": 0.06246116757392883, "4015": 0.11865071207284927, "4019": 0.03266380727291107, "4022": 0.5618454217910767, "4047": 0.17020416259765625, "4167": 0.24631060659885406, "4263": 0.304147332906723, "4275": 0.29619070887565613, "4295": 0.10203468054533005, "4313": 0.04394211992621422, "4346": 0.10379679501056671, "4359": 0.43938836455345154, "4395": 0.011650617234408855, "4442": 1.2059240341186523, "4443": 0.04207121208310127, "4469": 0.7898768186569214, "4519": 0.0354953333735466, "4573": 0.6654226183891296, "4621": 0.32199856638908386, "4622": 0.06520967930555344, "4651": 0.1718502640724182, "4652": 0.39762192964553833, "4654": 0.00875066313892603, "4667": 0.23787821829319, "4721": 0.4412745535373688, "4726": 0.15526613593101501, "4757": 0.7537717819213867, "4758": 0.3191637098789215, "4876": 0.29400965571403503, "4972": 0.4196864068508148, "5012": 0.06795065850019455, "5038": 0.8004589080810547, "5158": 0.004870930220931768, "5274": 0.4462870955467224, "5319": 0.31489628553390503, "5326": 0.48670899868011475, "5360": 0.0029254043474793434, "5425": 0.03831886500120163, "5449": 0.18329764902591705, "5450": 0.14433705806732178, "5547": 0.1905880719423294, "5600": 0.09406650811433792, "5668": 1.2721059322357178, "5688": 0.10467668622732162, "5758": 0.75193190574646, "5769": 0.16276304423809052, "5788": 0.020300358533859253, "5897": 0.26446542143821716, "5964": 0.1485546976327896, "5985": 0.2447827309370041, "6025": 0.3012613356113434, "6083": 0.0029254043474793434, "6164": 0.7809720039367676, "6179": 0.03360854089260101, "6459": 0.09938567131757736, "6591": 0.2018241584300995, "6592": 0.07431721687316895, "6671": 0.043007105588912964, "6726": 0.06337817758321762, "6806": 0.9827804565429688, "6807": 0.28450319170951843, "6961": 0.2622140049934387, "6985": 0.42225050926208496, "7118": 0.06703783571720123, "7337": 0.7028654217720032, "7366": 0.2478361576795578, "7371": 0.6999598741531372, "7383": 0.026025565341114998, "7461": 0.5197699069976807, "7485": 0.1685553640127182, "7551": 0.037378571927547455, "7591": 0.0797421783208847, "7645": 0.1685553640127182, "7694": 0.2105647772550583, "7711": 0.46117570996284485, "7790": 0.890972912311554, "7816": 0.7969439625740051, "7843": 0.13755162060260773, "7865": 0.804835319519043, "7872": 0.05139094591140747, "7885": 0.053244512528181076, "8000": 1.0051883459091187, "8114": 0.4855078160762787, "8122": 0.28743788599967957, "8153": 0.9225212931632996, "8223": 0.1889725625514984, "8360": 0.10906458646059036, "8361": 0.02412080205976963, "8387": 0.016465263441205025, "8449": 0.11256109178066254, "8469": 0.004870930220931768, "8478": 0.012615402229130268, "8729": 0.1751343309879303, "8737": 0.8289952278137207, "8803": 0.1221139207482338, "8878": 0.2741633653640747, "8948": 0.8600510358810425, "8985": 0.8600510358810425, "9099": 0.23015019297599792, "9230": 0.846739649772644, "9279": 0.679875910282135, "9319": 0.0913962796330452, "9350": 0.272677481174469, "9367": 0.5729197263717651, "9386": 0.4794800877571106, "9488": 0.018384648486971855, "9687": 0.3241194784641266, "9756": 0.16690383851528168, "9820": 0.15359249711036682, "9821": 0.37371641397476196, "9869": 0.04860413447022438, "9885": 0.20421554148197174, "9996": 0.2976420819759369, "10016": 0.06520967930555344, "10047": 0.43875885009765625, "10253": 0.2852376699447632, "10327": 0.0038986403960734606, "10372": 0.684319257736206, "10507": 0.6950984001159668, "10519": 0.08871890604496002, "10548": 0.2531573474407196, "10595": 0.4831010699272156, "10723": 0.3374483287334442, "10738": 0.5816917419433594, "10744": 0.08244366943836212, "10769": 0.7408206462860107, "10788": 0.0842406153678894, "10836": 0.06703783571720123, "10956": 0.0606246218085289, "11192": 0.9769153594970703, "11307": 0.026976587250828743, "11311": 0.6487176418304443, "11432": 0.2105647772550583, "11643": 0.1602703034877777, "11852": 0.22937409579753876, "11860": 0.22548456490039825, "12222": 0.9225212931632996, "12228": 0.020300358533859253, "12247": 0.012615402229130268, "12328": 0.9769153594970703, "12477": 0.1229778528213501, "12530": 0.2184450328350067, "12540": 0.45994341373443604, "12562": 0.06429435312747955, "12702": 0.0797421783208847, "12823": 0.4196864068508148, "13002": 0.02412080205976963, "13070": 0.12384103983640671, "13345": 0.4926934838294983, "13416": 0.16690383851528168, "13434": 0.8517522215843201, "13447": 0.5579402446746826, "13656": 0.030771657824516296, "13833": 0.6877616047859192, "14028": 0.02792670577764511, "14067": 0.28450319170951843, "14074": 0.010684899985790253, "14095": 0.8255793452262878, "14567": 0.14602625370025635, "14600": 0.42096930742263794, "14622": 0.5341835021972656, "14774": 0.015504186972975731, "14828": 0.013579257763922215, "14860": 0.8247235417366028, "15006": 0.1930064558982849, "15176": 0.8813109993934631, "15245": 0.6430866718292236, "15286": 0.23402166366577148, "15403": 0.52266925573349, "15612": 0.14433705806732178, "15660": 0.27564704418182373, "15689": 0.2018241584300995, "15698": 0.01934296265244484, "16263": 0.3519764244556427, "16281": 0.056018441915512085, "16514": 0.5506471395492554, "16523": 0.1946154683828354, "16610": 0.2969166338443756, "16639": 0.5455666780471802, "16888": 0.13925230503082275, "17250": 0.13670019805431366, "17347": 0.3070250153541565, "17404": 0.06154331564903259, "17603": 1.3170573711395264, "17614": 0.06612417846918106, "17657": 0.6754127144813538, "17749": 0.319873183965683, "17785": 0.07884006202220917, "17913": 0.22001366317272186, "17914": 0.20739519596099854, "18191": 0.7305257320404053, "18227": 0.06246116757392883, "18228": 0.5562619566917419, "18445": 0.4145384132862091, "18715": 0.10731173306703568, "18769": 0.009718249551951885, "18969": 0.015504186972975731, "19003": 0.24018502235412598, "19136": 0.02412080205976963, "19241": 0.2478361576795578, "19293": 0.052318159490823746, "19601": 0.026976587250828743, "19723": 0.04113444685935974, "19818": 0.016465263441205025, "19841": 0.16359257698059082, "19857": 0.997294545173645, "19872": 0.21687394380569458, "20125": 0.574020504951477, "20187": 0.6312094330787659, "21515": 1.2158164978027344, "21575": 0.6059582233428955, "21618": 0.40806588530540466, "21733": 0.7276995778083801, "21901": 0.2561853528022766, "21908": 0.083342544734478, "22248": 0.08064348995685577, "22262": 0.4938860833644867, "22371": 0.4374985992908478, "22780": 0.1718502640724182, "22806": 1.0914250612258911, "22931": 0.3241194784641266, "22975": 0.2145126610994339, "23041": 0.8100618124008179, "23247": 0.2800849378108978, "23350": 0.11951763927936554, "23692": 0.0770333781838417, "23746": 0.034552380442619324, "24093": 0.12642613053321838, "24137": 0.09228714555501938, "24269": 0.9455460906028748, "24442": 1.200058937072754, "24529": 0.16690383851528168, "24848": 0.2763880789279938, "25370": 0.20977331697940826, "25407": 0.12728634476661682, "25605": 0.016465263441205025, "25644": 0.175953671336174, "25714": 0.7656494975090027, "25969": 0.4041621685028076, "26013": 0.0038986403960734606, "26279": 0.20102575421333313, "26520": 0.15275461971759796, "26773": 0.8109301924705505, "26835": 0.9886114001274109, "27126": 0.06703783571720123, "27321": 0.22859740257263184, "27781": 0.3084607720375061, "28105": 0.16276304423809052, "28156": 0.2837681770324707, "28231": 0.10203468054533005, "28264": 0.055094651877880096, "28406": 0.01934296265244484, "28603": 0.006812678650021553, "28636": 0.5607312321662903, "28674": 0.7115318179130554, "28696": 0.11865071207284927, "28788": 0.5415972471237183, "28873": 1.094698429107666, "29222": 0.09672962874174118, "29397": 0.4624064862728119, "29417": 0.755608320236206, "29543": 0.9628462791442871} | 12100963 | Memory/effector T cells efficiently migrate into extralymphoid tissues and sites of infection, providing immunosurveillance and a first line of defense against invading pathogens. Even though it is a potential means to regulate the size, quality, and duration of a tissue infiltrate, T cell egress from infected tissues is poorly understood. Using a mouse model of influenza A virus infection, we found that CD8 effector T cells egressed from the infected lung in a CCR7-dependent manner. In contrast, following antigen recognition, effector CD8 T cell egress decreased and CCR7 function was reduced in vivo and in vitro, indicating that the exit of CD8 T cells from infected tissues is tightly regulated. Our data suggest that the regulation of T cell egress is a mechanism to retain antigen-specific effectors at the site of infection to promote viral clearance, while decreasing the numbers of bystander T cells and preventing overt inflammation. | Tissue exit: a novel control point in the accumulation of antigen-specific CD8 T cells in the influenza a virus-infected lung. |
{"1014": 0.5220900774002075, "1039": 0.10291612148284912, "1042": 0.06337817758321762, "1998": 0.020300358533859253, "2007": 0.013579257763922215, "2089": 0.10203468054533005, "2094": 0.6764062643051147, "2118": 0.3283478021621704, "2140": 0.2561853528022766, "2152": 0.6773988008499146, "2166": 0.20739519596099854, "2177": 0.1751343309879303, "2204": 0.19622190296649933, "2206": 0.037378571927547455, "2217": 0.1229778528213501, "2235": 0.20739519596099854, "2248": 0.3850763738155365, "2273": 0.35403475165367126, "2287": 0.4512746334075928, "2308": 0.5404602885246277, "2310": 0.11081436276435852, "2313": 0.4349733293056488, "2327": 0.10993985831737518, "2331": 0.5651806592941284, "2353": 0.34715715050697327, "2364": 0.13157635927200317, "2405": 0.6931471824645996, "2417": 0.8349450826644897, "2443": 0.08692999184131622, "2450": 0.28963330388069153, "2470": 0.5651806592941284, "2489": 0.18654440343379974, "2515": 0.2516399025917053, "2522": 0.43244171142578125, "2523": 0.757441520690918, "2535": 0.030771657824516296, "2540": 0.9531047344207764, "2541": 0.46914875507354736, "2542": 0.38905516266822815, "2592": 0.2531573474407196, "2599": 0.17267228662967682, "2615": 0.021256839856505394, "2628": 0.2447827309370041, "2640": 0.567397952079773, "2660": 0.678390383720398, "2724": 0.2447827309370041, "2740": 0.6064908504486084, "2765": 0.21687394380569458, "2812": 0.24171993136405945, "2817": 0.7647408246994019, "2820": 0.4067663550376892, "2824": 0.5517725944519043, "2827": 0.3656192123889923, "2833": 0.3662964701652527, "2854": 0.0797421783208847, "2862": 0.1734936386346817, "2913": 0.8500841856002808, "2918": 0.13071982562541962, "2920": 0.08513788133859634, "2931": 0.08513788133859634, "2946": 0.2516399025917053, "2951": 0.2447827309370041, "2988": 0.21214580535888672, "3014": 0.083342544734478, "3020": 0.32270604372024536, "3120": 0.5805994272232056, "3141": 0.3012613356113434, "3189": 0.4794800877571106, "3205": 0.026976587250828743, "3273": 0.6006163358688354, "3276": 0.5232481360435486, "3278": 0.11778303235769272, "3280": 0.0770333781838417, "3284": 0.3283478021621704, "3287": 0.0058422754518687725, "3378": 0.8625272512435913, "3426": 0.2516399025917053, "3445": 0.2160874605178833, "3446": 0.18492233753204346, "3452": 0.013579257763922215, "3463": 0.49864232540130615, "3466": 0.26296505331993103, "3491": 0.045809537172317505, "3516": 0.3077431619167328, "3556": 0.0842406153678894, "3582": 0.5607312321662903, "3630": 0.2184450328350067, "3643": 0.0038986403960734606, "3647": 0.37640097737312317, "3679": 0.013579257763922215, "3801": 0.052318159490823746, "3808": 0.11865071207284927, "3811": 0.022212404757738113, "3867": 0.06795065850019455, "3891": 1.0158531665802002, "3893": 0.029824240133166313, "3896": 0.4248080551624298, "3945": 0.05046287178993225, "3953": 0.12986256182193756, "3979": 0.25088030099868774, "3994": 0.7647408246994019, "4003": 0.1332872211933136, "4022": 0.3750596046447754, "4045": 0.045809537172317505, "4102": 0.5086748600006104, "4106": 0.8306987881660461, "4117": 0.45623743534088135, "4146": 0.23479416966438293, "4179": 0.6522845029830933, "4216": 0.5712664127349854, "4246": 0.13755162060260773, "4254": 0.16359257698059082, "4270": 0.037378571927547455, "4295": 0.6793810129165649, "4311": 0.4450363218784332, "4328": 0.26146242022514343, "4359": 0.1873544454574585, "4392": 0.15777134895324707, "4431": 0.6165571808815002, "4453": 0.6155022978782654, "4456": 0.29036402702331543, "4511": 1.2693654298782349, "4521": 0.46424978971481323, "4652": 0.05417001247406006, "4745": 0.30558720231056213, "4747": 0.06429435312747955, "4758": 0.0842406153678894, "4772": 0.1930064558982849, "4795": 0.37974658608436584, "4859": 0.04487626627087593, "4877": 0.4437839686870575, "4957": 0.09228714555501938, "4997": 0.053244512528181076, "5345": 0.22782009840011597, "5360": 0.1384023278951645, "5387": 0.3877306580543518, "5393": 0.25467249751091003, "5468": 0.41065993905067444, "5531": 0.5415972471237183, "5547": 0.21293537318706512, "5572": 1.057410478591919, "5617": 0.10731173306703568, "5643": 0.10379679501056671, "5717": 0.2034190446138382, "5739": 0.004870930220931768, "5740": 0.09317722171545029, "5761": 0.29109421372413635, "5769": 0.30989447236061096, "5770": 0.20421554148197174, "5790": 0.006812678650021553, "5799": 0.4400174915790558, "5816": 0.0058422754518687725, "5876": 0.5220900774002075, "5909": 0.7086513638496399, "5948": 0.2763880789279938, "5983": 0.4837033152580261, "6165": 0.010684899985790253, "6177": 0.4400174915790558, "6369": 0.0354953333735466, "6388": 0.176772341132164, "6463": 0.8893690705299377, "6485": 0.6492279767990112, "6501": 0.0058422754518687725, "6544": 0.40089741349220276, "6612": 0.1221139207482338, "6666": 0.24631060659885406, "6677": 0.0797421783208847, "6698": 0.13755162060260773, "6709": 0.15777134895324707, "6721": 0.06337817758321762, "6747": 0.25239890813827515, "6818": 0.1384023278951645, "6922": 0.32553088665008545, "7012": 0.3963087201118469, "7017": 0.4286321699619293, "7080": 0.49982786178588867, "7091": 0.7898768186569214, "7127": 0.2622140049934387, "7189": 0.05139094591140747, "7201": 0.2763880789279938, "7312": 0.04953393340110779, "7316": 0.03360854089260101, "7461": 0.2800849378108978, "7551": 0.1994270235300064, "7594": 0.5381823778152466, "7604": 0.2531573474407196, "7667": 0.4487839937210083, "7691": 0.34922540187835693, "7718": 0.09850110858678818, "7778": 0.10993985831737518, "7831": 0.7239188551902771, "7856": 0.2749055027961731, "7861": 0.37640097737312317, "7863": 0.979118824005127, "7870": 0.5220900774002075, "7882": 0.7038320899009705, "7885": 0.2881702482700348, "7959": 0.010684899985790253, "7965": 0.4494072198867798, "8290": 0.4938860833644867, "8319": 0.1873544454574585, "8381": 0.6603899002075195, "8524": 0.020300358533859253, "8599": 0.18654440343379974, "8729": 0.053244512528181076, "8738": 0.6739205718040466, "8924": 0.4938860833644867, "9002": 0.18816383183002472, "9035": 0.07884006202220917, "9280": 0.18492233753204346, "9312": 0.21135559678077698, "9367": 0.41001203656196594, "9440": 0.520350456237793, "9530": 0.18978065252304077, "9556": 0.3923587501049042, "9560": 0.25088030099868774, "9740": 0.04394211992621422, "9821": 0.045809537172317505, "9998": 0.1693800985813141, "10020": 0.034552380442619324, "10174": 0.151916041970253, "10199": 0.3106105625629425, "10202": 0.32270604372024536, "10258": 0.3339579105377197, "10266": 0.31845372915267944, "10381": 1.0094679594039917, "10426": 0.5063233375549316, "10460": 0.5301685929298401, "10483": 0.034552380442619324, "10611": 0.803087055683136, "10744": 0.28963330388069153, "10817": 0.0354953333735466, "10826": 0.018384648486971855, "10831": 0.7210738658905029, "10847": 0.1221139207482338, "10857": 0.1685553640127182, "10882": 0.03831886500120163, "10903": 0.1808556467294693, "10962": 0.7220231294631958, "11100": 0.6872705817222595, "11431": 1.2404102087020874, "11483": 0.0174254160374403, "11524": 0.13243216276168823, "11546": 0.6107416749000549, "11704": 0.10818854719400406, "11709": 0.09228714555501938, "11835": 0.28597161173820496, "11867": 0.0009760859538801014, "12026": 0.7445381283760071, "12044": 0.1011524572968483, "12327": 0.304147332906723, "12353": 0.10379679501056671, "12407": 0.045809537172317505, "12435": 0.34508460760116577, "12448": 0.12038381397724152, "12462": 0.4794800877571106, "12488": 0.016465263441205025, "12596": 0.09495500475168228, "12654": 0.31845372915267944, "12763": 0.1384023278951645, "12765": 0.23479416966438293, "12769": 0.07431721687316895, "12826": 0.3560888469219208, "12848": 0.15610189735889435, "12851": 0.030771657824516296, "12941": 0.10203468054533005, "13047": 0.020300358533859253, "13105": 0.28963330388069153, "13109": 1.1109062433242798, "13162": 0.4450363218784332, "13181": 0.056018441915512085, "13207": 0.2659635543823242, "13356": 0.8997484445571899, "13594": 0.20421554148197174, "13599": 0.3750596046447754, "13722": 0.6096806526184082, "13822": 0.8973627090454102, "13871": 0.13670019805431366, "14040": 0.1485546976327896, "14155": 0.5186077356338501, "14171": 0.4673144817352295, "14266": 0.28082266449928284, "14343": 0.026976587250828743, "14358": 0.6275664567947388, "14663": 0.040196798741817474, "14671": 0.23324857652187347, "14722": 0.28743788599967957, "14746": 0.7969439625740051, "14817": 0.10203468054533005, "14876": 0.6950984001159668, "14971": 0.043007105588912964, "14973": 0.4151833653450012, "15050": 0.43938836455345154, "15058": 0.755608320236206, "15077": 0.16110190749168396, "15189": 0.022212404757738113, "15306": 0.7426811456680298, "15316": 0.12038381397724152, "15354": 0.5370414853096008, "15415": 0.5528968572616577, "15559": 0.1064341589808464, "15782": 0.043007105588912964, "15901": 0.029824240133166313, "16014": 0.21135559678077698, "16134": 0.029824240133166313, "16211": 0.05139094591140747, "16228": 0.014542185701429844, "16330": 0.30989447236061096, "16478": 0.3409265875816345, "16515": 0.1994270235300064, "16519": 0.3346569836139679, "16575": 0.3547199070453644, "16605": 0.16690383851528168, "16678": 0.36426326632499695, "16902": 0.4974553883075714, "17076": 0.04860413447022438, "17080": 0.030771657824516296, "17175": 0.9333322048187256, "17193": 0.23324857652187347, "17245": 0.030771657824516296, "17464": 0.7537717819213867, "17544": 0.28082266449928284, "17631": 0.26446542143821716, "17663": 0.34508460760116577, "17785": 0.1477125883102417, "17889": 0.037378571927547455, "17908": 0.4425300657749176, "18539": 0.22157983481884003, "18621": 0.1212492436170578, "18804": 0.8829278349876404, "18845": 0.12384103983640671, "18891": 0.11865071207284927, "18949": 0.15943801403045654, "19037": 0.8109301924705505, "19064": 0.10555581003427505, "19098": 0.08154398202896118, "19158": 0.19381128251552582, "19184": 0.6603899002075195, "19188": 0.4311734735965729, "19300": 0.13071982562541962, "19857": 0.24554696679115295, "19960": 0.34577593207359314, "20077": 0.20660123229026794, "20272": 0.08961215615272522, "20302": 0.04487626627087593, "20418": 0.0317181795835495, "20435": 0.22392450273036957, "20467": 0.02792670577764511, "20576": 0.17759032547473907, "20597": 0.04860413447022438, "20794": 0.13243216276168823, "20824": 0.45870962738990784, "20871": 0.09672962874174118, "20968": 0.22548456490039825, "21092": 0.03831886500120163, "21150": 0.00875066313892603, "21371": 0.03831886500120163, "21408": 0.02316705882549286, "21447": 0.1946154683828354, "21731": 0.010684899985790253, "21778": 0.20102575421333313, "21821": 0.17267228662967682, "21879": 0.7500885725021362, "21887": 0.9333322048187256, "22681": 0.06154331564903259, "22935": 0.5098485946655273, "22963": 0.32129061222076416, "23444": 0.9553611874580383, "23900": 0.46853771805763245, "23910": 0.21530038118362427, "24081": 0.5139457583427429, "24552": 0.11865071207284927, "25022": 0.036437395960092545, "25095": 0.07068414986133575, "25613": 0.09050461649894714, "25654": 0.2830325961112976, "25659": 0.06520967930555344, "26163": 0.7086513638496399, "26462": 0.08513788133859634, "26531": 0.15860503911972046, "26780": 0.2881702482700348, "26906": 0.14179791510105133, "27204": 0.009718249551951885, "27794": 1.029200792312622, "27833": 0.4337083101272583, "27896": 0.0174254160374403, "28268": 0.4067663550376892, "28353": 0.030771657824516296, "29396": 0.09672962874174118, "29553": 0.14939609169960022} | 12102963 | Objective: To assess the association of dietary flavonol intake with the subsequent risk of coronary heart disease (CHD) mortality. Design: Meta-analysis of prospective cohort studies published before September 2001. Studies were identified by MEDLINE and EMBASE searches and by scanning relevant reference lists. The following information was extracted from published reports: size of cohort, mean age, mean duration of follow-up, number of fatal CHD events, mean flavonol intake, main sources of flavonol intake, degree of adjustment for potential confounders, and the relation of CHD mortality to dietary flavonol intake measured at baseline. Results: Seven prospective cohorts of men and women were identified including a total of 2087 fatal CHD events. Comparison of individuals in the top third with those in the bottom third of dietary flavonol intake yielded a combined risk ratio of 0.80 (95% CI 0.69–0.93) after adjustment for known CHD risk factors and other dietary components. Conclusion: This overview of prospective cohort studies indicates that high dietary intake of flavonols from a small number of fruits and vegetables, tea and red wine may be associated with a reduced risk from CHD mortality in free-living populations. Sponsorship: Institute for International Health, University of Sydney. | The relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies |
{"1011": 0.0029254043474793434, "1039": 0.053244512528181076, "1048": 0.8169882297515869, "1998": 0.17840765416622162, "2000": 0.18329764902591705, "2004": 0.10555581003427505, "2005": 0.13071982562541962, "2006": 0.4818955361843109, "2007": 0.3723714053630829, "2026": 0.659380316734314, "2029": 0.16359257698059082, "2039": 0.2184450328350067, "2043": 0.004870930220931768, "2051": 0.14349138736724854, "2064": 0.16110190749168396, "2069": 0.14433705806732178, "2071": 0.21765978634357452, "2075": 0.6405166387557983, "2077": 0.04394211992621422, "2084": 0.14349138736724854, "2086": 0.25694093108177185, "2092": 0.47463157773017883, "2093": 0.043007105588912964, "2095": 0.0797421783208847, "2109": 0.40481385588645935, "2116": 0.29473719000816345, "2135": 0.043007105588912964, "2146": 0.37102460861206055, "2159": 0.5232481360435486, "2168": 0.083342544734478, "2177": 0.13670019805431366, "2184": 0.14602625370025635, "2190": 0.637939989566803, "2206": 0.42608439922332764, "2213": 0.6664261221885681, "2224": 0.19862671196460724, "2241": 0.09050461649894714, "2265": 0.27786844968795776, "2316": 0.8885661959648132, "2323": 0.0038986403960734606, "2324": 0.5278670787811279, "2373": 0.0058422754518687725, "2443": 0.03266380727291107, "2458": 0.6086184978485107, "2460": 0.5914691090583801, "2470": 0.6950984001159668, "2478": 0.083342544734478, "2484": 0.38041436672210693, "2488": 0.18411032855510712, "2490": 0.6358738541603088, "2512": 0.674915611743927, "2531": 0.6170841455459595, "2539": 0.6186635494232178, "2546": 0.6112717390060425, "2557": 0.11517547070980072, "2561": 0.5278670787811279, "2589": 0.0174254160374403, "2628": 0.46853771805763245, "2686": 0.9084475636482239, "2720": 0.4980490207672119, "2744": 0.6244332790374756, "2751": 0.9021284580230713, "2753": 0.21530038118362427, "2764": 0.4950772523880005, "2771": 0.09495500475168228, "2777": 0.006812678650021553, "2788": 0.3269403576850891, "2817": 0.8004589080810547, "2825": 0.20739519596099854, "2836": 0.12728634476661682, "2863": 0.0009760859538801014, "2864": 0.3248254358768463, "2913": 0.7408206462860107, "2944": 0.0174254160374403, "2951": 0.07793712615966797, "2966": 0.09406650811433792, "2967": 0.08692999184131622, "3065": 0.06154331564903259, "3112": 0.6897233724594116, "3115": 0.6451379656791687, "3144": 0.8349450826644897, "3227": 0.09317722171545029, "3231": 0.5584990978240967, "3239": 0.6950984001159668, "3263": 0.6228629946708679, "3273": 0.3547199070453644, "3319": 0.06795065850019455, "3350": 0.2576959431171417, "3385": 0.16276304423809052, "3452": 0.13157635927200317, "3463": 0.176772341132164, "3491": 0.3588210940361023, "3512": 0.27044451236724854, "3517": 0.2749055027961731, "3556": 0.23402166366577148, "3569": 0.857568621635437, "3582": 0.777387797832489, "3659": 0.2576959431171417, "3671": 0.6446255445480347, "3674": 0.9333322048187256, "3729": 1.036847710609436, "3734": 0.13755162060260773, "3737": 0.10731173306703568, "3751": 0.045809537172317505, "3754": 0.4512746334075928, "3820": 0.46853771805763245, "3867": 0.35060185194015503, "3891": 0.11081436276435852, "3893": 0.02792670577764511, "3917": 0.8247235417366028, "3977": 0.2659635543823242, "3979": 0.3388410806655884, "4022": 0.9515975713729858, "4072": 0.0797421783208847, "4076": 0.13670019805431366, "4097": 0.07793712615966797, "4102": 0.5404602885246277, "4106": 0.8869584798812866, "4118": 0.7182208299636841, "4146": 0.10993985831737518, "4167": 0.2026219218969345, "4204": 0.18411032855510712, "4229": 0.28670501708984375, "4295": 0.7124901413917542, "4340": 0.08513788133859634, "4356": 0.05139094591140747, "4413": 0.4980490207672119, "4415": 0.12986256182193756, "4432": 0.5438674688339233, "4453": 0.4914994537830353, "4484": 0.1913948506116867, "4503": 0.6950984001159668, "4531": 0.04113444685935974, "4588": 0.4855078160762787, "4591": 0.6603899002075195, "4621": 0.16359257698059082, "4632": 0.1221139207482338, "4637": 0.1889725625514984, "4649": 0.12986256182193756, "4696": 0.6286086440086365, "4718": 0.2409527748823166, "4719": 0.040196798741817474, "4720": 0.2800849378108978, "4725": 0.6573580503463745, "4760": 0.15860503911972046, "4781": 0.15526613593101501, "4800": 0.022212404757738113, "4805": 0.28890204429626465, "4812": 0.0317181795835495, "4813": 0.011650617234408855, "4844": 0.03360854089260101, "4937": 0.23092569410800934, "4958": 1.1356772184371948, "4975": 0.4926934838294983, "4996": 0.4158279001712799, "5022": 0.7096124291419983, "5082": 0.24859806895256042, "5107": 0.3027053773403168, "5147": 0.3191637098789215, "5214": 0.5528968572616577, "5244": 0.9568626880645752, "5345": 0.9225212931632996, "5393": 0.10379679501056671, "5400": 0.20818853378295898, "5461": 0.23633737862110138, "5480": 0.02887592278420925, "5498": 0.3297532796859741, "5579": 0.09761575609445572, "5594": 0.20421554148197174, "5604": 0.36967599391937256, "5646": 0.1677299439907074, "5769": 0.009718249551951885, "5776": 0.6980181336402893, "5791": 0.08064348995685577, "5796": 1.2627575397491455, "5818": 0.09672962874174118, "5852": 0.49030399322509766, "5911": 0.7426811456680298, "5986": 0.1905880719423294, "5989": 0.043007105588912964, "5993": 0.11604541540145874, "5997": 0.0058422754518687725, "6011": 0.19782574474811554, "6028": 0.4412745535373688, "6075": 0.1808556467294693, "6131": 0.469759464263916, "6149": 0.034552380442619324, "6153": 0.10731173306703568, "6179": 0.3346569836139679, "6279": 0.04860413447022438, "6388": 0.07431721687316895, "6413": 0.77198725938797, "6427": 0.5290185213088989, "6483": 0.09495500475168228, "6508": 0.5925496220588684, "6555": 0.890972912311554, "6592": 0.03925827145576477, "6602": 0.06795065850019455, "6612": 1.024303913116455, "6709": 0.5016035437583923, "6753": 0.36697331070899963, "6767": 0.8022117614746094, "6845": 0.6348392367362976, "6878": 0.7692760229110718, "7012": 0.3339579105377197, "7017": 0.4487839937210083, "7028": 0.11604541540145874, "7077": 0.21530038118362427, "7218": 0.12556517124176025, "7236": 0.35677260160446167, "7242": 0.16276304423809052, "7315": 1.0641717910766602, "7403": 0.0752234235405922, "7515": 0.2184450328350067, "7551": 0.034552380442619324, "7590": 0.08692999184131622, "7645": 0.6181373596191406, "7667": 0.1221139207482338, "7709": 0.2447827309370041, "7718": 0.24248650670051575, "7763": 0.1751343309879303, "7831": 0.554580807685852, "7863": 0.10291612148284912, "7870": 0.4837033152580261, "7882": 0.06977381557226181, "7913": 0.03925827145576477, "8030": 0.16276304423809052, "8031": 0.022212404757738113, "8040": 0.6139179468154907, "8060": 0.27712854743003845, "8182": 0.05786345899105072, "8263": 0.3269403576850891, "8321": 0.9628462791442871, "8343": 0.48670899868011475, "8553": 0.056018441915512085, "8715": 0.48068851232528687, "8720": 0.2478361576795578, "8753": 0.11168810725212097, "8853": 0.0354953333735466, "8865": 0.18492233753204346, "8899": 0.052318159490823746, "8977": 0.05046287178993225, "9006": 0.306306391954422, "9113": 0.5517725944519043, "9289": 0.9115922451019287, "9312": 0.8666408061981201, "9349": 0.20660123229026794, "9359": 0.03925827145576477, "9367": 0.02792670577764511, "9380": 0.5162794589996338, "9398": 0.3777405619621277, "9447": 0.2447827309370041, "9496": 0.6512666940689087, "9556": 0.12642613053321838, "9608": 0.12556517124176025, "9626": 0.5990082025527954, "9723": 0.22937409579753876, "9859": 0.9485763907432556, "9896": 0.08871890604496002, "10003": 0.06337817758321762, "10014": 0.14179791510105133, "10173": 0.7592713832855225, "10238": 0.18492233753204346, "10343": 0.1685553640127182, "10465": 0.09050461649894714, "10467": 0.22392450273036957, "10539": 0.23787821829319, "10580": 0.46424978971481323, "10627": 0.015504186972975731, "10640": 0.8187123537063599, "10673": 0.7951818704605103, "10744": 0.1011524572968483, "10788": 0.29473719000816345, "10847": 0.10026945173740387, "10928": 0.37035053968429565, "10976": 0.1734936386346817, "11047": 0.05970508232712746, "11156": 0.35813871026039124, "11265": 0.6684301495552063, "11320": 0.014542185701429844, "11326": 0.41647201776504517, "11436": 0.10731173306703568, "11441": 0.9621002674102783, "11487": 0.35745587944984436, "11498": 0.49923527240753174, "11532": 0.3177432417869568, "11616": 1.1115491390228271, "11701": 0.2689530849456787, "11706": 0.08782484382390976, "11718": 0.1064341589808464, "11763": 0.18573370575904846, "11791": 0.19541899859905243, "11888": 0.8893690705299377, "11892": 0.09850110858678818, "12030": 0.13071982562541962, "12070": 0.06154331564903259, "12126": 0.757441520690918, "12151": 0.49864232540130615, "12207": 0.22548456490039825, "12210": 0.36697331070899963, "12353": 0.1710275560617447, "12435": 0.3262358605861664, "12546": 0.12986256182193756, "12596": 0.18573370575904846, "12650": 0.9470623731613159, "12669": 0.018384648486971855, "12733": 0.10993985831737518, "12826": 0.43812891840934753, "12941": 0.2881702482700348, "13378": 0.05694137513637543, "13594": 0.8925741910934448, "13599": 0.5404602885246277, "13625": 0.1510767638683319, "13706": 0.33115679025650024, "13722": 0.29400965571403503, "13770": 0.08154398202896118, "13908": 0.37371641397476196, "13931": 0.09761575609445572, "14031": 0.969535231590271, "14125": 0.4437839686870575, "14152": 0.1011524572968483, "14155": 0.13925230503082275, "14313": 0.5629584193229675, "14340": 0.19381128251552582, "14358": 0.1619328260421753, "14606": 0.05970508232712746, "14622": 0.06246116757392883, "14847": 0.2145126610994339, "14931": 0.8829278349876404, "14978": 0.1873544454574585, "15069": 0.5584990978240967, "15079": 0.19782574474811554, "15113": 0.0913962796330452, "15298": 1.0492360591888428, "15354": 0.5629584193229675, "15502": 0.0029254043474793434, "15549": 0.7482418417930603, "15573": 0.0174254160374403, "15596": 0.3560888469219208, "15644": 0.28890204429626465, "15698": 0.0009760859538801014, "15756": 0.06703783571720123, "15764": 0.37907835841178894, "15855": 0.23710809648036957, "15873": 0.09317722171545029, "15918": 0.6000806093215942, "16014": 1.0695481300354004, "16026": 1.0087559223175049, "16134": 0.4950772523880005, "16150": 1.2261852025985718, "16157": 0.3241194784641266, "16330": 0.4926934838294983, "16367": 0.2223619967699051, "16474": 1.0815403461456299, "16478": 0.16110190749168396, "16492": 0.26146242022514343, "16493": 0.0174254160374403, "16578": 0.1946154683828354, "16655": 0.5104349255561829, "16670": 0.037378571927547455, "16691": 0.35128939151763916, "16706": 0.08244366943836212, "16754": 0.07341018319129944, "16813": 0.17020416259765625, "16853": 0.2516399025917053, "16902": 0.036437395960092545, "17084": 0.10906458646059036, "17261": 0.1734936386346817, "17371": 0.045809537172317505, "17464": 0.7295845746994019, "17547": 0.8247235417366028, "17751": 0.0770333781838417, "17826": 0.21530038118362427, "17841": 0.014542185701429844, "17908": 0.7791815400123596, "18075": 0.045809537172317505, "18133": 0.9531047344207764, "18349": 0.8973627090454102, "18439": 0.1619328260421753, "18539": 0.1970241367816925, "18714": 0.38905516266822815, "18809": 0.16524957120418549, "18847": 1.0158531665802002, "18981": 0.3910386264324188, "19117": 0.058784693479537964, "19330": 0.6654226183891296, "19470": 0.7463917136192322, "19842": 0.1734936386346817, "19862": 0.21765978634357452, "19939": 0.3318578004837036, "19943": 0.02412080205976963, "20047": 0.016465263441205025, "20116": 1.0437490940093994, "20155": 0.14518201351165771, "20166": 1.108330488204956, "20214": 0.12384103983640671, "20253": 0.25088030099868774, "20302": 0.20421554148197174, "20389": 0.2852376699447632, "20464": 0.7009293437004089, "20467": 0.09317722171545029, "20492": 0.012615402229130268, "20594": 0.09228714555501938, "20647": 0.053244512528181076, "20752": 0.20660123229026794, "20828": 0.10203468054533005, "20932": 0.5220900774002075, "21026": 0.32270604372024536, "21104": 0.02316705882549286, "21150": 0.23633737862110138, "21425": 0.2983669638633728, "21778": 0.11168810725212097, "21901": 0.10818854719400406, "22520": 0.17431432008743286, "22816": 1.211173415184021, "22939": 0.04487626627087593, "22945": 0.01934296265244484, "22963": 0.3084607720375061, "22991": 0.04953393340110779, "23045": 0.7610978484153748, "23130": 0.3248254358768463, "23138": 0.04767346754670143, "23208": 0.2145126610994339, "23212": 0.029824240133166313, "23408": 0.8525851964950562, "23461": 1.0979610681533813, "23521": 0.14433705806732178, "23569": 0.33115679025650024, "23633": 0.37102460861206055, "23683": 0.2652147710323334, "23900": 0.09850110858678818, "24004": 0.043007105588912964, "24098": 0.32199856638908386, "24949": 0.05417001247406006, "25095": 0.021256839856505394, "25264": 0.42990362644195557, "25284": 0.30989447236061096, "25520": 0.10379679501056671, "25613": 0.012615402229130268, "25617": 0.036437395960092545, "25940": 0.2247048318386078, "26120": 0.18167030811309814, "26287": 0.07250232994556427, "26290": 0.21687394380569458, "26745": 0.9317949414253235, "27011": 1.5679646730422974, "27166": 0.018384648486971855, "27179": 0.0842406153678894, "27354": 0.0770333781838417, "27404": 0.5381823778152466, "27718": 0.4673144817352295, "28170": 1.1549384593963623, "28648": 0.055094651877880096, "28828": 0.4709797203540802, "29215": 0.3547199070453644, "29458": 0.8731874823570251} | 12122482 | We compared the diagnostic capabilities of MRI to CT, evoked potentials (EP), and CSF oligoclonal banding analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). MRI was the best method for demonstrating dissemination in space. An abnormal appropriate EP in monosymptomatic disease was usually supported by MRI and CSF analysis as being predictive of MS as a clinical diagnosis. A normal appropriate EP study was not satisfactory because MRI and CSF analysis often did not support a diagnosis of non-MS. When there is agreement between three of these paraclinical studies, the diagnosis of MS is probably unequivocal. For use in research studies, laboratory-supported definite MS (LSDMS) could be diagnosed in 85 patients of the total 200 (42.5%), in 19/38 (50%) of optic neuritis (ON) patients, and in 24/52 (46%) of chronic progressive myelopathy (CPM) patients. MRI was 100% successful in identifying patients who qualified for LSDMS in the ON and CPM groups. In a short follow-up (less than 1 year), 19/200 (10%) went on to develop clinically definite MS (CDMS), and MRI predicted that diagnosis in 18/19 (95%). Only long-term follow-up will show how well these studies and the category of LSDMS predict the development of CDMS. The clinical diagnosis of MS (CDMS), even though only 95% accurate, must remain the gold standard. | MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. |
{"1011": 0.1401015669107437, "1013": 0.2223619967699051, "1038": 0.7067264318466187, "1044": 0.11778303235769272, "1051": 1.102510929107666, "1996": 0.27342069149017334, "2002": 0.1808556467294693, "2011": 0.24171993136405945, "2029": 0.20977331697940826, "2033": 0.27342069149017334, "2073": 0.1905880719423294, "2080": 0.0797421783208847, "2109": 0.2247048318386078, "2140": 0.24325250089168549, "2179": 0.2983669638633728, "2203": 0.9776504039764404, "2213": 0.7105726003646851, "2278": 1.0655186176300049, "2368": 0.1602703034877777, "2415": 0.06886265426874161, "2433": 0.4158279001712799, "2439": 0.176772341132164, "2458": 0.3547199070453644, "2470": 0.043007105588912964, "2483": 0.4145384132862091, "2511": 0.38441169261932373, "2535": 0.53589928150177, "2550": 0.03266380727291107, "2618": 0.47584590315818787, "2666": 0.6260011196136475, "2668": 0.04767346754670143, "2686": 0.05970508232712746, "2719": 0.5506471395492554, "2765": 0.26820653676986694, "2817": 0.0038986403960734606, "2821": 0.1710275560617447, "2828": 0.083342544734478, "2864": 0.0038986403960734606, "2865": 0.0019512200960889459, "2913": 0.0058422754518687725, "2920": 0.6265231370925903, "2944": 0.6931471824645996, "2951": 0.10731173306703568, "3111": 0.41001203656196594, "3161": 0.24631060659885406, "3223": 0.34370049834251404, "3252": 0.03266380727291107, "3273": 0.13925230503082275, "3279": 0.5871354341506958, "3303": 0.43244171142578125, "3378": 0.7692760229110718, "3406": 0.10818854719400406, "3426": 0.3084607720375061, "3450": 0.32270604372024536, "3463": 0.2018241584300995, "3466": 0.03831886500120163, "3526": 0.9194108247756958, "3596": 0.11343330889940262, "3603": 0.10993985831737518, "3625": 0.15860503911972046, "3670": 0.015504186972975731, "3671": 0.2852376699447632, "3707": 0.0770333781838417, "3716": 0.26146242022514343, "3768": 0.009718249551951885, "3853": 0.04487626627087593, "3930": 0.05139094591140747, "4013": 0.4831010699272156, "4023": 0.7239188551902771, "4072": 0.056018441915512085, "4111": 0.07341018319129944, "4130": 0.8731874823570251, "4167": 0.18654440343379974, "4176": 0.13499516248703003, "4187": 0.3283478021621704, "4195": 1.0312920808792114, "4275": 0.5551415085792542, "4325": 0.040196798741817474, "4359": 0.175953671336174, "4395": 0.3560888469219208, "4442": 0.960606575012207, "4503": 0.0354953333735466, "4504": 0.176772341132164, "4515": 0.09495500475168228, "4523": 0.11865071207284927, "4525": 0.022212404757738113, "4558": 0.08961215615272522, "4574": 0.007782140281051397, "4588": 0.4067663550376892, "4786": 0.00875066313892603, "4812": 0.18411032855510712, "4824": 0.2493593990802765, "4876": 0.5734702348709106, "4877": 0.9929623603820801, "4945": 0.1011524572968483, "4962": 0.06977381557226181, "5041": 0.39762192964553833, "5054": 0.6714286804199219, "5292": 0.3683255612850189, "5320": 0.47827014327049255, "5323": 0.35745587944984436, "5332": 0.75193190574646, "5360": 0.010684899985790253, "5591": 0.15526613593101501, "5716": 0.5272908806800842, "5812": 0.5255602598190308, "5854": 0.12814582884311676, "5923": 0.9162907600402832, "5944": 0.5033760666847229, "6081": 0.06246116757392883, "6169": 0.5871354341506958, "6418": 0.7656494975090027, "6438": 0.5914691090583801, "6552": 0.0606246218085289, "6562": 0.6578640341758728, "6779": 0.014542185701429844, "6806": 0.06154331564903259, "6824": 0.07159364968538284, "6873": 1.0312920808792114, "6903": 0.1401015669107437, "6914": 0.5057345628738403, "7065": 0.371698260307312, "7192": 0.34370049834251404, "7337": 0.7445381283760071, "7356": 0.1602703034877777, "7366": 0.10467668622732162, "7371": 0.8109301924705505, "7411": 0.401551216840744, "7461": 0.03360854089260101, "7551": 0.026025565341114998, "7570": 0.22626367211341858, "7645": 0.2990913391113281, "7711": 0.021256839856505394, "7772": 0.11951763927936554, "7872": 1.341354250907898, "7885": 0.08513788133859634, "7898": 0.0038986403960734606, "7901": 0.554580807685852, "7941": 0.6613984704017639, "8000": 1.2835346460342407, "8153": 0.3622259199619293, "8347": 0.03925827145576477, "8469": 0.3485364317893982, "8523": 1.1431772708892822, "8556": 0.3070250153541565, "8586": 0.08603433519601822, "8776": 0.2501201331615448, "9007": 0.23092569410800934, "9031": 0.22782009840011597, "9067": 0.3141832649707794, "9125": 0.1212492436170578, "9239": 0.4831010699272156, "9350": 0.4837033152580261, "9412": 0.21293537318706512, "9468": 0.3170322775840759, "9556": 0.48670899868011475, "9808": 0.9842413663864136, "9962": 0.16359257698059082, "10085": 0.7863243818283081, "10091": 0.3464667797088623, "10448": 0.036437395960092545, "10451": 0.401551216840744, "10548": 0.1510767638683319, "10572": 0.7610978484153748, "10580": 0.1477125883102417, "10595": 0.7408206462860107, "10610": 0.9178520441055298, "10641": 0.0038986403960734606, "10744": 0.11343330889940262, "10803": 1.0999135971069336, "10847": 0.38374659419059753, "11157": 0.14939609169960022, "11192": 0.14433705806732178, "11432": 0.5116065740585327, "11538": 0.10906458646059036, "11598": 0.03266380727291107, "11601": 0.33675122261047363, "11643": 0.2822965085506439, "11663": 0.890972912311554, "11674": 0.8583967685699463, "11714": 0.7463917136192322, "12031": 0.11430477350950241, "12328": 1.2460440397262573, "12402": 0.6139179468154907, "12452": 0.06154331564903259, "12504": 0.022212404757738113, "12562": 0.2990913391113281, "12732": 0.35060185194015503, "13197": 0.495672345161438, "13433": 0.11081436276435852, "13656": 0.176772341132164, "13671": 0.17431432008743286, "13791": 0.014542185701429844, "13908": 0.13071982562541962, "13958": 0.20102575421333313, "14083": 0.07884006202220917, "14173": 0.0029254043474793434, "14440": 0.05046287178993225, "15316": 0.1477125883102417, "15422": 0.9515975713729858, "15472": 0.036437395960092545, "15527": 0.10291612148284912, "15578": 0.014542185701429844, "15589": 0.015504186972975731, "15660": 0.472198486328125, "15923": 0.09228714555501938, "15946": 0.1685553640127182, "16221": 0.2018241584300995, "16340": 0.058784693479537964, "16429": 0.861702561378479, "16487": 0.0770333781838417, "16505": 0.1718502640724182, "16691": 0.007782140281051397, "16731": 0.13243216276168823, "16910": 0.08513788133859634, "17059": 0.13243216276168823, "18111": 1.6356537342071533, "18234": 0.997294545173645, "18349": 0.34508460760116577, "18419": 0.7665573358535767, "18479": 0.04207121208310127, "19057": 0.06612417846918106, "19209": 0.10555581003427505, "19304": 0.2247048318386078, "19314": 0.0038986403960734606, "19539": 0.0019512200960889459, "19610": 1.0264055728912354, "19653": 0.5629584193229675, "19723": 0.016465263441205025, "19806": 0.22704219818115234, "20045": 0.15693697333335876, "20415": 0.22548456490039825, "20464": 1.0986123085021973, "20582": 1.057410478591919, "20792": 0.06886265426874161, "20870": 0.02412080205976963, "20875": 0.4437839686870575, "21009": 0.09584271162748337, "21032": 0.4002431631088257, "21262": 0.812664806842804, "22291": 0.35677260160446167, "22869": 0.20102575421333313, "23079": 0.6482070088386536, "23163": 0.524982750415802, "23737": 0.1751343309879303, "23900": 0.2561853528022766, "24269": 0.018384648486971855, "24374": 0.4855078160762787, "24710": 0.09584271162748337, "24960": 1.319148302078247, "25077": 0.10906458646059036, "25172": 0.6921701431274414, "25468": 0.38041436672210693, "25714": 0.11778303235769272, "25778": 0.1889725625514984, "26236": 1.3321186304092407, "26402": 0.0019512200960889459, "27287": 0.7389566898345947, "27321": 0.06337817758321762, "27885": 1.179255723953247, "28086": 0.5021947622299194, "28156": 0.5696102976799011, "28466": 0.12038381397724152, "28691": 0.22157983481884003, "28723": 1.034073829650879, "28788": 0.36697331070899963, "28828": 0.1718502640724182, "28829": 0.6684301495552063, "28927": 0.4158279001712799, "29109": 0.23015019297599792, "29290": 0.16524957120418549} | 12130067 | Formation of the hematopoietic stem cell (HSC) niche in bone marrow (BM) is tightly associated with endochondral ossification, but little is known about the mechanisms involved. We used the oc/oc mouse, a mouse model with impaired endochondral ossification caused by a loss of osteoclast (OCL) activity, to investigate the role of osteoblasts (OBLs) and OCLs in the HSC niche formation. The absence of OCL activity resulted in a defective HSC niche associated with an increased proportion of mesenchymal progenitors but reduced osteoblastic differentiation, leading to impaired HSC homing to the BM. Restoration of OCL activity reversed the defect in HSC niche formation. Our data demonstrate that OBLs are required for establishing HSC niches and that osteoblastic development is induced by OCLs. These findings broaden our knowledge of the HSC niche formation, which is critical for understanding normal and pathological hematopoiesis. | Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow |
{"1006": 0.03266380727291107, "1009": 0.3883931338787079, "1014": 0.2983669638633728, "1019": 0.2881702482700348, "1020": 0.052318159490823746, "1022": 0.10993985831737518, "1041": 0.940220832824707, "1052": 0.6260011196136475, "1999": 0.8853482007980347, "2004": 0.5914691090583801, "2012": 0.1994270235300064, "2022": 0.0752234235405922, "2026": 0.48970574140548706, "2039": 0.06246116757392883, "2044": 0.011650617234408855, "2051": 0.0019512200960889459, "2053": 0.0029254043474793434, "2063": 0.8022117614746094, "2064": 0.06612417846918106, "2086": 0.43875885009765625, "2094": 0.10379679501056671, "2095": 0.06154331564903259, "2098": 0.11951763927936554, "2101": 0.021256839856505394, "2102": 0.0606246218085289, "2109": 0.12642613053321838, "2116": 0.1710275560617447, "2146": 0.38041436672210693, "2152": 0.7565253376960754, "2158": 0.03925827145576477, "2166": 0.05046287178993225, "2177": 0.04113444685935974, "2184": 0.2018241584300995, "2193": 0.1221139207482338, "2241": 0.00875066313892603, "2273": 0.7057625651359558, "2274": 0.07612881064414978, "2275": 0.29400965571403503, "2287": 0.7295845746994019, "2313": 0.056018441915512085, "2331": 0.6634125709533691, "2340": 0.09584271162748337, "2349": 0.2034190446138382, "2362": 0.0797421783208847, "2426": 0.42353010177612305, "2470": 0.25088030099868774, "2478": 0.12986256182193756, "2491": 0.9037119746208191, "2504": 0.7436100244522095, "2511": 0.0174254160374403, "2540": 1.013020396232605, "2553": 0.7665573358535767, "2561": 0.3519764244556427, "2628": 0.4450363218784332, "2629": 0.2822965085506439, "2640": 0.6902132034301758, "2668": 0.8796916007995605, "2682": 0.3662964701652527, "2705": 0.2837681770324707, "2740": 0.4113073945045471, "2764": 0.22937409579753876, "2765": 0.20977331697940826, "2771": 0.8813109993934631, "2795": 0.0842406153678894, "2804": 0.05417001247406006, "2817": 0.7510106563568115, "2846": 0.4770587682723999, "2854": 0.20501139760017395, "2871": 0.3757305145263672, "2881": 0.12470348179340363, "2894": 0.09495500475168228, "2901": 0.043007105588912964, "2913": 0.6254787445068359, "2920": 0.04487626627087593, "2951": 0.21687394380569458, "2970": 0.04767346754670143, "2981": 1.004473328590393, "3020": 0.5393219590187073, "3024": 0.18411032855510712, "3025": 0.2822965085506439, "3115": 0.02412080205976963, "3176": 0.4734157919883728, "3188": 0.7276995778083801, "3189": 0.06154331564903259, "3231": 0.37907835841178894, "3273": 0.3283478021621704, "3278": 0.06612417846918106, "3280": 0.10906458646059036, "3284": 0.7239188551902771, "3287": 0.5860490798950195, "3367": 1.0001721382141113, "3378": 0.7898768186569214, "3388": 0.6358738541603088, "3426": 0.0797421783208847, "3445": 0.4512746334075928, "3446": 0.1913948506116867, "3452": 0.0842406153678894, "3460": 0.030771657824516296, "3463": 0.3982778787612915, "3471": 0.0009760859538801014, "3487": 0.14518201351165771, "3517": 0.14264501631259918, "3525": 0.07793712615966797, "3556": 0.26146242022514343, "3572": 0.5209306478500366, "3582": 0.37707099318504333, "3618": 0.08871890604496002, "3623": 0.18492233753204346, "3643": 0.6492279767990112, "3647": 0.2184450328350067, "3671": 0.0009760859538801014, "3767": 0.3949938118457794, "3778": 0.2317005842924118, "3798": 0.8289952278137207, "3802": 0.21687394380569458, "3808": 0.11343330889940262, "3811": 0.012615402229130268, "3867": 0.5272908806800842, "3891": 1.059443712234497, "3893": 0.026025565341114998, "3938": 0.8525851964950562, "3940": 0.28155985474586487, "3949": 0.31560876965522766, "3953": 0.8135309815406799, "3968": 0.040196798741817474, "3979": 0.4318077862262726, "4002": 0.27786844968795776, "4003": 0.31560876965522766, "4089": 0.11430477350950241, "4094": 0.10555581003427505, "4098": 0.08244366943836212, "4102": 0.010684899985790253, "4106": 0.5045560002326965, "4125": 0.1889725625514984, "4137": 0.3423145115375519, "4146": 0.2184450328350067, "4174": 0.24554696679115295, "4244": 0.417115718126297, "4292": 0.7295845746994019, "4295": 0.7267557382583618, "4304": 0.9005423784255981, "4372": 0.09050461649894714, "4456": 0.2160874605178833, "4489": 0.0009760859538801014, "4555": 0.3923587501049042, "4606": 0.018384648486971855, "4632": 0.030771657824516296, "4672": 0.04860413447022438, "4745": 0.41001203656196594, "4747": 0.8212929964065552, "4758": 0.6989894509315491, "4793": 0.28155985474586487, "4795": 0.27786844968795776, "4812": 0.04953393340110779, "4945": 0.20501139760017395, "4958": 0.15359249711036682, "4971": 0.09406650811433792, "5022": 0.2470736801624298, "5067": 0.36426326632499695, "5186": 0.01934296265244484, "5292": 0.04860413447022438, "5300": 0.7057625651359558, "5333": 0.28670501708984375, "5345": 0.8829278349876404, "5387": 0.6684301495552063, "5393": 0.007782140281051397, "5423": 1.005902886390686, "5443": 0.24171993136405945, "5468": 0.3956514894962311, "5486": 0.11081436276435852, "5531": 0.3141832649707794, "5604": 0.23092569410800934, "5617": 0.2637155055999756, "5666": 0.9155091643333435, "5739": 0.319873183965683, "5761": 0.14686977863311768, "5776": 0.22001366317272186, "5790": 0.009718249551951885, "5816": 0.9470623731613159, "5845": 0.4818955361843109, "5876": 0.6348392367362976, "5890": 0.11951763927936554, "5950": 0.7182208299636841, "5997": 0.27712854743003845, "6022": 0.21922965347766876, "6388": 0.17922431230545044, "6391": 0.4067663550376892, "6420": 0.06337817758321762, "6431": 0.1873544454574585, "6463": 0.11517547070980072, "6577": 0.1384023278951645, "6612": 0.19782574474811554, "6657": 0.7009293437004089, "6677": 0.0913962796330452, "6678": 0.6482070088386536, "6693": 0.21293537318706512, "6818": 0.8366385698318481, "6845": 0.025073638185858727, "6909": 0.8340972661972046, "7012": 0.4311734735965729, "7017": 0.5784112811088562, "7023": 1.0868242979049683, "7091": 0.38174858689308167, "7099": 0.6107416749000549, "7361": 0.3339579105377197, "7435": 0.2763880789279938, "7438": 0.27712854743003845, "7485": 0.10203468054533005, "7522": 0.6332852244377136, "7542": 0.11081436276435852, "7551": 0.31845372915267944, "7594": 0.18492233753204346, "7644": 0.07612881064414978, "7645": 0.02792670577764511, "7666": 0.00875066313892603, "7667": 0.5295937061309814, "7689": 0.16607704758644104, "7691": 0.0606246218085289, "7711": 0.7629209756851196, "7718": 0.15777134895324707, "7790": 0.255429208278656, "7831": 0.2696990668773651, "7863": 1.0271050930023193, "7870": 0.5534584522247314, "7885": 0.17020416259765625, "8072": 0.07250232994556427, "8168": 0.66441810131073, "8197": 0.7863243818283081, "8247": 0.040196798741817474, "8319": 0.9621002674102783, "8454": 0.07884006202220917, "8483": 0.13755162060260773, "8564": 0.07884006202220917, "8569": 0.6233867406845093, "8586": 0.08782484382390976, "8775": 1.0051883459091187, "8777": 0.6118015646934509, "8822": 0.04767346754670143, "9089": 0.9732321500778198, "9174": 0.4400174915790558, "9181": 0.014542185701429844, "9280": 0.13414156436920166, "9312": 0.2231435477733612, "9350": 0.07250232994556427, "9367": 0.33675122261047363, "9398": 0.1064341589808464, "9413": 0.14518201351165771, "9422": 0.23710809648036957, "9463": 0.8691008687019348, "9556": 0.37907835841178894, "9560": 0.678390383720398, "9657": 0.04953393340110779, "9686": 0.26146242022514343, "9742": 0.25694093108177185, "9750": 0.025073638185858727, "9756": 0.347847044467926, "9824": 0.0019512200960889459, "9834": 0.817850649356842, "9839": 0.08961215615272522, "9890": 0.10203468054533005, "9905": 0.055094651877880096, "9987": 0.7445381283760071, "10092": 0.0317181795835495, "10128": 0.5500838756561279, "10174": 0.15693697333335876, "10349": 0.2160874605178833, "10381": 0.36900100111961365, "10426": 0.674915611743927, "10611": 0.29400965571403503, "10640": 0.018384648486971855, "10744": 0.15860503911972046, "10831": 0.7220231294631958, "10847": 0.01934296265244484, "10857": 0.25239890813827515, "10861": 0.9425065517425537, "10880": 0.7872136831283569, "10903": 0.1485546976327896, "10906": 0.06703783571720123, "11100": 0.762009859085083, "11207": 0.1064341589808464, "11211": 0.06429435312747955, "11325": 0.5010119676589966, "11326": 0.22859740257263184, "11375": 0.1358480453491211, "11432": 0.007782140281051397, "11522": 0.05046287178993225, "11572": 0.6451379656791687, "11664": 0.03831886500120163, "11709": 0.20739519596099854, "11952": 0.5098485946655273, "12044": 0.34370049834251404, "12123": 1.1549384593963623, "12248": 0.14686977863311768, "12377": 0.7389566898345947, "12448": 0.5104349255561829, "12503": 0.04674193635582924, "12520": 0.05417001247406006, "12697": 0.13414156436920166, "12739": 0.4500300884246826, "12763": 0.0606246218085289, "12765": 0.10731173306703568, "12837": 0.6456501483917236, "13004": 0.030771657824516296, "13105": 0.619189441204071, "13113": 0.02887592278420925, "13153": 0.5255602598190308, "13180": 0.6080870032310486, "13221": 0.9485763907432556, "13331": 0.5033760666847229, "13356": 0.4419025182723999, "13371": 0.025073638185858727, "13483": 1.126855492591858, "13692": 0.5393219590187073, "14025": 0.7305257320404053, "14040": 0.18816383183002472, "14061": 0.11778303235769272, "14155": 0.5827828645706177, "14171": 0.5495203733444214, "14358": 0.7144040465354919, "14671": 1.0073304176330566, "14799": 0.4311734735965729, "14925": 0.18816383183002472, "14956": 0.10906458646059036, "14971": 1.0742288827896118, "15000": 0.04767346754670143, "15050": 0.6181373596191406, "15306": 0.6734226942062378, "15316": 0.20102575421333313, "15354": 0.619189441204071, "15502": 0.05046287178993225, "15559": 0.09761575609445572, "15660": 0.2501201331615448, "16014": 0.22859740257263184, "16134": 0.09938567131757736, "16157": 0.12556517124176025, "16227": 0.2976420819759369, "16287": 0.06795065850019455, "16330": 0.33953672647476196, "16381": 0.00875066313892603, "16480": 0.7445381283760071, "16515": 0.026025565341114998, "16519": 0.10203468054533005, "16578": 0.2786078155040741, "16749": 0.24171993136405945, "16902": 0.016465263441205025, "16913": 0.7333439588546753, "17076": 0.3750596046447754, "17080": 0.14602625370025635, "17201": 0.0797421783208847, "17208": 0.2830325961112976, "17245": 0.12728634476661682, "17338": 0.38308101892471313, "17371": 0.7182208299636841, "17464": 0.8583967685699463, "17531": 0.11517547070980072, "17577": 0.20739519596099854, "17631": 0.043007105588912964, "17663": 0.7934166193008423, "17785": 0.11343330889940262, "17844": 0.6107416749000549, "17908": 0.33675122261047363, "18166": 0.3416208028793335, "18231": 0.0606246218085289, "18260": 0.0354953333735466, "18419": 0.03360854089260101, "18422": 0.04953393340110779, "18423": 0.2447827309370041, "18609": 0.04207121208310127, "18622": 0.09495500475168228, "18639": 0.03925827145576477, "18847": 0.0606246218085289, "18886": 0.5573811531066895, "18925": 0.1994270235300064, "18949": 0.11430477350950241, "19037": 0.9546096324920654, "19064": 0.23247487843036652, "19101": 0.021256839856505394, "19158": 0.41001203656196594, "19188": 0.49864232540130615, "19210": 0.9209672808647156, "19875": 0.7105726003646851, "19934": 0.037378571927547455, "20077": 0.38041436672210693, "20155": 0.16607704758644104, "20162": 0.10731173306703568, "20194": 0.5968599319458008, "20282": 0.08244366943836212, "20435": 0.06520967930555344, "20569": 0.12384103983640671, "20794": 0.14939609169960022, "20868": 0.0029254043474793434, "20915": 0.7755908370018005, "21016": 0.1358480453491211, "21150": 0.12470348179340363, "21325": 0.09672962874174118, "21449": 0.09228714555501938, "21557": 0.0913962796330452, "21709": 0.8195732831954956, "21770": 0.6160298585891724, "21887": 1.1038070917129517, "21903": 0.0029254043474793434, "22458": 0.0009760859538801014, "22575": 0.026976587250828743, "22597": 0.32553088665008545, "22778": 0.129004567861557, "22935": 0.5562619566917419, "22939": 0.03831886500120163, "23238": 0.0174254160374403, "23260": 0.18248429894447327, "23760": 0.5816917419433594, "23900": 0.20022670924663544, "23911": 0.34370049834251404, "23969": 0.10993985831737518, "24004": 1.3813996315002441, "24010": 0.1718502640724182, "24081": 0.7201237678527832, "24353": 0.05417001247406006, "24755": 0.6223390698432922, "24848": 0.018384648486971855, "24854": 0.3381449282169342, "25015": 0.03360854089260101, "25070": 0.6754127144813538, "25086": 0.12470348179340363, "25212": 0.1710275560617447, "25331": 0.037378571927547455, "25473": 0.025073638185858727, "25604": 0.1011524572968483, "25613": 0.2990913391113281, "25643": 0.22626367211341858, "25654": 0.5191890001296997, "25714": 0.14349138736724854, "25808": 0.29981520771980286, "25937": 0.3423145115375519, "26033": 0.09850110858678818, "26089": 0.04953393340110779, "26163": 0.8074519634246826, "26226": 0.28155985474586487, "26404": 0.2607102394104004, "26462": 0.1384023278951645, "26836": 0.0058422754518687725, "27321": 0.4531385898590088, "27339": 0.21214580535888672, "27833": 1.278652548789978, "27896": 0.20421554148197174, "28038": 0.23015019297599792, "28093": 0.23633737862110138, "28353": 0.37102460861206055, "28403": 0.11517547070980072, "28436": 0.13499516248703003, "28616": 0.5500838756561279, "28689": 0.06429435312747955, "29048": 0.7163142561912537, "29166": 0.15943801403045654, "29299": 0.39762192964553833} | 12130200 | OBJECTIVE To assess prospectively the risk of coronary heart disease associated with elevated plasma levels of homocyst(e)ine. DESIGN Nested case-control study using prospectively collected blood samples. SETTING Participants in the Physicians' Health Study. PARTICIPANTS A total of 14,916 male physicians, aged 40 to 84 years, with no prior myocardial infarction (MI) or stroke provided plasma samples at baseline and were followed up for 5 years. Samples from 271 men who subsequently developed MI were analyzed for homocyst(e)ine levels together with paired controls, matched by age and smoking. MAIN OUTCOME MEASURE Acute MI or death due to coronary disease. RESULTS Levels of homocyst(e)ine were higher in cases than in controls (11.1 +/- 4.0 [SD] vs 10.5 +/- 2.8 nmol/mL; P = .03). The difference was attributable to an excess of high values among men who later had MIs. The relative risk for the highest 5% vs the bottom 90% of homocyst(e)ine levels was 3.1 (95% confidence interval, 1.4 to 6.9; P = .005). After additional adjustment for diabetes, hypertension, aspirin assignment, Quetelet's Index, and total/high-density lipoprotein cholesterol, this relative risk was 3.4 (95% confidence interval, 1.3 to 8.8) (P = .01). Thirteen controls and 31 cases (11%) had values above the 95th percentile of the controls. CONCLUSIONS Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors. Because high levels can often be easily treated with vitamin supplements, homocyst(e)ine may be an independent, modifiable risk factor. | A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. |
{"1011": 0.6400018334388733, "1016": 1.034767985343933, "1043": 0.6160298585891724, "1048": 0.272677481174469, "1051": 0.6186635494232178, "1059": 0.28450319170951843, "2003": 0.16110190749168396, "2011": 0.22626367211341858, "2029": 0.15526613593101501, "2035": 0.33115679025650024, "2048": 0.5584990978240967, "2053": 0.4926934838294983, "2099": 0.31560876965522766, "2117": 0.4891071021556854, "2119": 0.11951763927936554, "2203": 0.32058215141296387, "2239": 0.015504186972975731, "2361": 0.7683706283569336, "2365": 0.15610189735889435, "2389": 0.7144040465354919, "2396": 0.20580662786960602, "2401": 0.3683255612850189, "2427": 0.28890204429626465, "2462": 0.15023678541183472, "2475": 1.036847710609436, "2487": 0.8247235417366028, "2497": 0.052318159490823746, "2515": 0.18167030811309814, "2535": 0.4248080551624298, "2537": 0.46608972549438477, "2550": 0.2145126610994339, "2570": 0.021256839856505394, "2575": 0.5773153901100159, "2581": 0.3588210940361023, "2590": 0.13414156436920166, "2609": 0.29328158497810364, "2615": 0.8004589080810547, "2618": 0.35060185194015503, "2683": 0.47766464948654175, "2714": 0.2561853528022766, "2817": 0.045809537172317505, "2863": 0.8901712894439697, "2895": 0.07431721687316895, "2913": 0.0058422754518687725, "2920": 0.17759032547473907, "2953": 0.2667117714881897, "2981": 0.7047978043556213, "3078": 0.5947071313858032, "3149": 0.77198725938797, "3158": 0.8298473954200745, "3161": 0.319873183965683, "3170": 0.037378571927547455, "3255": 0.6764062643051147, "3273": 0.29400965571403503, "3278": 0.7408206462860107, "3283": 0.6075552701950073, "3350": 0.24401791393756866, "3351": 0.14686977863311768, "3366": 1.04512357711792, "3406": 0.056018441915512085, "3416": 0.13670019805431366, "3426": 0.24325250089168549, "3431": 0.08064348995685577, "3433": 0.22704219818115234, "3445": 0.36358460783958435, "3466": 0.574020504951477, "3526": 0.3526630103588104, "3543": 0.7610978484153748, "3593": 0.42990362644195557, "3623": 0.2409527748823166, "3635": 0.5920094847679138, "3670": 0.2696990668773651, "3747": 0.2478361576795578, "3760": 0.0009760859538801014, "3768": 0.18654440343379974, "3807": 0.026025565341114998, "3853": 0.3554046154022217, "3896": 0.5629584193229675, "3905": 1.175042748451233, "3952": 0.13925230503082275, "3972": 0.7153595685958862, "4013": 1.1325355768203735, "4014": 0.6714286804199219, "4022": 0.7201237678527832, "4101": 0.8600510358810425, "4102": 0.1212492436170578, "4167": 0.10555581003427505, "4176": 0.13157635927200317, "4263": 0.036437395960092545, "4353": 0.8091925978660583, "4359": 0.35334911942481995, "4395": 0.24631060659885406, "4442": 0.5756692886352539, "4502": 0.03360854089260101, "4523": 0.06429435312747955, "4539": 0.2247048318386078, "4573": 0.21135559678077698, "4742": 0.10993985831737518, "4747": 0.4938860833644867, "4812": 0.11256109178066254, "4958": 0.34577593207359314, "4962": 0.4500300884246826, "4972": 0.021256839856505394, "5028": 0.48068851232528687, "5042": 0.7683706283569336, "5105": 0.25995752215385437, "5127": 0.02887592278420925, "5228": 0.4093637466430664, "5250": 0.6674286723136902, "5320": 0.2247048318386078, "5360": 0.14179791510105133, "5449": 0.03266380727291107, "5468": 0.09317722171545029, "5500": 0.2561853528022766, "5668": 0.436867892742157, "5799": 0.040196798741817474, "6022": 0.6793810129165649, "6038": 0.6118015646934509, "6064": 0.06246116757392883, "6181": 1.2538783550262451, "6194": 0.00875066313892603, "6228": 0.9900637865066528, "6335": 0.757441520690918, "6551": 0.012615402229130268, "6624": 0.13157635927200317, "6643": 0.23092569410800934, "6693": 0.5871354341506958, "6740": 0.1011524572968483, "6767": 0.06795065850019455, "6833": 0.5930894017219543, "6924": 0.12814582884311676, "6937": 0.0913962796330452, "7244": 0.15693697333335876, "7337": 0.3777405619621277, "7403": 0.6833335757255554, "7457": 0.15359249711036682, "7461": 0.3662964701652527, "7591": 0.7086513638496399, "7594": 0.2105647772550583, "7645": 0.058784693479537964, "7682": 0.6709295511245728, "7711": 0.010684899985790253, "7716": 0.6563454270362854, "7741": 0.011650617234408855, "7784": 0.09495500475168228, "7790": 0.036437395960092545, "7831": 0.34023189544677734, "7889": 0.0174254160374403, "8000": 0.7863243818283081, "8004": 0.7791815400123596, "8015": 0.016465263441205025, "8031": 0.0029254043474793434, "8092": 0.018384648486971855, "8153": 0.13414156436920166, "8171": 0.40806588530540466, "8290": 0.014542185701429844, "8360": 0.0913962796330452, "8445": 1.0567318201065063, "8449": 0.9583619832992554, "8469": 0.12470348179340363, "8583": 0.09228714555501938, "8776": 0.052318159490823746, "8878": 1.2250384092330933, "8939": 0.6573580503463745, "9007": 0.3485364317893982, "9113": 0.17020416259765625, "9145": 0.34715715050697327, "9165": 0.3423145115375519, "9174": 0.19541899859905243, "9335": 0.5640701055526733, "9350": 0.8332487344741821, "9412": 0.3005385100841522, "9495": 0.1734936386346817, "9589": 0.10026945173740387, "9760": 0.05417001247406006, "9821": 0.09495500475168228, "9839": 0.0058422754518687725, "9885": 0.1994270235300064, "10120": 0.021256839856505394, "10163": 0.5220900774002075, "10486": 1.1469062566757202, "10548": 0.43623676896095276, "10572": 1.195341944694519, "10623": 0.7201237678527832, "10722": 0.02316705882549286, "10769": 1.3362338542938232, "10847": 0.3784096837043762, "10975": 0.2659635543823242, "11069": 0.29328158497810364, "11179": 0.034552380442619324, "11211": 1.0423725843429565, "11265": 0.2689530849456787, "11369": 0.8649974465370178, "11432": 0.9440274834632874, "11477": 0.02887592278420925, "11598": 0.15610189735889435, "11937": 0.23787821829319, "11968": 1.5663347244262695, "12146": 0.5690577030181885, "12190": 0.9805850982666016, "12328": 1.0437490940093994, "12333": 0.11778303235769272, "12435": 0.1485546976327896, "12616": 0.009718249551951885, "12817": 0.17840765416622162, "12928": 1.049919843673706, "12956": 0.24554696679115295, "12997": 1.0144377946853638, "13012": 0.006812678650021553, "13143": 0.08154398202896118, "13330": 0.38174858689308167, "13341": 0.5914691090583801, "13366": 0.07159364968538284, "13408": 0.3930181860923767, "13531": 0.1011524572968483, "13791": 1.2244645357131958, "13833": 1.2488490343093872, "13922": 0.0842406153678894, "14026": 0.11865071207284927, "14061": 0.36426326632499695, "14074": 0.12556517124176025, "14228": 0.052318159490823746, "14471": 0.1930064558982849, "14573": 0.450652539730072, "14639": 0.8340972661972046, "14728": 1.2905446290969849, "14736": 0.007782140281051397, "14828": 0.1485546976327896, "15265": 0.34300774335861206, "15356": 0.06246116757392883, "15527": 0.04113444685935974, "15663": 0.2969166338443756, "15698": 0.4113073945045471, "15946": 0.35403475165367126, "15956": 0.09584271162748337, "16026": 0.06795065850019455, "16221": 0.08871890604496002, "16389": 0.812664806842804, "16453": 0.05139094591140747, "16730": 0.04394211992621422, "17059": 0.07884006202220917, "17379": 0.9485763907432556, "17441": 0.7995813488960266, "17599": 0.06520967930555344, "17630": 0.7592713832855225, "17651": 0.8100618124008179, "17666": 0.3262358605861664, "17913": 0.08064348995685577, "17960": 0.987156867980957, "18234": 0.6664261221885681, "18260": 0.07431721687316895, "18348": 0.7500885725021362, "18370": 0.3910386264324188, "18647": 0.2719337046146393, "18699": 0.9827804565429688, "18714": 0.4926934838294983, "18715": 0.9635916948318481, "18888": 0.0797421783208847, "18903": 0.1677299439907074, "18981": 0.10291612148284912, "19053": 0.9225212931632996, "19345": 0.1710275560617447, "19481": 0.034552380442619324, "19653": 0.8682814836502075, "19737": 0.4444103240966797, "19780": 0.5347557663917542, "19817": 1.0855059623718262, "19872": 0.9886114001274109, "20132": 0.3676496744155884, "20187": 0.9929623603820801, "20455": 0.6950984001159668, "20544": 0.9178520441055298, "20591": 0.306306391954422, "20611": 0.018384648486971855, "20624": 0.5668440461158752, "20752": 0.4041621685028076, "20766": 0.38441169261932373, "20806": 0.03360854089260101, "20858": 0.3325583338737488, "20868": 0.08244366943836212, "20960": 0.08244366943836212, "21017": 0.6254787445068359, "21111": 0.0019512200960889459, "21252": 0.8941729068756104, "21412": 0.6773988008499146, "21466": 0.2696990668773651, "21472": 0.04860413447022438, "21619": 0.8298473954200745, "21714": 0.0009760859538801014, "21733": 0.7592713832855225, "21735": 0.006812678650021553, "21800": 0.022212404757738113, "21903": 0.5318912267684937, "21967": 0.4228905141353607, "22022": 0.2607102394104004, "22048": 0.861702561378479, "22330": 0.3346569836139679, "22574": 0.8748174905776978, "22597": 0.1677299439907074, "22799": 0.36697331070899963, "22889": 0.7047978043556213, "22930": 0.4400174915790558, "22991": 0.034552380442619324, "23216": 0.12728634476661682, "23238": 0.011650617234408855, "23408": 0.7124901413917542, "23461": 0.757441520690918, "23586": 0.45251765847206116, "23692": 0.010684899985790253, "23760": 0.7389566898345947, "24054": 0.2983669638633728, "24269": 0.1693800985813141, "24587": 0.5540198087692261, "24759": 0.42096930742263794, "24829": 0.7342816591262817, "24932": 0.8332487344741821, "25015": 0.037378571927547455, "25039": 0.07793712615966797, "25086": 0.05694137513637543, "25117": 0.9302552938461304, "25172": 0.4938860833644867, "25194": 0.35334911942481995, "25344": 0.0606246218085289, "25354": 0.9531047344207764, "25456": 0.053244512528181076, "25641": 0.0752234235405922, "25761": 0.5324648022651672, "25874": 0.3141832649707794, "26243": 0.13243216276168823, "26314": 0.5092619061470032, "26402": 0.255429208278656, "26651": 0.09495500475168228, "26721": 0.8366385698318481, "26802": 1.3882455825805664, "26942": 0.7124901413917542, "27058": 1.2499688863754272, "27099": 0.04207121208310127, "27491": 0.20580662786960602, "27572": 0.9485763907432556, "27641": 0.5540198087692261, "27846": 0.6744182109832764, "27854": 0.46363574266433716, "28156": 0.32058215141296387, "28227": 0.24325250089168549, "28687": 0.026976587250828743, "28691": 1.241539478302002, "28774": 0.28082266449928284, "29290": 0.6070231795310974, "29441": 0.09672962874174118} | 12130690 | Protease-activated receptor-2 (PAR-2) is a G-protein-coupled receptor activated through proteolytic cleavage. It is localized on epithelial, endothelial and inflammatory cells, as well as on transient receptor potential vanilloid 1 (TRPV1) receptor-expressing neurones. It plays an important role in inflammatory/nociceptive processes. Since there are few reports concerning PAR-2 function in joints, the effects of intraarticular PAR-2 activation on joint pain and inflammation were studied. Secondary hyperalgesia/allodynia, spontaneous weight distribution, swelling and inflammatory cytokine production were measured and the involvement of TRPV1 ion channels was investigated in rats and mice. Injection of the PAR-2 receptor agonist SLIGRL-NH(2) into the knee decreased touch sensitivity and weight bearing of the ipsilateral hindlimb in both species. Secondary mechanical allodynia/hyperalgesia and impaired weight distribution were significantly reduced by the TRPV1 antagonist SB366791 in rats and by the genetic deletion of this receptor in mice. PAR-2 activation did not cause significant joint swelling, but increased IL-1beta concentration which was not influenced by the lack of the TRPV1 channel. For comparison, intraplantar SLIGRL-NH(2) evoked similar primary mechanical hyperalgesia and impaired weight distribution in both WT and TRPV1 deficient mice, but oedema was smaller in the knockouts. The inactive peptide, LRGILS-NH(2), injected into either site did not induce any inflammatory or nociceptive changes. These data provide evidence for a significant role of TRPV1 receptors in secondary mechanical hyperalgesia/allodynia and spontaneous pain induced by PAR-2 receptor activation in the knee joint. Although intraplantar PAR-2 activation-induced oedema is also TRPV1 receptor-mediated, primary mechanical hyperalgesia, impaired weight distribution and IL-1beta production are independent of this channel. | Involvement of transient receptor potential vanilloid 1 receptors in protease-activated receptor-2-induced joint inflammation and nociception. |
{"1003": 0.03831886500120163, "1015": 0.29981520771980286, "1026": 0.10906458646059036, "1042": 0.043007105588912964, "1053": 0.23479416966438293, "1058": 0.2607102394104004, "1998": 0.4518963396549225, "2007": 0.30989447236061096, "2025": 0.3588210940361023, "2028": 0.07612881064414978, "2031": 0.24554696679115295, "2045": 0.16110190749168396, "2062": 0.08871890604496002, "2084": 0.05694137513637543, "2090": 0.28670501708984375, "2106": 0.16276304423809052, "2111": 0.08961215615272522, "2116": 0.07250232994556427, "2117": 0.755608320236206, "2121": 0.06612417846918106, "2130": 0.3318578004837036, "2158": 0.6492279767990112, "2168": 0.3723714053630829, "2174": 0.04674193635582924, "2235": 0.26820653676986694, "2241": 0.23710809648036957, "2273": 0.8845420479774475, "2294": 0.1011524572968483, "2308": 0.9546096324920654, "2313": 0.5232481360435486, "2362": 0.14939609169960022, "2367": 0.11517547070980072, "2382": 0.5290185213088989, "2384": 0.33605360984802246, "2416": 0.19220098853111267, "2421": 0.1485546976327896, "2426": 0.34023189544677734, "2443": 0.4177590310573578, "2450": 0.8109301924705505, "2470": 0.3554046154022217, "2475": 0.06337817758321762, "2486": 0.06886265426874161, "2487": 0.619189441204071, "2515": 0.28597161173820496, "2522": 0.17759032547473907, "2523": 0.15693697333335876, "2529": 0.1693800985813141, "2531": 0.6664261221885681, "2546": 0.022212404757738113, "2556": 0.0174254160374403, "2560": 0.2184450328350067, "2571": 0.440646231174469, "2615": 1.0999135971069336, "2625": 0.14179791510105133, "2659": 0.16276304423809052, "2674": 0.32129061222076416, "2711": 0.04207121208310127, "2714": 0.983511209487915, "2765": 0.053244512528181076, "2809": 0.1064341589808464, "2817": 0.5849615335464478, "2825": 0.1358480453491211, "2863": 0.029824240133166313, "2896": 0.29255300760269165, "2913": 0.7047978043556213, "2918": 0.0842406153678894, "2931": 0.672426164150238, "2944": 0.0354953333735466, "2953": 0.22001366317272186, "2988": 0.5174443125724792, "2992": 0.012615402229130268, "3020": 0.07341018319129944, "3140": 0.906871497631073, "3141": 0.41065993905067444, "3155": 0.5909284353256226, "3188": 0.15023678541183472, "3189": 0.4709797203540802, "3251": 0.23247487843036652, "3265": 0.2741633653640747, "3273": 0.41065993905067444, "3276": 0.812664806842804, "3278": 0.6853039860725403, "3284": 0.20660123229026794, "3287": 0.6512666940689087, "3337": 0.13157635927200317, "3348": 0.026025565341114998, "3359": 0.03266380727291107, "3378": 0.7408206462860107, "3382": 0.22782009840011597, "3426": 0.06429435312747955, "3445": 0.7647408246994019, "3446": 0.022212404757738113, "3463": 0.3012613356113434, "3466": 0.05694137513637543, "3476": 0.25239890813827515, "3497": 0.26296505331993103, "3517": 0.3297532796859741, "3547": 0.6950984001159668, "3549": 0.21214580535888672, "3551": 0.33115679025650024, "3567": 0.2160874605178833, "3570": 0.6415454745292664, "3618": 0.1229778528213501, "3623": 0.7827593088150024, "3633": 0.4145384132862091, "3647": 0.19541899859905243, "3767": 0.5324648022651672, "3801": 0.6275664567947388, "3807": 0.1229778528213501, "3811": 0.1485546976327896, "3823": 0.4974553883075714, "3853": 0.5718178153038025, "3867": 0.27564704418182373, "3872": 0.7124901413917542, "3891": 1.0768938064575195, "3893": 0.056018441915512085, "3896": 0.015504186972975731, "3938": 0.5381823778152466, "3945": 0.306306391954422, "3963": 0.4812922179698944, "3977": 0.25467249751091003, "3979": 0.004870930220931768, "4039": 0.04394211992621422, "4102": 0.6070231795310974, "4118": 0.27934664487838745, "4125": 0.10379679501056671, "4146": 0.3127557039260864, "4185": 0.255429208278656, "4244": 0.2184450328350067, "4281": 0.8525851964950562, "4295": 0.20102575421333313, "4298": 0.0174254160374403, "4311": 0.1384023278951645, "4358": 0.0797421783208847, "4359": 0.6719275116920471, "4453": 0.5827828645706177, "4456": 1.2432310581207275, "4492": 0.06429435312747955, "4603": 0.04394211992621422, "4654": 0.40220460295677185, "4659": 0.5662899017333984, "4725": 0.40741631388664246, "4788": 0.011650617234408855, "4795": 0.23787821829319, "4852": 0.38041436672210693, "4876": 0.08782484382390976, "4937": 0.175953671336174, "4957": 0.22157983481884003, "4972": 0.0019512200960889459, "5020": 0.07793712615966797, "5333": 0.5506471395492554, "5345": 0.8143964409828186, "5360": 0.09850110858678818, "5443": 0.12642613053321838, "5468": 0.004870930220931768, "5505": 0.31132611632347107, "5531": 0.2976420819759369, "5547": 0.5528968572616577, "5610": 0.7537717819213867, "5662": 0.21765978634357452, "5668": 0.05046287178993225, "5709": 0.011650617234408855, "5729": 0.2659635543823242, "5737": 0.07884006202220917, "5786": 0.1602703034877777, "5799": 0.44753631949424744, "5816": 0.23015019297599792, "5876": 0.03266380727291107, "5903": 0.18329764902591705, "5907": 0.4113073945045471, "5981": 0.11951763927936554, "5986": 0.13755162060260773, "5989": 0.4974553883075714, "6001": 0.04953393340110779, "6022": 0.34715715050697327, "6061": 0.1212492436170578, "6086": 0.1011524572968483, "6388": 0.05786345899105072, "6431": 0.27786844968795776, "6550": 0.1913948506116867, "6551": 0.1485546976327896, "6564": 0.22937409579753876, "6660": 0.3683255612850189, "6702": 0.26446542143821716, "6704": 0.6107416749000549, "6709": 0.045809537172317505, "6721": 0.029824240133166313, "6747": 0.22937409579753876, "6767": 0.18816383183002472, "6801": 1.0001721382141113, "6818": 0.53589928150177, "6819": 0.13670019805431366, "6875": 0.014542185701429844, "6904": 0.40806588530540466, "6932": 0.44753631949424744, "6937": 0.02887592278420925, "7012": 0.22937409579753876, "7017": 0.4873090982437134, "7023": 0.9673105478286743, "7080": 0.1994270235300064, "7091": 0.5168620347976685, "7189": 0.5045560002326965, "7235": 0.19381128251552582, "7290": 0.4437839686870575, "7312": 0.6778947114944458, "7316": 0.029824240133166313, "7453": 0.0770333781838417, "7457": 0.6533012986183167, "7461": 0.3339579105377197, "7524": 0.07431721687316895, "7551": 0.1332872211933136, "7583": 0.3824150264263153, "7645": 0.0019512200960889459, "7691": 0.018384648486971855, "7778": 0.16359257698059082, "7784": 0.4158279001712799, "7831": 0.603290855884552, "7865": 0.37974658608436584, "7885": 0.029824240133166313, "7959": 0.46424978971481323, "7978": 0.10291612148284912, "8053": 0.09228714555501938, "8161": 0.3106105625629425, "8197": 0.4624064862728119, "8290": 0.33675122261047363, "8319": 0.37371641397476196, "8335": 0.010684899985790253, "8360": 0.2954642176628113, "8776": 0.29109421372413635, "8920": 0.05139094591140747, "8948": 1.0179725885391235, "8949": 0.6699305176734924, "9047": 0.6674286723136902, "9098": 0.49923527240753174, "9148": 0.15943801403045654, "9280": 0.15442965924739838, "9308": 0.06520967930555344, "9336": 0.17020416259765625, "9367": 0.06612417846918106, "9412": 0.306306391954422, "9422": 0.9515975713729858, "9556": 0.15275461971759796, "9654": 0.1332872211933136, "9657": 0.03266380727291107, "9723": 0.19782574474811554, "9765": 0.06429435312747955, "9776": 0.03831886500120163, "9820": 0.11604541540145874, "9844": 0.1718502640724182, "9885": 0.4330752193927765, "9907": 0.8366385698318481, "10061": 0.21214580535888672, "10173": 0.9440274834632874, "10174": 0.009718249551951885, "10175": 0.0029254043474793434, "10238": 0.1873544454574585, "10256": 0.6970458030700684, "10266": 0.17759032547473907, "10349": 0.24401791393756866, "10426": 0.6086184978485107, "10465": 0.9440274834632874, "10548": 0.3248254358768463, "10671": 0.6921701431274414, "10736": 0.025073638185858727, "10744": 0.2763880789279938, "10754": 0.7809720039367676, "10768": 1.2510874271392822, "10819": 0.23402166366577148, "10831": 0.8057082891464233, "10847": 0.0797421783208847, "10861": 0.0797421783208847, "11119": 0.036437395960092545, "11156": 0.09584271162748337, "11187": 0.05694137513637543, "11192": 1.2862366437911987, "11211": 0.15023678541183472, "11215": 0.15943801403045654, "11259": 0.18573370575904846, "11310": 0.25467249751091003, "11326": 0.06612417846918106, "11436": 0.2034190446138382, "11455": 0.3897167444229126, "11703": 0.417115718126297, "11835": 0.08064348995685577, "11892": 0.1212492436170578, "12285": 0.27934664487838745, "12319": 0.5450005531311035, "12381": 0.11517547070980072, "12435": 0.7500885725021362, "12503": 0.15777134895324707, "12596": 0.17267228662967682, "12826": 0.3374483287334442, "13014": 0.045809537172317505, "13047": 0.1477125883102417, "13105": 0.018384648486971855, "13180": 0.1930064558982849, "13331": 0.16276304423809052, "13366": 0.020300358533859253, "13416": 0.16524957120418549, "13483": 1.004473328590393, "13599": 0.42225050926208496, "13656": 0.2837681770324707, "13720": 0.03360854089260101, "13735": 0.030771657824516296, "14025": 0.6363908052444458, "14171": 0.5685047507286072, "14267": 0.11517547070980072, "14396": 0.025073638185858727, "14402": 0.7314660549163818, "14613": 0.14686977863311768, "15001": 0.9155091643333435, "15058": 0.5370414853096008, "15074": 0.24325250089168549, "15088": 0.5010119676589966, "15238": 0.04207121208310127, "15306": 0.4412745535373688, "15559": 0.09495500475168228, "15911": 0.17431432008743286, "16007": 0.010684899985790253, "16014": 1.0101795196533203, "16134": 0.3910386264324188, "16211": 0.13157635927200317, "16259": 0.8957691192626953, "16464": 0.3325583338737488, "16515": 0.1064341589808464, "16519": 0.10731173306703568, "16593": 0.03925827145576477, "16677": 0.08064348995685577, "16778": 0.9194108247756958, "16781": 0.3956514894962311, "16824": 0.02792670577764511, "16902": 0.7389566898345947, "16922": 0.44753631949424744, "17282": 0.04674193635582924, "17464": 0.10731173306703568, "17547": 0.7845434546470642, "17631": 0.20022670924663544, "17666": 0.2018241584300995, "17676": 0.3304552733898163, "17678": 0.025073638185858727, "17913": 0.42416930198669434, "18234": 1.061472773551941, "18518": 0.02412080205976963, "18539": 0.1358480453491211, "18583": 0.2539152204990387, "18888": 0.16359257698059082, "18949": 0.12986256182193756, "19037": 0.5010119676589966, "19064": 0.2852376699447632, "19158": 0.21293537318706512, "19188": 0.4093637466430664, "19332": 0.2539152204990387, "19335": 0.055094651877880096, "19531": 0.1401015669107437, "19639": 0.09495500475168228, "19680": 0.007782140281051397, "19824": 0.1221139207482338, "19939": 0.43938836455345154, "20272": 0.1064341589808464, "20419": 0.15943801403045654, "20467": 0.01934296265244484, "20482": 0.3743882179260254, "20781": 0.3381449282169342, "20932": 0.567951500415802, "21068": 0.0029254043474793434, "21081": 0.6902132034301758, "21425": 0.175953671336174, "21434": 0.11430477350950241, "21461": 0.09761575609445572, "21663": 0.30989447236061096, "21864": 1.0560526847839355, "21908": 0.42544642090797424, "22035": 0.18978065252304077, "22750": 0.1930064558982849, "22963": 0.22392450273036957, "22991": 0.1602703034877777, "23086": 0.014542185701429844, "23150": 0.009718249551951885, "23350": 0.3019835948944092, "23900": 0.5844172835350037, "24004": 0.1873544454574585, "24081": 0.26820653676986694, "24209": 0.1221139207482338, "24501": 0.18492233753204346, "24528": 0.1358480453491211, "24759": 0.13755162060260773, "25006": 0.6022219061851501, "25022": 0.5876781344413757, "25172": 0.952351450920105, "25409": 0.8161250352859497, "25465": 0.13071982562541962, "25613": 0.04113444685935974, "25937": 0.22782009840011597, "25962": 0.06154331564903259, "26163": 0.2576959431171417, "26180": 0.0752234235405922, "26206": 0.0606246218085289, "26563": 0.09317722171545029, "26893": 0.09495500475168228, "27204": 0.06977381557226181, "27881": 0.02887592278420925, "28070": 0.10906458646059036, "28089": 0.07068414986133575, "28093": 0.2089812457561493, "28207": 0.08513788133859634, "28227": 0.07431721687316895, "28436": 0.04207121208310127, "28466": 0.255429208278656, "28578": 0.5506471395492554, "29207": 0.12814582884311676, "29308": 0.06795065850019455, "29458": 0.7881022095680237, "29474": 0.5255602598190308, "29516": 0.3084607720375061} | 12145359 | BACKGROUND Individuals with severely impaired lung function have an increased risk of lung cancer. Whether milder reductions in forced expiratory volume in 1 second (FEV(1)) also increase the risk of lung cancer is controversial. Moreover, there is little consensus on whether men and women have similar risks for lung cancer for similar decreases in FEV(1). METHODS A search was conducted of PubMed and EMBASE from January 1966 to January 2005 and studies that examined the relationship between FEV1 and lung cancer were identified. The search was limited to studies that were population based, employed a prospective design, were large in size (> or = 5000 participants), and adjusted for cigarette smoking status. RESULTS Twenty eight abstracts were identified, six of which did not report FEV1 and eight did not adjust for smoking. Included in this report are four studies that reported FEV1 in quintiles. The risk of lung cancer increased with decreasing FEV1. Compared with the highest quintile of FEV1 (> 100% of predicted), the lowest quintile of FEV1 (< approximately 70% of predicted) was associated with a 2.23 fold (95% confidence interval (CI) 1.73 to 2.86) increase in the risk for lung cancer in men and a 3.97 fold increase in women (95% CI 1.93 to 8.25). Even relatively small decrements in FEV1 ( approximately 90% of predicted) increased the risk for lung cancer by 30% in men (95% CI 1.05 to 1.62) and 2.64 fold in women (95% CI 1.30 to 5.31). CONCLUSION Reduced FEV1 is strongly associated with lung cancer. Even a relatively modest reduction in FEV1 is a significant predictor of lung cancer, especially among women. | Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: a systematic review and meta-analysis. |
{"1011": 0.2184450328350067, "1015": 0.3554046154022217, "1016": 0.022212404757738113, "1017": 0.08961215615272522, "1045": 0.8264343738555908, "1052": 0.5098485946655273, "1056": 0.08244366943836212, "1996": 0.1332872211933136, "1997": 0.1873544454574585, "2003": 0.03266380727291107, "2008": 0.08603433519601822, "2011": 0.5472630262374878, "2028": 0.06154331564903259, "2029": 0.2689530849456787, "2034": 0.6394867897033691, "2076": 0.27934664487838745, "2079": 0.053244512528181076, "2093": 0.012615402229130268, "2116": 0.25694093108177185, "2117": 0.18004031479358673, "2182": 0.10731173306703568, "2203": 0.5370414853096008, "2328": 0.06703783571720123, "2403": 0.5104349255561829, "2433": 0.15359249711036682, "2462": 0.4556184411048889, "2475": 0.16690383851528168, "2487": 0.371698260307312, "2515": 0.040196798741817474, "2532": 1.117955207824707, "2535": 0.23092569410800934, "2537": 0.32905077934265137, "2549": 0.45251765847206116, "2550": 0.3269403576850891, "2707": 0.0317181795835495, "2719": 0.16276304423809052, "2754": 0.4228905141353607, "2832": 0.3297532796859741, "2844": 0.4673144817352295, "2885": 0.05417001247406006, "2920": 0.2881702482700348, "2927": 0.04674193635582924, "2944": 0.6286086440086365, "2949": 0.06612417846918106, "3078": 0.037378571927547455, "3141": 0.056018441915512085, "3143": 0.53589928150177, "3161": 0.18411032855510712, "3189": 0.01934296265244484, "3223": 0.304147332906723, "3252": 0.9680526852607727, "3302": 0.5784112811088562, "3320": 0.10731173306703568, "3357": 0.5767669677734375, "3366": 0.24018502235412598, "3375": 0.23787821829319, "3378": 0.5045560002326965, "3449": 0.36426326632499695, "3450": 0.29109421372413635, "3508": 0.40481385588645935, "3526": 0.6260011196136475, "3563": 0.34715715050697327, "3596": 0.11778303235769272, "3625": 0.16276304423809052, "3800": 0.07884006202220917, "3853": 0.2637155055999756, "3930": 0.5127768516540527, "3965": 0.1064341589808464, "3988": 0.11778303235769272, "3997": 0.1221139207482338, "4008": 0.055094651877880096, "4023": 0.5313173532485962, "4084": 0.5381823778152466, "4168": 0.23633737862110138, "4195": 0.42161011695861816, "4275": 0.34577593207359314, "4310": 0.3318578004837036, "4403": 0.2719337046146393, "4413": 0.10555581003427505, "4442": 0.3777405619621277, "4490": 0.14349138736724854, "4515": 0.2145126610994339, "4525": 0.043007105588912964, "4563": 0.8813109993934631, "4588": 0.2516399025917053, "4593": 0.25845035910606384, "4667": 0.3443928062915802, "4679": 0.27564704418182373, "4724": 0.9409833550453186, "4942": 0.5952457785606384, "4962": 0.3784096837043762, "4982": 0.16607704758644104, "4987": 0.037378571927547455, "5017": 0.0029254043474793434, "5090": 0.678885817527771, "5158": 0.0842406153678894, "5250": 0.2018241584300995, "5258": 0.12642613053321838, "5387": 0.5330380201339722, "5390": 0.9447870850563049, "5402": 0.056018441915512085, "5416": 0.083342544734478, "5449": 0.6558387279510498, "5478": 0.27044451236724854, "5536": 0.8813109993934631, "5537": 0.15359249711036682, "5700": 0.12038381397724152, "5711": 0.41065993905067444, "5857": 0.007782140281051397, "5876": 0.3241194784641266, "5884": 0.8517522215843201, "5942": 0.35950297117233276, "6011": 0.13414156436920166, "6064": 0.33115679025650024, "6121": 0.9348671436309814, "6276": 0.013579257763922215, "6459": 0.06886265426874161, "6483": 0.45994341373443604, "6540": 0.03360854089260101, "6562": 0.5404602885246277, "6673": 0.6613984704017639, "6691": 0.08154398202896118, "6897": 0.1946154683828354, "6942": 0.7239188551902771, "6947": 0.890972912311554, "7137": 0.14939609169960022, "7327": 0.9123768210411072, "7336": 0.07884006202220917, "7337": 0.33675122261047363, "7342": 0.10379679501056671, "7366": 0.5336109399795532, "7426": 0.26296505331993103, "7677": 0.2969166338443756, "7783": 0.2184450328350067, "7816": 0.4974553883075714, "8171": 0.21293537318706512, "8290": 0.13243216276168823, "8332": 0.5811457633972168, "8360": 0.08244366943836212, "8827": 0.004870930220931768, "8873": 0.7445381283760071, "8893": 0.8212929964065552, "8946": 1.1051015853881836, "9002": 0.3177432417869568, "9006": 0.5415972471237183, "9007": 1.1659544706344604, "9096": 0.23247487843036652, "9124": 0.013579257763922215, "9285": 0.036437395960092545, "9563": 0.12986256182193756, "9585": 0.25845035910606384, "9597": 0.015504186972975731, "9677": 0.04953393340110779, "9972": 0.3560888469219208, "10128": 0.5778634548187256, "10210": 0.05046287178993225, "10266": 0.1913948506116867, "10327": 0.12814582884311676, "10335": 0.6358738541603088, "10473": 0.3910386264324188, "10496": 0.8433839678764343, "10624": 0.22626367211341858, "10737": 0.20501139760017395, "10738": 0.857568621635437, "10752": 1.176850438117981, "10867": 0.1332872211933136, "10956": 0.07341018319129944, "11022": 0.950843095779419, "11037": 0.004870930220931768, "11374": 0.15777134895324707, "11643": 0.14518201351165771, "11649": 0.6482070088386536, "11835": 0.18978065252304077, "11991": 0.029824240133166313, "12067": 0.15023678541183472, "12222": 0.5162794589996338, "12241": 1.0037577152252197, "12319": 0.15442965924739838, "12335": 0.08513788133859634, "12562": 0.15693697333335876, "12649": 0.010684899985790253, "12702": 0.24401791393756866, "12732": 0.1685553640127182, "12745": 0.12986256182193756, "12789": 0.4891071021556854, "12939": 0.42735910415649414, "12958": 0.045809537172317505, "12987": 1.54988694190979, "12997": 0.014542185701429844, "13100": 0.6674286723136902, "13791": 0.09584271162748337, "13922": 0.2719337046146393, "14193": 0.5718178153038025, "14336": 0.14349138736724854, "14438": 0.7028654217720032, "14674": 0.026025565341114998, "14774": 0.35950297117233276, "14955": 1.655247449874878, "14988": 0.1718502640724182, "15057": 0.42926809191703796, "15093": 0.38174858689308167, "15176": 0.1358480453491211, "15543": 0.8013357520103455, "15924": 0.8109301924705505, "16012": 0.9052929878234863, "16285": 1.020087480545044, "16305": 0.15860503911972046, "16416": 0.6312094330787659, "16605": 0.29036402702331543, "16613": 1.0312920808792114, "16706": 0.5461324453353882, "16884": 0.07159364968538284, "17350": 1.0519683361053467, "17487": 0.06520967930555344, "17543": 0.03360854089260101, "17703": 0.40285754203796387, "17782": 1.0848461389541626, "17820": 0.33675122261047363, "17890": 0.7656494975090027, "18079": 0.1685553640127182, "18260": 0.1510767638683319, "18330": 0.0797421783208847, "18597": 0.04767346754670143, "18856": 0.4002431631088257, "19137": 0.8666408061981201, "19304": 0.08513788133859634, "19386": 1.1616848707199097, "19395": 1.375494122505188, "19476": 0.10379679501056671, "19563": 0.15275461971759796, "19587": 0.06886265426874161, "19601": 0.08244366943836212, "19653": 0.24631060659885406, "20228": 0.3177432417869568, "20250": 0.025073638185858727, "20353": 0.39367714524269104, "20544": 0.004870930220931768, "21365": 0.3241194784641266, "21575": 0.2317005842924118, "21618": 0.38905516266822815, "21647": 0.2184450328350067, "21770": 0.49982786178588867, "21920": 0.3877306580543518, "21935": 0.02887592278420925, "21957": 1.20884370803833, "22022": 0.5795059204101562, "22026": 0.17759032547473907, "22172": 0.9936857223510742, "22694": 0.11865071207284927, "22869": 0.08961215615272522, "23233": 0.3012613356113434, "23376": 0.4132472574710846, "23561": 0.09406650811433792, "23572": 0.8567397594451904, "23737": 0.8731874823570251, "23758": 0.17431432008743286, "23777": 0.7086513638496399, "23797": 0.00875066313892603, "23807": 0.8039615154266357, "24004": 0.7863243818283081, "24203": 0.9929623603820801, "24312": 1.0920805931091309, "24628": 0.29109421372413635, "24635": 0.09938567131757736, "25002": 0.052318159490823746, "25102": 0.8169882297515869, "25167": 0.9576126337051392, "25269": 1.276475191116333, "25562": 0.02887592278420925, "25644": 0.0770333781838417, "25727": 0.5979346632957458, "25743": 0.14433705806732178, "25776": 0.75193190574646, "26224": 0.5936289429664612, "26356": 0.9440274834632874, "26396": 0.8366385698318481, "26512": 0.6543170213699341, "26572": 0.48670899868011475, "26601": 0.1913948506116867, "26616": 0.176772341132164, "26773": 0.2478361576795578, "27216": 0.49626702070236206, "27233": 0.1358480453491211, "27642": 1.1720224618911743, "27777": 0.1384023278951645, "28086": 0.011650617234408855, "28424": 0.09317722171545029, "28433": 0.056018441915512085, "28691": 1.147526502609253, "28848": 0.7610978484153748, "29060": 0.2470736801624298} | 12149169 | Synthesis of ribosomal RNA (rRNA) by RNA polymerase (Pol) I is the first step in ribosome biogenesis and a regulatory switch in eukaryotic cell growth. Here we report the 12 A cryo-electron microscopic structure for the complete 14-subunit yeast Pol I, a homology model for the core enzyme, and the crystal structure of the subcomplex A14/43. In the resulting hybrid structure of Pol I, A14/43, the clamp, and the dock domain contribute to a unique surface interacting with promoter-specific initiation factors. The Pol I-specific subunits A49 and A34.5 form a heterodimer near the enzyme funnel that acts as a built-in elongation factor and is related to the Pol II-associated factor TFIIF. In contrast to Pol II, Pol I has a strong intrinsic 3'-RNA cleavage activity, which requires the C-terminal domain of subunit A12.2 and, apparently, enables ribosomal RNA proofreading and 3'-end trimming. | Functional Architecture of RNA Polymerase I |
{"1011": 0.151916041970253, "1013": 0.026976587250828743, "1015": 0.29255300760269165, "1043": 0.17267228662967682, "1055": 0.6317287683486938, "1999": 0.10203468054533005, "2005": 0.1930064558982849, "2008": 0.022212404757738113, "2028": 0.08064348995685577, "2029": 0.3325583338737488, "2039": 0.2607102394104004, "2061": 0.5838727951049805, "2072": 0.5139457583427429, "2075": 0.5069117546081543, "2076": 0.026025565341114998, "2078": 0.7370892763137817, "2079": 0.1946154683828354, "2091": 0.15943801403045654, "2109": 0.00875066313892603, "2128": 0.6999598741531372, "2140": 0.5871354341506958, "2177": 0.28597161173820496, "2179": 0.29109421372413635, "2220": 0.4974553883075714, "2255": 0.12470348179340363, "2290": 1.1487655639648438, "2377": 0.27342069149017334, "2407": 0.07341018319129944, "2439": 0.05970508232712746, "2443": 0.0009760859538801014, "2475": 0.4337083101272583, "2487": 0.9348671436309814, "2491": 0.6833335757255554, "2515": 0.20022670924663544, "2522": 0.09672962874174118, "2535": 0.8349450826644897, "2546": 0.5069117546081543, "2549": 0.7096124291419983, "2590": 0.4568560719490051, "2717": 1.1506214141845703, "2734": 0.1221139207482338, "2765": 0.49982786178588867, "2817": 0.08513788133859634, "2890": 0.45870962738990784, "2898": 0.36358460783958435, "2913": 0.3750596046447754, "2920": 0.35677260160446167, "2967": 0.06246116757392883, "2969": 1.057410478591919, "3012": 0.3443928062915802, "3041": 0.08782484382390976, "3141": 0.5707147121429443, "3145": 0.5607312321662903, "3209": 0.18167030811309814, "3223": 0.4203280806541443, "3248": 0.4624064862728119, "3273": 0.1011524572968483, "3278": 0.004870930220931768, "3279": 0.6400018334388733, "3303": 0.14433705806732178, "3370": 0.6461620330810547, "3378": 0.16524957120418549, "3426": 0.06429435312747955, "3431": 0.29400965571403503, "3463": 0.5778634548187256, "3491": 0.05417001247406006, "3508": 0.2719337046146393, "3526": 0.7728893756866455, "3563": 0.0752234235405922, "3603": 0.05970508232712746, "3619": 0.14518201351165771, "3625": 0.38441169261932373, "3653": 0.4400174915790558, "3670": 0.9084475636482239, "3800": 0.07612881064414978, "3853": 0.6155022978782654, "3930": 0.02792670577764511, "4072": 0.22626367211341858, "4106": 0.4481603503227234, "4167": 0.15610189735889435, "4187": 0.7827593088150024, "4395": 0.7629209756851196, "4442": 0.7737906575202942, "4456": 0.18978065252304077, "4504": 0.1677299439907074, "4525": 0.08692999184131622, "4539": 0.803087055683136, "4548": 0.21922965347766876, "4671": 0.05786345899105072, "4758": 0.42416930198669434, "4943": 0.0913962796330452, "4962": 1.0992631912231445, "4972": 0.47463157773017883, "5041": 0.053244512528181076, "5197": 0.16110190749168396, "5228": 0.3963087201118469, "5250": 1.0648454427719116, "5302": 0.30917787551879883, "5320": 0.272677481174469, "5387": 0.1913948506116867, "5402": 1.0165601968765259, "5449": 0.07612881064414978, "5478": 0.016465263441205025, "5620": 0.6659244894981384, "5700": 0.18492233753204346, "5714": 0.34508460760116577, "5918": 0.04767346754670143, "5942": 0.04674193635582924, "6064": 0.450652539730072, "6072": 0.06520967930555344, "6309": 0.16524957120418549, "6409": 0.018384648486971855, "6573": 0.34715715050697327, "6622": 0.13414156436920166, "6887": 0.38041436672210693, "6893": 0.12470348179340363, "6895": 0.4330752193927765, "6914": 0.11604541540145874, "7065": 0.23247487843036652, "7096": 0.0842406153678894, "7324": 0.6139179468154907, "7337": 0.1510767638683319, "7361": 0.45994341373443604, "7366": 0.30558720231056213, "7403": 0.8057082891464233, "7461": 0.009718249551951885, "7473": 0.7537717819213867, "7645": 0.3070250153541565, "7698": 0.4286321699619293, "7711": 0.567951500415802, "7784": 0.0019512200960889459, "7816": 0.7592713832855225, "7872": 1.068206787109375, "7885": 0.13670019805431366, "7889": 0.7124901413917542, "7987": 1.3759875297546387, "8000": 0.8592242002487183, "8153": 0.12814582884311676, "8171": 0.9886114001274109, "8345": 0.5762182474136353, "8360": 0.2026219218969345, "8469": 0.10379679501056671, "8479": 0.7248653769493103, "8713": 0.7276995778083801, "8991": 0.2105647772550583, "9007": 0.48610860109329224, "9100": 0.45994341373443604, "9114": 0.034552380442619324, "9165": 1.179255723953247, "9175": 1.0927356481552124, "9247": 1.1350497007369995, "9308": 0.08871890604496002, "9350": 0.2741633653640747, "9416": 0.5086748600006104, "9496": 0.8433839678764343, "9670": 0.29619070887565613, "9686": 0.4487839937210083, "9756": 0.29981520771980286, "10047": 0.5324648022651672, "10085": 0.42225050926208496, "10381": 0.7934166193008423, "10580": 0.06703783571720123, "10591": 0.1970241367816925, "10708": 0.20022670924663544, "10738": 0.42225050926208496, "11008": 0.9500881433486938, "11099": 0.25467249751091003, "11311": 0.03266380727291107, "11369": 0.1384023278951645, "11423": 0.4500300884246826, "11432": 0.27934664487838745, "11486": 0.11604541540145874, "11494": 0.18978065252304077, "11916": 0.987156867980957, "12115": 0.11430477350950241, "12222": 0.6207655072212219, "12328": 1.1249549388885498, "12402": 0.2659635543823242, "12562": 0.18329764902591705, "12588": 0.04767346754670143, "12644": 0.7028654217720032, "12662": 0.45251765847206116, "12709": 0.5232481360435486, "12765": 0.9493325352668762, "12987": 0.5822374224662781, "13323": 1.243794322013855, "13458": 0.6170841455459595, "13512": 0.2409527748823166, "13708": 0.04207121208310127, "13791": 0.10906458646059036, "13908": 0.17922431230545044, "13922": 0.06520967930555344, "14026": 0.0842406153678894, "14126": 0.32553088665008545, "14193": 0.3106105625629425, "14471": 0.3656192123889923, "14494": 0.05694137513637543, "14524": 1.1356772184371948, "14828": 0.12814582884311676, "14863": 0.4450363218784332, "15053": 0.15693697333335876, "15115": 0.04767346754670143, "15176": 0.684319257736206, "15266": 0.15442965924739838, "15527": 0.23092569410800934, "15543": 1.1211429834365845, "16183": 1.2964379787445068, "16221": 0.3499138653278351, "16285": 0.24631060659885406, "16360": 0.11081436276435852, "16515": 0.7314660549163818, "16578": 0.0019512200960889459, "16626": 0.3588210940361023, "16691": 0.0797421783208847, "16705": 0.04674193635582924, "16706": 0.29619070887565613, "16745": 0.7454653382301331, "17379": 0.0029254043474793434, "17908": 0.23787821829319, "18195": 0.04860413447022438, "18274": 1.036847710609436, "18604": 0.06795065850019455, "18714": 0.083342544734478, "18856": 0.1332872211933136, "19337": 0.0752234235405922, "19653": 0.18248429894447327, "19723": 0.2852376699447632, "19872": 0.3723714053630829, "20045": 0.5734702348709106, "20228": 0.7220231294631958, "20250": 0.10203468054533005, "20363": 1.1665629148483276, "20467": 0.6389714479446411, "20582": 1.210009217262268, "20687": 0.9162907600402832, "21032": 0.3464667797088623, "21150": 0.2493593990802765, "21314": 0.018384648486971855, "21371": 0.06977381557226181, "21575": 0.6369074583053589, "21618": 0.5220900774002075, "21647": 0.13157635927200317, "21716": 1.039613962173462, "21903": 0.21530038118362427, "22330": 0.0842406153678894, "22863": 0.40806588530540466, "22931": 0.013579257763922215, "22953": 0.1011524572968483, "23041": 0.77198725938797, "23186": 0.4654768109321594, "23270": 0.8264343738555908, "23296": 0.30917787551879883, "23490": 0.09406650811433792, "23737": 0.2749055027961731, "24054": 0.0797421783208847, "24269": 0.3297532796859741, "24374": 0.5534584522247314, "24501": 0.013579257763922215, "24668": 0.5573811531066895, "24759": 0.23479416966438293, "24848": 1.158010721206665, "25117": 0.1221139207482338, "25136": 0.13755162060260773, "25141": 0.034552380442619324, "25430": 0.953857421875, "25644": 0.3163207769393921, "25708": 0.11168810725212097, "25714": 0.14518201351165771, "26402": 0.06429435312747955, "26512": 1.018678069114685, "26572": 0.6654226183891296, "26773": 0.6813592314720154, "26802": 0.9317949414253235, "27116": 0.06246116757392883, "27268": 0.7314660549163818, "27642": 0.056018441915512085, "27854": 0.02316705882549286, "27989": 0.0913962796330452, "28086": 1.179255723953247, "28156": 0.3134697377681732, "28327": 0.7987030148506165, "28405": 0.20102575421333313, "28964": 0.029824240133166313, "28991": 1.076228141784668, "29206": 0.23556606471538544, "29516": 0.0058422754518687725} | 12152977 | The SWI/SNF-Brg1 chromatin remodeling protein plays critical roles in cell-cycle control and differentiation through regulation of gene expression. Loss of Brg1 in mice results in early embryonic lethality, and recent studies have implicated a role for Brg1 in somatic stem cell self-renewal and differentiation. However, little is known about Brg1 function in preimplantation embryos and embryonic stem (ES) cells. Here we report that Brg1 is required for ES cell self-renewal and pluripotency. RNA interference-mediated knockdown of Brg1 in blastocysts caused aberrant expression of Oct4 and Nanog. In ES cells, knockdown of Brg1 resulted in phenotypic changes indicative of differentiation, downregulation of self-renewal and pluripotency genes (e.g., Oct4, Sox2, Sall4, Rest), and upregulation of differentiation genes. Using genome-wide promoter analysis (chromatin immunoprecipitation) we found that Brg1 occupied the promoters of key pluripotency-related genes, including Oct4, Sox2, Nanog, Sall4, Rest, and Polycomb group (PcG) proteins. Moreover, Brg1 co-occupied a subset of Oct4, Sox2, Nanog, and PcG protein target genes. These results demonstrate an important role for Brg1 in regulating self-renewal and pluripotency in ES cells. | SWI/SNF-Brg1 regulates self-renewal and occupies core pluripotency-related genes in embryonic stem cells. |
{"1011": 0.13243216276168823, "1038": 0.48068851232528687, "1056": 0.5324648022651672, "2004": 0.8022117614746094, "2008": 0.037378571927547455, "2010": 0.8845420479774475, "2011": 0.4412745535373688, "2015": 0.009718249551951885, "2029": 0.3554046154022217, "2035": 0.11430477350950241, "2050": 0.26146242022514343, "2057": 0.3963087201118469, "2063": 0.5651806592941284, "2076": 0.0752234235405922, "2080": 0.2659635543823242, "2094": 0.32058215141296387, "2119": 0.22859740257263184, "2139": 0.5629584193229675, "2140": 0.8450632095336914, "2203": 0.6102113127708435, "2239": 0.19782574474811554, "2303": 0.16276304423809052, "2368": 0.42990362644195557, "2419": 0.16276304423809052, "2427": 0.49030399322509766, "2459": 0.3388410806655884, "2475": 0.17759032547473907, "2487": 0.6941232681274414, "2497": 0.4145384132862091, "2522": 0.524982750415802, "2529": 0.5860490798950195, "2546": 0.6149744987487793, "2550": 0.04487626627087593, "2556": 0.010684899985790253, "2599": 0.17759032547473907, "2719": 0.08782484382390976, "2724": 0.04860413447022438, "2765": 0.129004567861557, "2818": 0.31489628553390503, "2824": 0.29473719000816345, "2890": 0.2394166737794876, "2905": 0.8442239761352539, "2920": 0.21765978634357452, "2936": 0.04767346754670143, "2968": 0.6769026517868042, "3078": 0.5903874635696411, "3091": 0.7942996621131897, "3161": 0.026025565341114998, "3266": 0.021256839856505394, "3283": 0.040196798741817474, "3303": 0.1734936386346817, "3366": 0.18654440343379974, "3370": 0.1221139207482338, "3378": 0.7610978484153748, "3393": 0.015504186972975731, "3399": 0.1485546976327896, "3426": 0.34508460760116577, "3433": 0.02412080205976963, "3445": 0.2394166737794876, "3466": 0.1693800985813141, "3508": 0.6280876994132996, "3526": 0.6568518877029419, "3569": 0.06795065850019455, "3603": 0.736154317855835, "3625": 0.16276304423809052, "3670": 0.4041621685028076, "3739": 0.40089741349220276, "3811": 0.04394211992621422, "3853": 0.10818854719400406, "3863": 0.8550800085067749, "3893": 0.3283478021621704, "3896": 0.08603433519601822, "4127": 0.018384648486971855, "4130": 0.2478361576795578, "4135": 0.33675122261047363, "4195": 0.5301685929298401, "4230": 0.8161250352859497, "4242": 0.10731173306703568, "4286": 0.5528968572616577, "4292": 0.1710275560617447, "4295": 0.16359257698059082, "4340": 0.25845035910606384, "4442": 0.7898768186569214, "4453": 0.08871890604496002, "4456": 1.0478670597076416, "4469": 0.6882523894309998, "4515": 0.469759464263916, "4522": 1.020087480545044, "4566": 0.07341018319129944, "4588": 0.12814582884311676, "4654": 0.6343214511871338, "4668": 0.18167030811309814, "4758": 0.4286321699619293, "4842": 1.0506030321121216, "4877": 0.3297532796859741, "4945": 0.08154398202896118, "4962": 0.8004589080810547, "4997": 0.5450005531311035, "5158": 0.09672962874174118, "5208": 0.43875885009765625, "5224": 0.306306391954422, "5250": 0.7701805830001831, "5258": 0.056018441915512085, "5320": 0.20501139760017395, "5360": 0.013579257763922215, "5387": 0.2089812457561493, "5441": 0.4151833653450012, "5449": 0.36967599391937256, "5456": 0.535327672958374, "5486": 0.0009760859538801014, "5524": 0.9052929878234863, "5643": 0.6578640341758728, "5666": 0.7258110046386719, "5903": 0.14602625370025635, "5910": 0.7647408246994019, "6032": 0.8492490649223328, "6033": 0.04207121208310127, "6064": 0.9394577741622925, "6072": 0.8893690705299377, "6075": 0.7076893448829651, "6118": 0.29473719000816345, "6132": 0.045809537172317505, "6215": 0.07068414986133575, "6377": 0.9100211262702942, "6415": 0.9123768210411072, "6459": 0.4734157919883728, "6493": 0.0913962796330452, "6529": 0.02412080205976963, "6585": 0.5092619061470032, "6605": 0.1710275560617447, "6672": 0.9279413223266602, "6675": 0.36426326632499695, "6678": 0.18248429894447327, "6753": 0.11430477350950241, "6887": 0.5347557663917542, "6897": 0.2501201331615448, "6903": 0.24325250089168549, "6970": 0.7115318179130554, "7096": 0.24171993136405945, "7277": 0.8349450826644897, "7337": 1.0828639268875122, "7347": 0.28450319170951843, "7356": 0.20580662786960602, "7366": 0.3560888469219208, "7403": 0.4349733293056488, "7406": 1.1147572994232178, "7453": 0.8091925978660583, "7461": 0.15359249711036682, "7523": 0.2034190446138382, "7531": 0.15693697333335876, "7568": 0.1602703034877777, "7610": 1.0815403461456299, "7645": 0.22782009840011597, "7711": 0.2607102394104004, "7816": 0.5751199722290039, "7870": 0.07884006202220917, "8040": 0.9108069539070129, "8153": 0.0606246218085289, "8171": 0.8004589080810547, "8178": 0.036437395960092545, "8281": 0.3615458607673645, "8319": 0.619189441204071, "8346": 0.5290185213088989, "8360": 0.052318159490823746, "8462": 1.182852864265442, "8465": 0.5596157908439636, "8498": 0.36967599391937256, "8612": 0.14518201351165771, "8715": 0.012615402229130268, "8761": 0.13414156436920166, "8878": 0.7934166193008423, "8989": 0.1401015669107437, "9007": 0.7172679901123047, "9069": 0.10555581003427505, "9078": 0.037378571927547455, "9099": 0.011650617234408855, "9165": 0.4770587682723999, "9285": 0.15610189735889435, "9319": 0.3519764244556427, "9495": 0.23015019297599792, "9504": 0.32199856638908386, "9509": 0.7482418417930603, "9662": 0.09317722171545029, "9706": 0.890972912311554, "9834": 0.8845420479774475, "9897": 0.22001366317272186, "10052": 0.05139094591140747, "10093": 1.202995777130127, "10210": 0.10379679501056671, "10381": 0.3743882179260254, "10450": 0.7124901413917542, "10509": 0.05139094591140747, "10572": 1.029200792312622, "10573": 0.1889725625514984, "10595": 0.8772575259208679, "10599": 0.44753631949424744, "10738": 0.36494144797325134, "10742": 0.20421554148197174, "10744": 1.0788878202438354, "10814": 1.1647365093231201, "10840": 0.14602625370025635, "10958": 0.841701865196228, "11020": 0.18816383183002472, "11024": 0.2689530849456787, "11115": 0.6563454270362854, "11211": 0.07793712615966797, "11290": 0.09317722171545029, "11369": 0.040196798741817474, "11993": 0.1685553640127182, "12115": 0.10993985831737518, "12222": 0.8813109993934631, "12285": 0.17267228662967682, "12456": 1.7047481536865234, "12562": 0.09495500475168228, "12732": 1.0080435276031494, "12987": 0.1970241367816925, "13139": 0.347847044467926, "13330": 0.3982778787612915, "13458": 0.056018441915512085, "13494": 0.06429435312747955, "13567": 0.47463157773017883, "13656": 0.41065993905067444, "13712": 0.34922540187835693, "13728": 1.254435658454895, "13791": 1.0808777809143066, "13874": 0.5057345628738403, "14045": 0.09850110858678818, "14084": 0.151916041970253, "14193": 0.4818955361843109, "14446": 0.25694093108177185, "14471": 0.037378571927547455, "14494": 0.2786078155040741, "14800": 0.15860503911972046, "14828": 0.34023189544677734, "14863": 0.058784693479537964, "15176": 0.46486347913742065, "15442": 0.18248429894447327, "15527": 0.35813871026039124, "15543": 0.2800849378108978, "15636": 0.016465263441205025, "15663": 0.1970241367816925, "15775": 1.0073304176330566, "15800": 0.7426811456680298, "15946": 1.2215901613235474, "15955": 0.28743788599967957, "16007": 0.20580662786960602, "16048": 0.3283478021621704, "16081": 0.7491656541824341, "16221": 0.4041621685028076, "16264": 0.030771657824516296, "16285": 0.43623676896095276, "16341": 0.9687942266464233, "16387": 0.03360854089260101, "16463": 0.12728634476661682, "16483": 0.7220231294631958, "16515": 0.8281423449516296, "16530": 0.1685553640127182, "16576": 0.8567397594451904, "16627": 0.1734936386346817, "16690": 0.15610189735889435, "16706": 1.1211429834365845, "16771": 0.25239890813827515, "16910": 0.8534175157546997, "17076": 0.15526613593101501, "17409": 0.02792670577764511, "17424": 0.8323994874954224, "17441": 0.6568518877029419, "17785": 0.03360854089260101, "17820": 0.37304413318634033, "17876": 0.1477125883102417, "17890": 0.34023189544677734, "18231": 0.1873544454574585, "18349": 0.21922965347766876, "18481": 0.018384648486971855, "18714": 0.09850110858678818, "19293": 0.18573370575904846, "19470": 0.08154398202896118, "19539": 0.007782140281051397, "19653": 1.094698429107666, "19762": 0.669430673122406, "19824": 0.24325250089168549, "19872": 0.27712854743003845, "20544": 0.7898768186569214, "20621": 0.07341018319129944, "20752": 0.08513788133859634, "20766": 0.32553088665008545, "20858": 0.08782484382390976, "20877": 0.9987343549728394, "21081": 0.13157635927200317, "21112": 0.39893341064453125, "21262": 0.011650617234408855, "21434": 0.36426326632499695, "21466": 0.3601844012737274, "21575": 0.1602703034877777, "21618": 0.2918238639831543, "21647": 0.04860413447022438, "21716": 0.7755908370018005, "21821": 1.1312761306762695, "21903": 0.4812922179698944, "21967": 0.20102575421333313, "22026": 0.15442965924739838, "22073": 0.7333439588546753, "22422": 0.33675122261047363, "22595": 0.7342816591262817, "22907": 0.3170322775840759, "22930": 0.07793712615966797, "22941": 0.3325583338737488, "23072": 0.25088030099868774, "23216": 0.20022670924663544, "23247": 0.13925230503082275, "23554": 0.13670019805431366, "23586": 0.38041436672210693, "23797": 1.1786550283432007, "23892": 0.16607704758644104, "23924": 0.026976587250828743, "24054": 0.35060185194015503, "24226": 0.1994270235300064, "24278": 0.07159364968538284, "24454": 0.469759464263916, "25194": 0.3241194784641266, "25206": 0.009718249551951885, "25409": 0.7134475708007812, "25456": 0.14264501631259918, "25468": 1.2215901613235474, "25644": 0.10993985831737518, "25761": 0.38574060797691345, "25812": 1.104454517364502, "25817": 0.0770333781838417, "26279": 0.15275461971759796, "26305": 0.1946154683828354, "26402": 0.29473719000816345, "26520": 0.21530038118362427, "26524": 0.7674643993377686, "26534": 0.3269403576850891, "26610": 0.10555581003427505, "26773": 0.6212902665138245, "26874": 0.8707374930381775, "27099": 0.04860413447022438, "27144": 0.030771657824516296, "27295": 0.020300358533859253, "27321": 0.42096930742263794, "27642": 0.5662899017333984, "27881": 0.05139094591140747, "27989": 0.23092569410800934, "28466": 0.861702561378479, "28696": 0.09672962874174118, "28828": 0.18004031479358673, "28873": 0.09672962874174118, "29170": 0.02792670577764511, "29206": 0.16110190749168396, "29290": 0.7067264318466187, "29516": 0.10731173306703568} | 12156187 | The mechanism of activation of the alternative lengthening of telomeres (ALT) pathway of mammalian chromosome-end maintenance has been unclear. We have now discovered that co-depletion of the histone chaperones ASF1a and ASF1b in human cells induced all hallmarks of ALT in both primary and cancer cells. These included the formation of ALT-associated PML (promyelocytic leukemia) bodies (APBs), the presence of extrachromosomal telomeric DNA species, an elevated frequency of telomeric sister chromatid exchanges (t-SCE) events and intertelomeric exchange of an integrated tag. The induction of ALT characteristics in this setting led to the simultaneous suppression of telomerase. We determined that ALT induction is positively regulated by the proteins RAD17 and BLM and negatively regulated by EXO1 and DNA2. The induction of ALT phenotypes as a consequence of ASF1 depletion strongly supports the hypothesis that ALT is a consequence of histone management dysfunction. | Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1 |
{"1011": 0.2786078155040741, "1048": 0.8608771562576294, "2003": 0.3297532796859741, "2005": 0.21372433006763458, "2006": 0.18573370575904846, "2024": 0.12986256182193756, "2064": 0.12470348179340363, "2071": 0.1751343309879303, "2079": 0.34023189544677734, "2100": 0.0606246218085289, "2109": 0.26146242022514343, "2140": 0.5191890001296997, "2155": 0.26296505331993103, "2179": 0.4518963396549225, "2182": 0.49030399322509766, "2229": 0.06337817758321762, "2235": 0.16607704758644104, "2339": 0.08782484382390976, "2378": 0.13071982562541962, "2389": 0.23864774405956268, "2458": 0.6096806526184082, "2470": 0.4311734735965729, "2504": 0.09317722171545029, "2515": 0.2830325961112976, "2535": 0.5629584193229675, "2580": 0.15693697333335876, "2609": 0.6441128253936768, "2764": 0.14433705806732178, "2765": 0.129004567861557, "2832": 0.009718249551951885, "2920": 0.14686977863311768, "3145": 0.6960725784301758, "3170": 0.9769153594970703, "3252": 0.6348392367362976, "3320": 0.791648268699646, "3366": 0.052318159490823746, "3370": 0.19782574474811554, "3375": 0.6374238729476929, "3378": 0.151916041970253, "3406": 0.7220231294631958, "3424": 0.45623743534088135, "3431": 0.18654440343379974, "3443": 0.3141832649707794, "3450": 0.0354953333735466, "3463": 0.11951763927936554, "3466": 0.06337817758321762, "3522": 0.07793712615966797, "3563": 0.5662899017333984, "3597": 0.49030399322509766, "3603": 0.567397952079773, "3625": 0.06977381557226181, "3670": 0.688742995262146, "3723": 0.9500881433486938, "3728": 0.13157635927200317, "3775": 0.15023678541183472, "3798": 0.29255300760269165, "3800": 0.1384023278951645, "3811": 0.7009293437004089, "3853": 0.2822965085506439, "3896": 0.06429435312747955, "3949": 0.503966212272644, "4022": 0.4891071021556854, "4023": 0.304147332906723, "4162": 0.06520967930555344, "4295": 0.2622140049934387, "4319": 0.512191891670227, "4395": 0.4228905141353607, "4456": 0.5116065740585327, "4469": 0.4349733293056488, "4503": 0.23479416966438293, "4539": 0.49626702070236206, "4573": 0.8715548515319824, "4588": 0.5478278398513794, "4758": 0.1734936386346817, "4957": 0.05970508232712746, "4962": 0.5640701055526733, "4972": 0.00875066313892603, "4975": 0.27342069149017334, "5072": 0.02887592278420925, "5082": 0.4374985992908478, "5090": 0.3353555500507355, "5097": 0.2763880789279938, "5149": 0.06612417846918106, "5228": 0.06795065850019455, "5250": 0.7182208299636841, "5302": 0.7229714393615723, "5449": 0.5707147121429443, "5456": 0.7934166193008423, "5521": 0.0752234235405922, "5536": 0.6931471824645996, "5799": 0.5517725944519043, "5850": 0.5925496220588684, "5939": 0.0752234235405922, "6064": 0.24859806895256042, "6066": 0.19862671196460724, "6074": 0.021256839856505394, "6309": 0.20818853378295898, "6310": 0.9417452812194824, "6370": 0.07341018319129944, "6612": 0.01934296265244484, "6655": 1.5905098915100098, "6887": 0.2223619967699051, "6914": 0.5139457583427429, "7065": 0.018384648486971855, "7242": 0.5069117546081543, "7274": 1.335720419883728, "7337": 0.9798521995544434, "7361": 0.7144040465354919, "7366": 0.29473719000816345, "7438": 0.38041436672210693, "7523": 0.19622190296649933, "7531": 0.176772341132164, "7578": 0.6244332790374756, "7711": 0.3995884954929352, "7790": 0.7144040465354919, "7816": 0.6202403903007507, "7865": 0.29473719000816345, "7870": 0.2531573474407196, "7889": 0.4002431631088257, "7987": 0.3897167444229126, "8113": 0.9754437208175659, "8171": 0.77198725938797, "8290": 0.7692760229110718, "8303": 0.07159364968538284, "8332": 0.3995884954929352, "8497": 0.4132472574710846, "8776": 0.40220460295677185, "8946": 0.8152611255645752, "8985": 0.40481385588645935, "9005": 0.3241194784641266, "9007": 0.6970458030700684, "9078": 1.2047537565231323, "9096": 0.14349138736724854, "9099": 0.13157635927200317, "9353": 0.3683255612850189, "9416": 0.469759464263916, "9498": 0.15359249711036682, "9513": 0.21687394380569458, "9527": 1.1555536985397339, "9568": 0.020300358533859253, "9706": 0.5483922958374023, "9905": 0.04767346754670143, "10015": 0.04207121208310127, "10266": 0.6813592314720154, "10381": 0.6202403903007507, "10586": 0.45251765847206116, "10595": 0.7863243818283081, "10737": 0.02316705882549286, "10738": 0.4337083101272583, "10744": 0.11865071207284927, "10803": 0.013579257763922215, "11211": 0.053244512528181076, "11320": 0.05417001247406006, "11336": 0.6754127144813538, "11423": 0.12728634476661682, "11477": 0.23864774405956268, "11806": 0.03266380727291107, "11835": 0.38905516266822815, "12219": 0.021256839856505394, "12222": 0.7683706283569336, "12247": 0.0038986403960734606, "12269": 0.25239890813827515, "12530": 0.06612417846918106, "12618": 0.14264501631259918, "12719": 1.1102628707885742, "12987": 0.24018502235412598, "13046": 0.011650617234408855, "13096": 0.3963087201118469, "13122": 0.014542185701429844, "13434": 0.7096124291419983, "13441": 0.255429208278656, "13490": 1.1555536985397339, "13744": 0.12986256182193756, "13776": 0.5696102976799011, "13791": 0.13157635927200317, "13806": 0.14602625370025635, "13833": 0.2531573474407196, "13859": 0.12470348179340363, "13908": 0.3923587501049042, "13922": 0.09938567131757736, "14074": 0.07793712615966797, "14080": 1.1592369079589844, "14126": 0.48430517315864563, "14184": 0.8366385698318481, "14193": 1.0506030321121216, "14201": 0.029824240133166313, "14290": 0.15442965924739838, "14494": 0.10818854719400406, "14606": 0.20102575421333313, "14667": 0.347847044467926, "14828": 0.0019512200960889459, "14863": 0.57457035779953, "15093": 0.006812678650021553, "15176": 0.9294845461845398, "15245": 0.28890204429626465, "15420": 0.8374842405319214, "15543": 0.12728634476661682, "15636": 0.2160874605178833, "16221": 0.40285754203796387, "16285": 0.37707099318504333, "16303": 0.176772341132164, "16305": 0.17922431230545044, "16505": 0.036437395960092545, "16514": 0.03360854089260101, "16515": 0.7067264318466187, "16567": 0.09050461649894714, "16705": 0.21922965347766876, "16706": 0.17759032547473907, "16771": 0.013579257763922215, "16834": 0.7592713832855225, "16840": 0.0797421783208847, "16913": 0.1602703034877777, "17241": 0.05046287178993225, "17261": 0.5756692886352539, "17379": 0.520350456237793, "17703": 0.21765978634357452, "17720": 0.151916041970253, "17820": 0.5461324453353882, "17890": 0.23787821829319, "18089": 0.02316705882549286, "18178": 0.255429208278656, "18191": 0.39367714524269104, "18503": 0.53589928150177, "18622": 0.030771657824516296, "18804": 0.04860413447022438, "19160": 0.3416208028793335, "19244": 0.24631060659885406, "19653": 0.05417001247406006, "19780": 0.41001203656196594, "19824": 0.7445381283760071, "19839": 0.022212404757738113, "19872": 0.0842406153678894, "19933": 0.469759464263916, "20051": 0.0174254160374403, "20187": 0.6754127144813538, "20232": 0.32341301441192627, "20350": 0.025073638185858727, "20353": 0.0029254043474793434, "20363": 1.0430610179901123, "20763": 0.020300358533859253, "20817": 0.0797421783208847, "20906": 0.014542185701429844, "20992": 0.1873544454574585, "21150": 0.25694093108177185, "21230": 0.014542185701429844, "21365": 0.42161011695861816, "21575": 0.4831010699272156, "21618": 0.8649974465370178, "21716": 0.9052929878234863, "21733": 0.7028654217720032, "21903": 0.6000806093215942, "21935": 0.1994270235300064, "22117": 0.034552380442619324, "22172": 0.11604541540145874, "22248": 0.3464667797088623, "22260": 0.09938567131757736, "22422": 0.0842406153678894, "22684": 0.011650617234408855, "22953": 1.3377727270126343, "23186": 0.6118015646934509, "23274": 0.25467249751091003, "23586": 0.841701865196228, "23737": 0.083342544734478, "23792": 0.18492233753204346, "23943": 0.1808556467294693, "24054": 1.207676887512207, "24093": 0.0317181795835495, "24312": 0.03831886500120163, "24479": 0.0797421783208847, "24797": 0.10731173306703568, "24848": 0.14095009863376617, "25002": 0.14264501631259918, "25003": 0.0797421783208847, "25194": 0.1946154683828354, "25449": 0.05046287178993225, "25456": 1.2047537565231323, "25502": 0.3622259199619293, "25644": 0.6322478652000427, "25727": 0.8332487344741821, "25761": 0.03266380727291107, "25776": 1.3950450420379639, "25778": 0.3743882179260254, "25969": 0.04207121208310127, "26014": 0.151916041970253, "26244": 0.19782574474811554, "26402": 0.7239188551902771, "26512": 0.07793712615966797, "26520": 0.0770333781838417, "26601": 0.04953393340110779, "26616": 0.15777134895324707, "26721": 0.1710275560617447, "26773": 0.9500881433486938, "26786": 0.21372433006763458, "26835": 0.1677299439907074, "27144": 0.46117570996284485, "27226": 0.06154331564903259, "27405": 0.17431432008743286, "27642": 0.09850110858678818, "27777": 0.04207121208310127, "27854": 0.23710809648036957, "28247": 1.0087559223175049, "28327": 0.8973627090454102, "28517": 0.0317181795835495, "28583": 0.21922965347766876, "29226": 0.535327672958374, "29475": 0.503966212272644} | 12172346 | Lysine acetylation is a key mechanism that regulates chromatin structure; aberrant acetylation levels have been linked to the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are small interaction modules found on diverse proteins, some of which have a key role in the acetylation-dependent assembly of transcriptional regulator complexes. These complexes can then initiate transcriptional programmes that result in phenotypic changes. The recent discovery of potent and highly specific inhibitors for the BET (bromodomain and extra-terminal) family of bromodomains has stimulated intensive research activity in diverse therapeutic areas, particularly in oncology, where BET proteins regulate the expression of key oncogenes and anti-apoptotic proteins. In addition, targeting BET bromodomains could hold potential for the treatment of inflammation and viral infection. Here, we highlight recent progress in the development of bromodomain inhibitors, and their potential applications in drug discovery. | Targeting bromodomains: epigenetic readers of lysine acetylation |
{"1009": 0.3547199070453644, "1019": 0.06612417846918106, "1020": 0.38441169261932373, "1022": 0.3134697377681732, "1023": 0.3554046154022217, "1041": 0.4450363218784332, "1047": 0.4337083101272583, "1052": 0.7592713832855225, "1999": 0.06886265426874161, "2004": 0.1229778528213501, "2007": 0.2018241584300995, "2008": 0.12986256182193756, "2011": 0.4337083101272583, "2012": 0.1889725625514984, "2015": 0.1332872211933136, "2024": 0.010684899985790253, "2026": 0.40220460295677185, "2029": 0.23710809648036957, "2039": 0.176772341132164, "2046": 0.10379679501056671, "2076": 0.037378571927547455, "2079": 0.3485364317893982, "2083": 0.15275461971759796, "2089": 0.013579257763922215, "2102": 0.9271688461303711, "2116": 0.06429435312747955, "2176": 0.2659635543823242, "2203": 0.35745587944984436, "2232": 0.49982786178588867, "2247": 0.018384648486971855, "2260": 0.1751343309879303, "2274": 0.025073638185858727, "2312": 0.07793712615966797, "2321": 0.4437839686870575, "2340": 0.5662899017333984, "2361": 0.9842413663864136, "2403": 0.4624064862728119, "2416": 0.33953672647476196, "2433": 0.11778303235769272, "2475": 0.3325583338737488, "2487": 0.0174254160374403, "2515": 0.3353555500507355, "2535": 0.20660123229026794, "2550": 0.15275461971759796, "2552": 0.14349138736724854, "2594": 0.13925230503082275, "2629": 0.1718502640724182, "2668": 0.3325583338737488, "2692": 0.7683706283569336, "2696": 0.5010119676589966, "2719": 0.4132472574710846, "2804": 0.04207121208310127, "2809": 0.31132611632347107, "2819": 0.00875066313892603, "2828": 0.021256839856505394, "2865": 0.5151132941246033, "2891": 0.48610860109329224, "2895": 0.6487176418304443, "2920": 0.23787821829319, "2953": 0.5990082025527954, "3001": 0.2026219218969345, "3149": 0.7105726003646851, "3157": 0.10906458646059036, "3161": 0.036437395960092545, "3170": 0.21687394380569458, "3215": 0.791648268699646, "3252": 0.3622259199619293, "3283": 0.13414156436920166, "3375": 0.012615402229130268, "3378": 0.025073638185858727, "3388": 0.4818955361843109, "3397": 0.004870930220931768, "3406": 0.49864232540130615, "3424": 0.42990362644195557, "3429": 0.34577593207359314, "3433": 0.06154331564903259, "3466": 0.5290185213088989, "3495": 0.1485546976327896, "3526": 0.1970241367816925, "3540": 0.5762182474136353, "3544": 0.11778303235769272, "3593": 0.4794800877571106, "3596": 0.1970241367816925, "3597": 0.020300358533859253, "3622": 0.37974658608436584, "3623": 0.014542185701429844, "3676": 0.10467668622732162, "3695": 0.5370414853096008, "3711": 0.21530038118362427, "3736": 0.2478361576795578, "3853": 0.6054253578186035, "3896": 0.53589928150177, "3965": 0.4158279001712799, "3968": 0.2918238639831543, "4013": 0.21530038118362427, "4015": 0.030771657824516296, "4017": 0.3903779089450836, "4023": 0.11865071207284927, "4047": 0.32905077934265137, "4167": 0.7629209756851196, "4195": 0.31845372915267944, "4263": 0.371698260307312, "4332": 0.05046287178993225, "4402": 0.23864774405956268, "4442": 0.39433568716049194, "4487": 0.4337083101272583, "4506": 0.4855078160762787, "4517": 0.6048921346664429, "4523": 0.43244171142578125, "4539": 0.07793712615966797, "4651": 0.010684899985790253, "4668": 0.14686977863311768, "4742": 0.7009293437004089, "4820": 0.30558720231056213, "4958": 0.9515975713729858, "4972": 0.495672345161438, "4991": 0.5936289429664612, "5017": 0.6989894509315491, "5072": 0.3824150264263153, "5100": 0.5860490798950195, "5144": 0.1913948506116867, "5158": 0.3134697377681732, "5250": 0.45499902963638306, "5258": 0.5010119676589966, "5280": 0.8525851964950562, "5326": 0.07884006202220917, "5383": 0.18167030811309814, "5403": 0.6369074583053589, "5417": 0.03360854089260101, "5428": 0.956112265586853, "5449": 0.08154398202896118, "5648": 0.6931471824645996, "5668": 0.49923527240753174, "5685": 0.04487626627087593, "5744": 0.966567873954773, "5770": 0.0842406153678894, "5847": 0.07250232994556427, "5850": 0.016465263441205025, "6187": 0.4512746334075928, "6204": 0.7737906575202942, "6258": 0.3325583338737488, "6370": 0.08692999184131622, "6377": 0.3077431619167328, "6459": 0.18411032855510712, "6470": 0.5640701055526733, "6499": 0.42225050926208496, "6528": 0.5827828645706177, "6591": 0.6862877607345581, "6650": 0.401551216840744, "6651": 0.40285754203796387, "6666": 0.2763880789279938, "6672": 0.49864232540130615, "6740": 0.6338034868240356, "6833": 0.7528522610664368, "6844": 0.14095009863376617, "6887": 0.469759464263916, "6980": 0.1011524572968483, "7096": 0.011650617234408855, "7137": 0.20580662786960602, "7231": 0.2561853528022766, "7337": 0.757441520690918, "7356": 0.0019512200960889459, "7366": 0.05970508232712746, "7367": 0.7629209756851196, "7380": 0.06337817758321762, "7416": 0.5528968572616577, "7461": 0.32905077934265137, "7507": 0.09584271162748337, "7531": 0.5080875158309937, "7584": 0.4311734735965729, "7755": 0.5398913025856018, "8031": 0.7153595685958862, "8171": 0.5472630262374878, "8290": 0.7276995778083801, "8360": 0.5930894017219543, "8363": 0.06977381557226181, "8428": 0.1946154683828354, "8449": 0.012615402229130268, "8454": 0.7352184057235718, "8458": 0.48670899868011475, "8524": 0.4113073945045471, "8740": 0.7463917136192322, "8878": 0.6533012986183167, "9007": 0.9005423784255981, "9096": 0.5651806592941284, "9099": 0.503966212272644, "9141": 0.00875066313892603, "9283": 0.04207121208310127, "9312": 0.14349138736724854, "9483": 0.7389566898345947, "9516": 0.5805994272232056, "9597": 0.17431432008743286, "9607": 0.025073638185858727, "9821": 0.574020504951477, "9897": 0.1510767638683319, "9905": 0.16442140936851501, "10052": 0.5573811531066895, "10163": 0.6862877607345581, "10266": 0.6233867406845093, "10332": 0.15610189735889435, "10463": 0.6950984001159668, "10509": 0.04487626627087593, "10536": 0.24171993136405945, "10572": 0.13499516248703003, "10595": 0.47827014327049255, "10737": 0.129004567861557, "10769": 0.8083226680755615, "10790": 0.129004567861557, "10804": 0.5618454217910767, "10893": 0.678390383720398, "11022": 0.36290550231933594, "11157": 0.15275461971759796, "11261": 0.757441520690918, "11290": 0.22704219818115234, "11498": 0.5995445251464844, "11636": 0.8764448165893555, "11713": 0.1970241367816925, "11714": 0.052318159490823746, "11835": 0.5495203733444214, "11837": 0.7647408246994019, "12005": 0.05970508232712746, "12141": 0.17267228662967682, "12247": 0.018384648486971855, "12374": 0.1751343309879303, "12376": 0.26296505331993103, "12436": 0.3519764244556427, "12495": 0.15610189735889435, "12649": 0.22937409579753876, "12728": 0.1332872211933136, "12732": 0.7352184057235718, "12737": 0.5707147121429443, "12740": 0.13414156436920166, "13122": 0.5057345628738403, "13186": 0.8400169610977173, "13265": 0.1913948506116867, "13502": 0.06977381557226181, "13531": 0.04207121208310127, "13791": 0.5186077356338501, "13819": 0.23479416966438293, "13833": 0.9732321500778198, "13853": 0.23556606471538544, "13922": 0.24859806895256042, "14142": 0.08961215615272522, "14187": 0.6430866718292236, "14234": 0.4673144817352295, "14828": 0.36900100111961365, "14956": 0.0842406153678894, "15189": 0.4512746334075928, "15431": 0.03266380727291107, "15869": 0.15442965924739838, "15956": 0.417115718126297, "16175": 0.1685553640127182, "16204": 0.08603433519601822, "16256": 0.857568621635437, "16285": 0.7537717819213867, "16305": 0.08154398202896118, "16315": 0.1873544454574585, "16330": 0.27342069149017334, "16401": 0.23710809648036957, "16515": 0.9470623731613159, "16627": 0.012615402229130268, "16730": 0.011650617234408855, "16846": 0.7629209756851196, "16862": 0.8238670229911804, "16882": 0.8861536383628845, "16910": 0.8109301924705505, "16935": 0.21214580535888672, "16942": 0.2749055027961731, "16952": 0.1808556467294693, "17046": 0.16690383851528168, "17062": 0.19622190296649933, "17076": 0.2637155055999756, "17080": 0.8450632095336914, "17379": 0.29036402702331543, "17441": 0.6254787445068359, "17637": 0.09672962874174118, "17663": 0.2394166737794876, "17770": 0.045809537172317505, "17820": 0.5336109399795532, "17890": 0.36967599391937256, "17985": 0.16359257698059082, "18037": 0.5871354341506958, "18089": 0.2652147710323334, "18147": 0.016465263441205025, "18227": 0.07431721687316895, "18260": 0.7067264318466187, "18479": 0.66441810131073, "18714": 0.38308101892471313, "19027": 0.9029204845428467, "19419": 0.9769153594970703, "19481": 0.4444103240966797, "19565": 0.8821197748184204, "19613": 0.5517725944519043, "19620": 0.5127768516540527, "19653": 0.12470348179340363, "19723": 0.9209672808647156, "19872": 0.13243216276168823, "19884": 0.6714286804199219, "19961": 1.3341783285140991, "20187": 0.7537717819213867, "20366": 1.12432062625885, "20544": 0.6853039860725403, "20598": 0.23015019297599792, "20752": 0.371698260307312, "20817": 0.6011518239974976, "20858": 0.025073638185858727, "20881": 0.03925827145576477, "20958": 0.15359249711036682, "21057": 0.04487626627087593, "21252": 0.06612417846918106, "21449": 0.9021284580230713, "21466": 0.1401015669107437, "21472": 0.6160298585891724, "21733": 0.5080875158309937, "21890": 0.03925827145576477, "21891": 0.9900637865066528, "21903": 0.34300774335861206, "21919": 0.21687394380569458, "21935": 0.10906458646059036, "21967": 0.08692999184131622, "22022": 0.18978065252304077, "22025": 0.0797421783208847, "22196": 0.8925741910934448, "22330": 1.2094266414642334, "22347": 0.11430477350950241, "22610": 0.10731173306703568, "22907": 0.11865071207284927, "22930": 0.5174443125724792, "22932": 0.46117570996284485, "22935": 0.007782140281051397, "23060": 0.27044451236724854, "23079": 0.2145126610994339, "23144": 1.1230508089065552, "23216": 0.18492233753204346, "23238": 0.07612881064414978, "23267": 0.8383291959762573, "23352": 0.0038986403960734606, "23370": 0.9643365740776062, "23408": 0.14939609169960022, "23499": 0.0038986403960734606, "23518": 0.3982778787612915, "23586": 0.7408206462860107, "23632": 0.015504186972975731, "23737": 0.33115679025650024, "23777": 0.401551216840744, "23923": 0.8965662121772766, "23971": 0.18411032855510712, "24054": 0.5685047507286072, "24087": 0.08244366943836212, "24137": 0.13414156436920166, "24171": 0.3464667797088623, "24312": 0.18654440343379974, "24315": 0.11604541540145874, "24345": 0.6659244894981384, "24755": 0.6502478122711182, "24774": 0.4267219603061676, "24972": 0.304147332906723, "25002": 0.7800771594047546, "25070": 0.1889725625514984, "25194": 0.0019512200960889459, "25212": 1.5776891708374023, "25456": 0.30558720231056213, "25731": 0.15359249711036682, "25856": 0.06703783571720123, "26187": 0.10467668622732162, "26224": 0.02887592278420925, "26402": 0.5330380201339722, "26616": 0.04487626627087593, "26721": 0.6624060273170471, "26773": 0.011650617234408855, "26775": 0.7473171949386597, "27009": 0.025073638185858727, "27295": 0.11081436276435852, "27531": 0.0058422754518687725, "27790": 0.0842406153678894, "27854": 0.17431432008743286, "28144": 0.9929623603820801, "28479": 0.9717550277709961, "28517": 0.013579257763922215, "28688": 0.09228714555501938, "28835": 1.2555493116378784, "28938": 0.05694137513637543, "29347": 0.15860503911972046} | 12197393 | Cytochrome P450 (CYP) epoxygenases convert arachidonic acid to four epoxyeicosatrienoic acid (EET) regioisomers, 5,6-, 8,9-, 11,12-, and 14,15-EET, that function as autacrine and paracrine mediators. EETs produce vascular relaxation by activating smooth muscle large-conductance Ca2+-activated K+ channels (BKCa). In addition, they have anti-inflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and brain. CYP epoxygenases also convert eicosapentaenoic acid to vasoactive epoxy-derivatives, and endocannabinoids containing 11,12- and 14,15-EET are formed. Many EET actions appear to be initiated by EET binding to a membrane receptor that activates ion channels and intracellular signal transduction pathways. However, EETs also are taken up by cells, are incorporated into phospholipids, and bind to cytosolic proteins and nuclear receptors, suggesting that some functions may occur through direct interaction of the EET with intracellular effector systems. Soluble epoxide hydrolase (sEH) converts EETs to dihydroxyeicosatrienoic acids (DHETs). Because this attenuates many of the functional effects of EETs, sEH inhibition is being evaluated as a mechanism for increasing and prolonging the beneficial actions of EETs. | Arachidonic acid cytochrome P450 epoxygenase pathway. |
{"1997": 0.1011524572968483, "1998": 0.16607704758644104, "1999": 0.10379679501056671, "2001": 0.08064348995685577, "2009": 0.2954642176628113, "2012": 0.3870677351951599, "2020": 0.4177590310573578, "2042": 0.19622190296649933, "2051": 0.23864774405956268, "2062": 0.48068851232528687, "2075": 0.14433705806732178, "2079": 0.24631060659885406, "2082": 0.4624064862728119, "2084": 0.12642613053321838, "2086": 0.3034266233444214, "2087": 0.036437395960092545, "2090": 0.34023189544677734, "2095": 0.08244366943836212, "2101": 0.5523349046707153, "2106": 0.2501201331615448, "2108": 0.08064348995685577, "2109": 0.30558720231056213, "2111": 0.47463157773017883, "2116": 0.22392450273036957, "2120": 0.5438674688339233, "2129": 0.055094651877880096, "2141": 0.5133614540100098, "2147": 0.3163207769393921, "2152": 0.2576959431171417, "2155": 0.0174254160374403, "2158": 0.22001366317272186, "2166": 0.4556184411048889, "2177": 0.3374483287334442, "2181": 0.055094651877880096, "2214": 0.39696553349494934, "2216": 0.04113444685935974, "2241": 0.052318159490823746, "2273": 0.6877616047859192, "2275": 0.23787821829319, "2287": 0.9162907600402832, "2302": 0.4190443754196167, "2308": 0.8400169610977173, "2313": 0.8349450826644897, "2323": 0.417115718126297, "2329": 0.10203468054533005, "2336": 0.7417513132095337, "2339": 0.3381449282169342, "2358": 0.0009760859538801014, "2367": 0.20739519596099854, "2372": 0.21765978634357452, "2374": 0.2160874605178833, "2377": 0.38041436672210693, "2388": 0.4126010537147522, "2394": 0.22782009840011597, "2399": 0.040196798741817474, "2402": 0.1485546976327896, "2411": 0.14518201351165771, "2414": 0.15275461971759796, "2450": 0.5723689198493958, "2458": 0.24325250089168549, "2470": 0.6107416749000549, "2488": 0.33953672647476196, "2493": 0.034552380442619324, "2495": 0.6548244953155518, "2504": 0.22859740257263184, "2522": 0.5973974466323853, "2523": 0.1685553640127182, "2529": 0.03831886500120163, "2535": 0.46486347913742065, "2551": 0.2409527748823166, "2554": 0.28155985474586487, "2563": 0.791648268699646, "2590": 0.3949938118457794, "2591": 0.6714286804199219, "2611": 0.10906458646059036, "2620": 0.11343330889940262, "2625": 0.48068851232528687, "2640": 0.6624060273170471, "2641": 0.3615458607673645, "2649": 0.23556606471538544, "2652": 0.11081436276435852, "2660": 0.21214580535888672, "2682": 0.4709797203540802, "2731": 0.020300358533859253, "2740": 0.5865923762321472, "2742": 0.11517547070980072, "2752": 0.10026945173740387, "2764": 0.15275461971759796, "2765": 0.0038986403960734606, "2775": 0.7791815400123596, "2779": 0.5584990978240967, "2816": 0.12986256182193756, "2817": 0.8853482007980347, "2825": 0.23402166366577148, "2827": 0.18004031479358673, "2828": 0.34577593207359314, "2846": 0.7163142561912537, "2866": 0.6833335757255554, "2881": 0.18329764902591705, "2885": 0.0606246218085289, "2913": 0.7463917136192322, "2925": 0.0606246218085289, "2931": 0.47827014327049255, "2939": 0.39893341064453125, "2944": 0.22157983481884003, "2951": 0.7182208299636841, "2967": 0.12384103983640671, "2983": 0.07341018319129944, "2988": 0.3141832649707794, "2998": 1.1287524700164795, "3008": 0.24325250089168549, "3020": 0.35334911942481995, "3025": 0.11691460013389587, "3032": 0.20580662786960602, "3037": 0.018384648486971855, "3057": 0.38041436672210693, "3080": 0.053244512528181076, "3125": 0.34715715050697327, "3130": 0.10026945173740387, "3141": 0.1751343309879303, "3155": 0.07159364968538284, "3161": 0.8658194541931152, "3163": 0.12814582884311676, "3167": 0.18167030811309814, "3171": 0.4974553883075714, "3189": 0.3615458607673645, "3209": 0.1970241367816925, "3231": 0.022212404757738113, "3265": 0.21922965347766876, "3273": 0.6833335757255554, "3276": 0.7898768186569214, "3278": 0.06429435312747955, "3287": 0.28963330388069153, "3289": 0.35950297117233276, "3291": 0.2719337046146393, "3314": 0.015504186972975731, "3328": 0.5833279490470886, "3336": 0.04113444685935974, "3337": 0.32764431834220886, "3348": 0.6857960224151611, "3350": 0.1808556467294693, "3360": 0.3923587501049042, "3378": 0.7076893448829651, "3395": 0.5640701055526733, "3399": 0.15359249711036682, "3445": 0.026025565341114998, "3446": 0.39893341064453125, "3450": 0.8853482007980347, "3455": 0.16276304423809052, "3463": 0.440646231174469, "3466": 0.2561853528022766, "3471": 0.45870962738990784, "3497": 0.0842406153678894, "3517": 0.11951763927936554, "3558": 1.0008903741836548, "3566": 0.1064341589808464, "3575": 0.9425065517425537, "3618": 0.0019512200960889459, "3633": 0.4337083101272583, "3667": 0.12986256182193756, "3695": 0.13925230503082275, "3725": 0.4855078160762787, "3747": 0.14095009863376617, "3767": 0.35745587944984436, "3771": 0.18654440343379974, "3788": 0.7951818704605103, "3798": 0.4145384132862091, "3800": 0.25694093108177185, "3801": 0.5080875158309937, "3811": 0.056018441915512085, "3871": 0.38308101892471313, "3885": 0.9052929878234863, "3896": 0.14264501631259918, "3901": 0.1332872211933136, "3905": 0.9878844022750854, "3920": 0.04207121208310127, "4023": 1.0933903455734253, "4029": 1.018678069114685, "4081": 0.23092569410800934, "4094": 0.06612417846918106, "4102": 0.18167030811309814, "4104": 0.5415972471237183, "4106": 0.3910386264324188, "4127": 0.37974658608436584, "4146": 0.3464667797088623, "4182": 0.9591107368469238, "4194": 0.3170322775840759, "4254": 0.08603433519601822, "4261": 0.06520967930555344, "4262": 0.21765978634357452, "4266": 0.5893046259880066, "4268": 0.30486753582954407, "4292": 0.5495203733444214, "4295": 0.5540198087692261, "4368": 1.1160377264022827, "4378": 0.00875066313892603, "4395": 0.3283478021621704, "4424": 0.151916041970253, "4426": 0.08064348995685577, "4466": 0.05786345899105072, "4469": 0.5483922958374023, "4489": 0.24018502235412598, "4495": 0.3127557039260864, "4503": 0.2607102394104004, "4531": 0.3283478021621704, "4541": 0.07068414986133575, "4547": 0.417115718126297, "4569": 0.08064348995685577, "4610": 0.16276304423809052, "4639": 0.5057345628738403, "4654": 0.28597161173820496, "4703": 0.2493593990802765, "4715": 0.4770587682723999, "4724": 0.4311734735965729, "4725": 0.015504186972975731, "4793": 0.5104349255561829, "4812": 0.21765978634357452, "4813": 0.6916812658309937, "4863": 0.32129061222076416, "4874": 0.24631060659885406, "4906": 0.34023189544677734, "4957": 0.0174254160374403, "4973": 0.07612881064414978, "4975": 0.4679262638092041, "5002": 0.40220460295677185, "5041": 0.48850810527801514, "5067": 0.2749055027961731, "5082": 0.1384023278951645, "5093": 0.22782009840011597, "5105": 0.0913962796330452, "5117": 0.7907629609107971, "5136": 0.4914994537830353, "5161": 0.5523349046707153, "5171": 0.04674193635582924, "5188": 0.49864232540130615, "5197": 0.6128603219985962, "5232": 0.1619328260421753, "5248": 0.2034190446138382, "5270": 0.1229778528213501, "5387": 0.49864232540130615, "5402": 0.08244366943836212, "5418": 0.7295845746994019, "5439": 0.3019835948944092, "5468": 0.39762192964553833, "5531": 0.2478361576795578, "5535": 0.2719337046146393, "5543": 0.5607312321662903, "5566": 0.21135559678077698, "5570": 0.5947071313858032, "5577": 0.23864774405956268, "5589": 0.6862877607345581, "5593": 1.034073829650879, "5617": 0.23247487843036652, "5635": 0.016465263441205025, "5666": 0.8109301924705505, "5688": 0.2837681770324707, "5739": 0.8845420479774475, "5742": 0.07341018319129944, "5761": 0.2652147710323334, "5779": 0.11256109178066254, "5799": 0.18167030811309814, "5822": 0.2105647772550583, "5844": 0.1710275560617447, "5876": 0.7510106563568115, "5907": 0.6374238729476929, "5966": 0.5701626539230347, "6001": 0.7333439588546753, "6075": 0.0797421783208847, "6083": 0.4500300884246826, "6107": 0.06795065850019455, "6124": 0.440646231174469, "6165": 0.42161011695861816, "6195": 0.1619328260421753, "6235": 0.49626702070236206, "6319": 0.29981520771980286, "6337": 0.14264501631259918, "6388": 0.025073638185858727, "6412": 0.14518201351165771, "6431": 0.04207121208310127, "6459": 0.861702561378479, "6461": 0.10291612148284912, "6480": 0.16690383851528168, "6482": 0.5162794589996338, "6550": 0.4580921530723572, "6553": 0.1619328260421753, "6577": 1.0464962720870972, "6592": 0.6389714479446411, "6614": 0.7737906575202942, "6624": 0.2145126610994339, "6628": 0.2493593990802765, "6689": 0.021256839856505394, "6695": 0.3526630103588104, "6721": 0.13499516248703003, "6747": 0.6980181336402893, "6785": 0.04674193635582924, "6808": 0.1212492436170578, "6818": 0.3019835948944092, "6825": 0.16690383851528168, "6848": 0.11691460013389587, "6875": 0.08782484382390976, "6897": 0.058784693479537964, "6912": 1.117955207824707, "6927": 0.08782484382390976, "6950": 0.14433705806732178, "6976": 0.6348392367362976, "7012": 0.07431721687316895, "7017": 0.1477125883102417, "7018": 0.0058422754518687725, "7060": 0.8366385698318481, "7080": 0.4337083101272583, "7091": 0.5220900774002075, "7099": 0.8039615154266357, "7189": 0.48068851232528687, "7254": 0.07793712615966797, "7356": 0.10026945173740387, "7365": 0.34023189544677734, "7419": 0.669430673122406, "7461": 0.23402166366577148, "7478": 0.19622190296649933, "7526": 0.20580662786960602, "7551": 0.49030399322509766, "7576": 0.176772341132164, "7594": 0.26296505331993103, "7667": 0.030771657824516296, "7694": 0.09406650811433792, "7778": 0.21922965347766876, "7784": 0.3409265875816345, "7810": 0.6048921346664429, "7831": 0.3560888469219208, "7848": 0.08603433519601822, "7851": 0.06795065850019455, "7863": 1.210591435432434, "7870": 0.34023189544677734, "7885": 0.21372433006763458, "7965": 0.44566190242767334, "7997": 0.15943801403045654, "8019": 0.6054253578186035, "8066": 0.5618454217910767, "8092": 0.12986256182193756, "8147": 0.503966212272644, "8168": 0.6492279767990112, "8183": 0.08603433519601822, "8186": 0.440646231174469, "8190": 0.11951763927936554, "8258": 0.24018502235412598, "8281": 0.5865923762321472, "8290": 0.014542185701429844, "8317": 0.15359249711036682, "8358": 0.02887592278420925, "8386": 0.14602625370025635, "8463": 0.5849615335464478, "8483": 0.32764431834220886, "8491": 0.11604541540145874, "8526": 0.450652539730072, "8556": 0.5244048833847046, "8609": 0.4938860833644867, "8627": 0.3423145115375519, "8640": 1.0073304176330566, "8698": 0.6286086440086365, "8704": 0.35950297117233276, "8882": 0.0019512200960889459, "8902": 0.09761575609445572, "8920": 0.2409527748823166, "8924": 0.08603433519601822, "9031": 0.4228905141353607, "9053": 0.05139094591140747, "9104": 0.2976420819759369, "9147": 0.1913948506116867, "9164": 0.29328158497810364, "9324": 0.004870930220931768, "9355": 0.22001366317272186, "9420": 0.04860413447022438, "9454": 0.5162794589996338, "9458": 0.2719337046146393, "9556": 0.8475768566131592, "9560": 0.30558720231056213, "9580": 0.2231435477733612, "9582": 0.417115718126297, "9584": 0.1889725625514984, "9670": 0.34577593207359314, "9723": 0.1358480453491211, "9726": 0.3824150264263153, "9750": 0.15943801403045654, "9874": 0.11604541540145874, "10032": 0.1401015669107437, "10080": 0.20022670924663544, "10081": 0.1602703034877777, "10149": 0.1384023278951645, "10165": 0.4580921530723572, "10173": 0.5773153901100159, "10427": 0.6659244894981384, "10516": 0.7629209756851196, "10517": 1.141931176185608, "10563": 0.3777405619621277, "10629": 0.011650617234408855, "10744": 0.4938860833644867, "10756": 0.5232481360435486, "10847": 0.38574060797691345, "10857": 0.29400965571403503, "10903": 0.3325583338737488, "10908": 0.1485546976327896, "10949": 0.0029254043474793434, "11062": 0.15610189735889435, "11100": 0.935633659362793, "11110": 0.66441810131073, "11234": 0.06246116757392883, "11434": 0.5330380201339722, "11507": 0.37035053968429565, "11524": 0.06246116757392883, "11538": 0.004870930220931768, "11628": 0.5098485946655273, "11647": 0.2622140049934387, "11702": 0.021256839856505394, "11709": 0.004870930220931768, "11765": 0.07612881064414978, "11799": 0.129004567861557, "11867": 0.08692999184131622, "11888": 0.6793810129165649, "11973": 0.5116065740585327, "12170": 0.6603899002075195, "12196": 0.11951763927936554, "12257": 0.9302552938461304, "12265": 0.12986256182193756, "12319": 0.01934296265244484, "12332": 0.2089812457561493, "12353": 0.1873544454574585, "12435": 0.09050461649894714, "12596": 0.10379679501056671, "12697": 0.08513788133859634, "12701": 0.24248650670051575, "12774": 0.5370414853096008, "12826": 0.05139094591140747, "12843": 0.053244512528181076, "12876": 0.14602625370025635, "12878": 0.3622259199619293, "12908": 0.46608972549438477, "12955": 0.5116065740585327, "13068": 0.09938567131757736, "13105": 0.3949938118457794, "13180": 0.2711893916130066, "13496": 0.42990362644195557, "13553": 0.17759032547473907, "13592": 0.06977381557226181, "13599": 0.10555581003427505, "13659": 0.016465263441205025, "13743": 0.05786345899105072, "13798": 0.043007105588912964, "13827": 0.04767346754670143, "13866": 0.28963330388069153, "13874": 0.056018441915512085, "13908": 0.0009760859538801014, "14002": 0.22859740257263184, "14118": 0.04767346754670143, "14243": 0.7960633039474487, "14286": 0.8550800085067749, "14354": 0.7047978043556213, "14396": 0.03266380727291107, "14428": 0.06520967930555344, "15306": 0.7827593088150024, "15318": 0.0770333781838417, "15354": 0.5450005531311035, "15509": 0.17267228662967682, "15592": 0.10906458646059036, "15846": 0.13755162060260773, "15905": 0.05139094591140747, "15982": 0.4849066734313965, "16014": 0.9287132620811462, "16134": 0.20501139760017395, "16165": 0.3034266233444214, "16171": 0.12728634476661682, "16227": 0.4374985992908478, "16452": 0.0606246218085289, "16515": 0.23864774405956268, "16519": 0.014542185701429844, "16736": 0.0797421783208847, "16902": 0.6348392367362976, "16928": 0.026976587250828743, "17083": 0.045809537172317505, "17237": 0.47584590315818787, "17464": 0.890972912311554, "17522": 0.8349450826644897, "17547": 0.4926934838294983, "17792": 0.045809537172317505, "17959": 0.4248080551624298, "18155": 0.8821197748184204, "18240": 0.12728634476661682, "18250": 0.25845035910606384, "18275": 0.3374483287334442, "18440": 0.23092569410800934, "18539": 0.0038986403960734606, "18643": 0.13243216276168823, "18730": 0.026025565341114998, "18925": 0.3127557039260864, "19064": 0.0797421783208847, "19205": 0.030771657824516296, "19350": 0.04860413447022438, "19634": 0.17020416259765625, "19785": 0.4337083101272583, "19939": 0.20501139760017395, "20134": 0.06520967930555344, "20155": 0.11081436276435852, "20195": 0.1221139207482338, "20205": 0.29981520771980286, "20272": 0.4248080551624298, "20274": 0.7827593088150024, "20390": 0.056018441915512085, "20464": 0.4974553883075714, "20480": 0.1751343309879303, "20576": 0.11865071207284927, "20589": 0.004870930220931768, "20932": 0.2969166338443756, "21024": 0.13157635927200317, "21529": 0.8315495252609253, "21619": 0.16110190749168396, "21813": 0.15359249711036682, "21877": 0.6064908504486084, "21912": 0.27044451236724854, "21960": 0.05694137513637543, "22011": 0.8731874823570251, "22133": 0.11691460013389587, "22249": 0.04207121208310127, "22559": 0.12728634476661682, "22807": 0.0038986403960734606, "22865": 0.06612417846918106, "22963": 0.01934296265244484, "23035": 0.7086513638496399, "23271": 0.05139094591140747, "23382": 0.01934296265244484, "23490": 0.25845035910606384, "23518": 0.2105647772550583, "23614": 0.1011524572968483, "23655": 0.05970508232712746, "23676": 0.09938567131757736, "23719": 0.9613537192344666, "23807": 0.06246116757392883, "23900": 0.44753631949424744, "24004": 0.0317181795835495, "24010": 0.1619328260421753, "24255": 0.11865071207284927, "24552": 0.19622190296649933, "24846": 0.18004031479358673, "25055": 0.1734936386346817, "25094": 0.18816383183002472, "25106": 0.08154398202896118, "25185": 0.07431721687316895, "25336": 0.1221139207482338, "25406": 0.11604541540145874, "25613": 0.08244366943836212, "25947": 0.8374842405319214, "26235": 0.16690383851528168, "26256": 0.16442140936851501, "26319": 0.1485546976327896, "26462": 0.12038381397724152, "26911": 0.1384023278951645, "27090": 0.6244332790374756, "27168": 0.1477125883102417, "27295": 0.06154331564903259, "27794": 1.117955207824707, "28093": 0.026025565341114998, "28321": 0.3750596046447754, "28428": 0.6664261221885681, "28436": 0.025073638185858727, "28809": 0.01934296265244484, "28899": 0.2478361576795578, "29068": 0.22704219818115234, "29101": 0.952351450920105, "29126": 0.012615402229130268, "29458": 0.6327666640281677} | 12205576 | OBJECTIVE The aim was to describe the sex and socioeconomic differences in patterns of physical activity at work and in leisure time of men and women aged 36 years, and to investigate factors in childhood and adolescence which predict high rates of participation in sports and recreational activities in later life. DESIGN Data collected in childhood, adolescence, and at 36 years on members of a national prospective birth cohort study were used. SETTING The population sample was resident in England, Scotland, and Wales. SUBJECTS A stratified sample of about 3500 men and women was studied regularly from birth until 43 years. MEASUREMENTS AND MAIN RESULTS More men than women reported high rates of sports and recreational activities, gardening, and do-it-yourself. In contrast women reported higher rates of bicycling and walking. Higher levels of education were associated with frequent participation in sports. Individuals often engaged in one type of activity without necessarily engaging in other types. Those who were most active in sport had been above average at sports in school, more outgoing socially in adolescence, had fewer health problems in childhood, were better educated, and had more mothers with a secondary education than those who were less active. CONCLUSIONS Studies that examine the relationship between physical activity and chronic disease should consider a broad range of pursuits rather than extrapolating from only one area of physical activity, and in their explanations should take account of the possible role of childhood characteristics. The findings suggest the importance of developing skills and habits in childhood as well as of encouraging healthier exercise habits in adults who may have had few opportunities or low motivation previously. | Physical activity at 36 years: patterns and childhood predictors in a longitudinal study. |
{"1003": 0.006812678650021553, "1016": 0.16524957120418549, "1044": 0.8957691192626953, "2001": 0.3077431619167328, "2020": 0.2561853528022766, "2039": 0.2247048318386078, "2042": 0.00875066313892603, "2043": 0.36358460783958435, "2051": 0.21293537318706512, "2058": 0.42608439922332764, "2084": 0.20580662786960602, "2086": 0.5805994272232056, "2095": 0.34508460760116577, "2106": 0.21293537318706512, "2109": 0.018384648486971855, "2119": 0.18573370575904846, "2128": 0.1401015669107437, "2137": 0.09761575609445572, "2142": 0.3077431619167328, "2145": 0.02412080205976963, "2146": 0.5151132941246033, "2149": 0.4512746334075928, "2152": 0.5651806592941284, "2166": 0.8039615154266357, "2172": 0.0842406153678894, "2190": 0.05417001247406006, "2197": 0.43053874373435974, "2214": 0.6862877607345581, "2232": 0.1913948506116867, "2241": 0.4113073945045471, "2270": 0.20977331697940826, "2273": 0.4624064862728119, "2287": 0.9944084882736206, "2290": 0.6405166387557983, "2308": 0.48670899868011475, "2313": 0.26446542143821716, "2320": 0.3005385100841522, "2323": 0.24631060659885406, "2349": 0.0354953333735466, "2350": 0.25694093108177185, "2361": 0.43623676896095276, "2364": 0.151916041970253, "2381": 0.13243216276168823, "2383": 0.036437395960092545, "2412": 0.10993985831737518, "2444": 0.09761575609445572, "2450": 0.29109421372413635, "2451": 0.3297532796859741, "2458": 0.347847044467926, "2470": 0.4145384132862091, "2489": 0.4624064862728119, "2504": 0.06429435312747955, "2506": 0.3318578004837036, "2511": 0.13157635927200317, "2531": 0.7258110046386719, "2540": 0.7086513638496399, "2558": 0.6451379656791687, "2620": 0.1064341589808464, "2640": 0.4177590310573578, "2641": 0.04113444685935974, "2649": 0.6598852276802063, "2668": 0.7124901413917542, "2682": 0.14686977863311768, "2687": 0.6793810129165649, "2690": 0.5762182474136353, "2727": 0.014542185701429844, "2740": 0.1332872211933136, "2744": 1.0601204633712769, "2750": 0.28743788599967957, "2754": 0.7370892763137817, "2764": 0.43812891840934753, "2765": 0.1718502640724182, "2777": 0.07612881064414978, "2815": 0.13499516248703003, "2817": 0.7047978043556213, "2825": 0.10993985831737518, "2846": 0.22001366317272186, "2856": 0.30486753582954407, "2881": 0.07159364968538284, "2896": 0.18411032855510712, "2901": 0.09584271162748337, "2913": 0.5651806592941284, "2925": 0.05970508232712746, "2931": 0.07612881064414978, "2936": 0.020300358533859253, "2951": 0.0913962796330452, "3020": 0.4190443754196167, "3026": 0.6369074583053589, "3041": 0.15610189735889435, "3054": 0.18492233753204346, "3078": 0.5838727951049805, "3080": 0.8161250352859497, "3112": 0.10379679501056671, "3118": 0.0038986403960734606, "3125": 0.022212404757738113, "3144": 0.05786345899105072, "3155": 0.3916989266872406, "3273": 0.27934664487838745, "3278": 0.037378571927547455, "3283": 0.034552380442619324, "3285": 0.24325250089168549, "3287": 0.10467668622732162, "3289": 0.1970241367816925, "3296": 0.1685553640127182, "3299": 0.9363996982574463, "3339": 0.8366385698318481, "3378": 0.1510767638683319, "3381": 0.08961215615272522, "3382": 0.013579257763922215, "3394": 0.02792670577764511, "3408": 0.1477125883102417, "3424": 0.5370414853096008, "3438": 0.8756314516067505, "3439": 0.08871890604496002, "3445": 0.38441169261932373, "3446": 0.16359257698059082, "3452": 0.021256839856505394, "3461": 0.5290185213088989, "3463": 0.2105647772550583, "3464": 0.06612417846918106, "3465": 0.06977381557226181, "3486": 0.3248254358768463, "3497": 0.6096806526184082, "3511": 1.0001721382141113, "3512": 0.07341018319129944, "3515": 0.5957841277122498, "3522": 0.4770587682723999, "3546": 0.16359257698059082, "3556": 0.1401015669107437, "3588": 0.4679262638092041, "3618": 0.7898768186569214, "3623": 0.4002431631088257, "3624": 0.23864774405956268, "3633": 0.04487626627087593, "3647": 0.24325250089168549, "3652": 0.020300358533859253, "3728": 0.2674594223499298, "3767": 0.0058422754518687725, "3778": 1.173231601715088, "3795": 0.015504186972975731, "3798": 0.09850110858678818, "3801": 0.02792670577764511, "3818": 0.07341018319129944, "3824": 0.5483922958374023, "3838": 0.5278670787811279, "3867": 0.319873183965683, "3882": 0.20660123229026794, "3891": 1.2655161619186401, "3915": 0.26820653676986694, "3938": 0.8315495252609253, "3947": 0.025073638185858727, "3949": 0.29981520771980286, "3961": 0.09495500475168228, "3979": 0.09317722171545029, "3982": 0.06246116757392883, "3999": 1.0409941673278809, "4003": 0.040196798741817474, "4008": 0.21372433006763458, "4013": 0.12986256182193756, "4051": 0.22626367211341858, "4073": 0.2247048318386078, "4094": 0.0317181795835495, "4102": 0.32341301441192627, "4106": 0.18573370575904846, "4131": 0.2852376699447632, "4146": 0.15275461971759796, "4200": 0.11865071207284927, "4242": 0.5324648022651672, "4279": 0.007782140281051397, "4292": 0.3777405619621277, "4293": 0.0019512200960889459, "4358": 0.5174443125724792, "4417": 0.05970508232712746, "4456": 0.029824240133166313, "4503": 0.5751199722290039, "4555": 0.0317181795835495, "4583": 0.7610978484153748, "4587": 0.27934664487838745, "4639": 0.650757372379303, "4652": 0.417115718126297, "4719": 0.28890204429626465, "4720": 0.2409527748823166, "4729": 0.055094651877880096, "4793": 0.5734702348709106, "4795": 0.401551216840744, "4841": 0.10993985831737518, "4842": 0.5773153901100159, "4852": 0.09672962874174118, "4853": 0.7047978043556213, "4909": 0.13755162060260773, "4975": 0.8973627090454102, "5020": 0.15777134895324707, "5050": 0.2881702482700348, "5082": 0.01934296265244484, "5091": 0.18004031479358673, "5179": 0.083342544734478, "5292": 0.1212492436170578, "5387": 0.14264501631259918, "5393": 0.010684899985790253, "5401": 0.18492233753204346, "5443": 0.0354953333735466, "5468": 0.5021947622299194, "5473": 0.2741633653640747, "5476": 0.036437395960092545, "5486": 0.11430477350950241, "5531": 0.27934664487838745, "5577": 0.24325250089168549, "5646": 0.06337817758321762, "5688": 0.18978065252304077, "5711": 0.27786844968795776, "5719": 0.5063233375549316, "5739": 0.043007105588912964, "5761": 0.39367714524269104, "5776": 0.083342544734478, "5786": 0.040196798741817474, "5836": 0.22548456490039825, "5845": 0.19862671196460724, "5850": 0.053244512528181076, "6001": 0.8013357520103455, "6022": 0.43812891840934753, "6025": 0.14264501631259918, "6075": 0.045809537172317505, "6086": 0.08064348995685577, "6123": 0.7201237678527832, "6146": 0.32270604372024536, "6162": 0.27786844968795776, "6235": 0.3388410806655884, "6344": 0.7417513132095337, "6412": 0.10379679501056671, "6422": 0.06703783571720123, "6431": 0.15023678541183472, "6463": 0.026976587250828743, "6480": 1.3175804615020752, "6493": 0.06795065850019455, "6553": 0.6970458030700684, "6600": 0.05139094591140747, "6678": 0.31560876965522766, "6689": 0.6466736793518066, "6721": 0.1930064558982849, "6747": 0.6155022978782654, "6818": 0.66441810131073, "6911": 0.034552380442619324, "6936": 0.1994270235300064, "6937": 0.27342069149017334, "6993": 0.15359249711036682, "7012": 0.2696990668773651, "7017": 0.5139457583427429, "7065": 0.2800849378108978, "7091": 0.5209306478500366, "7356": 0.0038986403960734606, "7389": 0.025073638185858727, "7438": 0.03831886500120163, "7457": 0.21214580535888672, "7524": 0.025073638185858727, "7539": 0.6265231370925903, "7551": 0.1677299439907074, "7552": 0.12470348179340363, "7594": 0.23092569410800934, "7667": 0.06337817758321762, "7691": 0.34715715050697327, "7778": 0.49864232540130615, "7784": 0.10291612148284912, "7831": 0.20977331697940826, "7863": 0.8748174905776978, "8148": 0.9263957738876343, "8319": 0.5855054259300232, "8353": 0.14518201351165771, "8380": 0.0797421783208847, "8442": 0.06977381557226181, "8487": 0.06886265426874161, "8574": 1.057410478591919, "8729": 0.3615458607673645, "8760": 0.2607102394104004, "8885": 0.004870930220931768, "9084": 0.15943801403045654, "9181": 0.0797421783208847, "9280": 0.07612881064414978, "9312": 0.14939609169960022, "9367": 0.34300774335861206, "9556": 0.2089812457561493, "9560": 0.7258110046386719, "9580": 0.2105647772550583, "9662": 0.037378571927547455, "9723": 0.9209672808647156, "9740": 0.5773153901100159, "9750": 0.8534175157546997, "9765": 0.31845372915267944, "9800": 0.02412080205976963, "9839": 0.5215105414390564, "9874": 0.7665573358535767, "9879": 0.6461620330810547, "10035": 0.3956514894962311, "10106": 0.18816383183002472, "10173": 0.23710809648036957, "10174": 0.3141832649707794, "10197": 0.6430866718292236, "10366": 0.4113073945045471, "10426": 0.5104349255561829, "10536": 0.48068851232528687, "10545": 0.030771657824516296, "10744": 0.1358480453491211, "10831": 0.9463045597076416, "10843": 0.05046287178993225, "10859": 0.7500885725021362, "10903": 0.14349138736724854, "10910": 0.30989447236061096, "11036": 0.06612417846918106, "11048": 0.24859806895256042, "11100": 0.7942996621131897, "11207": 0.13243216276168823, "11310": 0.05694137513637543, "11656": 0.26146242022514343, "11709": 0.1384023278951645, "11791": 0.06337817758321762, "11816": 0.16442140936851501, "12044": 0.31560876965522766, "12142": 0.1229778528213501, "12184": 0.27564704418182373, "12381": 0.6563454270362854, "12520": 0.5517725944519043, "12878": 0.7737906575202942, "13047": 0.25239890813827515, "13105": 0.638455867767334, "13180": 0.46302130818367004, "13331": 0.06795065850019455, "13356": 0.5427330136299133, "13376": 0.2394166737794876, "13483": 0.13670019805431366, "13506": 0.6165571808815002, "13918": 0.08871890604496002, "13993": 0.3409265875816345, "14155": 0.021256839856505394, "14168": 0.17020416259765625, "14378": 0.8349450826644897, "14667": 0.6296497583389282, "14671": 0.15023678541183472, "14874": 0.08871890604496002, "14883": 0.18329764902591705, "15050": 0.045809537172317505, "15170": 0.17020416259765625, "15304": 0.22079704701900482, "15306": 0.4556184411048889, "15308": 0.28082266449928284, "15330": 0.016465263441205025, "15354": 0.53589928150177, "15399": 0.0029254043474793434, "15509": 0.5220900774002075, "15559": 0.3353555500507355, "15596": 0.129004567861557, "15643": 0.004870930220931768, "15704": 0.8357921838760376, "15712": 0.15693697333335876, "15850": 0.8780695199966431, "15995": 0.4673144817352295, "16014": 0.27342069149017334, "16134": 0.0317181795835495, "16157": 0.16276304423809052, "16330": 0.2561853528022766, "16360": 0.036437395960092545, "16483": 0.13755162060260773, "16519": 0.11604541540145874, "16593": 0.10467668622732162, "16731": 0.14939609169960022, "16762": 0.21293537318706512, "16902": 0.03925827145576477, "16923": 0.1510767638683319, "17208": 0.24325250089168549, "17464": 0.6425731778144836, "17531": 1.2175520658493042, "17547": 0.18816383183002472, "17631": 0.14602625370025635, "17696": 0.3777405619621277, "17850": 0.2696990668773651, "18422": 0.24631060659885406, "18512": 0.06612417846918106, "18613": 0.01934296265244484, "18949": 0.950843095779419, "19035": 0.11168810725212097, "19037": 0.11951763927936554, "19064": 0.3956514894962311, "19188": 0.6139179468154907, "19723": 0.3916989266872406, "19879": 0.04394211992621422, "19927": 0.21922965347766876, "19960": 0.26146242022514343, "20241": 1.1425544023513794, "20272": 0.25239890813827515, "20341": 0.11691460013389587, "20480": 0.23015019297599792, "20592": 0.0174254160374403, "20652": 0.6301699280738831, "20781": 0.28670501708984375, "20992": 0.3170322775840759, "21024": 0.16359257698059082, "21449": 0.05046287178993225, "21600": 0.052318159490823746, "21755": 0.12470348179340363, "21961": 1.3243566751480103, "22010": 0.06337817758321762, "22307": 0.14518201351165771, "22571": 0.36290550231933594, "22663": 0.176772341132164, "22835": 0.4374985992908478, "22935": 0.2800849378108978, "23260": 1.0158531665802002, "23760": 1.179255723953247, "24010": 0.0058422754518687725, "24155": 0.4624064862728119, "24501": 0.25694093108177185, "24552": 0.026025565341114998, "24718": 0.11430477350950241, "24736": 0.23864774405956268, "24759": 0.1011524572968483, "25121": 0.29981520771980286, "25613": 0.1619328260421753, "25746": 0.2105647772550583, "25808": 0.9980146884918213, "26163": 0.6296497583389282, "26206": 0.04767346754670143, "26236": 0.2026219218969345, "26237": 0.007782140281051397, "26319": 0.37371641397476196, "26451": 0.06520967930555344, "26462": 0.9613537192344666, "26604": 0.18329764902591705, "26875": 0.06612417846918106, "26906": 0.469759464263916, "27564": 0.02792670577764511, "27768": 0.14518201351165771, "27794": 0.906871497631073, "27833": 0.0913962796330452, "28093": 0.8805016279220581, "28297": 0.2674594223499298, "28767": 0.012615402229130268, "29048": 1.2942990064620972, "29336": 0.1212492436170578, "29458": 0.19862671196460724, "29486": 0.18978065252304077} | 12206390 | CONTEXT The long-term risk for developing hypertension is best described by the lifetime risk statistic. The lifetime risk for hypertension and trends in this risk over time are unknown. OBJECTIVES To estimate the residual lifetime risk for hypertension in older US adults and to evaluate temporal trends in this risk. DESIGN, SETTING, AND PARTICIPANTS Community-based prospective cohort study of 1298 participants from the Framingham Heart Study who were aged 55 to 65 years and free of hypertension at baseline (1976-1998). MAIN OUTCOME MEASURES Residual lifetime risk (lifetime cumulative incidence not adjusted for competing causes of mortality) for hypertension, defined as blood pressure of 140/90 mm Hg or greater or use of antihypertensive medications. RESULTS The residual lifetime risks for developing hypertension and stage 1 high blood pressure or higher (greater-than-or-equal to 140/90 mm Hg regardless of treatment) were 90% in both 55- and 65-year-old participants. The lifetime probability of receiving antihypertensive medication was 60%. The risk for hypertension remained unchanged for women, but it was approximately 60% higher for men in the contemporary 1976-1998 period compared with an earlier 1952-1975 period. In contrast, the residual lifetime risk for stage 2 high blood pressure or higher (greater-than-or-equal to 160/100 mm Hg regardless of treatment) was considerably lower in both sexes in the recent period (35%-57% in 1952-1975 vs 35%-44% in 1976-1998), likely due to a marked increase in treatment of individuals with substantially elevated blood pressure. CONCLUSION The residual lifetime risk for hypertension for middle-aged and elderly individuals is 90%, indicating a huge public health burden. Although the decline in lifetime risk for stage 2 high blood pressure or higher represents a major achievement, efforts should be directed at the primary prevention of hypertension. | Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. |
{"1014": 0.05694137513637543, "1052": 0.2539152204990387, "1997": 0.10026945173740387, "1999": 0.09584271162748337, "2029": 0.04487626627087593, "2047": 0.3019835948944092, "2063": 0.06154331564903259, "2078": 0.1808556467294693, "2109": 0.19782574474811554, "2116": 0.18248429894447327, "2179": 0.11865071207284927, "2193": 0.06703783571720123, "2207": 0.15943801403045654, "2236": 0.2822965085506439, "2239": 0.043007105588912964, "2368": 0.7333439588546753, "2385": 0.09850110858678818, "2458": 0.23247487843036652, "2504": 0.029824240133166313, "2527": 0.018384648486971855, "2529": 0.5925496220588684, "2532": 0.011650617234408855, "2549": 0.22782009840011597, "2638": 0.6296497583389282, "2667": 0.00875066313892603, "2668": 0.03925827145576477, "2669": 0.21922965347766876, "2721": 0.21372433006763458, "2764": 0.1332872211933136, "2777": 0.1384023278951645, "2863": 0.4891071021556854, "2920": 0.006812678650021553, "2944": 0.8057082891464233, "2988": 0.010684899985790253, "3046": 0.7898768186569214, "3170": 0.680370569229126, "3252": 0.02792670577764511, "3283": 0.0038986403960734606, "3303": 0.19862671196460724, "3366": 0.7408206462860107, "3372": 0.28597161173820496, "3378": 0.00875066313892603, "3426": 0.4950772523880005, "3465": 0.015504186972975731, "3466": 0.2394166737794876, "3497": 0.04207121208310127, "3625": 0.05046287178993225, "3775": 0.6482070088386536, "3798": 0.24171993136405945, "3802": 0.5033760666847229, "3896": 0.3883931338787079, "3968": 0.28082266449928284, "3981": 0.4145384132862091, "4022": 0.0009760859538801014, "4048": 0.0174254160374403, "4053": 0.14686977863311768, "4111": 0.5151132941246033, "4167": 0.7144040465354919, "4176": 0.4145384132862091, "4179": 0.08154398202896118, "4195": 0.09850110858678818, "4221": 0.11951763927936554, "4270": 0.3304552733898163, "4275": 0.6223390698432922, "4286": 0.49864232540130615, "4442": 0.11604541540145874, "4453": 0.037378571927547455, "4456": 0.3723714053630829, "4503": 0.11865071207284927, "4668": 0.02887592278420925, "4677": 0.08961215615272522, "4819": 0.8152611255645752, "4962": 0.23556606471538544, "4975": 0.472198486328125, "4977": 0.016465263441205025, "5007": 0.13157635927200317, "5072": 0.5963221788406372, "5122": 0.0058422754518687725, "5159": 0.08513788133859634, "5250": 0.854249119758606, "5267": 0.3554046154022217, "5283": 0.036437395960092545, "5320": 0.4926934838294983, "5360": 0.5272908806800842, "5363": 0.022212404757738113, "5387": 0.3910386264324188, "5423": 0.0058422754518687725, "5449": 0.25845035910606384, "5524": 0.11168810725212097, "5643": 0.05417001247406006, "5648": 0.20421554148197174, "5717": 0.1384023278951645, "5802": 0.11081436276435852, "5850": 0.2607102394104004, "5876": 0.4437839686870575, "5919": 0.27342069149017334, "5923": 0.1212492436170578, "5939": 0.8459017872810364, "6064": 0.40481385588645935, "6132": 0.31845372915267944, "6370": 0.2969166338443756, "6388": 0.0029254043474793434, "6501": 0.02316705882549286, "6673": 0.07431721687316895, "6693": 0.5893046259880066, "6761": 0.06520967930555344, "6887": 0.8500841856002808, "6897": 0.10993985831737518, "6935": 0.021256839856505394, "6970": 0.8247235417366028, "7088": 0.12814582884311676, "7146": 0.09584271162748337, "7151": 0.06612417846918106, "7328": 0.11517547070980072, "7337": 0.07431721687316895, "7352": 1.0008903741836548, "7361": 0.5455666780471802, "7366": 0.0354953333735466, "7403": 0.06337817758321762, "7406": 0.01934296265244484, "7412": 0.011650617234408855, "7461": 0.47827014327049255, "7551": 0.026025565341114998, "7554": 0.20022670924663544, "7616": 0.0770333781838417, "7630": 0.040196798741817474, "7666": 0.25239890813827515, "7722": 0.0354953333735466, "7770": 0.28963330388069153, "7783": 0.083342544734478, "7861": 0.49030399322509766, "7870": 0.07068414986133575, "7885": 0.13157635927200317, "7911": 0.11343330889940262, "8000": 0.13499516248703003, "8089": 0.40285754203796387, "8148": 0.25845035910606384, "8153": 0.7076893448829651, "8171": 0.7408206462860107, "8332": 0.04953393340110779, "8343": 0.11081436276435852, "8381": 0.0606246218085289, "8458": 0.37907835841178894, "8516": 0.38308101892471313, "8524": 0.22704219818115234, "8586": 0.02887592278420925, "8625": 0.4400174915790558, "8674": 0.006812678650021553, "8715": 0.018384648486971855, "8859": 0.006812678650021553, "8948": 0.40285754203796387, "9007": 0.6075552701950073, "9048": 0.6244332790374756, "9063": 0.2018241584300995, "9126": 0.08154398202896118, "9335": 0.009718249551951885, "9350": 0.08961215615272522, "9420": 0.5957841277122498, "9488": 0.010684899985790253, "9589": 0.04953393340110779, "9597": 0.23092569410800934, "9947": 0.41647201776504517, "9998": 0.06246116757392883, "10092": 0.6043586730957031, "10099": 0.08513788133859634, "10222": 0.12038381397724152, "10266": 0.0354953333735466, "10288": 0.05046287178993225, "10327": 0.056018441915512085, "10509": 0.1808556467294693, "10581": 0.06520967930555344, "10586": 0.22157983481884003, "10609": 0.12038381397724152, "10610": 0.0354953333735466, "10672": 0.7934166193008423, "10698": 0.14433705806732178, "10722": 0.043007105588912964, "10737": 0.08603433519601822, "10752": 0.854249119758606, "10857": 0.016465263441205025, "10893": 0.029824240133166313, "11146": 0.004870930220931768, "11156": 0.14095009863376617, "11163": 0.06154331564903259, "11192": 0.49626702070236206, "11233": 0.10731173306703568, "11290": 0.1064341589808464, "11432": 0.1913948506116867, "11439": 0.08064348995685577, "11498": 0.0058422754518687725, "11636": 0.4444103240966797, "11643": 0.4556184411048889, "11704": 1.0519683361053467, "11709": 0.14518201351165771, "11923": 0.15860503911972046, "12123": 0.151916041970253, "12141": 0.42544642090797424, "12248": 0.021256839856505394, "12259": 0.012615402229130268, "12326": 0.18004031479358673, "12328": 0.2493593990802765, "12380": 0.007782140281051397, "12448": 0.1358480453491211, "12473": 0.4132472574710846, "12504": 0.15442965924739838, "12553": 0.034552380442619324, "12649": 0.2394166737794876, "12732": 0.06977381557226181, "12765": 0.3163207769393921, "12811": 0.22157983481884003, "12987": 0.2822965085506439, "13096": 0.12384103983640671, "13105": 0.0317181795835495, "13153": 0.07612881064414978, "13246": 0.06795065850019455, "13308": 0.09584271162748337, "13531": 0.3777405619621277, "13656": 0.025073638185858727, "13791": 0.14095009863376617, "13853": 0.1332872211933136, "13859": 0.04113444685935974, "13876": 0.42990362644195557, "13913": 0.2837681770324707, "13922": 0.3923587501049042, "14061": 0.7546905279159546, "14080": 0.010684899985790253, "14095": 0.5590575933456421, "14183": 0.08961215615272522, "14234": 0.018384648486971855, "14266": 0.4944818615913391, "14440": 0.01934296265244484, "14480": 0.0058422754518687725, "14545": 0.812664806842804, "14601": 0.07159364968538284, "14604": 0.04860413447022438, "14751": 0.07250232994556427, "14907": 0.0354953333735466, "14956": 0.36290550231933594, "15059": 0.13755162060260773, "15170": 0.015504186972975731, "15316": 0.3012613356113434, "15425": 0.39367714524269104, "15459": 0.0019512200960889459, "15464": 0.1693800985813141, "15530": 0.08064348995685577, "15596": 0.9232974052429199, "15738": 0.02887592278420925, "15813": 0.06246116757392883, "15869": 0.34370049834251404, "15877": 0.06337817758321762, "15923": 0.07250232994556427, "15928": 0.06520967930555344, "16012": 0.1905880719423294, "16014": 0.10203468054533005, "16031": 0.04394211992621422, "16149": 0.7482418417930603, "16221": 0.1011524572968483, "16231": 0.0317181795835495, "16285": 0.5220900774002075, "16464": 0.23864774405956268, "16480": 0.07793712615966797, "16505": 0.24859806895256042, "16515": 0.2667117714881897, "16567": 0.2470736801624298, "16627": 0.05970508232712746, "16643": 0.6139179468154907, "16734": 0.11778303235769272, "16771": 0.11951763927936554, "16781": 0.09050461649894714, "16785": 0.5438674688339233, "16910": 0.016465263441205025, "16923": 0.8298473954200745, "17086": 0.06977381557226181, "17271": 0.08154398202896118, "17344": 0.15610189735889435, "17359": 0.06886265426874161, "17365": 0.40220460295677185, "17403": 0.12038381397724152, "17531": 0.00875066313892603, "17577": 0.016465263441205025, "17631": 0.13755162060260773, "17663": 0.3982778787612915, "17681": 0.06520967930555344, "17696": 1.076228141784668, "17698": 0.037378571927547455, "17782": 0.23864774405956268, "17832": 0.4425300657749176, "17864": 0.02792670577764511, "17867": 0.6543170213699341, "17926": 0.029824240133166313, "17943": 0.8829278349876404, "18044": 0.09672962874174118, "18089": 0.7352184057235718, "18253": 0.15860503911972046, "18260": 0.32058215141296387, "18419": 0.18654440343379974, "18595": 0.38574060797691345, "18610": 0.4574742913246155, "18639": 0.0606246218085289, "18714": 0.1693800985813141, "18757": 0.1221139207482338, "18804": 0.2394166737794876, "18847": 0.2184450328350067, "18856": 0.020300358533859253, "18888": 0.04953393340110779, "18909": 0.05417001247406006, "18914": 0.22859740257263184, "19081": 0.02316705882549286, "19105": 0.1212492436170578, "19379": 1.0841858386993408, "19491": 0.02316705882549286, "19518": 0.052318159490823746, "19531": 0.11168810725212097, "19539": 0.1751343309879303, "19610": 0.1889725625514984, "19620": 0.04860413447022438, "19761": 0.030771657824516296, "19825": 0.18004031479358673, "19915": 0.045809537172317505, "20162": 0.1401015669107437, "20281": 0.1477125883102417, "20303": 0.36426326632499695, "20377": 0.029824240133166313, "20435": 0.4770587682723999, "20467": 0.036437395960092545, "20492": 0.0174254160374403, "20738": 0.03266380727291107, "20752": 0.29036402702331543, "20766": 0.08692999184131622, "20906": 0.0354953333735466, "20925": 0.6317287683486938, "21046": 0.09938567131757736, "21141": 1.024303913116455, "21262": 0.16110190749168396, "21281": 0.6613984704017639, "21396": 0.1994270235300064, "21453": 0.7445381283760071, "21486": 0.0913962796330452, "21618": 0.09938567131757736, "21647": 0.03266380727291107, "21709": 0.0174254160374403, "21716": 0.15860503911972046, "21766": 0.14095009863376617, "21890": 0.013579257763922215, "21903": 0.17431432008743286, "21908": 0.7537717819213867, "22242": 0.00875066313892603, "22412": 0.11430477350950241, "22419": 0.03925827145576477, "22423": 1.245482087135315, "22533": 0.25694093108177185, "22641": 0.567397952079773, "22644": 0.1011524572968483, "22684": 0.06795065850019455, "22698": 0.10555581003427505, "22930": 0.06520967930555344, "23079": 0.2837681770324707, "23096": 0.10993985831737518, "23144": 0.18492233753204346, "23310": 0.15777134895324707, "23335": 0.04860413447022438, "23518": 0.02316705882549286, "23572": 0.4679262638092041, "23681": 0.012615402229130268, "23737": 0.11691460013389587, "23790": 0.030771657824516296, "23823": 0.034552380442619324, "23827": 0.03266380727291107, "23943": 0.9287132620811462, "24054": 0.2763880789279938, "24090": 0.026976587250828743, "24124": 0.10203468054533005, "24198": 0.2478361576795578, "24203": 0.5773153901100159, "24229": 0.07612881064414978, "24269": 0.12642613053321838, "24278": 0.21135559678077698, "24312": 0.0752234235405922, "24395": 0.34508460760116577, "24501": 0.1221139207482338, "24520": 0.030771657824516296, "24556": 0.06703783571720123, "24661": 0.16276304423809052, "24710": 0.4412745535373688, "24729": 0.16690383851528168, "24797": 0.14602625370025635, "24848": 0.21922965347766876, "25002": 0.02887592278420925, "25003": 0.7737906575202942, "25060": 0.0009760859538801014, "25117": 0.40806588530540466, "25222": 0.15275461971759796, "25468": 0.23247487843036652, "25473": 0.32905077934265137, "25534": 0.151916041970253, "25557": 0.018384648486971855, "25627": 0.23247487843036652, "25654": 0.05417001247406006, "25714": 0.3005385100841522, "25874": 0.10731173306703568, "25950": 0.04674193635582924, "25969": 0.23864774405956268, "26190": 0.16607704758644104, "26243": 0.045809537172317505, "26244": 0.34508460760116577, "26402": 0.09406650811433792, "26524": 0.21687394380569458, "26641": 0.10555581003427505, "26642": 0.05694137513637543, "26702": 0.29400965571403503, "26780": 0.42225050926208496, "26835": 0.04394211992621422, "27194": 0.11343330889940262, "27407": 0.030771657824516296, "27441": 0.1064341589808464, "27497": 0.0019512200960889459, "27854": 0.011650617234408855, "27896": 0.01934296265244484, "28155": 0.05417001247406006, "28216": 0.053244512528181076, "28227": 0.2763880789279938, "28268": 0.630689799785614, "28434": 0.04860413447022438, "28485": 0.01934296265244484, "28502": 0.10203468054533005, "28691": 0.4041621685028076, "28835": 0.04953393340110779, "28846": 0.15610189735889435, "29090": 0.7683706283569336, "29167": 0.040196798741817474, "29237": 0.2105647772550583, "29458": 0.0019512200960889459, "29596": 0.32341301441192627, "29598": 0.6568518877029419, "29610": 0.06429435312747955} | 12207167 | PHENYLALANINE TOXICITY 158 Developing the 0. -M ethylphenylalanine Model. . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 Use of the a-Methyl phenylalanine Model in Brain Protein Synthesis . . . . . . . . . . . . . . . . . . . 161 TYROSINE TOXICITY 162 General Nutritional Observations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 Factors Affecting Tissue Concentrations of Tyrosine . ... .. .. .. ...... . . . . . . .. . . 163 Probable Cause of Tyrosine Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 A New Animal Model for Human Tyrosinemia II 165 TRYPTOPHAN TOXICITy 165 General Nutritional Observations . .. ....... . ....... . .... . . .. . . . .. . .. . .. ..... ......... 165 Factors Affecting Tryptophan Toxicity . . . .. . . . . . . . .... . ........ 166 Tryptophan and Ruminant Interstitial Pulmonary Emphysema and Edema ..... . . . . . . . 167 HISTIDINE TOXICITY 168 General Nutritional Observations ...... ........ . . . . ..... . ...... .. . 168 Metabolic Aspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 Alleviation of Histidine Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 METHIONINE TOXICITY 171 General Nutritional Observations . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 Tissue Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 172 Protective Effect of Glycine, Serine, or Retinol . . . .. ....... . ......... . ......... .. . .. . . ...... 172 Chemical Characteristics Related to the Toxicity of Methionine . . . . . . . . . . . . . . . . . . . . . . . . . 173 Damaging Effects of Methanethiol. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 173 Met�io,!ine To�i.city in Chickens 174 EthlOnme TOxIcIty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . ... . 174 | Adverse effects of excessive consumption of amino acids. |
{"1005": 0.11691460013389587, "1011": 0.06612417846918106, "1017": 0.3485364317893982, "1019": 0.3777405619621277, "1050": 0.46914875507354736, "1997": 0.06520967930555344, "2000": 0.11430477350950241, "2003": 0.0354953333735466, "2011": 0.4248080551624298, "2034": 0.2983669638633728, "2043": 0.014542185701429844, "2048": 0.36494144797325134, "2058": 0.4450363218784332, "2063": 0.38374659419059753, "2076": 0.2317005842924118, "2093": 0.2026219218969345, "2094": 0.306306391954422, "2098": 0.255429208278656, "2117": 0.6921701431274414, "2128": 0.31560876965522766, "2129": 0.4145384132862091, "2146": 0.12556517124176025, "2170": 0.23092569410800934, "2182": 0.1889725625514984, "2203": 1.1870332956314087, "2239": 0.08692999184131622, "2274": 0.3019835948944092, "2309": 0.6872705817222595, "2320": 0.0029254043474793434, "2339": 0.319873183965683, "2345": 0.17020416259765625, "2391": 0.4425300657749176, "2475": 0.5751199722290039, "2485": 0.255429208278656, "2487": 0.2749055027961731, "2491": 0.5701626539230347, "2497": 0.6568518877029419, "2512": 0.40871503949165344, "2537": 0.20660123229026794, "2550": 0.32553088665008545, "2571": 0.2719337046146393, "2581": 0.1930064558982849, "2587": 0.5404602885246277, "2595": 0.347847044467926, "2649": 0.040196798741817474, "2720": 0.8699195384979248, "2754": 0.27342069149017334, "2765": 0.026976587250828743, "2817": 0.013579257763922215, "2832": 0.7610978484153748, "2864": 0.16110190749168396, "2869": 0.27786844968795776, "2913": 0.20501139760017395, "2920": 0.17922431230545044, "2947": 0.13499516248703003, "3013": 0.29981520771980286, "3092": 0.5080875158309937, "3193": 0.2531573474407196, "3273": 0.036437395960092545, "3313": 1.033379077911377, "3319": 0.304147332906723, "3338": 1.0601204633712769, "3341": 0.05970508232712746, "3357": 0.5313173532485962, "3366": 0.01934296265244484, "3370": 0.20501139760017395, "3375": 0.41195443272590637, "3416": 0.13243216276168823, "3501": 0.18654440343379974, "3508": 0.7656494975090027, "3526": 0.4855078160762787, "3532": 0.5410289764404297, "3560": 0.45623743534088135, "3601": 0.45623743534088135, "3625": 0.04394211992621422, "3631": 0.469759464263916, "3668": 0.44566190242767334, "3670": 0.016465263441205025, "3693": 0.574020504951477, "3714": 0.7881022095680237, "3718": 0.08064348995685577, "3726": 0.45499902963638306, "3807": 0.036437395960092545, "3853": 0.034552380442619324, "3863": 0.7182208299636841, "3905": 0.004870930220931768, "3908": 0.05139094591140747, "3940": 0.3824150264263153, "3965": 0.41001203656196594, "3970": 0.07250232994556427, "3975": 0.016465263441205025, "4000": 0.13243216276168823, "4030": 0.04767346754670143, "4053": 0.9178520441055298, "4072": 0.021256839856505394, "4078": 0.03266380727291107, "4084": 0.6170841455459595, "4118": 0.1011524572968483, "4130": 0.2741633653640747, "4148": 0.012615402229130268, "4187": 0.6075552701950073, "4217": 0.01934296265244484, "4371": 0.16690383851528168, "4373": 0.045809537172317505, "4403": 0.1930064558982849, "4442": 0.2969166338443756, "4515": 0.817850649356842, "4566": 0.672426164150238, "4649": 0.1332872211933136, "4654": 0.3106105625629425, "4668": 0.4113073945045471, "4685": 0.036437395960092545, "4747": 0.6704301834106445, "4758": 0.4728073179721832, "4911": 0.6684301495552063, "4937": 0.4752389192581177, "4962": 0.5662899017333984, "4964": 0.0354953333735466, "4989": 0.04487626627087593, "5155": 0.022212404757738113, "5158": 0.574020504951477, "5241": 0.4248080551624298, "5243": 0.39433568716049194, "5258": 0.5795059204101562, "5320": 0.025073638185858727, "5331": 0.11081436276435852, "5343": 0.2105647772550583, "5358": 0.23324857652187347, "5402": 0.23092569410800934, "5449": 0.5450005531311035, "5450": 0.004870930220931768, "5462": 0.3381449282169342, "5536": 0.21372433006763458, "5537": 0.3683255612850189, "5549": 0.04767346754670143, "5591": 0.7182208299636841, "5656": 0.052318159490823746, "5676": 0.42096930742263794, "5711": 0.3269403576850891, "5725": 0.823009729385376, "5910": 1.059443712234497, "5970": 0.4831010699272156, "6003": 0.6573580503463745, "6028": 0.18816383183002472, "6064": 1.341354250907898, "6110": 0.053244512528181076, "6149": 0.22157983481884003, "6164": 0.1685553640127182, "6194": 0.4673144817352295, "6215": 0.31845372915267944, "6228": 0.07793712615966797, "6234": 0.1946154683828354, "6370": 0.07612881064414978, "6413": 0.26296505331993103, "6418": 0.3615458607673645, "6433": 0.09584271162748337, "6460": 0.1510767638683319, "6532": 0.11256109178066254, "6673": 0.12470348179340363, "6958": 0.025073638185858727, "6961": 0.022212404757738113, "7013": 0.46608972549438477, "7020": 1.005902886390686, "7065": 0.26146242022514343, "7137": 0.13414156436920166, "7178": 0.2852376699447632, "7192": 1.309177041053772, "7233": 0.3963087201118469, "7336": 0.17020416259765625, "7337": 1.0775588750839233, "7342": 0.3141832649707794, "7366": 0.4580921530723572, "7403": 0.5838727951049805, "7531": 0.8893690705299377, "7689": 0.3005385100841522, "7697": 0.18978065252304077, "7709": 0.2622140049934387, "7711": 0.45994341373443604, "7783": 1.072893738746643, "7807": 0.9576126337051392, "7816": 0.4248080551624298, "7818": 0.0038986403960734606, "7842": 0.7028654217720032, "7885": 0.08513788133859634, "7901": 0.2983669638633728, "7949": 0.6043586730957031, "8031": 0.06337817758321762, "8081": 0.4926934838294983, "8093": 0.05694137513637543, "8208": 0.11256109178066254, "8347": 0.06246116757392883, "8361": 0.14433705806732178, "8402": 0.27342069149017334, "8651": 0.07068414986133575, "8735": 0.5930894017219543, "8778": 0.13243216276168823, "8878": 0.42990362644195557, "8907": 0.0606246218085289, "8908": 0.09761575609445572, "8979": 0.02412080205976963, "8980": 0.04860413447022438, "8989": 0.1994270235300064, "8991": 0.14518201351165771, "9007": 0.7352184057235718, "9096": 0.176772341132164, "9099": 0.34508460760116577, "9114": 0.0058422754518687725, "9165": 0.2184450328350067, "9239": 0.1693800985813141, "9285": 0.3877306580543518, "9413": 0.2145126610994339, "9469": 0.045809537172317505, "9560": 0.35334911942481995, "9597": 0.22157983481884003, "9699": 0.500420093536377, "9756": 0.2652147710323334, "9794": 0.3077431619167328, "9804": 0.02887592278420925, "9818": 0.11778303235769272, "9896": 0.053244512528181076, "10066": 0.13243216276168823, "10077": 0.0019512200960889459, "10109": 0.10993985831737518, "10210": 0.22392450273036957, "10315": 0.7934166193008423, "10341": 0.3949938118457794, "10394": 0.026976587250828743, "10572": 0.347847044467926, "10573": 0.34370049834251404, "10595": 0.8525851964950562, "10738": 0.21372433006763458, "10752": 0.15023678541183472, "10797": 0.42161011695861816, "10838": 0.07068414986133575, "10951": 0.1905880719423294, "10956": 0.1477125883102417, "10958": 0.7408206462860107, "11022": 0.6603899002075195, "11226": 0.9673105478286743, "11514": 0.637939989566803, "11674": 0.10555581003427505, "11707": 0.4267219603061676, "11717": 0.21530038118362427, "12061": 0.23710809648036957, "12222": 0.7220231294631958, "12335": 0.08603433519601822, "12376": 0.4196864068508148, "12394": 0.319873183965683, "12527": 0.9029204845428467, "12554": 0.5232481360435486, "12562": 0.045809537172317505, "12636": 0.5696102976799011, "12702": 0.06886265426874161, "12725": 0.13755162060260773, "12732": 0.9409833550453186, "12739": 0.0797421783208847, "12859": 0.5562619566917419, "12987": 0.35745587944984436, "13105": 0.20580662786960602, "13248": 0.13670019805431366, "13330": 0.25239890813827515, "13368": 0.009718249551951885, "13369": 0.1905880719423294, "13458": 0.38574060797691345, "13557": 0.1905880719423294, "13595": 0.2719337046146393, "13671": 1.190008521080017, "13791": 0.8509185314178467, "13995": 0.012615402229130268, "14053": 0.3283478021621704, "14080": 0.20022670924663544, "14119": 0.812664806842804, "14193": 0.5398913025856018, "14194": 0.4818955361843109, "14321": 0.5244048833847046, "14471": 0.13071982562541962, "14526": 0.3883931338787079, "14570": 0.06429435312747955, "14578": 0.6543170213699341, "14584": 0.3077431619167328, "14591": 0.4926934838294983, "14828": 0.11951763927936554, "14931": 0.5893046259880066, "15011": 0.2018241584300995, "15059": 0.08603433519601822, "15100": 0.1946154683828354, "15176": 0.33325836062431335, "15420": 0.021256839856505394, "15527": 0.16442140936851501, "15577": 0.950843095779419, "15778": 0.3019835948944092, "15800": 0.27934664487838745, "15887": 0.24401791393756866, "15946": 0.2223619967699051, "16086": 0.043007105588912964, "16134": 0.0029254043474793434, "16221": 0.4462870955467224, "16233": 1.2047537565231323, "16285": 0.5618454217910767, "16305": 0.8699195384979248, "16316": 0.010684899985790253, "16371": 0.6170841455459595, "16599": 0.009718249551951885, "16610": 0.14349138736724854, "16627": 1.104454517364502, "16706": 0.49864232540130615, "16765": 0.22079704701900482, "16771": 0.5151132941246033, "16873": 0.1332872211933136, "16910": 0.7951818704605103, "16940": 0.4824984669685364, "17159": 0.09228714555501938, "17441": 0.2516399025917053, "17448": 1.005902886390686, "17598": 0.09228714555501938, "17630": 0.018384648486971855, "17820": 0.9052929878234863, "17850": 1.3408433198928833, "17890": 1.1018621921539307, "18003": 1.068206787109375, "18231": 0.03831886500120163, "18260": 0.020300358533859253, "18287": 0.7969439625740051, "18340": 0.4311734735965729, "18419": 0.021256839856505394, "18491": 1.3735177516937256, "18699": 1.070887804031372, "18856": 0.34508460760116577, "19391": 0.255429208278656, "19421": 0.5307431221008301, "19500": 0.2516399025917053, "19583": 0.11604541540145874, "19601": 0.27934664487838745, "19653": 0.4093637466430664, "19723": 0.14686977863311768, "19780": 0.040196798741817474, "19841": 0.3012613356113434, "19872": 0.23633737862110138, "19892": 0.3034266233444214, "19969": 0.1994270235300064, "20045": 0.4728073179721832, "20250": 0.1401015669107437, "20320": 0.6296497583389282, "20518": 1.2198615074157715, "20544": 0.5110208988189697, "20766": 0.848413348197937, "20960": 0.3982778787612915, "21053": 0.19622190296649933, "21114": 1.1102628707885742, "21197": 0.8117979168891907, "21252": 0.9500881433486938, "21306": 0.29619070887565613, "21312": 0.30558720231056213, "21476": 0.18573370575904846, "21486": 0.23324857652187347, "21557": 0.16442140936851501, "21575": 0.07250232994556427, "21618": 0.15860503911972046, "21647": 0.8649974465370178, "21716": 0.043007105588912964, "21770": 0.2026219218969345, "21903": 0.15693697333335876, "21933": 0.11343330889940262, "22026": 0.04487626627087593, "22069": 0.7683706283569336, "22203": 1.175042748451233, "22207": 0.04207121208310127, "22275": 0.4286321699619293, "22471": 0.9936857223510742, "22731": 0.08692999184131622, "22778": 0.6624060273170471, "22794": 0.28743788599967957, "23163": 0.026025565341114998, "23216": 0.013579257763922215, "23217": 0.0174254160374403, "23316": 0.19862671196460724, "23552": 0.6181373596191406, "23725": 0.9842413663864136, "23737": 0.129004567861557, "23767": 0.20421554148197174, "23770": 0.07884006202220917, "23797": 0.17020416259765625, "24004": 1.1147572994232178, "24170": 0.6075552701950073, "24501": 1.1786550283432007, "24558": 0.02887592278420925, "24733": 0.06703783571720123, "24854": 0.10467668622732162, "25416": 0.07793712615966797, "25449": 0.3027053773403168, "25743": 0.25239890813827515, "25746": 0.3325583338737488, "25761": 0.12384103983640671, "25874": 0.17840765416622162, "26118": 0.15442965924739838, "26131": 0.5882205963134766, "26224": 0.27786844968795776, "26244": 0.3485364317893982, "26296": 1.0815403461456299, "26384": 0.03831886500120163, "26394": 0.25694093108177185, "26402": 0.04953393340110779, "26520": 1.1481462717056274, "26601": 0.05139094591140747, "26616": 0.5232481360435486, "26773": 0.42225050926208496, "26872": 0.03360854089260101, "26874": 0.3897167444229126, "27009": 0.20660123229026794, "27642": 0.020300358533859253, "27777": 0.01934296265244484, "27791": 0.1064341589808464, "27846": 0.08871890604496002, "28024": 0.3656192123889923, "28154": 0.11865071207284927, "28173": 0.0019512200960889459, "28424": 0.5347557663917542, "28472": 0.4950772523880005, "28667": 0.9710156321525574, "28691": 0.26446542143821716, "28790": 0.5871354341506958, "28835": 0.025073638185858727, "28911": 0.6410312056541443, "29129": 0.04953393340110779, "29290": 0.09495500475168228} | 12207340 | The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5'-terminated strands in a process termed end resection. End resection generates 3'-single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and DNA strand exchange, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5'-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3'-ssDNA-tailed intermediates. Initiation of resection commits a cell to repair a DSB by HR because long ssDNA overhangs are poor substrates for non-homologous end joining (NHEJ). Thus, the initiation of end resection has emerged as a critical control point for repair pathway choice. Here, I review recent studies on the mechanism of end resection and how this process is regulated to ensure the most appropriate repair outcome. | Mechanism and regulation of DNA end resection in eukaryotes. |
{"1003": 0.19862671196460724, "1014": 0.06977381557226181, "1018": 0.2918238639831543, "1020": 0.3588210940361023, "1043": 0.0752234235405922, "1050": 0.36494144797325134, "2004": 0.13243216276168823, "2007": 0.16690383851528168, "2012": 0.16110190749168396, "2020": 0.04113444685935974, "2028": 0.08513788133859634, "2050": 0.24171993136405945, "2051": 0.1401015669107437, "2053": 0.9621002674102783, "2078": 0.24171993136405945, "2084": 0.4462870955467224, "2088": 0.49982786178588867, "2090": 0.34922540187835693, "2106": 0.1808556467294693, "2109": 0.2531573474407196, "2111": 0.013579257763922215, "2114": 0.040196798741817474, "2116": 0.23864774405956268, "2117": 0.02792670577764511, "2138": 0.2184450328350067, "2146": 0.19220098853111267, "2152": 0.011650617234408855, "2166": 0.22079704701900482, "2168": 0.10906458646059036, "2172": 0.3519764244556427, "2177": 0.4891071021556854, "2220": 0.495672345161438, "2224": 0.18573370575904846, "2302": 0.16690383851528168, "2309": 0.23556606471538544, "2313": 0.255429208278656, "2330": 0.17922431230545044, "2331": 0.6613984704017639, "2339": 0.38041436672210693, "2348": 0.01934296265244484, "2351": 0.4248080551624298, "2363": 0.1602703034877777, "2367": 0.34370049834251404, "2370": 0.255429208278656, "2401": 0.5871354341506958, "2406": 0.19782574474811554, "2416": 0.40285754203796387, "2426": 0.08154398202896118, "2458": 0.22079704701900482, "2470": 0.4337083101272583, "2478": 0.129004567861557, "2488": 0.13755162060260773, "2491": 0.45499902963638306, "2509": 0.36494144797325134, "2512": 0.15359249711036682, "2515": 0.040196798741817474, "2549": 0.5685047507286072, "2553": 0.7995813488960266, "2581": 0.4067663550376892, "2620": 0.43053874373435974, "2629": 0.2800849378108978, "2634": 0.20421554148197174, "2714": 0.08244366943836212, "2730": 0.21687394380569458, "2734": 0.1693800985813141, "2740": 0.11691460013389587, "2748": 0.1994270235300064, "2753": 0.8748174905776978, "2764": 0.4654768109321594, "2765": 0.3381449282169342, "2800": 0.3903779089450836, "2817": 0.4926934838294983, "2846": 0.004870930220931768, "2859": 0.08513788133859634, "2870": 0.10467668622732162, "2902": 0.27564704418182373, "2913": 0.5220900774002075, "2967": 0.2969166338443756, "2969": 1.068206787109375, "2988": 0.06520967930555344, "2993": 0.0606246218085289, "3012": 0.5882205963134766, "3020": 0.4400174915790558, "3032": 0.5010119676589966, "3041": 0.22079704701900482, "3068": 0.19381128251552582, "3078": 0.5495203733444214, "3088": 0.13071982562541962, "3102": 0.05417001247406006, "3112": 0.31132611632347107, "3144": 0.08603433519601822, "3161": 0.3683255612850189, "3209": 0.5957841277122498, "3231": 0.0317181795835495, "3251": 0.040196798741817474, "3262": 0.04953393340110779, "3264": 0.2674594223499298, "3269": 0.25995752215385437, "3273": 0.37304413318634033, "3280": 0.46117570996284485, "3327": 0.1358480453491211, "3409": 0.19541899859905243, "3446": 0.319873183965683, "3447": 0.5110208988189697, "3463": 0.23247487843036652, "3465": 0.053244512528181076, "3466": 0.14602625370025635, "3534": 0.7537717819213867, "3541": 1.1524739265441895, "3556": 0.13499516248703003, "3568": 0.12642613053321838, "3572": 0.5947071313858032, "3591": 0.32129061222076416, "3609": 0.22859740257263184, "3618": 0.09495500475168228, "3633": 0.11168810725212097, "3647": 0.32341301441192627, "3674": 1.0087559223175049, "3707": 0.11865071207284927, "3756": 0.9317949414253235, "3795": 0.10818854719400406, "3808": 0.34715715050697327, "3811": 0.6233867406845093, "3830": 0.4926934838294983, "3832": 0.11343330889940262, "3867": 0.5261374711990356, "3891": 0.3409265875816345, "3896": 0.20818853378295898, "3904": 0.3662964701652527, "3919": 0.7086513638496399, "3923": 0.012615402229130268, "3943": 0.1212492436170578, "3949": 0.6394867897033691, "3979": 0.9363996982574463, "4004": 0.41065993905067444, "4012": 0.129004567861557, "4021": 0.6773988008499146, "4029": 0.4974553883075714, "4044": 0.5838727951049805, "4090": 0.02792670577764511, "4094": 0.026025565341114998, "4102": 0.7352184057235718, "4106": 0.7047978043556213, "4118": 0.33675122261047363, "4146": 0.10026945173740387, "4187": 0.026976587250828743, "4236": 0.2478361576795578, "4264": 0.4481603503227234, "4270": 0.06977381557226181, "4281": 0.757441520690918, "4295": 0.1602703034877777, "4328": 0.08244366943836212, "4355": 0.06886265426874161, "4380": 0.014542185701429844, "4426": 0.21214580535888672, "4456": 0.3662964701652527, "4483": 0.2470736801624298, "4489": 0.5244048833847046, "4496": 0.20421554148197174, "4607": 0.5871354341506958, "4621": 0.6950984001159668, "4654": 0.034552380442619324, "4725": 0.4318077862262726, "4758": 0.7491656541824341, "4795": 0.5080875158309937, "4800": 0.4531385898590088, "4805": 0.2990913391113281, "4812": 0.06703783571720123, "4868": 0.2763880789279938, "4914": 0.3070250153541565, "4969": 0.08154398202896118, "4975": 0.7800771594047546, "4980": 0.04860413447022438, "5022": 0.5381823778152466, "5068": 0.7370892763137817, "5084": 0.4673144817352295, "5137": 0.07884006202220917, "5139": 0.06612417846918106, "5185": 0.7057625651359558, "5317": 0.5336109399795532, "5345": 0.4067663550376892, "5360": 0.2089812457561493, "5403": 0.1693800985813141, "5443": 0.5816917419433594, "5468": 0.5098485946655273, "5486": 0.1229778528213501, "5619": 0.029824240133166313, "5635": 0.10906458646059036, "5665": 0.2954642176628113, "5729": 0.03831886500120163, "5761": 0.38308101892471313, "5770": 0.32553088665008545, "5776": 0.4920966327190399, "5788": 0.06337817758321762, "5796": 0.3409265875816345, "5845": 0.5618454217910767, "5903": 0.823009729385376, "5920": 0.04113444685935974, "5966": 0.4512746334075928, "5986": 0.1229778528213501, "5989": 0.6070231795310974, "5996": 0.021256839856505394, "6020": 0.040196798741817474, "6022": 0.2689530849456787, "6027": 0.05970508232712746, "6075": 0.11168810725212097, "6120": 0.016465263441205025, "6131": 0.029824240133166313, "6165": 0.08961215615272522, "6168": 0.14349138736724854, "6179": 0.48670899868011475, "6239": 0.27564704418182373, "6365": 0.29473719000816345, "6388": 0.3560888469219208, "6428": 0.07612881064414978, "6431": 0.7172679901123047, "6447": 0.13925230503082275, "6449": 0.015504186972975731, "6463": 0.812664806842804, "6464": 0.19622190296649933, "6504": 0.1994270235300064, "6534": 0.5370414853096008, "6612": 0.2696990668773651, "6648": 0.12814582884311676, "6666": 0.259204238653183, "6677": 0.3784096837043762, "6693": 0.06977381557226181, "6721": 0.7960633039474487, "6747": 0.045809537172317505, "6749": 0.4481603503227234, "6808": 0.7182208299636841, "6818": 0.4914994537830353, "6939": 0.020300358533859253, "7012": 0.8973627090454102, "7017": 0.6430866718292236, "7102": 0.08603433519601822, "7103": 0.5762182474136353, "7153": 0.2223619967699051, "7242": 0.14939609169960022, "7252": 0.839173436164856, "7304": 0.8281423449516296, "7320": 0.26146242022514343, "7355": 0.037378571927547455, "7386": 0.11604541540145874, "7438": 0.5415972471237183, "7524": 0.3423145115375519, "7551": 0.39433568716049194, "7594": 0.2223619967699051, "7613": 0.20102575421333313, "7667": 0.38041436672210693, "7691": 0.5232481360435486, "7711": 0.14686977863311768, "7718": 0.0058422754518687725, "7730": 0.055094651877880096, "7778": 0.2018241584300995, "7831": 0.6441128253936768, "7848": 0.49864232540130615, "7870": 0.021256839856505394, "7885": 0.23247487843036652, "7951": 0.07793712615966797, "8017": 0.3170322775840759, "8079": 0.688742995262146, "8114": 0.0029254043474793434, "8323": 0.151916041970253, "8361": 0.025073638185858727, "8469": 0.10203468054533005, "8564": 0.43244171142578125, "8599": 0.09938567131757736, "8664": 0.2231435477733612, "8729": 0.040196798741817474, "8746": 0.5718178153038025, "8819": 0.11081436276435852, "8878": 1.0621482133865356, "8949": 0.23556606471538544, "9048": 0.3070250153541565, "9063": 0.0009760859538801014, "9141": 0.5534584522247314, "9252": 0.4349733293056488, "9305": 0.04953393340110779, "9367": 0.3127557039260864, "9377": 0.08871890604496002, "9410": 0.8788808584213257, "9526": 0.05970508232712746, "9556": 0.6960725784301758, "9560": 0.8707374930381775, "9587": 0.004870930220931768, "9634": 0.5483922958374023, "9723": 0.17020416259765625, "9728": 0.052318159490823746, "9756": 0.08603433519601822, "9947": 1.1141164302825928, "9969": 0.1510767638683319, "9998": 0.8004589080810547, "10043": 0.02412080205976963, "10058": 0.10993985831737518, "10111": 0.0019512200960889459, "10114": 0.012615402229130268, "10124": 0.23710809648036957, "10174": 0.0174254160374403, "10193": 0.03360854089260101, "10238": 1.02149498462677, "10318": 0.004870930220931768, "10426": 0.7124901413917542, "10572": 0.22782009840011597, "10611": 1.0601204633712769, "10671": 0.0009760859538801014, "10833": 0.46486347913742065, "10847": 0.08154398202896118, "10873": 0.2689530849456787, "11174": 0.009718249551951885, "11219": 0.129004567861557, "11234": 0.7191727757453918, "11343": 0.21922965347766876, "11433": 0.21687394380569458, "11631": 0.7086513638496399, "11656": 0.1229778528213501, "11704": 1.0001721382141113, "11829": 0.053244512528181076, "11890": 0.7018978595733643, "11904": 0.00875066313892603, "11934": 0.03925827145576477, "12005": 0.03360854089260101, "12070": 0.46608972549438477, "12141": 0.11081436276435852, "12243": 1.0960047245025635, "12269": 0.25088030099868774, "12318": 0.15610189735889435, "12353": 0.6244332790374756, "12376": 0.18167030811309814, "12435": 0.37640097737312317, "12596": 0.09938567131757736, "12599": 0.10467668622732162, "12637": 0.15023678541183472, "12654": 0.08064348995685577, "12765": 0.777387797832489, "12826": 0.4330752193927765, "12832": 0.5104349255561829, "12899": 0.25845035910606384, "12941": 0.04207121208310127, "12951": 0.0317181795835495, "12967": 0.21214580535888672, "12980": 0.045809537172317505, "13004": 0.8625272512435913, "13070": 0.17840765416622162, "13105": 0.8100618124008179, "13180": 0.16690383851528168, "13341": 0.00875066313892603, "13356": 1.001607894897461, "13433": 0.26820653676986694, "13441": 0.3956514894962311, "13464": 0.04674193635582924, "13483": 0.7389566898345947, "13599": 0.48068851232528687, "13661": 0.27044451236724854, "13699": 0.5220900774002075, "13749": 0.6118015646934509, "13791": 0.535327672958374, "14025": 0.6568518877029419, "14155": 0.5347557663917542, "14168": 0.9739698171615601, "14171": 0.21922965347766876, "14211": 0.12384103983640671, "14267": 0.1011524572968483, "14358": 0.5127768516540527, "14506": 0.24325250089168549, "14615": 0.12642613053321838, "14667": 0.0038986403960734606, "15017": 0.7028654217720032, "15063": 0.3601844012737274, "15115": 0.09850110858678818, "15170": 0.3084607720375061, "15184": 0.3499138653278351, "15189": 0.07884006202220917, "15306": 0.20739519596099854, "15316": 0.28082266449928284, "15396": 0.06886265426874161, "15432": 0.9798521995544434, "15464": 0.08244366943836212, "15559": 0.007782140281051397, "15589": 0.9363996982574463, "15663": 0.3903779089450836, "15734": 0.4818955361843109, "15743": 0.0058422754518687725, "15779": 0.34715715050697327, "15786": 0.18004031479358673, "15877": 0.0913962796330452, "15946": 0.10379679501056671, "16134": 0.4151833653450012, "16149": 1.1929750442504883, "16159": 0.6043586730957031, "16224": 0.11168810725212097, "16311": 0.056018441915512085, "16330": 0.026025565341114998, "16452": 0.015504186972975731, "16478": 0.04860413447022438, "16483": 0.49626702070236206, "16505": 0.09495500475168228, "16515": 0.026976587250828743, "16666": 0.8212929964065552, "16670": 0.42353010177612305, "16703": 0.4764525294303894, "16710": 1.0312920808792114, "16734": 0.13755162060260773, "16755": 0.5255602598190308, "17062": 0.42096930742263794, "17128": 0.23015019297599792, "17403": 0.1477125883102417, "17441": 0.3443928062915802, "17473": 0.14264501631259918, "17503": 0.33325836062431335, "17603": 0.043007105588912964, "17631": 0.3850763738155365, "17672": 0.4770587682723999, "17696": 0.469759464263916, "17760": 0.3084607720375061, "17826": 0.05139094591140747, "17830": 0.0842406153678894, "17867": 0.0842406153678894, "17908": 0.26820653676986694, "17938": 0.7491656541824341, "17943": 0.8057082891464233, "17944": 0.4337083101272583, "18154": 0.33325836062431335, "18178": 0.151916041970253, "18539": 0.07431721687316895, "18701": 0.08603433519601822, "18872": 1.5365312099456787, "18906": 0.10467668622732162, "18949": 0.436867892742157, "18976": 0.02316705882549286, "19015": 0.2516399025917053, "19037": 0.3499138653278351, "19061": 0.08961215615272522, "19064": 0.2689530849456787, "19132": 0.4286321699619293, "19158": 0.0029254043474793434, "19288": 0.21293537318706512, "19301": 0.02887592278420925, "19353": 0.20739519596099854, "19450": 0.09761575609445572, "19491": 0.3077431619167328, "19510": 1.0855059623718262, "19541": 0.21372433006763458, "19653": 0.21765978634357452, "19711": 0.0354953333735466, "19763": 0.08064348995685577, "19883": 0.21765978634357452, "19966": 0.016465263441205025, "20077": 0.09672962874174118, "20247": 0.38308101892471313, "20272": 0.11256109178066254, "20303": 0.06520967930555344, "20304": 0.11081436276435852, "20372": 0.472198486328125, "20502": 0.21135559678077698, "20544": 0.4132472574710846, "20666": 0.4920966327190399, "20694": 0.3127557039260864, "20739": 0.9139442443847656, "20802": 0.4002431631088257, "20871": 0.3547199070453644, "20900": 0.010684899985790253, "21035": 0.32905077934265137, "21046": 0.23015019297599792, "21081": 0.16524957120418549, "21150": 0.4938860833644867, "21211": 0.11256109178066254, "21249": 0.9294845461845398, "21370": 0.007782140281051397, "21391": 0.23633737862110138, "21486": 0.11343330889940262, "21489": 0.15023678541183472, "21497": 0.1064341589808464, "21656": 0.7389566898345947, "21752": 0.7969439625740051, "21879": 0.5882205963134766, "21967": 0.15860503911972046, "22018": 0.1734936386346817, "22022": 0.21765978634357452, "22025": 0.0752234235405922, "22115": 0.9115922451019287, "22238": 0.2561853528022766, "22275": 0.17840765416622162, "22407": 0.30917787551879883, "22423": 0.8004589080810547, "22533": 0.1710275560617447, "22602": 0.2674594223499298, "22641": 0.9045027494430542, "22684": 0.14686977863311768, "22698": 0.8109301924705505, "22884": 0.18573370575904846, "22932": 0.23710809648036957, "22963": 0.3656192123889923, "22989": 0.07250232994556427, "23086": 0.021256839856505394, "23681": 0.20818853378295898, "23692": 0.026976587250828743, "24081": 0.03831886500120163, "24191": 0.3127557039260864, "24395": 0.17922431230545044, "24594": 0.8135309815406799, "25022": 0.21372433006763458, "25135": 0.0029254043474793434, "25401": 0.0752234235405922, "25478": 0.3777405619621277, "25746": 0.1905880719423294, "25761": 0.10203468054533005, "25775": 0.09850110858678818, "26075": 0.14433705806732178, "26094": 0.026976587250828743, "26163": 0.08782484382390976, "26180": 0.1873544454574585, "26245": 0.417115718126297, "26462": 0.20660123229026794, "26641": 0.3656192123889923, "26702": 0.2223619967699051, "26835": 0.0606246218085289, "26897": 0.083342544734478, "26906": 0.09495500475168228, "26953": 0.010684899985790253, "26976": 0.07250232994556427, "27009": 0.9021284580230713, "27082": 0.08244366943836212, "27144": 0.07431721687316895, "27204": 0.08064348995685577, "27395": 0.03925827145576477, "27536": 0.24631060659885406, "27974": 0.3297532796859741, "27988": 0.18248429894447327, "28093": 0.0029254043474793434, "28332": 0.34300774335861206, "28389": 0.012615402229130268, "28436": 0.020300358533859253, "28817": 0.5893046259880066, "28847": 0.29619070887565613, "29090": 0.5811457633972168, "29215": 0.02412080205976963, "29596": 0.255429208278656} | 12209494 | BACKGROUND The case-fatality for intentional self-poisoning in the rural developing world is 10-50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. METHODS We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. FINDINGS Mortality did not differ between the groups. 97 (6.3%) of 1531 participants in the multiple-dose group died, compared with 105 (6.8%) of 1554 in the no charcoal group (adjusted odds ratio 0.96, 95% CI 0.70-1.33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. INTERPRETATION We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed. | Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial |
{"1011": 0.13499516248703003, "1054": 0.17431432008743286, "2000": 0.034552380442619324, "2003": 0.11430477350950241, "2006": 0.8247235417366028, "2008": 0.07793712615966797, "2011": 0.4487839937210083, "2029": 0.2394166737794876, "2034": 0.01934296265244484, "2044": 0.3910386264324188, "2046": 0.03925827145576477, "2059": 0.3297532796859741, "2060": 0.2983669638633728, "2063": 0.4412745535373688, "2075": 0.0058422754518687725, "2076": 0.24325250089168549, "2077": 0.00875066313892603, "2079": 0.0317181795835495, "2083": 0.23710809648036957, "2109": 0.10731173306703568, "2124": 0.44566190242767334, "2129": 0.23324857652187347, "2135": 0.4624064862728119, "2147": 0.016465263441205025, "2170": 0.10818854719400406, "2186": 0.25995752215385437, "2203": 0.684319257736206, "2206": 0.5427330136299133, "2213": 0.3381449282169342, "2344": 0.055094651877880096, "2389": 0.3127557039260864, "2482": 0.6197150945663452, "2487": 0.6286086440086365, "2491": 0.57457035779953, "2527": 0.22392450273036957, "2550": 0.08244366943836212, "2628": 0.25694093108177185, "2695": 0.9147270321846008, "2754": 0.15860503911972046, "2777": 0.40481385588645935, "2788": 0.2763880789279938, "2794": 0.6123310327529907, "2804": 0.5640701055526733, "2832": 0.7881022095680237, "2863": 0.08513788133859634, "2864": 0.12556517124176025, "2881": 0.41001203656196594, "2895": 0.08603433519601822, "2920": 0.17840765416622162, "2970": 0.15526613593101501, "3123": 0.25088030099868774, "3176": 0.1064341589808464, "3256": 0.3241194784641266, "3357": 0.565735399723053, "3366": 0.7665573358535767, "3370": 0.7863243818283081, "3375": 0.5838727951049805, "3431": 0.12038381397724152, "3466": 0.0029254043474793434, "3526": 0.6441128253936768, "3582": 0.015504186972975731, "3593": 0.7314660549163818, "3597": 0.8450632095336914, "3619": 0.31132611632347107, "3625": 0.09584271162748337, "3630": 0.5925496220588684, "3653": 1.1160377264022827, "3670": 0.13157635927200317, "3695": 0.04860413447022438, "3723": 0.02316705882549286, "3796": 0.0058422754518687725, "3921": 0.472198486328125, "3930": 0.1889725625514984, "3935": 0.32270604372024536, "3949": 0.17267228662967682, "3979": 0.09761575609445572, "3989": 0.0354953333735466, "4013": 0.678885817527771, "4076": 0.18492233753204346, "4084": 0.6461620330810547, "4118": 0.08154398202896118, "4310": 0.5947071313858032, "4319": 0.21687394380569458, "4383": 0.09672962874174118, "4403": 0.22782009840011597, "4442": 0.5827828645706177, "4456": 1.1121915578842163, "4539": 0.757441520690918, "4588": 0.43875885009765625, "4621": 0.1994270235300064, "4668": 0.29400965571403503, "4710": 0.12038381397724152, "4758": 0.5472630262374878, "4890": 1.2204381227493286, "4937": 0.5450005531311035, "4962": 0.524982750415802, "4987": 0.0770333781838417, "5072": 0.09317722171545029, "5158": 0.2800849378108978, "5244": 0.0606246218085289, "5250": 1.0973093509674072, "5258": 0.15943801403045654, "5402": 0.021256839856505394, "5421": 0.07884006202220917, "5423": 1.0601204633712769, "5449": 0.996573805809021, "5537": 0.045809537172317505, "5587": 0.28670501708984375, "5711": 0.26146242022514343, "5735": 0.3554046154022217, "5740": 0.13243216276168823, "5815": 0.39367714524269104, "5850": 0.46363574266433716, "6028": 0.07612881064414978, "6064": 0.3676496744155884, "6074": 0.00875066313892603, "6194": 0.46117570996284485, "6204": 0.02316705882549286, "6310": 0.6813592314720154, "6364": 0.8349450826644897, "6433": 0.23787821829319, "6494": 0.6793810129165649, "6612": 0.20580662786960602, "6761": 0.06612417846918106, "6914": 0.5209306478500366, "6924": 0.2763880789279938, "7012": 0.259204238653183, "7065": 0.026976587250828743, "7148": 0.058784693479537964, "7242": 0.4431571960449219, "7336": 0.13157635927200317, "7337": 0.4349733293056488, "7361": 0.6533012986183167, "7366": 0.27342069149017334, "7403": 0.3526630103588104, "7531": 0.7592713832855225, "7709": 0.25995752215385437, "7711": 0.5438674688339233, "7889": 0.6212902665138245, "8018": 0.26446542143821716, "8107": 0.32270604372024536, "8171": 1.0894558429718018, "8180": 0.05417001247406006, "8466": 0.14095009863376617, "8516": 0.4974553883075714, "8552": 0.1873544454574585, "8602": 0.1510767638683319, "8758": 0.8255793452262878, "8776": 0.436867892742157, "8778": 0.18573370575904846, "8780": 0.7038320899009705, "8853": 0.025073638185858727, "8878": 0.1718502640724182, "9007": 0.9425065517425537, "9096": 0.10467668622732162, "9099": 0.5045560002326965, "9165": 0.10731173306703568, "9253": 0.037378571927547455, "9276": 0.272677481174469, "9323": 0.09672962874174118, "9416": 0.5267143249511719, "9508": 0.11168810725212097, "9513": 0.31845372915267944, "9556": 0.07431721687316895, "9597": 0.33325836062431335, "9601": 0.5865923762321472, "9756": 0.3676496744155884, "9821": 0.5324648022651672, "9909": 0.15860503911972046, "10234": 0.05694137513637543, "10572": 0.2637155055999756, "10595": 0.06520967930555344, "10708": 0.38441169261932373, "10752": 0.014542185701429844, "10803": 0.2223619967699051, "10838": 0.11951763927936554, "10958": 0.026976587250828743, "11022": 0.38441169261932373, "11163": 0.8298473954200745, "11233": 0.04394211992621422, "11477": 0.27934664487838745, "11598": 0.014542185701429844, "12222": 0.07341018319129944, "12335": 0.09761575609445572, "12353": 0.12642613053321838, "12359": 0.0174254160374403, "12377": 0.5313173532485962, "12562": 0.16276304423809052, "12644": 0.15860503911972046, "12649": 0.10203468054533005, "12667": 0.10203468054533005, "12719": 0.9100211262702942, "12732": 0.32129061222076416, "12889": 0.0317181795835495, "12987": 0.3127557039260864, "13046": 0.1477125883102417, "13134": 0.04674193635582924, "13186": 0.02792670577764511, "13330": 0.22392450273036957, "13490": 1.1350497007369995, "13532": 0.24171993136405945, "13595": 0.9739698171615601, "13656": 0.4794800877571106, "13685": 0.2394166737794876, "13776": 0.45499902963638306, "13791": 0.2763880789279938, "13806": 0.15359249711036682, "13922": 0.12642613053321838, "13995": 0.846739649772644, "14080": 0.9531047344207764, "14126": 0.4196864068508148, "14193": 0.3784096837043762, "14255": 0.22001366317272186, "14613": 0.034552380442619324, "14667": 0.15442965924739838, "14910": 0.08692999184131622, "14956": 0.23015019297599792, "14996": 0.4412745535373688, "15007": 0.07793712615966797, "15053": 0.16524957120418549, "15115": 0.010684899985790253, "15460": 0.08603433519601822, "15472": 0.5822374224662781, "15527": 0.13670019805431366, "15543": 0.15275461971759796, "15547": 0.052318159490823746, "15663": 0.21530038118362427, "15869": 0.05046287178993225, "15928": 0.11430477350950241, "15946": 0.07068414986133575, "16007": 0.3560888469219208, "16012": 0.0797421783208847, "16081": 0.018384648486971855, "16221": 0.3297532796859741, "16285": 0.5816917419433594, "16305": 0.2881702482700348, "16505": 1.0546929836273193, "16627": 0.28082266449928284, "16690": 0.030771657824516296, "16705": 0.2394166737794876, "16715": 0.1401015669107437, "16771": 0.5696102976799011, "16910": 0.1994270235300064, "16924": 0.010684899985790253, "17083": 0.16110190749168396, "17215": 0.4349733293056488, "17261": 0.07250232994556427, "17379": 0.3883931338787079, "17463": 0.4158279001712799, "17820": 0.77198725938797, "17890": 0.7201237678527832, "18072": 0.49686139822006226, "18089": 0.1332872211933136, "18136": 0.1930064558982849, "18178": 0.38041436672210693, "18260": 0.2830325961112976, "18639": 0.0019512200960889459, "18647": 0.03831886500120163, "18804": 0.07159364968538284, "19101": 0.05970508232712746, "19345": 0.09317722171545029, "19601": 0.06154331564903259, "19653": 0.3005385100841522, "19824": 0.347847044467926, "19872": 0.129004567861557, "19933": 0.31204116344451904, "20250": 1.0688776969909668, "20492": 1.498855471611023, "20544": 0.1718502640724182, "20710": 1.6685909032821655, "20752": 0.0913962796330452, "20766": 0.9013357162475586, "20817": 0.16110190749168396, "20992": 0.09317722171545029, "20996": 0.1384023278951645, "21081": 0.45499902963638306, "21114": 0.029824240133166313, "21150": 0.46608972549438477, "21230": 0.2637155055999756, "21371": 0.0317181795835495, "21434": 0.3601844012737274, "21709": 0.8583967685699463, "21752": 0.0019512200960889459, "21891": 0.23402166366577148, "21903": 0.6317287683486938, "22026": 0.09584271162748337, "22110": 0.9302552938461304, "22248": 0.3622259199619293, "22422": 0.14179791510105133, "22476": 0.011650617234408855, "22684": 0.08603433519601822, "22698": 0.10026945173740387, "22731": 0.12642613053321838, "22916": 0.13157635927200317, "22931": 0.05139094591140747, "23150": 0.08961215615272522, "23339": 0.021256839856505394, "23468": 0.04394211992621422, "23572": 0.27342069149017334, "23586": 0.8559102416038513, "23713": 0.03360854089260101, "23737": 0.5936289429664612, "23924": 0.24248650670051575, "23943": 0.11256109178066254, "24054": 1.0695481300354004, "24278": 0.5607312321662903, "24388": 0.02887592278420925, "24576": 0.18411032855510712, "24582": 1.2510874271392822, "24793": 0.055094651877880096, "25003": 1.3222765922546387, "25015": 0.08961215615272522, "25117": 0.0009760859538801014, "25175": 0.013579257763922215, "25409": 0.6533012986183167, "25456": 1.0735615491867065, "25468": 0.1889725625514984, "25690": 0.09584271162748337, "25761": 0.15860503911972046, "26014": 0.13499516248703003, "26244": 0.6075552701950073, "26402": 0.7352184057235718, "26512": 0.022212404757738113, "26520": 0.22626367211341858, "26563": 0.30917787551879883, "26616": 0.40481385588645935, "26652": 0.08871890604496002, "26709": 0.021256839856505394, "26786": 0.1401015669107437, "26927": 0.09584271162748337, "27058": 1.151856780052185, "27099": 0.045809537172317505, "27144": 0.35745587944984436, "27268": 0.6446255445480347, "27605": 0.08692999184131622, "27651": 0.18004031479358673, "27709": 1.0519683361053467, "27833": 0.03266380727291107, "28139": 1.1018621921539307, "28144": 0.255429208278656, "28835": 0.1677299439907074, "29129": 0.7978238463401794, "29226": 0.39367714524269104} | 12217662 | RAS and many other oncogenic proteins undergo a complex series of post-translational modifications that are initiated by the addition of an isoprenoid lipid through a process known as prenylation. Following prenylation, these proteins usually undergo endoproteolytic processing by the RCE1 protease and then carboxyl methylation by a unique methyltransferase known as isoprenylcysteine carboxyl methyltransferase (ICMT). Although inhibitors that have been designed to target the prenylation step are now in advanced-stage clinical trials, their utility and efficacy seem to be limited. Recent findings, however, indicate that the inhibition of these post-prenylation-processing steps — particularly that of ICMT-catalysed methylation — might provide a better approach to the control of cancer-cell proliferation. | Post-prenylation-processing enzymes as new targets in oncogenesis |
{"1014": 0.0174254160374403, "1038": 0.306306391954422, "1040": 0.20818853378295898, "1055": 0.09406650811433792, "1057": 0.11517547070980072, "1061": 0.1808556467294693, "1081": 0.6374238729476929, "2003": 0.02316705882549286, "2043": 0.04767346754670143, "2091": 0.08154398202896118, "2095": 0.07341018319129944, "2109": 0.0019512200960889459, "2111": 0.06429435312747955, "2116": 0.2089812457561493, "2137": 0.129004567861557, "2142": 0.562402069568634, "2149": 0.4419025182723999, "2154": 0.3683255612850189, "2163": 0.14602625370025635, "2169": 0.06246116757392883, "2172": 0.4349733293056488, "2188": 0.20102575421333313, "2224": 0.11691460013389587, "2230": 0.38174858689308167, "2268": 0.3381449282169342, "2287": 0.6813592314720154, "2313": 0.47827014327049255, "2323": 0.14939609169960022, "2336": 0.06337817758321762, "2339": 0.10203468054533005, "2402": 0.20977331697940826, "2421": 0.18816383183002472, "2426": 0.2447827309370041, "2443": 0.35677260160446167, "2456": 0.512191891670227, "2470": 0.19782574474811554, "2482": 0.03266380727291107, "2497": 1.1671710014343262, "2560": 0.4349733293056488, "2566": 0.32129061222076416, "2591": 0.15526613593101501, "2604": 0.14264501631259918, "2625": 0.28743788599967957, "2637": 0.03360854089260101, "2639": 0.7845434546470642, "2640": 0.32199856638908386, "2641": 0.06154331564903259, "2659": 0.14518201351165771, "2740": 0.5324648022651672, "2779": 0.306306391954422, "2817": 0.4132472574710846, "2833": 0.3601844012737274, "2846": 0.08244366943836212, "2896": 0.26296505331993103, "2913": 0.3262358605861664, "2933": 0.07884006202220917, "2943": 0.7701805830001831, "2951": 0.08692999184131622, "2998": 0.6064908504486084, "3026": 0.09406650811433792, "3036": 0.2969166338443756, "3125": 0.10203468054533005, "3256": 0.11778303235769272, "3273": 0.11865071207284927, "3279": 0.24631060659885406, "3289": 0.09317722171545029, "3360": 0.9500881433486938, "3366": 0.5756692886352539, "3378": 0.44691193103790283, "3429": 0.055094651877880096, "3446": 0.04953393340110779, "3455": 0.05139094591140747, "3463": 0.24018502235412598, "3465": 0.04953393340110779, "3529": 0.18816383183002472, "3576": 0.12038381397724152, "3594": 0.004870930220931768, "3643": 0.129004567861557, "3676": 0.32129061222076416, "3679": 0.6456501483917236, "3762": 0.08603433519601822, "3815": 0.20580662786960602, "3867": 0.2561853528022766, "3915": 0.32270604372024536, "4081": 0.15693697333335876, "4086": 0.9769153594970703, "4102": 0.2689530849456787, "4106": 0.2822965085506439, "4146": 0.0019512200960889459, "4157": 0.8065804839134216, "4268": 0.18816383183002472, "4281": 0.9739698171615601, "4358": 0.011650617234408855, "4359": 0.5579402446746826, "4368": 0.46302130818367004, "4387": 0.4330752193927765, "4392": 0.7934166193008423, "4398": 0.0009760859538801014, "4521": 0.25694093108177185, "4530": 0.09495500475168228, "4539": 0.029824240133166313, "4639": 0.6902132034301758, "4712": 0.0038986403960734606, "4793": 0.1913948506116867, "4841": 0.35128939151763916, "5092": 0.6043586730957031, "5159": 0.27044451236724854, "5171": 0.08603433519601822, "5201": 0.053244512528181076, "5247": 0.09584271162748337, "5300": 0.0038986403960734606, "5326": 0.36494144797325134, "5418": 0.26296505331993103, "5468": 0.11430477350950241, "5531": 0.0354953333735466, "5547": 0.8247235417366028, "5572": 0.6679295301437378, "5656": 0.7463917136192322, "5699": 1.2710106372833252, "5761": 0.02316705882549286, "5909": 0.5021947622299194, "5910": 1.1153976917266846, "5938": 0.13499516248703003, "5948": 0.5478278398513794, "5983": 0.3027053773403168, "6001": 0.8433839678764343, "6143": 0.23247487843036652, "6273": 0.3127557039260864, "6463": 0.11081436276435852, "6501": 0.06795065850019455, "6544": 0.1930064558982849, "6587": 0.04674193635582924, "6675": 0.9515975713729858, "6689": 0.371698260307312, "6691": 0.14686977863311768, "6747": 0.12642613053321838, "6749": 0.6075552701950073, "6818": 0.05139094591140747, "7017": 0.45623743534088135, "7020": 1.4236729145050049, "7060": 0.3923587501049042, "7080": 0.11951763927936554, "7091": 0.3241194784641266, "7096": 0.009718249551951885, "7099": 0.3982778787612915, "7231": 0.812664806842804, "7312": 0.7610978484153748, "7325": 0.07250232994556427, "7367": 0.5162794589996338, "7383": 0.8195732831954956, "7406": 0.15777134895324707, "7419": 0.043007105588912964, "7551": 0.04953393340110779, "7668": 0.2696990668773651, "7686": 0.02316705882549286, "7694": 0.12470348179340363, "7831": 0.2837681770324707, "7863": 0.9798521995544434, "7954": 0.43623676896095276, "7959": 0.12814582884311676, "7965": 0.5438674688339233, "8156": 0.07431721687316895, "8161": 0.9209672808647156, "8168": 0.24018502235412598, "8192": 0.6000806093215942, "8247": 0.0913962796330452, "8339": 0.16110190749168396, "8381": 1.1437997817993164, "8491": 0.2026219218969345, "8738": 0.5495203733444214, "8828": 0.16359257698059082, "8974": 0.7352184057235718, "9002": 0.07159364968538284, "9035": 0.24401791393756866, "9053": 0.012615402229130268, "9084": 0.013579257763922215, "9131": 0.9363996982574463, "9232": 0.13071982562541962, "9367": 0.26296505331993103, "9383": 0.17922431230545044, "9440": 0.4400174915790558, "9454": 0.2749055027961731, "9458": 0.43434104323387146, "9556": 0.08603433519601822, "9566": 0.10467668622732162, "9582": 0.3353555500507355, "9614": 0.053244512528181076, "9648": 0.04674193635582924, "9750": 0.0009760859538801014, "9818": 0.272677481174469, "9874": 0.8731874823570251, "9885": 0.7647408246994019, "9942": 0.6064908504486084, "9992": 0.10467668622732162, "10035": 0.016465263441205025, "10126": 0.07341018319129944, "10174": 0.1011524572968483, "10199": 0.18978065252304077, "10202": 0.8885661959648132, "10250": 0.791648268699646, "10322": 0.4093637466430664, "10390": 0.1011524572968483, "10426": 0.5433003902435303, "10427": 0.026976587250828743, "10548": 0.5232481360435486, "10563": 0.22937409579753876, "10754": 0.045809537172317505, "10962": 0.20660123229026794, "11100": 0.672426164150238, "11382": 0.05694137513637543, "11433": 0.43053874373435974, "11594": 0.03360854089260101, "11703": 0.10467668622732162, "11709": 0.036437395960092545, "11799": 0.11517547070980072, "12278": 0.16276304423809052, "12353": 0.009718249551951885, "12520": 0.18167030811309814, "12832": 0.48670899868011475, "12878": 0.8161250352859497, "12908": 0.3374483287334442, "13105": 0.009718249551951885, "13416": 0.4286321699619293, "13496": 0.371698260307312, "13592": 0.09317722171545029, "13751": 0.07884006202220917, "13822": 0.812664806842804, "13845": 0.4067663550376892, "13993": 0.006812678650021553, "14075": 0.11951763927936554, "14168": 0.2674594223499298, "14243": 0.07884006202220917, "14266": 0.36086538434028625, "14492": 0.2160874605178833, "14506": 0.37707099318504333, "14671": 0.4487839937210083, "14879": 0.4158279001712799, "14904": 1.0001721382141113, "15077": 0.4556184411048889, "15170": 0.013579257763922215, "15185": 0.07612881064414978, "15270": 0.32129061222076416, "15306": 0.2145126610994339, "15349": 0.06977381557226181, "15406": 0.06337817758321762, "15451": 0.012615402229130268, "15502": 0.5393219590187073, "15558": 0.31132611632347107, "15683": 0.20580662786960602, "15878": 0.09761575609445572, "15995": 0.1229778528213501, "16429": 0.16442140936851501, "16452": 0.02792670577764511, "16578": 0.00875066313892603, "16678": 0.7995813488960266, "16755": 0.17759032547473907, "16922": 0.2652147710323334, "17722": 0.8039615154266357, "17913": 0.49030399322509766, "18423": 0.472198486328125, "18478": 0.08154398202896118, "18699": 0.5979346632957458, "18909": 0.966567873954773, "19037": 0.1710275560617447, "19279": 0.3464667797088623, "19634": 0.4437839686870575, "19645": 0.861702561378479, "19736": 0.18329764902591705, "19782": 0.5925496220588684, "19892": 0.2160874605178833, "20274": 0.1751343309879303, "20372": 0.1358480453491211, "20850": 0.007782140281051397, "21117": 0.8567397594451904, "21195": 0.417115718126297, "21447": 0.13925230503082275, "21705": 0.6649205088615417, "22214": 0.255429208278656, "23210": 0.08961215615272522, "23353": 0.42735910415649414, "23444": 0.6568518877029419, "23900": 0.03360854089260101, "24454": 0.3743882179260254, "24552": 0.0009760859538801014, "24689": 0.29255300760269165, "25006": 0.4920966327190399, "25604": 0.2105647772550583, "25947": 0.10555581003427505, "26163": 0.31845372915267944, "26780": 0.03266380727291107, "26844": 0.3824150264263153, "26866": 0.05417001247406006, "27102": 0.2969166338443756, "27197": 0.4980490207672119, "27237": 0.04113444685935974, "27421": 0.12642613053321838, "27773": 0.12642613053321838, "27962": 0.5127768516540527, "28268": 0.23710809648036957, "28591": 0.26146242022514343, "28910": 0.058784693479537964, "29292": 0.15275461971759796} | 12224536 | BACKGROUND Reducing sugar-sweetened beverage (SSB) consumption is a recommended strategy to promote optimal health. OBJECTIVE The objective was to describe trends in SSB consumption among youth and adults in the United States. DESIGN We analyzed energy intake from SSBs among 22,367 youth aged 2-19 y and 29,133 adults aged ≥20 y who participated in a 24-h dietary recall as part of NHANES, a nationally representative sample of the US population with a cross-sectional design, between 1999 and 2010. SSBs included soda, fruit drinks, sports and energy drinks, sweetened coffee and tea, and other sweetened beverages. Patterns of SSB consumption, including location of consumption and meal occasion associated with consumption, were also examined. RESULTS In 2009-2010, youth consumed a mean (±SE) of 155 ± 7 kcal/d from SSBs, and adults consumed an age-adjusted mean (±SE) of 151 ± 5 kcal/d from SSBs--a decrease from 1999 to 2000 of 68 kcal/d and 45 kcal/d, respectively (P-trend < 0.001 for each). In 2009-2010, SSBs contributed 8.0% ± 0.4% and 6.9% ± 0.2% of daily energy intake among youth and adults, respectively, which reflected a decrease compared with 1999-2000 (P-trend < 0.001 for both). Decreases in SSB consumption, both in the home and away from home and also with both meals and snacks, occurred over the 12-y study duration (P-trend < 0.01 for each). CONCLUSION A decrease in SSB consumption among youth and adults in the United States was observed between 1999 and 2010. | Trends in sugar-sweetened beverage consumption among youth and adults in the United States: 1999-2010. |
{"1011": 0.14095009863376617, "1015": 0.17020416259765625, "1017": 0.5313173532485962, "1041": 1.0855059623718262, "1043": 0.2478361576795578, "1045": 0.535327672958374, "1048": 0.5080875158309937, "1049": 0.6223390698432922, "1050": 0.2607102394104004, "1057": 1.105748176574707, "1996": 0.058784693479537964, "1997": 0.04113444685935974, "1998": 0.18004031479358673, "1999": 0.08064348995685577, "2005": 0.15023678541183472, "2006": 0.05417001247406006, "2007": 0.1602703034877777, "2008": 0.09672962874174118, "2010": 0.5635144114494324, "2011": 0.417115718126297, "2014": 0.8332487344741821, "2029": 0.3930181860923767, "2048": 0.1930064558982849, "2063": 0.12470348179340363, "2064": 0.13499516248703003, "2076": 0.15442965924739838, "2079": 0.16359257698059082, "2090": 0.27044451236724854, "2091": 0.20739519596099854, "2093": 0.38041436672210693, "2118": 0.15359249711036682, "2135": 0.3615458607673645, "2140": 0.1064341589808464, "2179": 0.25088030099868774, "2197": 0.6634125709533691, "2203": 0.4914994537830353, "2309": 0.31845372915267944, "2345": 0.43875885009765625, "2350": 0.18978065252304077, "2353": 0.1212492436170578, "2433": 0.06977381557226181, "2465": 0.5596157908439636, "2475": 0.5381823778152466, "2487": 0.7295845746994019, "2491": 0.6149744987487793, "2497": 0.10731173306703568, "2509": 1.0312920808792114, "2515": 0.15860503911972046, "2523": 0.40285754203796387, "2535": 0.21922965347766876, "2556": 0.1808556467294693, "2615": 0.0009760859538801014, "2618": 0.0770333781838417, "2633": 0.0019512200960889459, "2719": 0.0029254043474793434, "2734": 0.043007105588912964, "2754": 0.129004567861557, "2777": 0.05694137513637543, "2800": 0.12986256182193756, "2828": 0.6139179468154907, "2832": 0.13925230503082275, "2865": 0.5427330136299133, "2920": 0.28155985474586487, "2947": 0.0752234235405922, "3012": 0.3930181860923767, "3064": 0.8869584798812866, "3161": 0.08244366943836212, "3170": 0.535327672958374, "3223": 0.4151833653450012, "3229": 0.0009760859538801014, "3239": 0.15023678541183472, "3252": 0.23402166366577148, "3357": 0.4734157919883728, "3366": 0.5255602598190308, "3370": 0.3005385100841522, "3375": 0.6911921501159668, "3378": 0.6086184978485107, "3397": 0.034552380442619324, "3406": 0.638455867767334, "3433": 0.06886265426874161, "3436": 0.06246116757392883, "3468": 0.19622190296649933, "3487": 0.1212492436170578, "3508": 0.9409833550453186, "3523": 0.12384103983640671, "3526": 0.5584990978240967, "3550": 0.015504186972975731, "3563": 0.7951818704605103, "3596": 0.15610189735889435, "3603": 0.06337817758321762, "3625": 0.8845420479774475, "3670": 0.22001366317272186, "3723": 0.06246116757392883, "3739": 0.5307431221008301, "3755": 0.401551216840744, "3768": 0.2516399025917053, "3802": 0.0770333781838417, "3853": 0.5640701055526733, "3989": 0.6006163358688354, "4072": 0.083342544734478, "4084": 0.5162794589996338, "4127": 0.46302130818367004, "4130": 0.07793712615966797, "4160": 0.2231435477733612, "4195": 0.5517725944519043, "4280": 0.29473719000816345, "4371": 0.175953671336174, "4395": 0.006812678650021553, "4432": 0.10993985831737518, "4442": 0.33115679025650024, "4539": 0.09406650811433792, "4668": 0.2317005842924118, "4722": 0.30558720231056213, "4745": 0.11865071207284927, "4758": 0.5925496220588684, "4816": 0.1734936386346817, "4820": 0.4002431631088257, "4937": 0.3005385100841522, "4962": 0.5255602598190308, "4972": 0.4624064862728119, "5041": 0.41195443272590637, "5051": 0.26446542143821716, "5070": 1.061472773551941, "5072": 0.06703783571720123, "5106": 0.026976587250828743, "5158": 0.5104349255561829, "5178": 0.4518963396549225, "5228": 0.045809537172317505, "5250": 0.6527929902076721, "5258": 0.6160298585891724, "5332": 0.7144040465354919, "5383": 0.09938567131757736, "5402": 0.06154331564903259, "5416": 0.8550800085067749, "5422": 0.129004567861557, "5449": 0.5151132941246033, "5478": 0.25467249751091003, "5536": 0.37102460861206055, "5537": 0.0038986403960734606, "5638": 0.8941729068756104, "5666": 0.791648268699646, "5711": 0.30558720231056213, "5725": 0.9131608605384827, "5884": 0.8957691192626953, "5942": 0.2447827309370041, "6064": 0.4132472574710846, "6178": 0.1718502640724182, "6648": 0.06154331564903259, "6761": 0.9317949414253235, "6873": 0.7076893448829651, "6897": 0.030771657824516296, "7274": 0.9864287376403809, "7337": 0.4450363218784332, "7342": 0.9754437208175659, "7356": 0.036437395960092545, "7366": 0.38574060797691345, "7559": 0.10291612148284912, "7591": 0.8298473954200745, "7629": 0.9546096324920654, "7645": 0.05694137513637543, "7711": 0.848413348197937, "7712": 0.3084607720375061, "7783": 0.20501139760017395, "7801": 0.7863243818283081, "7816": 0.678885817527771, "7865": 0.6522845029830933, "7976": 0.6649205088615417, "8010": 0.2470736801624298, "8018": 1.420846700668335, "8171": 0.7047978043556213, "8247": 0.8699195384979248, "8290": 0.08513788133859634, "8360": 0.14939609169960022, "8523": 1.0001721382141113, "8553": 0.8143964409828186, "8583": 0.2576959431171417, "8602": 0.9915141463279724, "8621": 0.2531573474407196, "8924": 0.18248429894447327, "9006": 0.7436100244522095, "9007": 1.2742929458618164, "9096": 0.4770587682723999, "9165": 0.25088030099868774, "9232": 0.2105647772550583, "9276": 0.19782574474811554, "9285": 0.4425300657749176, "9547": 0.7818660736083984, "9597": 0.2231435477733612, "9686": 0.1332872211933136, "9700": 0.10379679501056671, "9756": 0.31489628553390503, "10066": 0.083342544734478, "10085": 0.5197699069976807, "10196": 0.2501201331615448, "10210": 0.0752234235405922, "10266": 0.02887592278420925, "10322": 0.037378571927547455, "10374": 0.8383291959762573, "10509": 0.07250232994556427, "10556": 0.7380234599113464, "10586": 0.4487839937210083, "10595": 0.0913962796330452, "10737": 0.7665573358535767, "10738": 0.38905516266822815, "10803": 0.2576959431171417, "11022": 0.4349733293056488, "11031": 0.6553317308425903, "11158": 0.6769026517868042, "11163": 0.6573580503463745, "11254": 0.0913962796330452, "11343": 0.2576959431171417, "11486": 0.1064341589808464, "11835": 0.09228714555501938, "12222": 0.8306987881660461, "12322": 0.11951763927936554, "12359": 0.6212902665138245, "12519": 0.1510767638683319, "12562": 0.6218147873878479, "12649": 0.14095009863376617, "12732": 0.9531047344207764, "12987": 0.5116065740585327, "13096": 0.11865071207284927, "13100": 0.7038320899009705, "13248": 0.021256839856505394, "13434": 0.39762192964553833, "13463": 0.011650617234408855, "13490": 0.1619328260421753, "13592": 0.056018441915512085, "13595": 0.02316705882549286, "13770": 1.2238903045654297, "13791": 0.15442965924739838, "13833": 0.15359249711036682, "13876": 0.4349733293056488, "13922": 0.755608320236206, "14087": 0.3588210940361023, "14193": 0.5156965255737305, "14399": 0.75193190574646, "14578": 0.02792670577764511, "14621": 0.14264501631259918, "14639": 0.619189441204071, "14719": 1.5092722177505493, "14925": 0.04113444685935974, "15148": 0.02887592278420925, "15176": 0.5295937061309814, "15420": 0.32905077934265137, "15431": 0.07159364968538284, "15527": 0.053244512528181076, "15543": 0.036437395960092545, "15549": 1.20884370803833, "15778": 0.14179791510105133, "16211": 0.06520967930555344, "16221": 0.08871890604496002, "16257": 1.0361549854278564, "16285": 1.20884370803833, "16305": 1.1720224618911743, "16567": 0.8829278349876404, "16627": 0.5860490798950195, "16690": 0.1994270235300064, "16771": 0.46117570996284485, "16910": 0.7389566898345947, "16950": 0.08692999184131622, "17181": 0.18492233753204346, "17250": 0.02412080205976963, "17338": 0.2822965085506439, "17379": 0.05046287178993225, "17448": 0.6022219061851501, "17695": 0.7592713832855225, "17785": 0.1734936386346817, "18062": 0.14264501631259918, "18191": 0.4974553883075714, "18260": 0.2247048318386078, "18477": 0.22079704701900482, "18906": 0.6394867897033691, "18924": 0.14433705806732178, "19312": 0.0770333781838417, "19386": 0.01934296265244484, "19601": 0.0842406153678894, "19653": 0.13670019805431366, "19696": 0.06520967930555344, "19872": 0.2918238639831543, "19882": 0.5696102976799011, "20544": 0.03360854089260101, "20766": 0.890972912311554, "20817": 0.12642613053321838, "20886": 0.12642613053321838, "20904": 0.28450319170951843, "21114": 0.06337817758321762, "21442": 0.7791815400123596, "21575": 0.2689530849456787, "21618": 0.3683255612850189, "21647": 0.17020416259765625, "21755": 0.8315495252609253, "21903": 0.28890204429626465, "22123": 0.5925496220588684, "22311": 0.14264501631259918, "22318": 0.06337817758321762, "22330": 0.6553317308425903, "22644": 0.8195732831954956, "22731": 0.21372433006763458, "23079": 0.040196798741817474, "23350": 0.7333439588546753, "23586": 0.14433705806732178, "23661": 0.04394211992621422, "23725": 0.8195732831954956, "23737": 0.053244512528181076, "24054": 0.255429208278656, "24093": 0.2089812457561493, "24137": 0.1710275560617447, "24169": 0.05694137513637543, "24170": 0.08961215615272522, "24284": 0.14939609169960022, "24312": 0.06977381557226181, "24768": 0.6759096384048462, "24848": 0.040196798741817474, "24952": 0.8057082891464233, "25002": 0.10906458646059036, "25194": 0.01934296265244484, "25423": 0.31560876965522766, "25456": 0.03360854089260101, "25525": 0.14602625370025635, "25644": 0.10993985831737518, "25690": 0.4568560719490051, "26013": 0.1718502640724182, "26089": 0.045809537172317505, "26127": 0.016465263441205025, "26131": 0.7163142561912537, "26244": 0.4556184411048889, "26394": 0.33953672647476196, "26402": 0.2969166338443756, "26520": 0.18816383183002472, "26651": 0.10993985831737518, "26721": 0.77198725938797, "26773": 0.6420594453811646, "27321": 0.24859806895256042, "27571": 0.07884006202220917, "28389": 0.02887592278420925, "28691": 0.3283478021621704, "28835": 0.13243216276168823, "28940": 0.2674594223499298, "29320": 0.28890204429626465} | 12225214 | Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminus of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases encoded by Kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompatibility complex class I (MHC I) molecules and subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down-regulation of MHC I molecules lacking lysine residues in their intracytoplasmic domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and their association with ubiquitin was sensitive to beta2-mercaptoethanol, unlike lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a single cysteine residue in an artificial glycine and alanine intracytoplasmic domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination can occur on proteins lacking accessible lysines or an accessible N terminus. | Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase. |
{"1011": 0.13414156436920166, "1043": 0.029824240133166313, "1060": 0.07793712615966797, "1062": 1.2047537565231323, "2006": 0.23092569410800934, "2011": 0.5712664127349854, "2025": 0.0038986403960734606, "2051": 0.16110190749168396, "2061": 0.34370049834251404, "2064": 0.21922965347766876, "2070": 0.11081436276435852, "2075": 0.21922965347766876, "2076": 0.41195443272590637, "2089": 0.20022670924663544, "2090": 0.49626702070236206, "2098": 0.056018441915512085, "2106": 0.12470348179340363, "2109": 0.19622190296649933, "2129": 0.26446542143821716, "2158": 0.3554046154022217, "2166": 0.5795059204101562, "2175": 0.7800771594047546, "2179": 0.1710275560617447, "2235": 0.3191637098789215, "2247": 0.32058215141296387, "2248": 0.2026219218969345, "2273": 0.319873183965683, "2308": 0.2089812457561493, "2334": 0.07612881064414978, "2335": 0.0029254043474793434, "2339": 0.41840189695358276, "2348": 0.1602703034877777, "2389": 0.4248080551624298, "2391": 0.23556606471538544, "2426": 0.11430477350950241, "2427": 0.13414156436920166, "2445": 0.46670228242874146, "2450": 0.1358480453491211, "2470": 0.0752234235405922, "2480": 0.4879087805747986, "2491": 0.07250232994556427, "2504": 0.5495203733444214, "2512": 0.05046287178993225, "2515": 0.2447827309370041, "2535": 0.004870930220931768, "2560": 0.15693697333335876, "2566": 0.15860503911972046, "2579": 0.10555581003427505, "2590": 0.13071982562541962, "2611": 0.13925230503082275, "2625": 0.19622190296649933, "2689": 0.23247487843036652, "2750": 0.28450319170951843, "2779": 0.3723714053630829, "2825": 0.08244366943836212, "2828": 0.23556606471538544, "2879": 0.2317005842924118, "2897": 0.29109421372413635, "2904": 0.029824240133166313, "2922": 0.4932899475097656, "2931": 0.7482418417930603, "2937": 0.7370892763137817, "3057": 0.18654440343379974, "3064": 0.018384648486971855, "3265": 0.24631060659885406, "3273": 0.24631060659885406, "3287": 0.8315495252609253, "3294": 0.20580662786960602, "3337": 0.18167030811309814, "3348": 0.9915141463279724, "3350": 0.13071982562541962, "3399": 0.026976587250828743, "3431": 0.12986256182193756, "3452": 0.672426164150238, "3466": 0.6699305176734924, "3477": 0.3163207769393921, "3599": 0.030771657824516296, "3603": 0.6497380137443542, "3618": 0.1477125883102417, "3670": 0.9333322048187256, "3745": 0.004870930220931768, "3747": 0.28963330388069153, "3760": 0.21765978634357452, "3767": 0.8788808584213257, "3768": 0.8013357520103455, "3775": 0.10818854719400406, "3795": 1.0144377946853638, "3798": 0.4879087805747986, "3801": 0.8957691192626953, "3825": 0.29255300760269165, "3853": 0.2247048318386078, "3896": 0.6327666640281677, "4012": 0.500420093536377, "4072": 0.009718249551951885, "4081": 0.4831010699272156, "4111": 0.49982786178588867, "4118": 0.2622140049934387, "4167": 0.5957841277122498, "4176": 0.678390383720398, "4187": 0.6624060273170471, "4254": 0.13670019805431366, "4270": 0.8238670229911804, "4286": 0.1358480453491211, "4340": 0.6160298585891724, "4394": 0.10203468054533005, "4424": 0.44566190242767334, "4468": 0.12814582884311676, "4474": 0.011650617234408855, "4489": 0.31560876965522766, "4498": 0.5882205963134766, "4527": 0.07068414986133575, "4531": 0.16359257698059082, "4602": 0.009718249551951885, "4639": 0.45623743534088135, "4671": 0.13755162060260773, "4675": 0.6714286804199219, "4725": 0.28963330388069153, "4743": 0.9115922451019287, "4758": 0.5278670787811279, "4812": 0.304147332906723, "4839": 0.07793712615966797, "4863": 0.011650617234408855, "4876": 0.22392450273036957, "4957": 0.35745587944984436, "4962": 1.158010721206665, "4969": 0.08244366943836212, "5055": 1.0655186176300049, "5101": 0.5244048833847046, "5105": 0.2607102394104004, "5221": 0.09672962874174118, "5228": 0.4537591338157654, "5257": 0.3656192123889923, "5278": 0.04953393340110779, "5360": 0.39893341064453125, "5393": 0.4673144817352295, "5402": 0.817850649356842, "5418": 0.8425432443618774, "5456": 0.6338034868240356, "5555": 0.016465263441205025, "5646": 0.1718502640724182, "5769": 0.36697331070899963, "5799": 0.7009293437004089, "5863": 0.35677260160446167, "5866": 0.0019512200960889459, "5907": 0.5773153901100159, "5963": 0.2561853528022766, "5966": 0.24554696679115295, "5967": 0.15359249711036682, "6001": 0.3547199070453644, "6064": 0.5963221788406372, "6083": 0.7827593088150024, "6125": 0.36967599391937256, "6135": 0.06429435312747955, "6228": 0.04207121208310127, "6310": 0.2786078155040741, "6337": 0.0606246218085289, "6455": 0.15442965924739838, "6459": 0.00875066313892603, "6480": 0.14602625370025635, "6592": 0.674915611743927, "6698": 0.14602625370025635, "6755": 0.10906458646059036, "6775": 0.09228714555501938, "6789": 0.1229778528213501, "6827": 0.5767669677734375, "6897": 0.10555581003427505, "6939": 0.0913962796330452, "6999": 0.5685047507286072, "7060": 0.6254787445068359, "7066": 0.35128939151763916, "7079": 0.043007105588912964, "7099": 0.12986256182193756, "7127": 0.14095009863376617, "7178": 0.22392450273036957, "7290": 0.17840765416622162, "7337": 1.0087559223175049, "7366": 0.36967599391937256, "7371": 0.6296497583389282, "7403": 1.0101795196533203, "7444": 1.0151457786560059, "7461": 0.6043586730957031, "7485": 0.04113444685935974, "7523": 0.2539152204990387, "7551": 0.04394211992621422, "7591": 0.10555581003427505, "7667": 0.1970241367816925, "7711": 0.24859806895256042, "7790": 0.11691460013389587, "7816": 0.8805016279220581, "7900": 0.3191637098789215, "7975": 1.126855492591858, "8023": 0.12038381397724152, "8092": 0.26296505331993103, "8119": 0.3750596046447754, "8137": 0.6522845029830933, "8153": 0.7907629609107971, "8168": 0.47766464948654175, "8358": 0.04113444685935974, "8360": 0.3547199070453644, "8381": 0.19541899859905243, "8386": 0.34577593207359314, "8521": 0.12642613053321838, "8556": 0.2637155055999756, "8672": 0.0009760859538801014, "8713": 0.637939989566803, "8776": 0.07341018319129944, "8787": 0.013579257763922215, "8920": 0.01934296265244484, "8991": 0.5427330136299133, "9001": 0.4624064862728119, "9104": 0.4487839937210083, "9128": 0.8264343738555908, "9147": 0.10203468054533005, "9165": 1.0519683361053467, "9197": 0.17759032547473907, "9223": 0.5127768516540527, "9426": 0.5450005531311035, "9430": 1.4227317571640015, "9556": 0.10379679501056671, "9670": 0.1693800985813141, "9671": 0.27934664487838745, "9756": 0.2918238639831543, "9783": 0.6369074583053589, "9998": 1.202995777130127, "10288": 0.12986256182193756, "10338": 0.3903779089450836, "10381": 0.2954642176628113, "10426": 0.15275461971759796, "10450": 0.021256839856505394, "10462": 0.0797421783208847, "10472": 0.47402387857437134, "10479": 0.6275664567947388, "10595": 0.9379299283027649, "10641": 0.1064341589808464, "10671": 0.9394577741622925, "10738": 0.4500300884246826, "10744": 0.3339579105377197, "10755": 0.18411032855510712, "10847": 0.6181373596191406, "10927": 0.29619070887565613, "11095": 0.11430477350950241, "11158": 0.6176109313964844, "11219": 0.18654440343379974, "11234": 0.19381128251552582, "11268": 0.39367714524269104, "11341": 0.1751343309879303, "11423": 0.4734157919883728, "11538": 0.12814582884311676, "11658": 1.0051883459091187, "11681": 0.8161250352859497, "11837": 0.3930181860923767, "12173": 0.11778303235769272, "12221": 0.11691460013389587, "12222": 0.9987343549728394, "12247": 0.06886265426874161, "12261": 0.05046287178993225, "12269": 0.38174858689308167, "12284": 0.09050461649894714, "12285": 0.14095009863376617, "12407": 0.7445381283760071, "12473": 0.10555581003427505, "12515": 0.27044451236724854, "12530": 0.1734936386346817, "12581": 0.3443928062915802, "12590": 0.2622140049934387, "12644": 0.5629584193229675, "12709": 0.46055975556373596, "12732": 0.33675122261047363, "12745": 0.40351006388664246, "12748": 0.09672962874174118, "12839": 0.04394211992621422, "12887": 0.46117570996284485, "12955": 0.14095009863376617, "13004": 0.9279413223266602, "13195": 0.11256109178066254, "13228": 0.0842406153678894, "13341": 0.11343330889940262, "13366": 0.04674193635582924, "13369": 0.13414156436920166, "13458": 0.35403475165367126, "13531": 0.46363574266433716, "13639": 0.1332872211933136, "13700": 0.05417001247406006, "13749": 0.03831886500120163, "13767": 0.08782484382390976, "13811": 0.6553317308425903, "13827": 1.0621482133865356, "13908": 0.02792670577764511, "13923": 0.14686977863311768, "14026": 0.04207121208310127, "14048": 0.006812678650021553, "14080": 0.1913948506116867, "14087": 0.29109421372413635, "14095": 0.4879087805747986, "14127": 0.15860503911972046, "14155": 0.29473719000816345, "14163": 0.015504186972975731, "14171": 0.03831886500120163, "14193": 0.11691460013389587, "14206": 0.08782484382390976, "14258": 0.45499902963638306, "14267": 0.0019512200960889459, "14358": 0.4574742913246155, "14471": 0.678390383720398, "14494": 0.1212492436170578, "14556": 0.39762192964553833, "14627": 0.4537591338157654, "14800": 0.4494072198867798, "14930": 0.5551415085792542, "15100": 0.23324857652187347, "15124": 0.08244366943836212, "15176": 0.7009293437004089, "15380": 0.3662964701652527, "15439": 0.4770587682723999, "15527": 0.21765978634357452, "15813": 0.25088030099868774, "15850": 0.5805994272232056, "15928": 0.01934296265244484, "15929": 0.053244512528181076, "16014": 0.056018441915512085, "16026": 0.009718249551951885, "16118": 0.014542185701429844, "16133": 0.3297532796859741, "16169": 0.34370049834251404, "16221": 0.49864232540130615, "16281": 0.9371650815010071, "16396": 0.43875885009765625, "16452": 0.6420594453811646, "16463": 0.3141832649707794, "16505": 0.05786345899105072, "16515": 0.30486753582954407, "16516": 0.022212404757738113, "16530": 0.1212492436170578, "16594": 0.3615458607673645, "16706": 1.184049129486084, "16754": 0.09406650811433792, "16846": 0.1685553640127182, "16874": 0.04207121208310127, "16910": 0.48670899868011475, "17245": 0.306306391954422, "17264": 1.0735615491867065, "17325": 0.2531573474407196, "17785": 0.23324857652187347, "17970": 0.175953671336174, "18047": 0.2447827309370041, "18077": 0.036437395960092545, "18134": 0.18978065252304077, "18275": 0.16276304423809052, "18313": 0.07793712615966797, "18700": 0.02887592278420925, "18714": 0.11691460013389587, "18886": 0.016465263441205025, "18888": 0.15359249711036682, "18908": 0.46117570996284485, "18925": 0.06612417846918106, "18931": 0.04953393340110779, "18938": 0.0797421783208847, "18963": 0.4318077862262726, "19037": 0.0174254160374403, "19079": 0.9139442443847656, "19293": 0.3982778787612915, "19345": 0.46914875507354736, "19389": 0.036437395960092545, "19500": 0.19862671196460724, "19515": 0.401551216840744, "19539": 0.08064348995685577, "19670": 0.026976587250828743, "19723": 0.2659635543823242, "19872": 0.2822965085506439, "20047": 0.12728634476661682, "20063": 0.06612417846918106, "20077": 0.0913962796330452, "20390": 0.07612881064414978, "20467": 0.0019512200960889459, "20598": 0.1384023278951645, "20649": 0.3554046154022217, "20689": 0.6793810129165649, "20704": 1.036847710609436, "20752": 0.09228714555501938, "21024": 0.2160874605178833, "21376": 0.08064348995685577, "21425": 0.043007105588912964, "21575": 0.5789587497711182, "21618": 0.3723714053630829, "21656": 0.6296497583389282, "21709": 0.026025565341114998, "21716": 0.2954642176628113, "21758": 0.29473719000816345, "21863": 0.18492233753204346, "21868": 0.9470623731613159, "21891": 0.05046287178993225, "22026": 0.04113444685935974, "22368": 0.21687394380569458, "22423": 0.08513788133859634, "22468": 0.3519764244556427, "22471": 0.1718502640724182, "22530": 0.5584990978240967, "22570": 0.11778303235769272, "22991": 0.06795065850019455, "23490": 0.23710809648036957, "23750": 0.034552380442619324, "23940": 0.09761575609445572, "24094": 0.29328158497810364, "24370": 0.25467249751091003, "24668": 0.2786078155040741, "24848": 0.2160874605178833, "24872": 0.029824240133166313, "24936": 0.3910386264324188, "25206": 0.24554696679115295, "25336": 0.18167030811309814, "25352": 1.0464962720870972, "25389": 1.0030416250228882, "25426": 0.24248650670051575, "25524": 0.026976587250828743, "25644": 0.08154398202896118, "25937": 0.5010119676589966, "26083": 0.5438674688339233, "26305": 0.5805994272232056, "26462": 0.34300774335861206, "26534": 0.08064348995685577, "26641": 0.09317722171545029, "26702": 0.08603433519601822, "26741": 0.15943801403045654, "26773": 0.6502478122711182, "26874": 0.9531047344207764, "27000": 0.11081436276435852, "27567": 0.18167030811309814, "27642": 0.7845434546470642, "27681": 0.3019835948944092, "28086": 0.9084475636482239, "28290": 0.083342544734478, "28309": 0.10555581003427505, "28436": 0.1734936386346817, "28696": 0.1384023278951645, "28935": 0.16524957120418549, "28987": 0.18816383183002472, "29091": 0.12038381397724152, "29206": 0.03925827145576477, "29258": 1.3428852558135986, "29260": 0.23864774405956268, "29427": 0.3519764244556427, "29516": 0.14939609169960022} | 12232678 | Recent reports have suggested that birds lack a mechanism of wholesale dosage compensation for the Z sex chromosome. This discovery was rather unexpected, as all other animals investigated with chromosomal mechanisms of sex determination have some method to counteract the effects of gene dosage of the dominant sex chromosome in males and females. Despite the lack of a global mechanism of avian dosage compensation, the pattern of gene expression difference between males and females varies a great deal for individual Z-linked genes. This suggests that some genes may be individually dosage compensated, and that some less-than-global pattern of dosage compensation, such as local or temporal, exists on the avian Z chromosome. We used global gene expression profiling in males and females for both somatic and gonadal tissue at several time points in the life cycle of the chicken to assess the pattern of sex-biased gene expression on the Z chromosome. Average fold-change between males and females varied somewhat among tissue time-point combinations, with embryonic brain samples having the smallest gene dosage effects, and adult gonadal tissue having the largest degree of male bias. Overall, there were no neighborhoods of overall dosage compensation along the Z. Taken together, this suggests that dosage compensation is regulated on the Z chromosome entirely on a gene-by-gene level, and can vary during the life cycle and by tissue type. This regulation may be an indication of how critical a given gene's functionality is, as the expression level for essential genes will be tightly regulated in order to avoid perturbing important pathways and networks with differential expression levels in males and females. | All dosage compensation is local: Gene-by-gene regulation of sex-biased expression on the chicken Z chromosome |
{"1009": 0.07793712615966797, "1041": 0.00875066313892603, "1044": 0.07159364968538284, "1051": 0.1619328260421753, "1052": 0.07431721687316895, "1056": 0.16276304423809052, "1061": 0.37640097737312317, "2005": 0.11604541540145874, "2007": 0.1710275560617447, "2025": 0.2881702482700348, "2043": 0.0354953333735466, "2044": 0.3381449282169342, "2045": 0.2223619967699051, "2048": 0.2674594223499298, "2053": 0.14939609169960022, "2067": 0.5865923762321472, "2076": 0.28155985474586487, "2077": 0.0174254160374403, "2078": 0.40089741349220276, "2086": 0.3519764244556427, "2090": 0.43623676896095276, "2094": 0.3499138653278351, "2095": 0.15777134895324707, "2099": 0.28963330388069153, "2102": 1.0901126861572266, "2106": 0.03831886500120163, "2109": 0.03925827145576477, "2146": 0.055094651877880096, "2147": 0.030771657824516296, "2152": 0.11517547070980072, "2168": 0.1994270235300064, "2214": 0.0058422754518687725, "2273": 0.2983669638633728, "2287": 0.6833335757255554, "2308": 0.7827593088150024, "2309": 0.32058215141296387, "2367": 0.2800849378108978, "2423": 0.21372433006763458, "2439": 0.23864774405956268, "2445": 0.2852376699447632, "2450": 0.472198486328125, "2470": 0.1905880719423294, "2515": 0.2493593990802765, "2522": 0.44753631949424744, "2529": 0.009718249551951885, "2609": 0.034552380442619324, "2618": 0.4788752794265747, "2629": 0.4228905141353607, "2638": 0.49030399322509766, "2689": 0.7201237678527832, "2695": 0.7426811456680298, "2714": 0.03925827145576477, "2812": 0.2493593990802765, "2817": 0.5784112811088562, "2846": 0.08692999184131622, "2864": 0.401551216840744, "2884": 0.6704301834106445, "2896": 0.36967599391937256, "2904": 0.3134697377681732, "2913": 0.4938860833644867, "2931": 0.42544642090797424, "2953": 0.04394211992621422, "2999": 0.4286321699619293, "3020": 0.0009760859538801014, "3112": 0.10555581003427505, "3141": 0.07341018319129944, "3144": 0.28963330388069153, "3161": 0.010684899985790253, "3170": 0.03266380727291107, "3215": 0.5607312321662903, "3231": 0.16359257698059082, "3273": 0.5295937061309814, "3276": 0.38374659419059753, "3278": 0.669430673122406, "3279": 0.8989537954330444, "3296": 0.5398913025856018, "3322": 0.34023189544677734, "3334": 0.38041436672210693, "3372": 0.17267228662967682, "3378": 0.3870677351951599, "3385": 0.034552380442619324, "3419": 0.5528968572616577, "3426": 0.08871890604496002, "3429": 0.040196798741817474, "3431": 0.5909284353256226, "3433": 0.011650617234408855, "3438": 0.4462870955467224, "3445": 0.3191637098789215, "3446": 0.6118015646934509, "3463": 0.15610189735889435, "3466": 0.37102460861206055, "3549": 0.7028654217720032, "3619": 0.1619328260421753, "3623": 0.08603433519601822, "3635": 0.0009760859538801014, "3643": 0.3070250153541565, "3653": 0.6778947114944458, "3742": 0.17922431230545044, "3801": 0.32341301441192627, "3867": 0.10203468054533005, "3891": 0.2749055027961731, "3893": 0.09228714555501938, "3896": 0.3134697377681732, "3949": 0.5849615335464478, "3974": 0.3784096837043762, "3979": 0.1212492436170578, "3988": 0.5478278398513794, "4002": 0.259204238653183, "4008": 0.4950772523880005, "4053": 0.014542185701429844, "4102": 0.28082266449928284, "4295": 0.8272887468338013, "4304": 1.1935672760009766, "4308": 0.3416208028793335, "4413": 0.38041436672210693, "4489": 0.05694137513637543, "4558": 0.6000806093215942, "4573": 0.32129061222076416, "4621": 0.9944084882736206, "4652": 0.7028654217720032, "4793": 0.1221139207482338, "5022": 0.6533012986183167, "5082": 0.13414156436920166, "5278": 0.42225050926208496, "5300": 0.3464667797088623, "5301": 0.021256839856505394, "5335": 0.2145126610994339, "5345": 0.9724938273429871, "5388": 0.11343330889940262, "5393": 0.06703783571720123, "5449": 0.058784693479537964, "5468": 0.6317287683486938, "5531": 0.4067663550376892, "5643": 0.3269403576850891, "5672": 0.6260011196136475, "5761": 0.40285754203796387, "5776": 0.5941681861877441, "5799": 0.10026945173740387, "5845": 0.3464667797088623, "5860": 0.3012613356113434, "5923": 1.2499688863754272, "5944": 1.0953518152236938, "6022": 0.7610978484153748, "6024": 0.45623743534088135, "6075": 0.06154331564903259, "6110": 1.1185935735702515, "6163": 0.567397952079773, "6165": 0.5139457583427429, "6179": 0.1011524572968483, "6190": 0.678885817527771, "6215": 0.12814582884311676, "6409": 0.31845372915267944, "6419": 0.371698260307312, "6431": 0.016465263441205025, "6463": 0.23710809648036957, "6464": 0.41001203656196594, "6604": 0.3519764244556427, "6747": 0.35060185194015503, "6812": 1.147526502609253, "6937": 0.030771657824516296, "7012": 0.24018502235412598, "7017": 0.3956514894962311, "7023": 1.0278041362762451, "7028": 0.07612881064414978, "7065": 0.025073638185858727, "7242": 1.001607894897461, "7315": 0.9155091643333435, "7361": 0.45870962738990784, "7438": 0.45499902963638306, "7457": 0.10026945173740387, "7461": 0.18004031479358673, "7594": 0.7076893448829651, "7620": 0.15693697333335876, "7645": 0.07431721687316895, "7691": 0.11343330889940262, "7718": 0.04953393340110779, "7778": 0.8845420479774475, "7784": 0.22001366317272186, "7831": 0.17840765416622162, "7870": 0.5640701055526733, "8093": 0.5450005531311035, "8114": 0.15860503911972046, "8321": 0.04953393340110779, "8335": 0.17020416259765625, "8449": 0.04860413447022438, "8557": 0.6543170213699341, "8560": 1.1444218158721924, "8564": 0.11256109178066254, "8729": 0.5393219590187073, "8977": 1.0165601968765259, "9015": 0.037378571927547455, "9314": 0.5116065740585327, "9367": 0.09584271162748337, "9526": 0.1212492436170578, "9535": 0.23556606471538544, "9556": 0.25845035910606384, "9560": 0.16690383851528168, "9657": 0.10818854719400406, "9711": 0.24554696679115295, "9740": 0.7610978484153748, "9742": 0.5370414853096008, "9750": 0.12384103983640671, "9765": 0.056018441915512085, "9808": 0.8957691192626953, "9888": 0.4537591338157654, "10111": 0.040196798741817474, "10174": 0.22157983481884003, "10258": 0.5979346632957458, "10349": 0.009718249551951885, "10383": 0.6603899002075195, "10426": 0.14602625370025635, "10548": 0.004870930220931768, "10640": 0.20739519596099854, "10723": 0.272677481174469, "10744": 0.011650617234408855, "10847": 0.1332872211933136, "10867": 0.36426326632499695, "10903": 0.35677260160446167, "11201": 0.45623743534088135, "11234": 0.2145126610994339, "11326": 0.06977381557226181, "11467": 0.06246116757392883, "11631": 0.9820492267608643, "12126": 0.21293537318706512, "12171": 0.5284429788589478, "12177": 0.9194108247756958, "12318": 0.151916041970253, "12353": 0.8109301924705505, "12381": 0.058784693479537964, "12435": 0.34508460760116577, "12452": 0.018384648486971855, "12503": 0.030771657824516296, "12859": 0.06154331564903259, "12898": 0.7333439588546753, "13046": 0.3027053773403168, "13105": 0.19220098853111267, "13186": 0.6664261221885681, "13341": 0.10555581003427505, "13441": 0.29473719000816345, "13483": 0.777387797832489, "13526": 0.28743788599967957, "13594": 0.20580662786960602, "13599": 0.1229778528213501, "13675": 0.6107416749000549, "13706": 0.26146242022514343, "13806": 0.5941681861877441, "13853": 0.3034266233444214, "13876": 0.07884006202220917, "14025": 0.6970458030700684, "14155": 0.18978065252304077, "14173": 0.23787821829319, "14267": 0.15275461971759796, "14343": 0.6950984001159668, "14358": 0.06246116757392883, "14417": 0.49626702070236206, "14604": 1.0519683361053467, "14621": 0.00875066313892603, "14667": 0.4487839937210083, "14689": 0.2493593990802765, "14708": 0.5370414853096008, "14931": 0.0058422754518687725, "14967": 0.0354953333735466, "15157": 0.22626367211341858, "15255": 1.1786550283432007, "15258": 0.040196798741817474, "15306": 0.03360854089260101, "15354": 0.40351006388664246, "15384": 0.45994341373443604, "16014": 0.15023678541183472, "16026": 0.5855054259300232, "16118": 0.2763880789279938, "16148": 0.2969166338443756, "16211": 0.23556606471538544, "16263": 0.3519764244556427, "16330": 0.0842406153678894, "16344": 0.004870930220931768, "16492": 1.187628984451294, "16515": 0.06612417846918106, "16557": 0.09850110858678818, "16596": 0.06977381557226181, "16643": 0.02887592278420925, "16670": 0.18654440343379974, "16844": 0.736154317855835, "16902": 1.0768938064575195, "17086": 0.7665573358535767, "17119": 0.015504186972975731, "17208": 0.055094651877880096, "17261": 0.2576959431171417, "17359": 1.0080435276031494, "17464": 0.6011518239974976, "17599": 0.055094651877880096, "17785": 0.02887592278420925, "17850": 1.3398208618164062, "17869": 0.0842406153678894, "17886": 0.3757305145263672, "18020": 0.32553088665008545, "18313": 0.0009760859538801014, "18422": 0.02316705882549286, "18714": 1.1888195276260376, "18886": 0.2184450328350067, "18949": 0.06612417846918106, "18994": 0.3005385100841522, "19037": 0.38574060797691345, "19064": 0.22859740257263184, "19126": 0.5590575933456421, "19294": 0.28963330388069153, "19357": 0.8748174905776978, "19583": 0.43812891840934753, "19680": 0.11865071207284927, "19731": 0.04394211992621422, "20014": 0.4400174915790558, "20026": 0.0058422754518687725, "20136": 0.13755162060260773, "20155": 0.8281423449516296, "20187": 1.225611925125122, "20272": 0.6970458030700684, "20368": 0.08961215615272522, "20415": 0.417115718126297, "20694": 0.41840189695358276, "20736": 0.0770333781838417, "20752": 1.020087480545044, "20868": 0.48430517315864563, "20900": 0.5104349255561829, "20992": 0.09938567131757736, "21025": 0.15275461971759796, "21150": 0.5506471395492554, "21307": 0.6989894509315491, "21391": 0.055094651877880096, "21726": 0.040196798741817474, "21733": 0.8500841856002808, "22248": 0.1734936386346817, "22597": 0.026976587250828743, "22678": 0.5421652793884277, "22802": 0.1693800985813141, "22943": 0.3923587501049042, "22991": 0.7086513638496399, "23807": 0.04207121208310127, "23900": 0.848413348197937, "23926": 0.13499516248703003, "23936": 0.22782009840011597, "23971": 0.28670501708984375, "24081": 0.013579257763922215, "24110": 0.17431432008743286, "24279": 0.24631060659885406, "24428": 0.014542185701429844, "24475": 0.014542185701429844, "24479": 0.1930064558982849, "24806": 0.5871354341506958, "24937": 0.14518201351165771, "24952": 0.3297532796859741, "25269": 0.21687394380569458, "25517": 0.3346569836139679, "25604": 0.14179791510105133, "25937": 0.3409265875816345, "26261": 0.16276304423809052, "26319": 0.0770333781838417, "26383": 0.520350456237793, "26563": 0.3388410806655884, "26591": 0.13243216276168823, "26677": 0.06246116757392883, "26721": 0.10555581003427505, "26786": 0.4617912769317627, "26788": 0.09938567131757736, "26819": 0.1064341589808464, "27312": 0.01934296265244484, "27441": 1.309704303741455, "27641": 0.15275461971759796, "28093": 0.3170322775840759, "28144": 0.12556517124176025, "28228": 0.791648268699646, "28329": 0.1734936386346817, "28436": 0.09228714555501938, "28549": 0.055094651877880096, "28696": 0.13243216276168823, "28711": 0.04767346754670143, "28929": 0.31489628553390503, "29110": 0.04860413447022438, "29278": 0.17431432008743286, "29401": 0.04394211992621422, "29477": 0.9263957738876343, "29514": 0.32129061222076416} | 12236208 | Patients with inflammatory bowel disease have an increased prevalence of osteoporosis, and suffer high rates of spinal bone loss. Hormone replacement therapy (HRT) is effective in the treatment and prevention of osteoporosis but has not been studied in patients with inflammatory bowel disease. A two year prospective study of HRT in inflammatory bowel disease was performed in 47 postmenopausal women aged 44 to 67 years with ulcerative colitis (25) or Crohn's disease (22). Patients had radial and spinal bone density measured annually by single photon absorptiometry and quantitative computed tomography respectively. The mean (95% confidence intervals) annual change in radial bone density was +1.42%/yr (+0.58 to +2.26; P < 0.005) and for spinal bone +2.60%/yr (+1.06 to +4.15; p < 0.005). There was no significant correlation between rates of change of bone density at the two sites, or between the rates of change and the initial bone density either in the radius or spine. Twelve patients were given prednisolone during the study, and their rates of change for spinal bone density were lower, but values were not statistically significantly different from those who did not receive corticosteroids. Changes in bone density for patients with ulcerative colitis and Crohn's disease were not significantly different. The change in bone density did not correlate with the patients' age or number of years after the menopause. It is concluded that HRT is effective in prevention of bone loss in postmenopausal women with inflammatory bowel disease. | Hormone replacement therapy prevents bone loss in patients with inflammatory bowel disease. |
{"1011": 0.2493593990802765, "1019": 0.22626367211341858, "1038": 0.23092569410800934, "1044": 0.17759032547473907, "1052": 0.5844172835350037, "1054": 0.630689799785614, "2003": 0.24859806895256042, "2007": 0.014542185701429844, "2011": 0.18816383183002472, "2015": 0.10379679501056671, "2019": 0.7473171949386597, "2029": 0.09938567131757736, "2050": 1.1070401668548584, "2058": 0.2184450328350067, "2179": 0.14095009863376617, "2188": 0.46117570996284485, "2213": 0.5990082025527954, "2274": 0.1970241367816925, "2304": 1.2666174173355103, "2361": 0.4374985992908478, "2401": 0.29981520771980286, "2475": 0.47463157773017883, "2539": 0.2145126610994339, "2566": 0.2501201331615448, "2571": 0.28743788599967957, "2572": 0.40285754203796387, "2599": 0.055094651877880096, "2601": 0.6075552701950073, "2617": 0.0019512200960889459, "2629": 0.678390383720398, "2666": 0.31845372915267944, "2668": 0.21293537318706512, "2732": 0.15526613593101501, "2765": 0.04674193635582924, "2817": 0.04767346754670143, "2845": 0.11604541540145874, "2865": 0.37304413318634033, "2892": 0.6043586730957031, "2913": 0.19862671196460724, "2920": 0.0354953333735466, "2944": 0.18573370575904846, "3022": 0.36697331070899963, "3057": 0.040196798741817474, "3064": 0.2231435477733612, "3160": 0.5816917419433594, "3165": 0.17267228662967682, "3235": 0.0009760859538801014, "3273": 0.04487626627087593, "3303": 0.5629584193229675, "3313": 0.7978238463401794, "3350": 0.4568560719490051, "3358": 0.39367714524269104, "3371": 0.8500841856002808, "3378": 0.06977381557226181, "3426": 0.5607312321662903, "3433": 0.8074519634246826, "3466": 0.0009760859538801014, "3491": 0.259204238653183, "3508": 0.12642613053321838, "3526": 0.5186077356338501, "3587": 0.07159364968538284, "3603": 0.056018441915512085, "3625": 0.10203468054533005, "3853": 0.02887592278420925, "3921": 0.20660123229026794, "4013": 0.6578640341758728, "4053": 0.06795065850019455, "4059": 0.09584271162748337, "4130": 0.015504186972975731, "4295": 0.5278670787811279, "4442": 0.678885817527771, "4523": 0.5685047507286072, "4570": 0.056018441915512085, "4588": 0.06520967930555344, "4625": 0.7258110046386719, "4650": 0.043007105588912964, "4668": 0.2881702482700348, "4777": 0.02792670577764511, "4786": 0.11865071207284927, "4850": 0.03925827145576477, "4935": 0.6553317308425903, "4945": 0.0317181795835495, "4962": 0.7791815400123596, "4997": 0.5139457583427429, "5153": 0.6223390698432922, "5187": 0.40611594915390015, "5250": 0.6649205088615417, "5292": 0.5723689198493958, "5301": 0.0038986403960734606, "5320": 0.6916812658309937, "5387": 0.08154398202896118, "5393": 0.06612417846918106, "5400": 0.034552380442619324, "5450": 0.2719337046146393, "5470": 0.22392450273036957, "5591": 0.3283478021621704, "5769": 0.11081436276435852, "6064": 0.3084607720375061, "6079": 0.22859740257263184, "6190": 0.45932671427726746, "6323": 1.6582280397415161, "6525": 0.6980181336402893, "6573": 0.44753631949424744, "6578": 0.013579257763922215, "6689": 0.5590575933456421, "6821": 0.2184450328350067, "6873": 0.6492279767990112, "6911": 0.8091925978660583, "6914": 0.5197699069976807, "7065": 0.11778303235769272, "7153": 0.04953393340110779, "7301": 0.21530038118362427, "7324": 0.8281423449516296, "7337": 0.8475768566131592, "7356": 0.15275461971759796, "7361": 0.5238267183303833, "7366": 0.0913962796330452, "7403": 0.6482070088386536, "7461": 0.0842406153678894, "7591": 0.6181373596191406, "7645": 0.14518201351165771, "7784": 0.04394211992621422, "7790": 0.41065993905067444, "7809": 0.055094651877880096, "7816": 0.24631060659885406, "7818": 0.2696990668773651, "7821": 0.4311734735965729, "7870": 0.24325250089168549, "7900": 0.2034190446138382, "7901": 0.57457035779953, "8000": 0.9591107368469238, "8022": 0.14349138736724854, "8093": 0.7163142561912537, "8171": 0.6744182109832764, "8270": 0.3499138653278351, "8290": 0.9470623731613159, "8360": 0.5629584193229675, "8392": 0.9178520441055298, "8523": 1.0030416250228882, "8602": 0.11865071207284927, "8715": 0.5267143249511719, "8761": 0.24631060659885406, "8776": 0.14939609169960022, "8781": 0.11778303235769272, "8878": 0.6754127144813538, "9001": 0.09938567131757736, "9002": 0.37102460861206055, "9007": 0.5816917419433594, "9096": 0.09495500475168228, "9108": 1.1774523258209229, "9165": 0.7836518287658691, "9186": 0.06429435312747955, "9223": 0.020300358533859253, "9258": 0.12642613053321838, "9285": 0.37707099318504333, "9309": 0.44691193103790283, "9314": 0.8691008687019348, "9350": 0.28082266449928284, "9412": 0.06520967930555344, "9413": 0.5701626539230347, "9556": 0.38574060797691345, "9597": 0.14602625370025635, "9617": 0.23479416966438293, "9626": 0.07431721687316895, "10090": 0.28082266449928284, "10092": 0.4624064862728119, "10266": 0.8143964409828186, "10335": 0.27786844968795776, "10448": 0.8057082891464233, "10509": 0.0354953333735466, "10572": 0.6699305176734924, "10591": 0.35745587944984436, "10595": 0.6497380137443542, "10610": 0.6704301834106445, "10738": 0.03831886500120163, "10744": 0.10993985831737518, "10811": 0.5860490798950195, "10823": 0.4093637466430664, "10840": 0.19782574474811554, "10960": 0.2837681770324707, "11335": 0.4617912769317627, "11369": 0.4437839686870575, "11432": 0.2741633653640747, "11477": 0.009718249551951885, "11548": 0.03266380727291107, "11674": 0.8699195384979248, "11719": 1.2900071144104004, "11761": 0.0058422754518687725, "11835": 0.5805994272232056, "11921": 0.011650617234408855, "12014": 0.004870930220931768, "12059": 0.18978065252304077, "12130": 0.045809537172317505, "12222": 0.176772341132164, "12328": 0.9929623603820801, "12359": 0.3346569836139679, "12377": 0.4624064862728119, "12491": 0.319873183965683, "12645": 0.2247048318386078, "12650": 0.2447827309370041, "12732": 0.7124901413917542, "12944": 0.15943801403045654, "12987": 0.08603433519601822, "13070": 0.13071982562541962, "13228": 0.7047978043556213, "13233": 0.0606246218085289, "13366": 0.3723714053630829, "13494": 0.013579257763922215, "13713": 0.20022670924663544, "13791": 1.0116009712219238, "13922": 0.014542185701429844, "13947": 0.24018502235412598, "13987": 0.1930064558982849, "14117": 0.5110208988189697, "14120": 0.13670019805431366, "14142": 0.7925328612327576, "14153": 0.12986256182193756, "14194": 0.319873183965683, "14353": 0.09938567131757736, "14462": 0.05417001247406006, "14471": 0.1946154683828354, "14494": 0.3810817003250122, "14639": 0.8264343738555908, "14800": 0.32129061222076416, "14863": 0.4734157919883728, "15092": 0.011650617234408855, "15115": 0.23479416966438293, "15143": 1.5398868322372437, "15176": 0.026025565341114998, "15197": 0.1930064558982849, "15527": 0.40806588530540466, "15550": 0.15275461971759796, "15608": 0.016465263441205025, "15660": 0.9287132620811462, "15663": 0.06246116757392883, "15820": 0.004870930220931768, "15946": 0.9440274834632874, "16012": 0.5773153901100159, "16127": 0.16359257698059082, "16147": 0.9209672808647156, "16221": 0.5838727951049805, "16238": 0.03831886500120163, "16285": 0.11081436276435852, "16335": 0.20022670924663544, "16428": 0.08064348995685577, "16505": 0.23710809648036957, "16549": 0.08871890604496002, "16605": 0.28450319170951843, "16706": 0.6970458030700684, "16910": 0.5651806592941284, "16915": 0.2969166338443756, "16962": 1.4551570415496826, "17070": 0.49686139822006226, "17086": 0.6420594453811646, "17181": 0.4873090982437134, "17364": 0.07341018319129944, "17441": 0.46670228242874146, "17577": 1.335720419883728, "17820": 0.20421554148197174, "17890": 0.06795065850019455, "18089": 0.04487626627087593, "18211": 0.045809537172317505, "18419": 0.8829278349876404, "18714": 0.04487626627087593, "18888": 0.8074519634246826, "19009": 0.6400018334388733, "19058": 0.1619328260421753, "19137": 0.6160298585891724, "19186": 0.20501139760017395, "19389": 0.5963221788406372, "19395": 1.109619140625, "19470": 0.18004031479358673, "19500": 0.19622190296649933, "19610": 0.6022219061851501, "19653": 0.8057082891464233, "19825": 0.013579257763922215, "19872": 0.9769153594970703, "20132": 0.5313173532485962, "20166": 0.07884006202220917, "20275": 0.6533012986183167, "20296": 0.2763880789279938, "20461": 0.8004589080810547, "20524": 0.1510767638683319, "20534": 0.0019512200960889459, "20544": 0.6374238729476929, "20569": 0.007782140281051397, "20644": 0.18167030811309814, "20689": 0.9037119746208191, "20766": 0.034552380442619324, "20806": 0.8212929964065552, "20975": 0.2160874605178833, "21123": 0.08782484382390976, "21262": 1.0298984050750732, "21466": 0.08603433519601822, "21472": 0.11168810725212097, "21486": 0.512191891670227, "21618": 0.6223390698432922, "21709": 0.6907027959823608, "21903": 0.2231435477733612, "21923": 0.1873544454574585, "21935": 0.2317005842924118, "21967": 0.015504186972975731, "22116": 0.0317181795835495, "22123": 0.9037119746208191, "22203": 0.15777134895324707, "22275": 1.4227317571640015, "22312": 0.04674193635582924, "22394": 0.06977381557226181, "22571": 0.8004589080810547, "22943": 0.22548456490039825, "23079": 0.31204116344451904, "23150": 0.18978065252304077, "23163": 0.5197699069976807, "23216": 0.004870930220931768, "23217": 0.6734226942062378, "23238": 0.6086184978485107, "23586": 0.6970458030700684, "23737": 0.8143964409828186, "23760": 0.029824240133166313, "23777": 0.10026945173740387, "24054": 0.5381823778152466, "24191": 0.022212404757738113, "24269": 0.9317949414253235, "24535": 0.14518201351165771, "24587": 0.11951763927936554, "24594": 0.3304552733898163, "24759": 0.5990082025527954, "25194": 0.05694137513637543, "25456": 0.28963330388069153, "25468": 0.2711893916130066, "25644": 0.2501201331615448, "25714": 0.7969439625740051, "25746": 0.0038986403960734606, "25761": 0.26446542143821716, "25788": 0.19622190296649933, "26402": 0.5415972471237183, "26475": 0.7417513132095337, "26651": 0.07793712615966797, "26682": 0.0317181795835495, "26773": 0.1751343309879303, "26835": 0.014542185701429844, "26874": 0.20580662786960602, "27009": 0.3374483287334442, "27287": 0.7248653769493103, "27480": 1.178053855895996, "27531": 0.020300358533859253, "27642": 0.8357921838760376, "27717": 0.03360854089260101, "27989": 0.19541899859905243, "28077": 0.19782574474811554, "28156": 0.2160874605178833, "28227": 0.5562619566917419, "28290": 0.14602625370025635, "28685": 0.18248429894447327, "28691": 0.07159364968538284, "28696": 0.9531047344207764, "28765": 0.9100211262702942, "28828": 0.30486753582954407, "28829": 0.33325836062431335, "29125": 0.7665573358535767, "29290": 0.38308101892471313, "29296": 0.03925827145576477, "29300": 1.4669378995895386, "29388": 0.10731173306703568, "29610": 0.27786844968795776} | 12240507 | Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by haploinsufficiency of genes encoding ribosomal proteins (RPs). Perturbed ribosome biogenesis in DBA has been shown to induce a p53-mediated ribosomal stress response. However, the mechanisms of p53 activation and its relevance for the erythroid defect remain elusive. Previous studies have indicated that activation of p53 is caused by the inhibition of mouse double minute 2 (Mdm2), the main negative regulator of p53, by the 5S ribonucleoprotein particle (RNP). Meanwhile, it is not clear whether this mechanism solely mediates the p53-dependent component found in DBA. To approach this question, we crossed our mouse model for RPS19-deficient DBA with Mdm2C305F knock-in mice that have a disrupted 5S RNP–Mdm2 interaction. Upon induction of the Rps19 deficiency, Mdm2C305F reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo. Unexpectedly, disruption of the 5S RNP–Mdm2 interaction also led to selective defect in erythropoiesis. Our findings highlight the sensitivity of erythroid progenitor cells to aberrations in p53 homeostasis mediated by the 5S RNP–Mdm2 interaction. Finally, we provide evidence indicating that physiological activation of the 5S RNP-Mdm2-p53 pathway may contribute to functional decline of the hematopoietic system in a cell-autonomous manner over time. | Disruption of the 5S RNP–Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia |
{"1003": 0.08064348995685577, "1015": 0.25845035910606384, "1016": 0.16524957120418549, "1017": 0.14433705806732178, "1018": 0.2105647772550583, "1019": 0.2881702482700348, "1020": 0.025073638185858727, "1021": 0.14686977863311768, "1022": 0.15023678541183472, "1026": 0.04487626627087593, "1052": 0.4624064862728119, "1999": 0.2160874605178833, "2001": 0.3034266233444214, "2004": 0.007782140281051397, "2012": 0.14433705806732178, "2020": 0.20421554148197174, "2025": 0.026976587250828743, "2038": 0.04394211992621422, "2042": 0.3560888469219208, "2043": 0.30558720231056213, "2044": 0.3353555500507355, "2051": 0.5729197263717651, "2063": 0.36358460783958435, "2065": 0.040196798741817474, "2076": 0.4770587682723999, "2077": 0.5668440461158752, "2090": 0.06977381557226181, "2095": 0.13157635927200317, "2106": 0.3601844012737274, "2116": 0.2674594223499298, "2128": 0.15023678541183472, "2136": 0.4624064862728119, "2146": 0.38041436672210693, "2154": 0.1384023278951645, "2168": 0.11865071207284927, "2173": 0.016465263441205025, "2177": 0.14349138736724854, "2184": 0.14686977863311768, "2193": 0.4203280806541443, "2217": 0.1619328260421753, "2226": 1.0409941673278809, "2229": 0.5696102976799011, "2251": 0.3916989266872406, "2255": 0.33953672647476196, "2260": 0.1889725625514984, "2266": 0.37640097737312317, "2271": 0.1685553640127182, "2274": 0.007782140281051397, "2275": 0.23633737862110138, "2278": 0.026025565341114998, "2335": 0.25694093108177185, "2337": 0.3982778787612915, "2339": 0.19622190296649933, "2344": 0.8941729068756104, "2349": 0.2561853528022766, "2363": 0.3423145115375519, "2364": 0.4248080551624298, "2372": 0.2026219218969345, "2385": 0.28963330388069153, "2403": 0.2231435477733612, "2420": 0.5685047507286072, "2430": 0.12814582884311676, "2440": 0.3723714053630829, "2459": 0.2852376699447632, "2461": 0.8022117614746094, "2470": 0.2976420819759369, "2491": 0.9485763907432556, "2501": 0.6441128253936768, "2511": 0.17020416259765625, "2535": 0.06977381557226181, "2549": 0.06429435312747955, "2558": 0.6280876994132996, "2566": 0.619189441204071, "2575": 0.27712854743003845, "2586": 0.11430477350950241, "2629": 0.09050461649894714, "2636": 0.7746911644935608, "2640": 0.7038320899009705, "2644": 0.07341018319129944, "2655": 0.36494144797325134, "2680": 0.46363574266433716, "2695": 0.2749055027961731, "2722": 0.0009760859538801014, "2724": 0.6744182109832764, "2727": 0.4624064862728119, "2729": 0.684319257736206, "2753": 0.43244171142578125, "2754": 0.20102575421333313, "2765": 0.34023189544677734, "2780": 0.021256839856505394, "2786": 0.7898768186569214, "2800": 0.24171993136405945, "2802": 0.4330752193927765, "2804": 0.3248254358768463, "2807": 0.8625272512435913, "2815": 0.3084607720375061, "2817": 0.7791815400123596, "2824": 0.8152611255645752, "2826": 0.1994270235300064, "2828": 0.08603433519601822, "2836": 0.030771657824516296, "2837": 0.18492233753204346, "2851": 0.7295845746994019, "2857": 0.6410312056541443, "2864": 0.15860503911972046, "2881": 0.32341301441192627, "2902": 0.8707374930381775, "2913": 0.47827014327049255, "2920": 0.02412080205976963, "2923": 0.6430866718292236, "2951": 0.1358480453491211, "2959": 0.0038986403960734606, "2966": 0.5957841277122498, "2967": 0.15693697333335876, "2968": 0.11865071207284927, "2988": 0.0354953333735466, "2994": 0.04394211992621422, "3000": 0.026976587250828743, "3025": 0.03925827145576477, "3026": 0.9162907600402832, "3085": 0.6296497583389282, "3089": 0.40806588530540466, "3112": 0.21135559678077698, "3131": 0.996573805809021, "3141": 0.129004567861557, "3188": 0.42990362644195557, "3189": 0.058784693479537964, "3197": 0.8161250352859497, "3233": 0.20421554148197174, "3247": 0.12728634476661682, "3251": 0.33325836062431335, "3256": 0.04113444685935974, "3258": 0.5685047507286072, "3273": 0.4818955361843109, "3303": 0.25467249751091003, "3319": 1.109619140625, "3405": 0.27786844968795776, "3446": 0.7665573358535767, "3447": 0.006812678650021553, "3460": 0.0029254043474793434, "3463": 0.6165571808815002, "3465": 0.757441520690918, "3466": 0.6482070088386536, "3479": 0.669430673122406, "3491": 0.5893046259880066, "3616": 0.10993985831737518, "3641": 0.7229714393615723, "3653": 0.817850649356842, "3693": 0.11430477350950241, "3737": 0.012615402229130268, "3739": 0.4709797203540802, "3800": 0.056018441915512085, "3808": 0.2689530849456787, "3867": 0.25239890813827515, "3896": 0.4374985992908478, "3923": 0.5145297050476074, "3929": 0.036437395960092545, "3961": 0.1808556467294693, "3970": 0.7737906575202942, "3979": 0.4330752193927765, "4029": 0.5427330136299133, "4047": 0.06977381557226181, "4081": 0.176772341132164, "4102": 0.4574742913246155, "4106": 0.5461324453353882, "4127": 0.013579257763922215, "4146": 0.3070250153541565, "4158": 0.012615402229130268, "4194": 0.5330380201339722, "4200": 0.4067663550376892, "4217": 0.3070250153541565, "4252": 0.5244048833847046, "4254": 0.1685553640127182, "4292": 0.5517725944519043, "4319": 0.7463917136192322, "4322": 0.022212404757738113, "4359": 0.5573811531066895, "4374": 0.2493593990802765, "4391": 0.7546905279159546, "4403": 0.87237149477005, "4449": 0.9598589539527893, "4453": 0.57457035779953, "4455": 0.08961215615272522, "4468": 0.2160874605178833, "4506": 0.0058422754518687725, "4595": 0.23247487843036652, "4607": 0.04113444685935974, "4621": 0.2719337046146393, "4652": 1.0271050930023193, "4748": 1.005902886390686, "4758": 0.7028654217720032, "4812": 0.23479416966438293, "4844": 0.3588210940361023, "4866": 0.13157635927200317, "4909": 0.03831886500120163, "4914": 0.5057345628738403, "4928": 0.06337817758321762, "4955": 0.014542185701429844, "4989": 0.4734157919883728, "5002": 0.18411032855510712, "5022": 0.5882205963134766, "5034": 0.0019512200960889459, "5043": 0.4002431631088257, "5117": 0.0058422754518687725, "5130": 0.5973974466323853, "5138": 0.5489565134048462, "5219": 0.1905880719423294, "5345": 0.9827804565429688, "5360": 0.058784693479537964, "5366": 0.5284429788589478, "5402": 0.0752234235405922, "5468": 0.5489565134048462, "5531": 0.25088030099868774, "5547": 0.45623743534088135, "5548": 0.1873544454574585, "5585": 0.5590575933456421, "5589": 0.7220231294631958, "5617": 0.2830325961112976, "5711": 0.11081436276435852, "5761": 0.7755908370018005, "5764": 0.5415972471237183, "5776": 0.9100211262702942, "5779": 0.045809537172317505, "5790": 0.053244512528181076, "5837": 0.034552380442619324, "5850": 0.6212902665138245, "5859": 0.151916041970253, "5890": 0.07159364968538284, "5986": 0.1913948506116867, "5989": 0.11951763927936554, "6075": 0.27934664487838745, "6109": 0.03925827145576477, "6123": 1.1702059507369995, "6165": 0.5936289429664612, "6226": 0.4974553883075714, "6241": 1.035461664199829, "6305": 0.6634125709533691, "6365": 0.09495500475168228, "6388": 0.23247487843036652, "6449": 0.32553088665008545, "6450": 0.175953671336174, "6463": 0.16276304423809052, "6577": 1.1211429834365845, "6612": 0.4914994537830353, "6624": 0.23247487843036652, "6694": 0.6405166387557983, "6721": 0.9470623731613159, "6749": 0.5489565134048462, "6818": 0.4444103240966797, "6887": 0.7827593088150024, "6939": 0.021256839856505394, "6959": 0.2689530849456787, "6993": 0.40481385588645935, "7012": 0.41840189695358276, "7017": 0.5330380201339722, "7023": 1.1051015853881836, "7091": 0.42735910415649414, "7276": 0.2674594223499298, "7312": 0.11865071207284927, "7316": 0.10203468054533005, "7375": 0.24325250089168549, "7435": 0.09228714555501938, "7461": 0.3248254358768463, "7522": 0.5278670787811279, "7528": 0.32270604372024536, "7551": 0.19220098853111267, "7561": 0.8109301924705505, "7594": 0.2659635543823242, "7645": 0.3824150264263153, "7667": 0.06520967930555344, "7687": 0.06520967930555344, "7709": 0.030771657824516296, "7711": 0.5021947622299194, "7778": 0.07068414986133575, "7784": 0.10906458646059036, "7831": 0.7592713832855225, "7848": 0.09228714555501938, "7863": 1.031988263130188, "7941": 0.14349138736724854, "8001": 0.20818853378295898, "8010": 0.46363574266433716, "8019": 0.6022219061851501, "8089": 0.17759032547473907, "8147": 0.11865071207284927, "8161": 0.22626367211341858, "8182": 0.7951818704605103, "8302": 0.3127557039260864, "8323": 0.603290855884552, "8329": 0.1946154683828354, "8551": 0.11691460013389587, "8729": 0.674915611743927, "8775": 0.0174254160374403, "8778": 0.12384103983640671, "8822": 0.13925230503082275, "8830": 1.0464962720870972, "8832": 0.1751343309879303, "8930": 0.41195443272590637, "9312": 0.4654768109321594, "9349": 0.12470348179340363, "9367": 0.1332872211933136, "9450": 0.010684899985790253, "9556": 0.29255300760269165, "9560": 0.8925741910934448, "9634": 0.6950984001159668, "9657": 0.1619328260421753, "9723": 0.16524957120418549, "9740": 0.5871354341506958, "9756": 0.4879087805747986, "9867": 0.13414156436920166, "9871": 0.06977381557226181, "9885": 0.319873183965683, "9920": 1.0101795196533203, "10003": 0.10818854719400406, "10066": 0.03266380727291107, "10174": 0.07612881064414978, "10309": 0.0038986403960734606, "10316": 0.1401015669107437, "10408": 0.07884006202220917, "10426": 0.05046287178993225, "10472": 0.6911921501159668, "10502": 0.3423145115375519, "10548": 0.42608439922332764, "10552": 0.5168620347976685, "10564": 0.4228905141353607, "10640": 0.21135559678077698, "10697": 0.8756314516067505, "10723": 0.47463157773017883, "10771": 0.07884006202220917, "10847": 0.22079704701900482, "10903": 0.1994270235300064, "10920": 0.04394211992621422, "11020": 0.3910386264324188, "11028": 0.19782574474811554, "11100": 0.812664806842804, "11325": 0.21293537318706512, "11326": 0.11951763927936554, "11343": 0.06795065850019455, "11433": 0.7124901413917542, "11572": 0.4349733293056488, "11594": 0.10379679501056671, "11806": 1.068206787109375, "12027": 0.14179791510105133, "12044": 0.27934664487838745, "12335": 0.7144040465354919, "12353": 0.34715715050697327, "12435": 0.3005385100841522, "12504": 0.1401015669107437, "12596": 0.24554696679115295, "12654": 0.1946154683828354, "12697": 0.30558720231056213, "12763": 0.0009760859538801014, "12826": 0.3662964701652527, "12832": 0.7314660549163818, "13063": 0.791648268699646, "13070": 0.022212404757738113, "13105": 0.8323994874954224, "13114": 0.11081436276435852, "13180": 0.6160298585891724, "13323": 0.05046287178993225, "13385": 0.15275461971759796, "13416": 0.3106105625629425, "13483": 0.9178520441055298, "13494": 0.029824240133166313, "13599": 0.5461324453353882, "13859": 0.5629584193229675, "13882": 0.7809720039367676, "14025": 0.5278670787811279, "14155": 0.034552380442619324, "14300": 0.21372433006763458, "14455": 0.11081436276435852, "14664": 0.004870930220931768, "14667": 0.9379299283027649, "14893": 0.040196798741817474, "14972": 0.10026945173740387, "14997": 0.09495500475168228, "15050": 0.23247487843036652, "15252": 0.823009729385376, "15258": 0.05970508232712746, "15306": 0.7086513638496399, "15316": 1.154322862625122, "15338": 0.848413348197937, "15354": 0.21687394380569458, "15643": 0.016465263441205025, "15704": 0.7295845746994019, "15727": 0.3443928062915802, "15802": 0.1212492436170578, "15995": 0.3949938118457794, "16053": 0.9929623603820801, "16134": 0.1889725625514984, "16191": 0.0029254043474793434, "16210": 0.0029254043474793434, "16222": 0.10818854719400406, "16250": 0.06154331564903259, "16263": 0.5347557663917542, "16302": 0.07159364968538284, "16330": 0.21135559678077698, "16571": 0.07068414986133575, "16578": 0.2145126610994339, "16646": 0.13499516248703003, "16755": 0.5232481360435486, "17047": 0.056018441915512085, "17060": 0.09761575609445572, "17208": 0.16524957120418549, "17257": 0.16524957120418549, "17404": 0.05786345899105072, "17423": 0.23247487843036652, "17463": 0.2247048318386078, "17473": 0.5762182474136353, "17479": 0.19622190296649933, "17503": 0.2223619967699051, "17630": 0.029824240133166313, "17722": 0.09317722171545029, "17739": 0.16524957120418549, "17770": 0.15943801403045654, "17785": 0.11081436276435852, "17826": 0.04953393340110779, "17830": 0.1970241367816925, "17908": 0.34023189544677734, "17927": 0.151916041970253, "18046": 0.015504186972975731, "18154": 0.817850649356842, "18447": 0.6744182109832764, "18539": 0.4093637466430664, "18793": 0.306306391954422, "19388": 0.9635916948318481, "19804": 0.0019512200960889459, "19940": 0.26146242022514343, "19960": 0.5033760666847229, "20162": 0.3547199070453644, "20202": 0.06795065850019455, "20247": 0.755608320236206, "20253": 0.0752234235405922, "20422": 0.32058215141296387, "20523": 0.5174443125724792, "20793": 0.020300358533859253, "20960": 0.255429208278656, "20992": 0.4818955361843109, "21150": 0.500420093536377, "21557": 0.1685553640127182, "21718": 0.46117570996284485, "21887": 0.7124901413917542, "22110": 0.036437395960092545, "22283": 0.043007105588912964, "22597": 0.2409527748823166, "22684": 0.1602703034877777, "22935": 0.1229778528213501, "22963": 0.272677481174469, "23329": 0.0058422754518687725, "23363": 0.7333439588546753, "23614": 0.3519764244556427, "24054": 0.11691460013389587, "24117": 0.02412080205976963, "24343": 0.129004567861557, "24479": 0.2160874605178833, "24582": 0.9886114001274109, "24735": 0.10731173306703568, "24797": 0.3499138653278351, "24887": 0.1229778528213501, "25006": 0.10818854719400406, "25022": 0.6512666940689087, "25136": 0.06337817758321762, "25344": 0.029824240133166313, "25604": 0.8740028142929077, "26021": 0.07159364968538284, "26163": 0.9900637865066528, "26226": 0.20977331697940826, "26402": 0.06795065850019455, "26563": 0.1477125883102417, "26703": 0.20818853378295898, "26897": 0.07341018319129944, "26939": 0.18573370575904846, "27144": 0.14349138736724854, "27292": 1.0478670597076416, "27354": 0.1384023278951645, "27491": 0.010684899985790253, "27615": 0.3683255612850189, "27918": 0.17431432008743286, "28436": 0.20501139760017395, "28581": 0.10555581003427505, "28616": 0.03831886500120163, "28687": 0.1011524572968483, "28805": 0.04674193635582924, "28849": 0.09672962874174118, "29234": 0.42096930742263794, "29361": 0.0038986403960734606} | 12258338 | CONTEXT Pharmacist review of medication orders in the intensive care unit (ICU) has been shown to prevent errors, and pharmacist consultation has reduced drug costs. However, whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied. OBJECTIVE To measure the effect of pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events (ADEs) caused by ordering errors. DESIGN Before-after comparison between phase 1 (baseline) and phase 2 (after intervention implemented) and phase 2 comparison with a control unit that did not receive the intervention. SETTING A medical ICU (study unit) and a coronary care unit (control unit) in a large urban teaching hospital. PATIENTS Seventy-five patients randomly selected from each of 3 groups: all admissions to the study unit from February 1, 1993, through July 31, 1993 (baseline) and all admissions to the study unit (postintervention) and control unit from October 1, 1994, through July 7, 1995. In addition, 50 patients were selected at random from the control unit during the baseline period. INTERVENTION A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning, and was available on call throughout the day. MAIN OUTCOME MEASURES Preventable ADEs due to ordering (prescribing) errors and the number, type, and acceptance of interventions made by the pharmacist. Preventable ADEs were identified by review of medical records of the randomly selected patients during both preintervention and postintervention phases. Pharmacists recorded all recommendations, which were then analyzed by type and acceptance. RESULTS The rate of preventable ordering ADEs decreased by 66% from 10.4 per 1000 patient-days (95% confidence interval [CI], 7-14) before the intervention to 3.5 (95% CI, 1-5; P<.001) after the intervention. In the control unit, the rate was essentially unchanged during the same time periods: 10.9 (95% CI, 6-16) and 12.4 (95% CI, 8-17) per 1000 patient-days. The pharmacist made 366 recommendations related to drug ordering, of which 362 (99%) were accepted by physicians. CONCLUSIONS The presence of a pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors. Nearly all the changes were readily accepted by physicians. | Pharmacist participation on physician rounds and adverse drug events in the intensive care unit. |
{"1006": 0.02316705882549286, "1011": 0.23710809648036957, "1047": 0.812664806842804, "1997": 0.2089812457561493, "2000": 0.058784693479537964, "2005": 0.19541899859905243, "2007": 0.16690383851528168, "2029": 0.04207121208310127, "2064": 0.3930181860923767, "2075": 0.12642613053321838, "2099": 0.9485763907432556, "2109": 0.7239188551902771, "2116": 0.010684899985790253, "2125": 0.7881022095680237, "2129": 0.16607704758644104, "2169": 0.0842406153678894, "2182": 0.06154331564903259, "2184": 0.0019512200960889459, "2200": 0.4818955361843109, "2224": 0.3662964701652527, "2241": 0.055094651877880096, "2312": 0.42799583077430725, "2362": 0.016465263441205025, "2396": 0.3170322775840759, "2433": 0.30989447236061096, "2470": 0.25995752215385437, "2478": 0.29255300760269165, "2504": 0.018384648486971855, "2511": 0.4067663550376892, "2531": 0.1718502640724182, "2557": 0.030771657824516296, "2571": 0.37640097737312317, "2572": 0.12384103983640671, "2638": 0.5186077356338501, "2649": 0.5021947622299194, "2671": 0.05970508232712746, "2719": 0.23556606471538544, "2742": 0.22001366317272186, "2800": 0.2837681770324707, "2817": 0.57457035779953, "2825": 0.3127557039260864, "2832": 0.16110190749168396, "2844": 0.319873183965683, "2846": 0.02792670577764511, "2850": 0.8408597707748413, "2864": 0.04860413447022438, "2869": 0.016465263441205025, "2892": 0.32058215141296387, "2913": 0.5506471395492554, "2920": 0.00875066313892603, "2922": 0.18816383183002472, "2944": 0.13071982562541962, "2946": 0.0019512200960889459, "2974": 0.04953393340110779, "3078": 0.7482418417930603, "3098": 0.17840765416622162, "3117": 0.4437839686870575, "3170": 0.053244512528181076, "3231": 0.2852376699447632, "3252": 0.7647408246994019, "3273": 0.6583697199821472, "3319": 0.5584990978240967, "3370": 0.7201237678527832, "3375": 1.0546929836273193, "3384": 0.0842406153678894, "3435": 0.0058422754518687725, "3468": 0.36697331070899963, "3594": 0.21922965347766876, "3596": 0.20102575421333313, "3730": 0.11081436276435852, "3898": 0.66441810131073, "3905": 0.0038986403960734606, "3921": 0.5990082025527954, "3989": 0.011650617234408855, "4106": 0.43875885009765625, "4115": 0.02792670577764511, "4118": 0.7809720039367676, "4146": 0.1229778528213501, "4162": 0.09938567131757736, "4187": 0.5255602598190308, "4195": 0.6118015646934509, "4340": 0.6456501483917236, "4389": 0.9842413663864136, "4423": 0.3870677351951599, "4453": 0.03831886500120163, "4517": 1.001607894897461, "4539": 1.036847710609436, "4555": 0.1693800985813141, "4621": 0.0029254043474793434, "4659": 0.1619328260421753, "4710": 0.05786345899105072, "4725": 0.812664806842804, "4801": 0.15943801403045654, "4812": 0.8315495252609253, "4860": 0.12038381397724152, "4876": 0.3588210940361023, "4958": 0.9958525896072388, "4973": 0.11256109178066254, "5005": 0.00875066313892603, "5056": 0.7737906575202942, "5072": 0.2184450328350067, "5090": 0.4728073179721832, "5144": 0.1064341589808464, "5186": 0.03266380727291107, "5299": 0.17020416259765625, "5302": 0.5080875158309937, "5391": 1.276475191116333, "5410": 1.020087480545044, "5416": 0.4196864068508148, "5449": 0.06612417846918106, "5461": 0.6080870032310486, "5468": 0.1510767638683319, "5576": 0.6613984704017639, "5604": 0.31132611632347107, "5646": 0.46670228242874146, "5675": 0.06246116757392883, "5702": 0.0019512200960889459, "5716": 0.7987030148506165, "5741": 0.037378571927547455, "5753": 0.10379679501056671, "5770": 0.011650617234408855, "5787": 0.22001366317272186, "5813": 0.06337817758321762, "5851": 0.09495500475168228, "5852": 0.10379679501056671, "5906": 0.040196798741817474, "5911": 0.04207121208310127, "6028": 0.75193190574646, "6061": 0.18411032855510712, "6075": 0.6679295301437378, "6118": 0.3723714053630829, "6121": 0.3177432417869568, "6179": 0.08871890604496002, "6235": 0.0913962796330452, "6370": 0.4794800877571106, "6388": 0.27342069149017334, "6412": 0.1401015669107437, "6494": 0.022212404757738113, "6537": 0.11256109178066254, "6540": 0.2741633653640747, "6602": 0.1718502640724182, "6666": 0.20102575421333313, "6709": 0.007782140281051397, "6848": 0.20739519596099854, "6851": 0.43623676896095276, "6936": 0.47402387857437134, "6939": 1.3352066278457642, "6958": 0.04953393340110779, "6980": 0.13670019805431366, "6994": 0.04394211992621422, "7245": 0.2800849378108978, "7270": 0.29619070887565613, "7300": 0.4431571960449219, "7337": 0.38374659419059753, "7371": 0.966567873954773, "7512": 0.08692999184131622, "7551": 0.21922965347766876, "7594": 0.15359249711036682, "7645": 0.1229778528213501, "7709": 0.28890204429626465, "7718": 0.40806588530540466, "7801": 0.7239188551902771, "7818": 0.21214580535888672, "7860": 0.013579257763922215, "7885": 0.3141832649707794, "7889": 0.8625272512435913, "8031": 1.2910817861557007, "8060": 1.02149498462677, "8107": 0.49923527240753174, "8114": 0.20022670924663544, "8182": 0.49864232540130615, "8185": 0.022212404757738113, "8189": 0.6461620330810547, "8290": 0.6613984704017639, "8332": 0.7728893756866455, "8360": 0.20580662786960602, "8382": 0.40285754203796387, "8552": 0.21687394380569458, "8553": 0.31132611632347107, "8556": 0.4734157919883728, "8720": 0.0038986403960734606, "8778": 0.21530038118362427, "8790": 0.037378571927547455, "8849": 0.030771657824516296, "8920": 0.15526613593101501, "9128": 0.8117979168891907, "9138": 0.41195443272590637, "9186": 0.08154398202896118, "9211": 0.14095009863376617, "9307": 0.19862671196460724, "9312": 0.2231435477733612, "9373": 0.04207121208310127, "9398": 0.020300358533859253, "9412": 0.1064341589808464, "9416": 0.4487839937210083, "9447": 0.04674193635582924, "9462": 0.09938567131757736, "9483": 0.34023189544677734, "9547": 0.2184450328350067, "9593": 0.2837681770324707, "9751": 0.31845372915267944, "9839": 0.07250232994556427, "9896": 0.09406650811433792, "10003": 0.11951763927936554, "10163": 0.19381128251552582, "10266": 0.7755908370018005, "10351": 0.20660123229026794, "10473": 0.17759032547473907, "10556": 0.15860503911972046, "10572": 0.015504186972975731, "10610": 0.04207121208310127, "10641": 0.25694093108177185, "10708": 0.5116065740585327, "10737": 0.040196798741817474, "10788": 0.12384103983640671, "10847": 0.5800528526306152, "10949": 0.13499516248703003, "10988": 0.00875066313892603, "11207": 0.2105647772550583, "11211": 0.1734936386346817, "11251": 0.6181373596191406, "11321": 0.5168620347976685, "11326": 0.9394577741622925, "11343": 0.14179791510105133, "11382": 0.11604541540145874, "11487": 0.09317722171545029, "11538": 0.38574060797691345, "11628": 0.0009760859538801014, "11643": 0.12038381397724152, "11709": 0.20501139760017395, "11835": 0.33115679025650024, "11853": 0.4400174915790558, "12016": 0.3923587501049042, "12020": 0.20977331697940826, "12117": 0.13157635927200317, "12238": 0.4794800877571106, "12302": 0.1685553640127182, "12322": 0.2954642176628113, "12347": 0.5903874635696411, "12477": 0.0842406153678894, "12515": 0.42416930198669434, "12546": 0.27786844968795776, "12637": 0.8691008687019348, "12646": 0.09938567131757736, "12881": 0.08154398202896118, "13042": 0.05694137513637543, "13070": 0.04953393340110779, "13139": 0.21922965347766876, "13221": 1.1487655639648438, "13792": 0.09672962874174118, "13887": 0.4974553883075714, "13922": 0.0842406153678894, "13943": 0.1064341589808464, "13986": 0.255429208278656, "14037": 0.12642613053321838, "14064": 0.20022670924663544, "14126": 0.34508460760116577, "14187": 0.9394577741622925, "14207": 0.0797421783208847, "14336": 0.07341018319129944, "14366": 1.1947507858276367, "14442": 0.19622190296649933, "14573": 0.9886114001274109, "14679": 0.21214580535888672, "14856": 0.02887592278420925, "14889": 0.043007105588912964, "14991": 0.04674193635582924, "15113": 0.3423145115375519, "15148": 0.026025565341114998, "15420": 1.0116009712219238, "15431": 1.029200792312622, "15494": 0.20421554148197174, "15863": 0.48008447885513306, "16026": 0.025073638185858727, "16134": 1.034073829650879, "16330": 0.16442140936851501, "16463": 0.5618454217910767, "16578": 0.12038381397724152, "16730": 0.13243216276168823, "16744": 0.06429435312747955, "16771": 0.04860413447022438, "16853": 0.46608972549438477, "16902": 0.05694137513637543, "17011": 1.109619140625, "17225": 0.1358480453491211, "17541": 0.8152611255645752, "17592": 0.026976587250828743, "17737": 0.05786345899105072, "17779": 0.15943801403045654, "17785": 0.07341018319129944, "17826": 0.19622190296649933, "17830": 0.0174254160374403, "17908": 0.45623743534088135, "18044": 0.12556517124176025, "18178": 0.24859806895256042, "18639": 1.0973093509674072, "18711": 0.3683255612850189, "18845": 0.09761575609445572, "18861": 0.01934296265244484, "19034": 0.10291612148284912, "19064": 0.036437395960092545, "19202": 0.20580662786960602, "19441": 0.11256109178066254, "19613": 0.014542185701429844, "19780": 0.03831886500120163, "19882": 0.3870677351951599, "19934": 0.10818854719400406, "20155": 0.0913962796330452, "20253": 0.02412080205976963, "20302": 0.3743882179260254, "20502": 0.9515975713729858, "20766": 0.02412080205976963, "20770": 0.23092569410800934, "20792": 0.33953672647476196, "20817": 0.8195732831954956, "20828": 0.1734936386346817, "20886": 0.02316705882549286, "21117": 0.07431721687316895, "21150": 0.014542185701429844, "21225": 0.11517547070980072, "21245": 0.28082266449928284, "21471": 0.012615402229130268, "21579": 0.007782140281051397, "21677": 0.2990913391113281, "21775": 0.014542185701429844, "21792": 0.012615402229130268, "21800": 0.022212404757738113, "21935": 0.04674193635582924, "22100": 0.8109301924705505, "22248": 0.1718502640724182, "22360": 1.0986123085021973, "22616": 0.16607704758644104, "22718": 0.23015019297599792, "22945": 0.0019512200960889459, "23021": 0.09317722171545029, "23191": 0.12814582884311676, "23370": 0.6441128253936768, "23599": 0.0317181795835495, "23608": 0.02887592278420925, "23691": 0.1913948506116867, "23758": 1.2301886081695557, "23767": 0.22079704701900482, "23900": 0.5301685929298401, "24010": 0.05139094591140747, "24110": 0.12728634476661682, "24198": 0.11604541540145874, "24345": 0.24018502235412598, "24577": 0.18004031479358673, "24710": 0.11430477350950241, "24774": 0.21214580535888672, "24879": 0.5255602598190308, "25228": 0.9139442443847656, "25354": 0.8997484445571899, "25437": 0.1358480453491211, "25458": 0.8550800085067749, "26228": 0.3127557039260864, "26384": 0.030771657824516296, "26461": 0.07612881064414978, "26632": 0.9900637865066528, "26721": 0.045809537172317505, "27011": 0.1619328260421753, "27142": 0.22548456490039825, "27310": 0.14349138736724854, "27322": 0.16276304423809052, "27570": 0.004870930220931768, "27854": 1.4189581871032715, "28251": 0.6212902665138245, "28696": 0.07159364968538284, "29060": 0.22859740257263184, "29237": 0.015504186972975731, "29458": 0.045809537172317505, "29490": 0.18329764902591705} | 12265561 | The conformation of the ligand in complex with a macromolecular target can be studied by nuclear magnetic resonance (NMR) in solution for both tightly and weakly forming complexes. In the weak binding regime (k(off) > 10(4) Hz), the structure of the bound ligand is accessible also for very large complexes (>100 kDa), which are not amenable to NMR studies in the tight binding regime. Here I review the state-of-the-art NMR methodology used for screening ligands and for the structural investigation of bound ligand conformations, in both tight and weak binding regimes. The advantages and disadvantages of each approach are critically described. The NMR methodology used to investigate transiently forming complexes has expanded considerably in the past few years, opening new possibilities for a detailed description of ligand-target interactions. Novel methods for the determination of the bound ligand conformation, in particular transferred cross-correlated relaxation, are thoroughly reviewed, and their advantages with respect to established methodology are discussed, using the epothilone-tubulin complex as a primary example. | Ligand-target interactions: what can we learn from NMR? |
{"1014": 0.44753631949424744, "1043": 0.46853771805763245, "1045": 0.20022670924663544, "1052": 0.48670899868011475, "1997": 0.043007105588912964, "2000": 0.10906458646059036, "2035": 0.030771657824516296, "2042": 0.23556606471538544, "2045": 0.13414156436920166, "2047": 0.28155985474586487, "2064": 0.32058215141296387, "2075": 0.02412080205976963, "2079": 0.29619070887565613, "2083": 0.3127557039260864, "2109": 0.42608439922332764, "2116": 0.2719337046146393, "2129": 0.2918238639831543, "2193": 0.052318159490823746, "2213": 0.04860413447022438, "2224": 0.05417001247406006, "2226": 0.21530038118362427, "2235": 0.3601844012737274, "2278": 0.3464667797088623, "2291": 0.38441169261932373, "2339": 0.29328158497810364, "2361": 0.5596157908439636, "2373": 0.3464667797088623, "2427": 0.4752389192581177, "2430": 0.6882523894309998, "2445": 0.47463157773017883, "2458": 0.25845035910606384, "2470": 0.20977331697940826, "2478": 0.24171993136405945, "2491": 0.17759032547473907, "2515": 0.1808556467294693, "2529": 0.7258110046386719, "2532": 0.055094651877880096, "2555": 0.26146242022514343, "2572": 0.058784693479537964, "2592": 0.1619328260421753, "2594": 0.5370414853096008, "2609": 0.32058215141296387, "2625": 0.020300358533859253, "2640": 0.0019512200960889459, "2649": 0.18004031479358673, "2664": 0.39433568716049194, "2683": 0.4041621685028076, "2742": 0.3012613356113434, "2764": 0.13414156436920166, "2765": 0.18573370575904846, "2800": 0.09317722171545029, "2817": 0.06703783571720123, "2844": 0.27342069149017334, "2863": 0.9864287376403809, "2898": 0.8332487344741821, "2944": 0.6400018334388733, "2946": 0.34370049834251404, "2951": 0.8109301924705505, "3001": 0.11604541540145874, "3029": 0.40611594915390015, "3073": 0.12728634476661682, "3192": 0.347847044467926, "3252": 0.18492233753204346, "3273": 0.0029254043474793434, "3274": 0.11951763927936554, "3291": 0.12038381397724152, "3305": 0.8247235417366028, "3350": 0.7352184057235718, "3375": 0.5381823778152466, "3397": 0.4500300884246826, "3399": 0.22704219818115234, "3406": 0.5838727951049805, "3446": 0.4679262638092041, "3463": 0.4132472574710846, "3471": 0.08244366943836212, "3491": 0.11865071207284927, "3594": 0.02887592278420925, "3603": 0.4126010537147522, "3640": 0.030771657824516296, "3642": 0.04767346754670143, "3669": 0.619189441204071, "3697": 0.1229778528213501, "3787": 0.947819709777832, "3921": 0.5478278398513794, "3928": 0.09495500475168228, "3947": 0.08064348995685577, "4007": 0.010684899985790253, "4018": 0.21765978634357452, "4073": 0.3019835948944092, "4094": 0.9052929878234863, "4106": 0.42990362644195557, "4118": 0.41389304399490356, "4119": 0.7863243818283081, "4130": 0.20501139760017395, "4160": 0.6451379656791687, "4204": 0.17431432008743286, "4235": 0.2089812457561493, "4275": 0.32764431834220886, "4281": 0.9576126337051392, "4286": 0.5415972471237183, "4411": 0.2711893916130066, "4503": 0.18167030811309814, "4523": 0.05970508232712746, "4531": 0.05970508232712746, "4539": 0.08782484382390976, "4541": 0.09495500475168228, "4573": 0.5762182474136353, "4588": 0.44753631949424744, "4655": 0.520350456237793, "4725": 0.5438674688339233, "4758": 0.38041436672210693, "4812": 0.03925827145576477, "4820": 0.08871890604496002, "4824": 0.6363908052444458, "4838": 0.22937409579753876, "4839": 0.3381449282169342, "4863": 0.0317181795835495, "4868": 0.5662899017333984, "4875": 0.2719337046146393, "4928": 0.09317722171545029, "4949": 1.1192315816879272, "4962": 1.1629066467285156, "4973": 0.38041436672210693, "4975": 0.3656192123889923, "5041": 0.05786345899105072, "5173": 0.07431721687316895, "5187": 0.12728634476661682, "5319": 0.3012613356113434, "5383": 0.4679262638092041, "5387": 0.07159364968538284, "5436": 0.036437395960092545, "5449": 0.04207121208310127, "5456": 0.7647408246994019, "5461": 0.1946154683828354, "5502": 0.11604541540145874, "5531": 0.0606246218085289, "5537": 0.6400018334388733, "5656": 0.05786345899105072, "5717": 0.1873544454574585, "5783": 0.8408597707748413, "6013": 0.6441128253936768, "6022": 0.4794800877571106, "6028": 0.2539152204990387, "6064": 1.0278041362762451, "6165": 0.14686977863311768, "6179": 0.5186077356338501, "6270": 0.6492279767990112, "6325": 0.36967599391937256, "6377": 0.669430673122406, "6388": 0.5990082025527954, "6444": 0.14518201351165771, "6550": 0.1808556467294693, "6551": 0.07612881064414978, "6558": 0.04953393340110779, "6594": 0.07612881064414978, "6673": 0.006812678650021553, "6747": 0.5844172835350037, "6848": 0.2763880789279938, "6882": 0.18167030811309814, "6897": 0.6275664567947388, "6914": 0.12728634476661682, "6936": 0.42799583077430725, "6939": 0.1510767638683319, "6947": 0.0770333781838417, "7013": 0.1718502640724182, "7017": 0.1332872211933136, "7040": 0.6583697199821472, "7091": 0.12814582884311676, "7289": 0.15023678541183472, "7297": 0.04767346754670143, "7337": 0.08692999184131622, "7341": 0.9256220459938049, "7356": 0.5635144114494324, "7361": 0.49030399322509766, "7366": 0.846739649772644, "7367": 0.5612884759902954, "7403": 0.9256220459938049, "7523": 0.2719337046146393, "7551": 0.3588210940361023, "7645": 0.5838727951049805, "7667": 0.20501139760017395, "7705": 0.022212404757738113, "7711": 0.23402166366577148, "7721": 0.49864232540130615, "7778": 0.5893046259880066, "7809": 0.36967599391937256, "7816": 1.1798561811447144, "7860": 0.757441520690918, "7885": 0.3325583338737488, "7908": 0.15275461971759796, "8000": 0.9470623731613159, "8031": 0.11778303235769272, "8073": 0.1930064558982849, "8107": 0.3464667797088623, "8185": 0.567397952079773, "8290": 0.21135559678077698, "8299": 0.3241194784641266, "8315": 0.2317005842924118, "8321": 0.5489565134048462, "8346": 0.6218147873878479, "8552": 0.07341018319129944, "8556": 0.14433705806732178, "8740": 0.8600510358810425, "8824": 0.0038986403960734606, "8991": 0.7239188551902771, "9090": 0.6639154553413391, "9165": 1.035461664199829, "9259": 0.055094651877880096, "9335": 0.6249561905860901, "9350": 0.16690383851528168, "9381": 0.2983669638633728, "9539": 0.4891071021556854, "9556": 0.1384023278951645, "9581": 0.11517547070980072, "9699": 0.35813871026039124, "9706": 0.5318912267684937, "9756": 0.05970508232712746, "9798": 0.18248429894447327, "9839": 0.0058422754518687725, "9896": 0.4158279001712799, "10003": 0.026976587250828743, "10029": 0.18654440343379974, "10071": 0.47463157773017883, "10100": 0.1384023278951645, "10125": 0.021256839856505394, "10161": 0.4400174915790558, "10266": 0.5767669677734375, "10368": 0.5973974466323853, "10467": 0.13071982562541962, "10580": 0.2539152204990387, "10640": 0.7305257320404053, "10641": 0.07341018319129944, "10715": 0.004870930220931768, "10738": 1.335720419883728, "10744": 0.7144040465354919, "10769": 0.2622140049934387, "10827": 0.13925230503082275, "11157": 1.0768938064575195, "11233": 0.12470348179340363, "11432": 0.2160874605178833, "11568": 0.1485546976327896, "11619": 0.21765978634357452, "11643": 0.35334911942481995, "11717": 0.46608972549438477, "11718": 0.18004031479358673, "11767": 0.012615402229130268, "11772": 0.28743788599967957, "11778": 0.48068851232528687, "11835": 0.1751343309879303, "11989": 0.2018241584300995, "12016": 0.04860413447022438, "12105": 0.6522845029830933, "12107": 0.31132611632347107, "12139": 0.46914875507354736, "12222": 0.9857001900672913, "12328": 0.8893690705299377, "12359": 0.43434104323387146, "12375": 1.0137293338775635, "12376": 0.13414156436920166, "12504": 0.42990362644195557, "12596": 0.6773988008499146, "12644": 0.3297532796859741, "12702": 0.012615402229130268, "12728": 0.440646231174469, "12732": 0.7067264318466187, "12789": 0.27934664487838745, "12884": 0.812664806842804, "12987": 0.25088030099868774, "13100": 0.058784693479537964, "13113": 0.25995752215385437, "13115": 0.04394211992621422, "13159": 0.020300358533859253, "13296": 0.055094651877880096, "13369": 0.0019512200960889459, "13458": 1.1506214141845703, "13589": 0.7398891448974609, "13648": 0.1384023278951645, "13792": 0.3963087201118469, "13833": 0.28597161173820496, "13912": 0.11691460013389587, "13938": 0.2247048318386078, "14080": 0.08961215615272522, "14155": 0.4624064862728119, "14193": 0.5573811531066895, "14313": 0.1751343309879303, "14358": 0.3127557039260864, "14471": 0.6674286723136902, "14504": 0.7105726003646851, "14573": 0.21687394380569458, "14606": 0.08782484382390976, "14679": 0.00875066313892603, "14800": 0.176772341132164, "14828": 0.06612417846918106, "15078": 0.7737906575202942, "15113": 0.02887592278420925, "15176": 0.762009859085083, "15306": 0.46608972549438477, "15406": 0.10731173306703568, "15485": 0.8004589080810547, "15514": 0.4879087805747986, "15543": 0.3170322775840759, "15841": 0.07884006202220917, "15873": 0.07159364968538284, "16012": 0.6374238729476929, "16014": 0.040196798741817474, "16044": 0.1873544454574585, "16134": 0.4980490207672119, "16221": 0.11604541540145874, "16226": 1.2347444295883179, "16253": 0.6254787445068359, "16351": 0.09406650811433792, "16505": 0.12470348179340363, "16515": 0.06977381557226181, "16578": 0.14686977863311768, "16691": 0.13755162060260773, "16706": 0.2711893916130066, "16840": 0.567397952079773, "16861": 0.5450005531311035, "16910": 0.757441520690918, "17181": 0.0752234235405922, "17366": 0.920189380645752, "17409": 0.3877306580543518, "17547": 0.06977381557226181, "17592": 0.46117570996284485, "17666": 0.4145384132862091, "17701": 0.11865071207284927, "17715": 0.6999598741531372, "17834": 0.9333322048187256, "17908": 0.5370414853096008, "18155": 0.09495500475168228, "18168": 0.6882523894309998, "18259": 0.7352184057235718, "18547": 0.28670501708984375, "18780": 0.7683706283569336, "18953": 0.23324857652187347, "19345": 0.26146242022514343, "19421": 0.055094651877880096, "19518": 0.22937409579753876, "19539": 0.06246116757392883, "19587": 0.02316705882549286, "19723": 0.43434104323387146, "20155": 0.15359249711036682, "20253": 0.4580921530723572, "20350": 0.02412080205976963, "20353": 0.49982786178588867, "20470": 0.07884006202220917, "20532": 0.2145126610994339, "20600": 0.272677481174469, "21150": 0.0038986403960734606, "21197": 0.09850110858678818, "21472": 0.08782484382390976, "21477": 0.5186077356338501, "21486": 0.05046287178993225, "21520": 0.5162794589996338, "21575": 0.688742995262146, "21618": 0.6181373596191406, "21685": 0.3963087201118469, "21903": 0.015504186972975731, "21957": 0.8109301924705505, "22025": 0.12038381397724152, "22026": 0.7286425232887268, "22203": 0.32058215141296387, "22275": 1.0822023153305054, "22311": 0.0354953333735466, "22334": 0.41195443272590637, "22346": 0.13670019805431366, "22380": 0.026976587250828743, "22394": 0.05417001247406006, "22422": 0.09584271162748337, "22444": 0.030771657824516296, "22517": 0.3077431619167328, "22571": 0.48670899868011475, "22769": 0.31560876965522766, "23072": 0.7370892763137817, "23087": 0.839173436164856, "23191": 0.1905880719423294, "23274": 0.2493593990802765, "23777": 0.06520967930555344, "24010": 0.045809537172317505, "24286": 0.06612417846918106, "24558": 0.36967599391937256, "24710": 0.19782574474811554, "24848": 0.12814582884311676, "24902": 0.27712854743003845, "25095": 0.0058422754518687725, "25169": 0.4412745535373688, "25206": 0.1905880719423294, "25524": 0.7934166193008423, "25644": 0.46608972549438477, "25705": 0.0317181795835495, "25746": 0.3850763738155365, "25840": 0.36426326632499695, "25852": 0.9650808572769165, "26083": 0.27934664487838745, "26163": 0.16442140936851501, "26224": 0.09406650811433792, "26282": 0.058784693479537964, "26319": 0.33115679025650024, "26512": 0.034552380442619324, "26524": 0.10731173306703568, "26773": 0.7537717819213867, "26775": 0.02887592278420925, "27009": 0.3443928062915802, "27531": 0.1619328260421753, "27642": 0.010684899985790253, "27814": 0.14264501631259918, "28093": 0.1064341589808464, "28156": 0.23247487843036652, "28311": 0.06612417846918106, "28436": 0.7028654217720032, "28637": 0.0752234235405922, "29206": 0.33115679025650024, "29458": 0.151916041970253} | 12271486 | BACKGROUND A central challenge of biology is to map and understand gene regulation on a genome-wide scale. For any given genome, only a small fraction of the regulatory elements embedded in the DNA sequence have been characterized, and there is great interest in developing computational methods to systematically map all these elements and understand their relationships. Such computational efforts, however, are significantly hindered by the overwhelming size of non-coding regions and the statistical variability and complex spatial organizations of regulatory elements and interactions. Genome-wide catalogs of regulatory elements for all model species simply do not yet exist. RESULTS The MotifMap system uses databases of transcription factor binding motifs, refined genome alignments, and a comparative genomic statistical approach to provide comprehensive maps of candidate regulatory elements encoded in the genomes of model species. The system is used to derive new genome-wide maps for yeast, fly, worm, mouse, and human. The human map contains 519,108 sites for 570 matrices with a False Discovery Rate of 0.1 or less. The new maps are assessed in several ways, for instance using high-throughput experimental ChIP-seq data and AUC statistics, providing strong evidence for their accuracy and coverage. The maps can be usefully integrated with many other kinds of omic data and are available at http://motifmap.igb.uci.edu/. CONCLUSIONS MotifMap and its integration with other data provide a foundation for analyzing gene regulation on a genome-wide scale, and for automatically generating regulatory pathways and hypotheses. The power of this approach is demonstrated and discussed using the P53 apoptotic pathway and the Gli hedgehog pathways as examples. | MotifMap: integrative genome-wide maps of regulatory motif sites for model species |
{"1011": 0.05046287178993225, "1015": 0.3106105625629425, "1016": 0.3949938118457794, "1043": 0.7047978043556213, "1044": 0.42096930742263794, "1059": 0.5512100458145142, "1060": 0.2837681770324707, "1062": 0.9929623603820801, "2004": 1.0437490940093994, "2005": 0.29981520771980286, "2012": 0.29036402702331543, "2024": 0.034552380442619324, "2029": 0.013579257763922215, "2048": 0.2822965085506439, "2050": 0.06246116757392883, "2075": 0.25694093108177185, "2079": 0.24325250089168549, "2099": 0.46302130818367004, "2109": 0.14179791510105133, "2135": 0.5168620347976685, "2152": 0.04674193635582924, "2188": 0.48430517315864563, "2207": 0.4177590310573578, "2235": 0.13755162060260773, "2243": 0.44691193103790283, "2271": 0.05970508232712746, "2278": 0.176772341132164, "2470": 0.18248429894447327, "2475": 0.053244512528181076, "2487": 0.5330380201339722, "2491": 0.2983669638633728, "2504": 0.04487626627087593, "2512": 0.22157983481884003, "2515": 0.22392450273036957, "2521": 0.9052929878234863, "2522": 0.11865071207284927, "2527": 0.0174254160374403, "2535": 0.3034266233444214, "2549": 0.7276995778083801, "2556": 0.42353010177612305, "2561": 0.5313173532485962, "2575": 0.20580662786960602, "2683": 0.7009293437004089, "2713": 0.5255602598190308, "2765": 0.28890204429626465, "2817": 0.4831010699272156, "2828": 0.23864774405956268, "2860": 0.9658246636390686, "2895": 0.16607704758644104, "2896": 0.11865071207284927, "2913": 0.42096930742263794, "3231": 0.26146242022514343, "3273": 0.3409265875816345, "3283": 0.5871354341506958, "3401": 0.4196864068508148, "3424": 0.11168810725212097, "3435": 0.4286321699619293, "3445": 0.5324648022651672, "3447": 0.75193190574646, "3463": 0.3930181860923767, "3466": 0.6960725784301758, "3491": 0.15526613593101501, "3623": 0.6415454745292664, "3642": 0.009718249551951885, "3676": 0.7764897346496582, "3755": 0.09406650811433792, "3796": 0.804835319519043, "3798": 0.3381449282169342, "3853": 0.11778303235769272, "3858": 0.8212929964065552, "3896": 0.7445381283760071, "3928": 0.1619328260421753, "3949": 0.6674286723136902, "3979": 0.15275461971759796, "4005": 0.13755162060260773, "4106": 0.11691460013389587, "4125": 0.1477125883102417, "4176": 0.18329764902591705, "4308": 0.037378571927547455, "4319": 0.30558720231056213, "4355": 0.5795059204101562, "4359": 0.02412080205976963, "4530": 0.3077431619167328, "4621": 0.21214580535888672, "4719": 0.004870930220931768, "4758": 0.28155985474586487, "4812": 0.09317722171545029, "4852": 0.06337817758321762, "5038": 0.34715715050697327, "5072": 0.07431721687316895, "5092": 0.02887592278420925, "5171": 0.255429208278656, "5267": 0.8281423449516296, "5326": 0.2478361576795578, "5333": 0.38041436672210693, "5360": 0.1889725625514984, "5393": 0.5517725944519043, "5423": 0.13925230503082275, "5547": 0.10818854719400406, "5648": 1.0361549854278564, "5656": 0.6689305305480957, "5668": 0.0174254160374403, "5699": 0.7333439588546753, "5705": 0.175953671336174, "5769": 0.09938567131757736, "5845": 0.4337083101272583, "5850": 0.469759464263916, "5991": 0.777387797832489, "6022": 0.6482070088386536, "6074": 0.3824150264263153, "6162": 0.07250232994556427, "6190": 0.02887592278420925, "6388": 0.14518201351165771, "6461": 0.39893341064453125, "6528": 0.6808650493621826, "6551": 0.045809537172317505, "6591": 0.09050461649894714, "6614": 0.05139094591140747, "6638": 0.4574742913246155, "6666": 0.03831886500120163, "6678": 0.22782009840011597, "6693": 0.4487839937210083, "6807": 0.20580662786960602, "6812": 0.1401015669107437, "6864": 0.12038381397724152, "6939": 0.19622190296649933, "7011": 0.06886265426874161, "7012": 0.2447827309370041, "7085": 0.27786844968795776, "7096": 0.44566190242767334, "7242": 0.53589928150177, "7328": 0.0058422754518687725, "7337": 0.17431432008743286, "7438": 0.554580807685852, "7457": 0.5517725944519043, "7461": 0.45437926054000854, "7485": 0.10906458646059036, "7551": 0.08603433519601822, "7630": 0.12814582884311676, "7645": 0.4067663550376892, "7711": 0.34370049834251404, "7712": 0.3084607720375061, "7790": 0.4196864068508148, "7843": 0.4002431631088257, "7885": 0.20660123229026794, "8000": 0.2969166338443756, "8153": 0.3304552733898163, "8290": 0.15943801403045654, "8319": 0.5903874635696411, "8469": 0.06703783571720123, "8534": 0.38174858689308167, "8564": 0.6543170213699341, "8700": 0.7692760229110718, "8729": 0.022212404757738113, "8830": 0.08154398202896118, "8878": 0.4926934838294983, "8898": 0.09317722171545029, "9007": 0.4356052577495575, "9063": 0.5415972471237183, "9078": 0.14179791510105133, "9096": 0.0797421783208847, "9102": 0.932563841342926, "9289": 0.6471850275993347, "9312": 0.19541899859905243, "9314": 0.3163207769393921, "9328": 0.0797421783208847, "9333": 0.22079704701900482, "9350": 0.9363996982574463, "9416": 0.0019512200960889459, "9513": 0.15526613593101501, "9535": 0.08154398202896118, "9623": 0.15693697333335876, "9869": 0.2830325961112976, "9885": 0.43623676896095276, "9890": 0.1332872211933136, "9942": 0.5557019114494324, "9997": 0.056018441915512085, "9998": 0.24401791393756866, "10266": 0.04207121208310127, "10548": 0.4151833653450012, "10572": 0.8756314516067505, "10580": 0.1946154683828354, "10671": 0.417115718126297, "10738": 0.0174254160374403, "10768": 0.6369074583053589, "10769": 0.6492279767990112, "10847": 0.04767346754670143, "10851": 0.3963087201118469, "10924": 0.4337083101272583, "11290": 0.8492490649223328, "11387": 0.09584271162748337, "11432": 1.0587663650512695, "11463": 0.5936289429664612, "11835": 0.011650617234408855, "12123": 0.7546905279159546, "12170": 0.11430477350950241, "12207": 0.09850110858678818, "12222": 0.0058422754518687725, "12318": 0.2145126610994339, "12328": 0.66441810131073, "12407": 0.1751343309879303, "12654": 0.32199856638908386, "12737": 1.0894558429718018, "12740": 0.6960725784301758, "12765": 0.04674193635582924, "13004": 0.23479416966438293, "13070": 0.14095009863376617, "13096": 0.2089812457561493, "13275": 0.0752234235405922, "13331": 0.3269403576850891, "13341": 0.33953672647476196, "13416": 0.007782140281051397, "13441": 0.3956514894962311, "13531": 0.24018502235412598, "13791": 0.7969439625740051, "13833": 0.6405166387557983, "13845": 0.2983669638633728, "13986": 0.6512666940689087, "14061": 0.48970574140548706, "14067": 0.3241194784641266, "14080": 0.21922965347766876, "14095": 0.05417001247406006, "14277": 1.12432062625885, "14313": 0.006812678650021553, "14600": 0.41389304399490356, "14622": 0.1930064558982849, "14667": 0.4113073945045471, "14671": 1.1592369079589844, "14708": 0.22859740257263184, "14956": 0.2659635543823242, "15115": 0.055094651877880096, "15166": 0.1485546976327896, "15316": 0.02316705882549286, "15663": 0.06612417846918106, "15813": 0.055094651877880096, "15909": 0.6096806526184082, "15928": 0.10555581003427505, "15946": 0.1685553640127182, "16012": 0.06886265426874161, "16086": 0.04207121208310127, "16122": 0.1619328260421753, "16285": 0.3127557039260864, "16326": 0.812664806842804, "16330": 0.16524957120418549, "16480": 0.2447827309370041, "16670": 0.009718249551951885, "16691": 0.08961215615272522, "16834": 0.9302552938461304, "16844": 0.043007105588912964, "16888": 0.5404602885246277, "16913": 0.8901712894439697, "16950": 1.1456648111343384, "17059": 0.010684899985790253, "17086": 0.16359257698059082, "17261": 0.6689305305480957, "17282": 0.09584271162748337, "17350": 0.02887592278420925, "17379": 0.5584990978240967, "17441": 0.23710809648036957, "17629": 0.08692999184131622, "17886": 0.42608439922332764, "17913": 0.2501201331615448, "18089": 0.8845420479774475, "18178": 0.11517547070980072, "18260": 0.4425300657749176, "18410": 0.16690383851528168, "18423": 0.9568626880645752, "18452": 0.08782484382390976, "18622": 0.03831886500120163, "18639": 0.12814582884311676, "18647": 0.29255300760269165, "18714": 0.1011524572968483, "18804": 0.09672962874174118, "18969": 0.347847044467926, "19101": 0.7809720039367676, "19126": 0.7445381283760071, "19279": 1.3530324697494507, "19653": 0.6882523894309998, "20014": 1.1153976917266846, "20194": 0.08692999184131622, "20350": 1.156782865524292, "20544": 0.5562619566917419, "20549": 0.13414156436920166, "20598": 0.026025565341114998, "20766": 0.10906458646059036, "20828": 0.0038986403960734606, "20842": 0.23092569410800934, "20858": 0.16607704758644104, "20900": 0.0058422754518687725, "20915": 1.0828639268875122, "20952": 1.210591435432434, "20992": 0.2711893916130066, "20998": 0.11691460013389587, "21084": 1.0051883459091187, "21150": 0.22626367211341858, "21453": 1.0066169500350952, "21486": 0.10993985831737518, "21497": 0.27934664487838745, "21510": 0.21135559678077698, "21611": 0.9987343549728394, "21618": 0.11256109178066254, "21656": 0.22782009840011597, "21903": 0.23864774405956268, "21950": 0.4831010699272156, "22275": 0.01934296265244484, "22466": 0.036437395960092545, "22597": 1.1051015853881836, "22799": 0.13755162060260773, "22930": 0.021256839856505394, "22939": 0.36494144797325134, "22943": 0.04207121208310127, "23292": 1.086165428161621, "23467": 0.06337817758321762, "23564": 0.15777134895324707, "23586": 0.9417452812194824, "23974": 1.7341413497924805, "24054": 1.2443572282791138, "24063": 0.014542185701429844, "24171": 0.7408206462860107, "24950": 0.09228714555501938, "24952": 0.2160874605178833, "25194": 0.09228714555501938, "25246": 0.3170322775840759, "25456": 1.0986123085021973, "25502": 0.4537591338157654, "25643": 0.04207121208310127, "25644": 0.05139094591140747, "25714": 0.06886265426874161, "25808": 0.09406650811433792, "26033": 0.4679262638092041, "26187": 0.1212492436170578, "26402": 0.8255793452262878, "26677": 0.10555581003427505, "26721": 0.07341018319129944, "26773": 0.018384648486971855, "26942": 0.7389566898345947, "26976": 0.02412080205976963, "27144": 0.06520967930555344, "27441": 0.04953393340110779, "27605": 0.02316705882549286, "27833": 0.10993985831737518, "28156": 0.33115679025650024, "28696": 1.0960047245025635, "28756": 0.26146242022514343, "28848": 0.1734936386346817, "28965": 0.004870930220931768, "29290": 0.2145126610994339, "29333": 0.8829278349876404} | 12280462 | Bile acids are recognized as metabolic modulators. The present study was aimed at evaluating the effects of a potent Asbt inhibitor (264W94), which blocks intestinal absorption of bile acids, on glucose homeostasis in Zucker Diabetic Fatty (ZDF) rats. Oral administration of 264W94 for two wk increased fecal bile acid concentrations and elevated non-fasting plasma total Glp-1. Treatment of 264W94 significantly decreased HbA1c and glucose, and prevented the drop of insulin levels typical of ZDF rats in a dose-dependent manner. An oral glucose tolerance test revealed up to two-fold increase in plasma total Glp-1 and three-fold increase in insulin in 264W94 treated ZDF rats at doses sufficient to achieve glycemic control. Tissue mRNA analysis indicated a decrease in farnesoid X receptor (Fxr) activation in small intestines and the liver but co-administration of a Fxr agonist (GW4064) did not attenuate 264W94 induced glucose lowering effects. In summary, our results demonstrate that inhibition of Asbt increases bile acids in the distal intestine, promotes Glp-1 release and may offer a new therapeutic strategy for type 2 diabetes mellitus. | Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes. |
{"1011": 0.05970508232712746, "1015": 0.5696102976799011, "1039": 0.1946154683828354, "1052": 0.20660123229026794, "1996": 0.058784693479537964, "2002": 0.07341018319129944, "2007": 0.02316705882549286, "2010": 0.7445381283760071, "2011": 0.26146242022514343, "2012": 0.22937409579753876, "2026": 0.77198725938797, "2028": 0.3127557039260864, "2029": 0.18654440343379974, "2034": 0.4093637466430664, "2059": 0.19541899859905243, "2064": 0.32058215141296387, "2076": 0.17759032547473907, "2083": 0.2800849378108978, "2099": 0.6684301495552063, "2110": 0.46424978971481323, "2128": 0.1751343309879303, "2129": 0.26446542143821716, "2135": 0.07612881064414978, "2163": 0.6563454270362854, "2169": 0.1685553640127182, "2182": 0.036437395960092545, "2287": 0.1221139207482338, "2291": 0.637939989566803, "2302": 0.6759096384048462, "2306": 0.3388410806655884, "2309": 0.06337817758321762, "2320": 0.2674594223499298, "2362": 0.28670501708984375, "2377": 0.18167030811309814, "2430": 0.7898768186569214, "2440": 0.2674594223499298, "2448": 1.005902886390686, "2458": 0.956112265586853, "2470": 0.18978065252304077, "2483": 0.5795059204101562, "2487": 0.8813109993934631, "2491": 0.2034190446138382, "2504": 0.4617912769317627, "2511": 0.6769026517868042, "2535": 0.6348392367362976, "2537": 0.0174254160374403, "2546": 0.5838727951049805, "2565": 0.3723714053630829, "2595": 0.8917738795280457, "2649": 0.1212492436170578, "2652": 0.025073638185858727, "2666": 0.6931471824645996, "2743": 0.5174443125724792, "2754": 0.8425432443618774, "2764": 0.1602703034877777, "2770": 0.45499902963638306, "2817": 0.007782140281051397, "2832": 0.05046287178993225, "2913": 0.06246116757392883, "2920": 0.26296505331993103, "2921": 0.12470348179340363, "2928": 0.08961215615272522, "2944": 0.6348392367362976, "3001": 0.5092619061470032, "3025": 0.015504186972975731, "3111": 0.7124901413917542, "3145": 0.4400174915790558, "3160": 0.18816383183002472, "3161": 1.018678069114685, "3188": 0.7500885725021362, "3216": 0.5010119676589966, "3223": 0.24554696679115295, "3248": 0.18004031479358673, "3265": 0.5301685929298401, "3375": 0.7229714393615723, "3378": 0.04394211992621422, "3454": 0.1905880719423294, "3466": 0.24325250089168549, "3491": 0.053244512528181076, "3526": 0.49626702070236206, "3563": 0.8195732831954956, "3579": 0.3346569836139679, "3625": 0.20501139760017395, "3633": 0.12470348179340363, "3670": 0.9915141463279724, "3747": 0.07793712615966797, "3787": 0.47827014327049255, "3798": 0.2667117714881897, "3853": 0.5267143249511719, "3896": 0.1358480453491211, "3928": 0.34023189544677734, "3929": 0.018384648486971855, "3930": 0.0038986403960734606, "3961": 0.1332872211933136, "3980": 0.2689530849456787, "4023": 0.1930064558982849, "4130": 0.036437395960092545, "4195": 0.5261374711990356, "4208": 0.40285754203796387, "4242": 0.5882205963134766, "4275": 0.44753631949424744, "4395": 0.6000806093215942, "4403": 0.5104349255561829, "4442": 0.30486753582954407, "4503": 0.38574060797691345, "4523": 0.2478361576795578, "4539": 0.791648268699646, "4588": 0.5838727951049805, "4603": 0.08244366943836212, "4671": 0.18654440343379974, "4730": 0.3318578004837036, "4758": 0.39762192964553833, "4769": 0.34023189544677734, "4919": 0.09672962874174118, "4962": 1.0628231763839722, "4972": 0.3241194784641266, "4975": 0.5301685929298401, "4984": 0.9886114001274109, "5050": 0.21765978634357452, "5069": 0.5893046259880066, "5072": 0.12470348179340363, "5082": 0.18978065252304077, "5182": 0.08513788133859634, "5224": 0.8135309815406799, "5228": 0.3916989266872406, "5292": 0.25845035910606384, "5302": 0.306306391954422, "5323": 0.4734157919883728, "5360": 0.3676496744155884, "5387": 0.981317400932312, "5441": 0.7201237678527832, "5449": 0.16110190749168396, "5450": 0.5069117546081543, "5452": 0.04860413447022438, "5478": 0.29328158497810364, "5479": 0.1477125883102417, "5486": 0.19782574474811554, "5524": 0.47402387857437134, "5593": 0.08064348995685577, "5701": 0.8756314516067505, "5711": 0.6734226942062378, "5741": 0.06977381557226181, "5783": 0.3949938118457794, "5836": 0.23864774405956268, "5876": 0.8517522215843201, "5939": 0.0606246218085289, "5942": 0.3304552733898163, "6017": 0.4944818615913391, "6025": 0.02792670577764511, "6032": 0.8861536383628845, "6064": 0.4879087805747986, "6228": 0.0009760859538801014, "6337": 0.7295845746994019, "6370": 0.009718249551951885, "6388": 0.7201237678527832, "6431": 0.4132472574710846, "6459": 0.0317181795835495, "6540": 1.0855059623718262, "6560": 0.05417001247406006, "6562": 0.8567397594451904, "6873": 1.005902886390686, "6897": 0.021256839856505394, "7012": 0.0913962796330452, "7040": 0.3262358605861664, "7077": 0.1994270235300064, "7337": 0.9052929878234863, "7356": 0.7380234599113464, "7366": 0.35403475165367126, "7403": 0.7473171949386597, "7411": 0.3423145115375519, "7461": 0.6128603219985962, "7531": 0.2539152204990387, "7551": 0.6420594453811646, "7645": 0.5990082025527954, "7679": 0.15693697333335876, "7687": 0.20977331697940826, "7711": 0.5092619061470032, "7816": 0.9710156321525574, "7885": 0.7333439588546753, "7889": 0.6773988008499146, "8031": 0.8813109993934631, "8092": 0.1619328260421753, "8280": 0.20022670924663544, "8281": 0.17267228662967682, "8303": 0.176772341132164, "8332": 0.1485546976327896, "8338": 0.06886265426874161, "8355": 0.5849615335464478, "8360": 0.2105647772550583, "8382": 0.6664261221885681, "8498": 0.5696102976799011, "8878": 0.41840189695358276, "8979": 0.14939609169960022, "8991": 0.19541899859905243, "9007": 0.3519764244556427, "9031": 0.009718249551951885, "9099": 0.3615458607673645, "9165": 0.9944084882736206, "9211": 0.7898768186569214, "9247": 0.8973627090454102, "9279": 0.029824240133166313, "9319": 0.7333439588546753, "9416": 0.3870677351951599, "9563": 0.036437395960092545, "9662": 0.08961215615272522, "9675": 0.02887592278420925, "9690": 0.045809537172317505, "9756": 0.2034190446138382, "10381": 0.7881022095680237, "10467": 0.16607704758644104, "10580": 0.5220900774002075, "10595": 0.9739698171615601, "10610": 0.8682814836502075, "10737": 0.2478361576795578, "10738": 1.241539478302002, "10744": 0.0842406153678894, "10769": 0.6517757177352905, "10838": 0.030771657824516296, "10857": 0.14433705806732178, "11115": 0.083342544734478, "11165": 0.7182208299636841, "11211": 0.025073638185858727, "11423": 0.47402387857437134, "11596": 0.05970508232712746, "11643": 0.3877306580543518, "11658": 1.0540125370025635, "11799": 0.00875066313892603, "12222": 0.9621002674102783, "12335": 0.3191637098789215, "12473": 0.19220098853111267, "12504": 0.0913962796330452, "12506": 0.25239890813827515, "12562": 0.6317287683486938, "12662": 0.20501139760017395, "12732": 0.7827593088150024, "12786": 0.11604541540145874, "12987": 0.42608439922332764, "13248": 0.4145384132862091, "13433": 0.26820653676986694, "13458": 0.17840765416622162, "13531": 0.36290550231933594, "13595": 0.2034190446138382, "13683": 0.13414156436920166, "13782": 0.8212929964065552, "13791": 0.05786345899105072, "13819": 0.020300358533859253, "13833": 0.7445381283760071, "13908": 1.182852864265442, "13909": 0.9783848524093628, "13922": 0.2247048318386078, "14026": 0.052318159490823746, "14126": 0.22079704701900482, "14187": 0.37640097737312317, "14193": 1.34847891330719, "14258": 0.36494144797325134, "14313": 0.2954642176628113, "14442": 0.04394211992621422, "14471": 0.3897167444229126, "14480": 0.27564704418182373, "14606": 0.1401015669107437, "14800": 0.11604541540145874, "14828": 0.2800849378108978, "14967": 0.0038986403960734606, "15176": 0.7898768186569214, "15308": 0.1718502640724182, "15420": 0.8666408061981201, "15543": 0.43938836455345154, "15924": 0.22001366317272186, "15946": 0.00875066313892603, "16285": 0.09050461649894714, "16389": 0.2501201331615448, "16405": 1.3086495399475098, "16463": 0.0354953333735466, "16515": 0.00875066313892603, "16599": 0.08961215615272522, "16691": 0.3409265875816345, "16706": 0.3034266233444214, "16731": 0.045809537172317505, "16840": 0.07431721687316895, "16910": 0.6400018334388733, "16984": 0.28155985474586487, "17118": 0.3485364317893982, "17253": 0.045809537172317505, "17441": 0.12038381397724152, "17487": 0.417115718126297, "17785": 0.026976587250828743, "17820": 0.4728073179721832, "17879": 0.7086513638496399, "17890": 0.9037119746208191, "18349": 1.1537069082260132, "18479": 0.0842406153678894, "18549": 0.18573370575904846, "18856": 0.19541899859905243, "19009": 0.22001366317272186, "19199": 0.3588210940361023, "19220": 0.04207121208310127, "19518": 0.0058422754518687725, "19601": 0.1477125883102417, "19610": 0.9944084882736206, "19653": 0.2493593990802765, "19723": 0.12556517124176025, "19872": 0.732405424118042, "20116": 0.9240728616714478, "20199": 0.8332487344741821, "20350": 0.255429208278656, "20363": 1.0492360591888428, "20544": 0.015504186972975731, "20582": 1.2387138605117798, "20752": 0.04953393340110779, "20817": 0.4500300884246826, "20852": 0.06886265426874161, "20858": 0.1332872211933136, "21009": 0.35128939151763916, "21032": 0.4673144817352295, "21425": 0.2741633653640747, "21508": 0.6588751673698425, "21575": 0.7592713832855225, "21618": 0.8885661959648132, "21716": 0.9263957738876343, "21903": 0.2470736801624298, "21919": 0.052318159490823746, "22119": 0.41195443272590637, "22422": 0.20977331697940826, "22493": 0.12986256182193756, "22901": 0.4914994537830353, "23216": 0.2478361576795578, "23614": 0.06154331564903259, "23737": 0.22626367211341858, "23758": 0.2160874605178833, "24051": 0.4481603503227234, "24054": 0.05139094591140747, "24374": 0.6684301495552063, "24710": 0.1685553640127182, "24720": 0.012615402229130268, "24848": 0.058784693479537964, "24899": 0.03831886500120163, "25206": 0.7191727757453918, "25354": 0.9732321500778198, "25644": 0.8813109993934631, "26288": 0.04113444685935974, "26402": 0.04113444685935974, "26512": 0.371698260307312, "26520": 0.20739519596099854, "26534": 0.27044451236724854, "26616": 0.37371641397476196, "26773": 0.7220231294631958, "26775": 0.6492279767990112, "26927": 0.8925741910934448, "27295": 0.9029204845428467, "27642": 0.05970508232712746, "27673": 0.19622190296649933, "27697": 0.23633737862110138, "27790": 0.29255300760269165, "27854": 0.04953393340110779, "28086": 0.46117570996284485, "29101": 0.22392450273036957, "29129": 0.18329764902591705, "29206": 0.05694137513637543} | 12315072 | At the cellular level, development progresses through successive regulatory states, each characterized by their specific gene expression profile. However, the molecular mechanisms regulating first the priming and then maintenance of gene expression within one developmental pathway are essentially unknown. The hematopoietic system represents a powerful experimental model to address these questions and here we have focused on a regulatory circuit playing a central role in myelopoiesis: the transcription factor PU.1, its target gene colony-stimulating-factor 1 receptor (Csf1r), and key upstream regulators such as RUNX1. We find that during ontogeny, chromatin unfolding precedes the establishment of active histone marks and the formation of stable transcription factor complexes at the Pu.1 locus and we show that chromatin remodeling is mediated by the transient binding of RUNX1 to Pu.1 cis-elements. By contrast, chromatin reorganization of Csf1r requires prior expression of PU.1 together with RUNX1 binding. Once the full hematopoietic program is established, stable transcription factor complexes and active chromatin can be maintained without RUNX1. Our experiments therefore demonstrate how individual transcription factors function in a differentiation stage-specific manner to differentially affect the initiation versus maintenance of a developmental program. | Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program. |
{"1011": 0.0058422754518687725, "1038": 1.179255723953247, "1039": 0.04207121208310127, "2007": 0.0317181795835495, "2020": 0.026025565341114998, "2025": 0.1229778528213501, "2029": 0.24554696679115295, "2033": 0.1693800985813141, "2034": 0.13414156436920166, "2039": 0.5021947622299194, "2042": 0.055094651877880096, "2043": 0.1913948506116867, "2044": 0.01934296265244484, "2075": 0.0317181795835495, "2076": 0.5914691090583801, "2099": 0.2696990668773651, "2101": 0.016465263441205025, "2106": 0.15526613593101501, "2125": 0.10026945173740387, "2166": 0.19541899859905243, "2179": 0.08782484382390976, "2185": 0.25845035910606384, "2197": 0.14686977863311768, "2220": 0.8195732831954956, "2246": 0.12556517124176025, "2265": 0.016465263441205025, "2287": 0.49626702070236206, "2290": 0.8559102416038513, "2313": 0.5324648022651672, "2397": 0.6931471824645996, "2407": 0.25088030099868774, "2408": 0.3777405619621277, "2439": 0.06337817758321762, "2497": 0.26146242022514343, "2512": 0.8004589080810547, "2515": 0.18411032855510712, "2525": 0.18329764902591705, "2555": 0.2231435477733612, "2565": 0.31204116344451904, "2609": 0.25088030099868774, "2644": 0.3077431619167328, "2689": 0.5865923762321472, "2752": 0.2637155055999756, "2754": 0.8117979168891907, "2765": 0.05139094591140747, "2777": 0.45499902963638306, "2802": 0.1710275560617447, "2817": 0.040196798741817474, "2818": 0.4537591338157654, "2819": 0.49982786178588867, "2832": 0.02316705882549286, "2838": 0.016465263441205025, "2864": 0.012615402229130268, "2878": 0.7182208299636841, "2890": 0.3318578004837036, "2904": 0.6654226183891296, "2906": 0.1212492436170578, "2908": 0.07612881064414978, "2913": 0.013579257763922215, "2920": 0.4938860833644867, "2936": 0.16690383851528168, "2972": 0.5398913025856018, "3022": 0.29109421372413635, "3025": 0.1332872211933136, "3030": 0.1401015669107437, "3041": 0.39367714524269104, "3065": 0.11430477350950241, "3080": 0.09761575609445572, "3130": 0.3883931338787079, "3145": 0.3005385100841522, "3231": 0.11256109178066254, "3264": 0.05786345899105072, "3273": 0.27786844968795776, "3283": 0.029824240133166313, "3370": 0.9147270321846008, "3378": 0.6538092494010925, "3391": 0.176772341132164, "3431": 0.6853039860725403, "3445": 0.05417001247406006, "3454": 0.11430477350950241, "3463": 0.13925230503082275, "3466": 0.5947071313858032, "3491": 0.29328158497810364, "3508": 0.5517725944519043, "3526": 1.0066169500350952, "3563": 0.01934296265244484, "3603": 0.11343330889940262, "3662": 0.0842406153678894, "3668": 0.638455867767334, "3670": 0.00875066313892603, "3671": 0.6744182109832764, "3674": 0.31560876965522766, "3696": 0.06154331564903259, "3701": 0.2954642176628113, "3718": 0.31560876965522766, "3734": 0.17020416259765625, "3867": 0.16276304423809052, "3896": 0.5640701055526733, "3988": 0.020300358533859253, "4102": 0.020300358533859253, "4106": 0.31845372915267944, "4168": 0.025073638185858727, "4221": 0.5381823778152466, "4227": 0.22937409579753876, "4254": 0.45994341373443604, "4304": 0.4926934838294983, "4340": 0.4462870955467224, "4383": 0.15442965924739838, "4384": 0.06429435312747955, "4394": 0.05970508232712746, "4403": 0.5197699069976807, "4417": 0.06154331564903259, "4442": 0.9576126337051392, "4453": 0.11343330889940262, "4456": 0.9139442443847656, "4489": 0.1011524572968483, "4558": 0.056018441915512085, "4573": 0.637939989566803, "4647": 0.04113444685935974, "4653": 0.20022670924663544, "4655": 0.5596157908439636, "4703": 0.11951763927936554, "4760": 0.21214580535888672, "4866": 0.6674286723136902, "4872": 0.12728634476661682, "4895": 0.04207121208310127, "4942": 0.5466978549957275, "4962": 0.7500885725021362, "5114": 0.46363574266433716, "5158": 0.13670019805431366, "5159": 0.5180262327194214, "5182": 0.06886265426874161, "5244": 0.083342544734478, "5258": 0.026025565341114998, "5278": 0.3141832649707794, "5331": 0.13157635927200317, "5360": 0.7665573358535767, "5387": 0.47584590315818787, "5418": 0.7473171949386597, "5419": 0.6128603219985962, "5449": 0.06154331564903259, "5462": 0.6543170213699341, "5468": 0.11430477350950241, "5537": 0.5957841277122498, "5604": 0.0606246218085289, "5620": 0.3325583338737488, "5646": 0.22079704701900482, "5700": 0.6332852244377136, "5711": 0.8281423449516296, "5761": 0.07159364968538284, "5799": 0.4926934838294983, "5852": 0.06429435312747955, "5876": 0.4837033152580261, "5892": 0.3283478021621704, "5966": 0.151916041970253, "6022": 0.28670501708984375, "6024": 0.43623676896095276, "6064": 1.1524739265441895, "6168": 0.1212492436170578, "6366": 0.16442140936851501, "6438": 0.12986256182193756, "6459": 0.09672962874174118, "6480": 0.18411032855510712, "6529": 0.11865071207284927, "6689": 0.04767346754670143, "6698": 0.1905880719423294, "6762": 0.3034266233444214, "6835": 0.29328158497810364, "6897": 0.2447827309370041, "6903": 0.02792670577764511, "6913": 0.3388410806655884, "6914": 0.020300358533859253, "6923": 0.4158279001712799, "7017": 0.4002431631088257, "7060": 0.6363908052444458, "7068": 0.6327666640281677, "7080": 0.17840765416622162, "7337": 0.06154331564903259, "7356": 0.1693800985813141, "7366": 0.6254787445068359, "7403": 0.6070231795310974, "7461": 0.7546905279159546, "7551": 0.11865071207284927, "7578": 0.0058422754518687725, "7594": 0.42735910415649414, "7616": 0.2539152204990387, "7645": 0.2026219218969345, "7654": 0.12986256182193756, "7718": 0.10291612148284912, "7831": 0.11691460013389587, "7885": 0.2105647772550583, "7949": 0.4041621685028076, "8000": 0.0317181795835495, "8077": 0.7417513132095337, "8085": 0.8264343738555908, "8153": 0.10993985831737518, "8176": 0.3416208028793335, "8247": 0.37371641397476196, "8303": 0.4855078160762787, "8327": 0.2184450328350067, "8360": 0.5990082025527954, "8402": 0.3381449282169342, "8426": 1.0519683361053467, "8462": 0.9922385215759277, "8548": 0.12038381397724152, "8776": 0.2983669638633728, "8790": 1.1205062866210938, "8834": 0.16276304423809052, "8878": 0.10291612148284912, "8920": 0.05139094591140747, "8944": 0.23710809648036957, "8991": 0.4041621685028076, "9007": 0.10993985831737518, "9031": 0.06154331564903259, "9165": 0.9060825705528259, "9253": 0.6059582233428955, "9412": 0.8796916007995605, "9420": 0.2231435477733612, "9447": 0.8829278349876404, "9513": 0.6128603219985962, "9556": 0.04767346754670143, "9601": 0.43623676896095276, "9614": 0.06612417846918106, "9677": 0.8731874823570251, "9750": 0.05786345899105072, "9869": 0.053244512528181076, "9878": 0.3601844012737274, "9885": 0.05970508232712746, "9955": 0.10993985831737518, "9962": 0.27934664487838745, "10071": 0.3084607720375061, "10381": 0.0842406153678894, "10436": 0.8861536383628845, "10624": 0.3163207769393921, "10637": 0.12728634476661682, "10708": 0.4855078160762787, "10797": 0.5267143249511719, "10799": 0.055094651877880096, "10803": 0.020300358533859253, "10847": 0.14095009863376617, "10903": 0.0038986403960734606, "10949": 0.732405424118042, "11027": 0.12814582884311676, "11031": 0.9531047344207764, "11156": 0.1718502640724182, "11233": 0.29109421372413635, "11234": 0.00875066313892603, "11477": 0.1905880719423294, "11487": 0.06703783571720123, "11598": 1.0601204633712769, "11674": 0.18329764902591705, "11703": 0.20421554148197174, "11806": 0.0770333781838417, "11949": 0.29255300760269165, "12115": 0.09406650811433792, "12154": 0.25088030099868774, "12222": 0.14518201351165771, "12228": 0.23015019297599792, "12276": 0.14264501631259918, "12328": 0.1751343309879303, "12335": 0.38174858689308167, "12473": 0.5080875158309937, "12520": 0.8135309815406799, "12562": 0.4158279001712799, "12702": 0.4337083101272583, "12719": 0.00875066313892603, "12987": 0.1602703034877777, "13236": 0.04113444685935974, "13406": 0.6075552701950073, "13458": 0.8349450826644897, "13512": 0.0913962796330452, "13523": 0.996573805809021, "13531": 0.5584990978240967, "13595": 0.5220900774002075, "13599": 0.10467668622732162, "13637": 0.09317722171545029, "13656": 0.2394166737794876, "13685": 0.022212404757738113, "13791": 0.1889725625514984, "13819": 0.07159364968538284, "13874": 0.007782140281051397, "13912": 0.6654226183891296, "14080": 0.02412080205976963, "14193": 0.9021284580230713, "14376": 0.015504186972975731, "14446": 0.3241194784641266, "14471": 0.21687394380569458, "14489": 0.49982786178588867, "14494": 0.2105647772550583, "14562": 0.3423145115375519, "14670": 0.04394211992621422, "14798": 0.14349138736724854, "14828": 0.07341018319129944, "14863": 0.00875066313892603, "14996": 0.4974553883075714, "15115": 0.052318159490823746, "15308": 0.1619328260421753, "15330": 0.16524957120418549, "15370": 0.2763880789279938, "15476": 0.04767346754670143, "15527": 0.23787821829319, "15543": 0.12986256182193756, "15982": 0.021256839856505394, "16007": 0.17267228662967682, "16012": 0.26446542143821716, "16014": 0.09761575609445572, "16081": 0.0174254160374403, "16119": 0.8161250352859497, "16221": 0.5045560002326965, "16222": 0.846739649772644, "16330": 0.014542185701429844, "16340": 0.9317949414253235, "16360": 0.3870677351951599, "16387": 0.01934296265244484, "16442": 0.47463157773017883, "16463": 0.34370049834251404, "16515": 0.13243216276168823, "16578": 0.41195443272590637, "16705": 0.27044451236724854, "16706": 0.3683255612850189, "16736": 0.5336109399795532, "16873": 0.417115718126297, "17144": 0.603290855884552, "17183": 1.1695996522903442, "17215": 0.11256109178066254, "17459": 0.01934296265244484, "17786": 0.7881022095680237, "17908": 0.37371641397476196, "17913": 0.022212404757738113, "18133": 1.2238903045654297, "18195": 0.04487626627087593, "18212": 0.21765978634357452, "18274": 0.7683706283569336, "18419": 0.09672962874174118, "18804": 0.2317005842924118, "18924": 0.920189380645752, "18925": 0.04860413447022438, "19199": 0.06337817758321762, "19209": 0.2394166737794876, "19293": 0.5607312321662903, "19335": 0.22392450273036957, "19539": 0.1064341589808464, "19723": 0.1384023278951645, "19811": 0.10818854719400406, "19824": 0.056018441915512085, "20226": 0.5197699069976807, "20253": 0.23402166366577148, "20363": 0.6265231370925903, "20377": 0.8989537954330444, "20582": 1.3212348222732544, "20852": 0.2026219218969345, "21007": 1.0894558429718018, "21032": 0.6989894509315491, "21081": 0.04113444685935974, "21262": 0.05417001247406006, "21434": 0.1229778528213501, "21477": 0.09850110858678818, "21600": 0.03925827145576477, "21716": 0.6358738541603088, "21770": 0.6197150945663452, "21903": 0.19541899859905243, "21906": 0.08692999184131622, "22281": 0.14686977863311768, "22330": 0.058784693479537964, "22415": 0.8091925978660583, "22422": 0.14518201351165771, "22863": 0.09938567131757736, "22922": 0.055094651877880096, "22963": 0.004870930220931768, "23150": 0.03360854089260101, "23217": 0.07341018319129944, "23296": 0.11081436276435852, "23737": 0.0058422754518687725, "23900": 0.13670019805431366, "23943": 0.8925741910934448, "24051": 0.058784693479537964, "24374": 0.7105726003646851, "24558": 0.9650808572769165, "24759": 0.6338034868240356, "24848": 1.0881409645080566, "24866": 0.02316705882549286, "25003": 1.4615178108215332, "25145": 0.0058422754518687725, "25202": 0.0770333781838417, "25336": 0.06246116757392883, "25409": 0.5478278398513794, "25468": 0.1734936386346817, "25524": 0.1477125883102417, "25708": 0.0913962796330452, "25887": 0.4132472574710846, "25932": 0.10026945173740387, "26014": 0.06520967930555344, "26305": 0.08244366943836212, "26462": 0.7086513638496399, "26475": 0.11517547070980072, "26520": 0.14518201351165771, "26572": 0.3601844012737274, "26702": 0.06337817758321762, "26775": 0.0752234235405922, "26838": 0.20501139760017395, "26874": 0.12384103983640671, "26906": 0.1930064558982849, "26986": 0.006812678650021553, "27166": 0.15610189735889435, "27226": 0.08603433519601822, "27794": 0.2026219218969345, "28086": 0.0354953333735466, "28424": 0.07793712615966797, "28828": 0.07159364968538284, "28964": 0.1011524572968483, "29129": 0.4891071021556854, "29206": 0.30558720231056213, "29491": 0.5139457583427429, "29598": 0.18248429894447327} | 12324049 | We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation. | Whole-genome fingerprint of the DNA methylome during human B cell differentiation |
{"1011": 0.1930064558982849, "1021": 0.4537591338157654, "1038": 0.026025565341114998, "1999": 0.0019512200960889459, "2005": 0.07341018319129944, "2008": 0.04394211992621422, "2010": 0.14095009863376617, "2011": 0.2231435477733612, "2026": 0.9783848524093628, "2029": 0.26146242022514343, "2058": 0.417115718126297, "2078": 0.5860490798950195, "2079": 0.056018441915512085, "2109": 0.2026219218969345, "2121": 0.06246116757392883, "2152": 0.48670899868011475, "2155": 0.669430673122406, "2205": 0.08513788133859634, "2217": 0.09938567131757736, "2278": 0.49982786178588867, "2292": 1.2533208131790161, "2378": 0.11778303235769272, "2458": 0.5827828645706177, "2475": 0.05139094591140747, "2497": 0.8195732831954956, "2504": 0.11168810725212097, "2511": 0.09584271162748337, "2515": 0.3777405619621277, "2532": 0.6862877607345581, "2535": 0.6583697199821472, "2581": 0.6999598741531372, "2606": 0.053244512528181076, "2620": 0.39696553349494934, "2654": 0.672426164150238, "2659": 0.19220098853111267, "2676": 0.3339579105377197, "2698": 0.1710275560617447, "2765": 0.3077431619167328, "2832": 0.25467249751091003, "2863": 0.6343214511871338, "2920": 0.2018241584300995, "2944": 0.34370049834251404, "2945": 0.29036402702331543, "2953": 0.06337817758321762, "2981": 0.7047978043556213, "3020": 0.055094651877880096, "3231": 0.09050461649894714, "3258": 0.31132611632347107, "3283": 0.026976587250828743, "3284": 0.25239890813827515, "3367": 0.040196798741817474, "3378": 0.09938567131757736, "3426": 0.2018241584300995, "3433": 0.04207121208310127, "3445": 0.38574060797691345, "3463": 0.3005385100841522, "3466": 0.25088030099868774, "3491": 0.09050461649894714, "3508": 0.22548456490039825, "3526": 0.5209306478500366, "3623": 0.12384103983640671, "3625": 0.12556517124176025, "3662": 0.17840765416622162, "3670": 0.9783848524093628, "3671": 0.3683255612850189, "3796": 0.46608972549438477, "3798": 0.3554046154022217, "3811": 0.014542185701429844, "3818": 0.27786844968795776, "3853": 0.24248650670051575, "3891": 0.757441520690918, "3896": 0.3269403576850891, "3929": 0.31204116344451904, "3930": 0.14518201351165771, "3949": 0.03831886500120163, "4102": 0.05417001247406006, "4115": 0.27564704418182373, "4167": 0.5557019114494324, "4183": 0.5415972471237183, "4275": 0.04674193635582924, "4295": 0.036437395960092545, "4319": 0.03266380727291107, "4395": 0.4067663550376892, "4417": 0.38574060797691345, "4442": 0.6813592314720154, "4456": 1.15000319480896, "4496": 0.016465263441205025, "4503": 0.08154398202896118, "4504": 0.14602625370025635, "4539": 0.21135559678077698, "4671": 0.24325250089168549, "4742": 0.6446255445480347, "4748": 0.35128939151763916, "4758": 0.1619328260421753, "4783": 0.04860413447022438, "4795": 0.04394211992621422, "4796": 0.0038986403960734606, "4866": 0.36697331070899963, "4962": 0.8829278349876404, "4975": 0.08692999184131622, "5228": 0.4824984669685364, "5250": 0.7692760229110718, "5320": 0.05046287178993225, "5387": 0.3381449282169342, "5449": 0.052318159490823746, "5599": 0.5162794589996338, "5638": 0.11081436276435852, "5769": 0.014542185701429844, "5850": 0.16442140936851501, "5876": 0.14179791510105133, "5991": 0.32341301441192627, "6064": 0.14686977863311768, "6091": 0.02887592278420925, "6194": 0.3170322775840759, "6245": 0.09850110858678818, "6310": 0.026025565341114998, "6678": 0.3070250153541565, "6761": 0.025073638185858727, "7242": 0.4374985992908478, "7337": 0.21765978634357452, "7339": 0.0029254043474793434, "7356": 0.0317181795835495, "7389": 0.8682814836502075, "7403": 0.31845372915267944, "7438": 0.012615402229130268, "7457": 0.02887592278420925, "7461": 0.20818853378295898, "7645": 0.22704219818115234, "7711": 0.37974658608436584, "7755": 0.5701626539230347, "7816": 0.3409265875816345, "7875": 0.12384103983640671, "7889": 0.036437395960092545, "8000": 0.9287132620811462, "8077": 0.01934296265244484, "8153": 0.5517725944519043, "8171": 0.5827828645706177, "8247": 0.18248429894447327, "8290": 0.11081436276435852, "8303": 0.10818854719400406, "8319": 0.7295845746994019, "8428": 0.055094651877880096, "8534": 0.45499902963638306, "8840": 0.08871890604496002, "8898": 0.574020504951477, "8991": 0.5573811531066895, "9007": 0.5272908806800842, "9113": 0.5562619566917419, "9165": 0.49864232540130615, "9174": 0.16110190749168396, "9178": 0.2247048318386078, "9253": 0.2447827309370041, "9285": 0.3870677351951599, "9331": 0.7067264318466187, "9335": 0.2763880789279938, "9350": 0.2881702482700348, "9416": 0.13670019805431366, "9513": 0.12728634476661682, "9556": 0.16442140936851501, "9560": 0.24325250089168549, "9568": 0.06429435312747955, "9626": 0.22782009840011597, "9869": 0.46486347913742065, "9987": 0.10379679501056671, "9997": 0.034552380442619324, "10015": 0.022212404757738113, "10024": 0.17431432008743286, "10266": 0.15023678541183472, "10288": 0.4518963396549225, "10572": 0.6916812658309937, "10627": 0.03360854089260101, "10738": 0.304147332906723, "10831": 0.3662964701652527, "10851": 0.1905880719423294, "10924": 0.5734702348709106, "10976": 0.7239188551902771, "11082": 0.053244512528181076, "11099": 0.9271688461303711, "11265": 0.4891071021556854, "11335": 0.5381823778152466, "11409": 1.4413889646530151, "11422": 0.35950297117233276, "11423": 0.3416208028793335, "11432": 0.20739519596099854, "11649": 0.8039615154266357, "12115": 0.09938567131757736, "12222": 0.5920094847679138, "12322": 0.29255300760269165, "12328": 0.8933739066123962, "12618": 0.18411032855510712, "12702": 0.75193190574646, "12732": 0.7096124291419983, "12789": 0.956112265586853, "12798": 0.20739519596099854, "12837": 0.3547199070453644, "12863": 0.5941681861877441, "12987": 0.7647408246994019, "13026": 1.0073304176330566, "13091": 0.010684899985790253, "13105": 0.2184450328350067, "13321": 0.42990362644195557, "13331": 0.21530038118362427, "13458": 0.026025565341114998, "13656": 0.9958525896072388, "13712": 0.036437395960092545, "13791": 0.17840765416622162, "13833": 0.1930064558982849, "13908": 0.9485763907432556, "13922": 0.2561853528022766, "14026": 0.010684899985790253, "14080": 0.28450319170951843, "14095": 0.42096930742263794, "14193": 0.34508460760116577, "14494": 0.10379679501056671, "14526": 0.053244512528181076, "14719": 1.1413075923919678, "14800": 0.025073638185858727, "14828": 0.7408206462860107, "14863": 0.8161250352859497, "15115": 0.9147270321846008, "15136": 0.11604541540145874, "15176": 0.5871354341506958, "15251": 0.11517547070980072, "15316": 0.8039615154266357, "15527": 0.10555581003427505, "15538": 0.19381128251552582, "15543": 0.2531573474407196, "15660": 0.1930064558982849, "15698": 0.22782009840011597, "15756": 0.28082266449928284, "15946": 0.15777134895324707, "16007": 0.42735910415649414, "16026": 0.3982778787612915, "16033": 0.8796916007995605, "16081": 0.36967599391937256, "16221": 0.3297532796859741, "16285": 0.1602703034877777, "16341": 0.40806588530540466, "16554": 0.026025565341114998, "16706": 0.1718502640724182, "16910": 0.5607312321662903, "16913": 0.8289952278137207, "17245": 0.15442965924739838, "17261": 0.45870962738990784, "17379": 0.2105647772550583, "17631": 0.08244366943836212, "17938": 0.20501139760017395, "18062": 0.0797421783208847, "18178": 0.23787821829319, "18639": 0.18167030811309814, "18714": 0.567397952079773, "18969": 0.11081436276435852, "19188": 0.04767346754670143, "19199": 0.10467668622732162, "19653": 0.6107416749000549, "19811": 0.05417001247406006, "19824": 0.4400174915790558, "19872": 0.18004031479358673, "20110": 0.6405166387557983, "20350": 0.23402166366577148, "20360": 0.46670228242874146, "20567": 0.1619328260421753, "20582": 0.848413348197937, "20752": 0.30917787551879883, "20858": 0.07159364968538284, "20996": 0.06337817758321762, "21017": 0.1011524572968483, "21081": 0.4624064862728119, "21122": 0.03925827145576477, "21360": 0.2394166737794876, "21434": 0.848413348197937, "21575": 0.2749055027961731, "21618": 0.4349733293056488, "21823": 0.04767346754670143, "21903": 0.5261374711990356, "21919": 0.3297532796859741, "22026": 0.8349450826644897, "22066": 0.25995752215385437, "22319": 0.4926934838294983, "22407": 1.4037197828292847, "22422": 0.953857421875, "22694": 0.05417001247406006, "22907": 0.6487176418304443, "22931": 0.14686977863311768, "22989": 0.13670019805431366, "23130": 0.11168810725212097, "23216": 0.004870930220931768, "23217": 0.2018241584300995, "23586": 0.2983669638633728, "23737": 0.16607704758644104, "23833": 0.28155985474586487, "24054": 0.4512746334075928, "24169": 0.13499516248703003, "24269": 0.997294545173645, "24284": 0.1332872211933136, "24324": 0.7629209756851196, "24374": 0.01934296265244484, "24594": 0.4462870955467224, "24921": 0.058784693479537964, "25194": 0.04860413447022438, "25409": 0.7370892763137817, "25456": 0.17431432008743286, "25468": 0.1913948506116867, "25502": 0.6080870032310486, "25524": 0.4624064862728119, "25644": 0.10555581003427505, "25714": 0.5191890001296997, "26402": 0.2674594223499298, "26534": 0.1221139207482338, "26773": 0.8442239761352539, "26879": 0.06520967930555344, "26986": 0.05786345899105072, "27022": 0.5696102976799011, "27054": 0.4444103240966797, "27144": 0.22626367211341858, "27211": 0.036437395960092545, "27295": 0.056018441915512085, "27781": 0.35060185194015503, "27854": 0.3910386264324188, "27881": 0.06703783571720123, "28086": 0.16607704758644104, "28156": 0.1734936386346817, "28327": 0.12986256182193756, "28522": 1.1906025409698486, "28667": 0.5376120805740356, "28848": 0.2026219218969345, "28976": 0.3949938118457794, "29290": 0.14686977863311768, "29431": 0.0174254160374403} | 12337611 | LIN28B regulates developmental processes by modulating microRNAs (miRNAs) of the let-7 family. A role for LIN28B in cancer has been proposed but has not been established in vivo. Here, we report that LIN28B showed genomic aberrations and extensive overexpression in high-risk neuroblastoma compared to several other tumor entities and normal tissues. High LIN28B expression was an independent risk factor for adverse outcome in neuroblastoma. LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. LIN28B–let-7–MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells. These findings were fully recapitulated in a mouse model in which LIN28B expression in the sympathetic adrenergic lineage induced development of neuroblastomas marked by low let-7 miRNA levels and high MYCN protein expression. Interference with this pathway might offer therapeutic perspectives. | LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression |
{"1011": 0.3750596046447754, "1014": 0.28743788599967957, "1040": 0.14939609169960022, "1041": 0.47463157773017883, "1043": 0.15526613593101501, "1052": 0.6312094330787659, "1056": 0.9052929878234863, "2003": 0.23247487843036652, "2029": 0.13499516248703003, "2062": 0.07884006202220917, "2084": 0.17267228662967682, "2152": 0.7537717819213867, "2179": 0.2711893916130066, "2203": 0.7683706283569336, "2235": 0.9170717000961304, "2241": 0.07884006202220917, "2278": 0.10555581003427505, "2290": 0.32764431834220886, "2361": 0.7057625651359558, "2410": 0.03360854089260101, "2459": 0.22157983481884003, "2475": 0.3519764244556427, "2504": 0.34922540187835693, "2512": 0.9680526852607727, "2535": 0.3949938118457794, "2546": 0.35677260160446167, "2590": 0.21530038118362427, "2618": 0.05694137513637543, "2640": 0.1913948506116867, "2649": 0.5729197263717651, "2659": 0.2674594223499298, "2754": 0.11430477350950241, "2765": 0.28743788599967957, "2828": 0.07884006202220917, "2832": 0.026976587250828743, "2891": 0.6043586730957031, "2906": 0.02412080205976963, "2920": 0.6369074583053589, "3020": 0.18004031479358673, "3065": 0.03831886500120163, "3231": 0.20818853378295898, "3278": 0.004870930220931768, "3284": 0.4267219603061676, "3351": 0.13414156436920166, "3378": 0.7408206462860107, "3384": 0.11951763927936554, "3424": 0.5557019114494324, "3445": 0.3409265875816345, "3452": 0.5584990978240967, "3463": 0.46486347913742065, "3491": 0.5811457633972168, "3522": 0.2837681770324707, "3526": 0.777387797832489, "3550": 0.29109421372413635, "3563": 0.026976587250828743, "3572": 0.3084607720375061, "3590": 0.07793712615966797, "3623": 0.026025565341114998, "3643": 0.022212404757738113, "3662": 0.24171993136405945, "3670": 1.001607894897461, "3694": 1.0526502132415771, "3695": 1.0023250579833984, "3728": 0.5444341897964478, "3760": 0.12038381397724152, "3798": 0.4879087805747986, "3850": 0.2969166338443756, "3893": 0.8877626657485962, "3930": 0.9857001900672913, "3935": 0.22079704701900482, "3936": 0.2983669638633728, "3968": 0.04674193635582924, "3979": 0.503966212272644, "3989": 0.28743788599967957, "4008": 0.5127768516540527, "4013": 0.7067264318466187, "4094": 0.06337817758321762, "4106": 0.5220900774002075, "4195": 0.12038381397724152, "4295": 0.29619070887565613, "4328": 0.5415972471237183, "4372": 0.07250232994556427, "4395": 0.19862671196460724, "4402": 0.025073638185858727, "4442": 0.7028654217720032, "4456": 1.223315715789795, "4570": 0.3141832649707794, "4649": 0.10291612148284912, "4668": 0.1212492436170578, "4671": 0.2223619967699051, "4710": 0.020300358533859253, "4714": 0.12814582884311676, "4748": 0.3810817003250122, "4788": 0.2674594223499298, "4834": 0.02887592278420925, "4958": 0.3027053773403168, "4962": 0.46363574266433716, "4982": 0.06429435312747955, "4997": 0.8583967685699463, "5012": 0.07250232994556427, "5022": 0.30486753582954407, "5072": 0.1734936386346817, "5127": 0.979118824005127, "5159": 0.24631060659885406, "5173": 1.034073829650879, "5228": 0.5139457583427429, "5250": 0.10555581003427505, "5360": 0.30917787551879883, "5387": 1.02149498462677, "5393": 0.10906458646059036, "5396": 0.7537717819213867, "5443": 0.0606246218085289, "5577": 0.056018441915512085, "5603": 0.1677299439907074, "5666": 0.05417001247406006, "5769": 0.1873544454574585, "5776": 0.2763880789279938, "5840": 0.29981520771980286, "5850": 0.02412080205976963, "5852": 0.04860413447022438, "5876": 0.6950984001159668, "5970": 0.2822965085506439, "6064": 0.11691460013389587, "6083": 0.07068414986133575, "6132": 0.45932671427726746, "6190": 0.4462870955467224, "6235": 0.08692999184131622, "6388": 0.04860413447022438, "6470": 0.08064348995685577, "6592": 0.2976420819759369, "6612": 0.029824240133166313, "6624": 0.07793712615966797, "6643": 0.037378571927547455, "6721": 0.6931471824645996, "6887": 0.6265231370925903, "6914": 0.5887627601623535, "6936": 0.1221139207482338, "7012": 0.5882205963134766, "7017": 0.20580662786960602, "7022": 0.5057345628738403, "7290": 0.05139094591140747, "7356": 0.09672962874174118, "7366": 0.0797421783208847, "7461": 0.26820653676986694, "7485": 0.9232974052429199, "7487": 0.053244512528181076, "7591": 0.10731173306703568, "7645": 0.26446542143821716, "7657": 0.09938567131757736, "7667": 0.49982786178588867, "7691": 0.6016870141029358, "7730": 0.8247235417366028, "7816": 0.5180262327194214, "7831": 0.03831886500120163, "7870": 0.1011524572968483, "7875": 0.6999598741531372, "8153": 0.15693697333335876, "8249": 0.053244512528181076, "8319": 0.5701626539230347, "8382": 0.0009760859538801014, "8449": 0.040196798741817474, "8458": 0.4093637466430664, "8777": 0.28670501708984375, "8948": 0.9635916948318481, "9007": 1.1018621921539307, "9078": 0.06795065850019455, "9096": 0.25088030099868774, "9103": 0.7510106563568115, "9253": 0.29036402702331543, "9312": 0.23710809648036957, "9336": 0.15610189735889435, "9376": 0.7969439625740051, "9556": 0.18816383183002472, "9617": 0.03831886500120163, "9626": 0.056018441915512085, "9813": 0.603290855884552, "9908": 0.12642613053321838, "10047": 0.14264501631259918, "10074": 0.7491656541824341, "10253": 0.8117979168891907, "10479": 0.11865071207284927, "10509": 0.5404602885246277, "10572": 0.4891071021556854, "10672": 0.8117979168891907, "10722": 0.2696990668773651, "10735": 0.2223619967699051, "10737": 0.3615458607673645, "10738": 0.21687394380569458, "10744": 0.022212404757738113, "10752": 0.037378571927547455, "10803": 0.0797421783208847, "10857": 0.0797421783208847, "10893": 0.7258110046386719, "10927": 0.23015019297599792, "11022": 0.11604541540145874, "11156": 0.1693800985813141, "11192": 1.2910817861557007, "11311": 0.011650617234408855, "11368": 0.9100211262702942, "11375": 0.10555581003427505, "11423": 0.371698260307312, "11441": 0.34370049834251404, "11487": 0.0019512200960889459, "11616": 0.37974658608436584, "11631": 0.14433705806732178, "11707": 0.5104349255561829, "12115": 0.20818853378295898, "12222": 0.38308101892471313, "12456": 0.176772341132164, "12541": 0.6212902665138245, "12562": 0.053244512528181076, "12702": 0.07250232994556427, "12818": 0.1693800985813141, "12943": 0.503966212272644, "12987": 0.06246116757392883, "13045": 0.854249119758606, "13070": 0.1889725625514984, "13461": 0.6492279767990112, "13656": 0.7863243818283081, "13791": 0.1229778528213501, "13871": 0.09317722171545029, "13874": 0.5551415085792542, "13922": 0.5914691090583801, "14026": 0.22157983481884003, "14031": 0.1685553640127182, "14155": 0.2516399025917053, "14164": 0.6389714479446411, "14193": 0.10291612148284912, "14358": 0.2184450328350067, "14573": 0.7737906575202942, "14639": 0.2749055027961731, "14925": 1.1141164302825928, "14974": 0.20421554148197174, "15176": 0.18004031479358673, "15177": 1.0207915306091309, "15308": 0.6527929902076721, "15431": 0.06429435312747955, "15509": 0.18004031479358673, "15527": 0.2478361576795578, "15530": 0.5827828645706177, "15543": 0.14264501631259918, "15725": 0.15359249711036682, "15869": 0.6016870141029358, "15946": 0.08064348995685577, "16007": 0.17759032547473907, "16026": 0.953857421875, "16157": 0.17922431230545044, "16175": 0.05786345899105072, "16185": 0.04860413447022438, "16221": 0.3241194784641266, "16285": 0.9650808572769165, "16330": 0.46608972549438477, "16463": 0.030771657824516296, "16474": 0.06795065850019455, "16505": 0.8357921838760376, "16515": 0.8065804839134216, "16677": 0.2105647772550583, "16745": 0.7210738658905029, "16882": 0.9568626880645752, "17076": 1.3530324697494507, "17345": 0.0752234235405922, "17503": 0.20977331697940826, "17826": 0.004870930220931768, "17908": 0.13670019805431366, "18178": 0.9944084882736206, "18195": 0.2501201331615448, "18260": 0.27934664487838745, "18491": 0.1384023278951645, "18547": 0.11256109178066254, "18583": 0.05139094591140747, "18586": 0.009718249551951885, "18714": 0.6118015646934509, "18720": 0.05046287178993225, "18804": 0.2223619967699051, "18847": 0.38174858689308167, "18941": 0.9546096324920654, "18994": 0.06612417846918106, "19009": 0.4462870955467224, "19539": 0.2018241584300995, "19554": 0.14433705806732178, "19653": 0.8315495252609253, "19762": 0.07341018319129944, "19824": 0.5573811531066895, "19872": 0.18411032855510712, "20077": 0.045809537172317505, "20250": 0.1710275560617447, "20282": 0.07431721687316895, "20310": 0.3850763738155365, "20360": 0.7473171949386597, "20464": 0.5483922958374023, "20467": 0.09317722171545029, "20483": 0.5618454217910767, "20576": 0.02792670577764511, "20582": 0.17759032547473907, "20752": 0.5033760666847229, "20794": 0.14349138736724854, "20806": 0.2607102394104004, "21081": 0.47158926725387573, "21252": 0.09317722171545029, "21281": 0.347847044467926, "21434": 0.6011518239974976, "21449": 1.2975058555603027, "21575": 0.040196798741817474, "21618": 0.23787821829319, "21823": 0.06337817758321762, "21877": 0.043007105588912964, "21903": 0.3170322775840759, "21908": 0.2990913391113281, "21976": 0.319873183965683, "22471": 0.6118015646934509, "22731": 0.055094651877880096, "22851": 1.1012130975723267, "22931": 0.7942996621131897, "22991": 0.22626367211341858, "23041": 0.5133614540100098, "23216": 0.04207121208310127, "23713": 0.13414156436920166, "23737": 1.4794715642929077, "23746": 0.05786345899105072, "23760": 0.04953393340110779, "23797": 0.007782140281051397, "23900": 0.10291612148284912, "23924": 0.6363908052444458, "23969": 0.36494144797325134, "24054": 0.22704219818115234, "24269": 1.0087559223175049, "24278": 0.21922965347766876, "24501": 0.5860490798950195, "24587": 1.0030416250228882, "24663": 0.015504186972975731, "24759": 0.28670501708984375, "24848": 0.24248650670051575, "24872": 0.8074519634246826, "25002": 0.9717550277709961, "25090": 0.5370414853096008, "25409": 0.8195732831954956, "25468": 0.0174254160374403, "25540": 0.0317181795835495, "25644": 0.021256839856505394, "25708": 1.3804177045822144, "25714": 0.9409833550453186, "25778": 0.18492233753204346, "26305": 0.2409527748823166, "26702": 0.09050461649894714, "26721": 0.8039615154266357, "26745": 0.8374842405319214, "26773": 0.3027053773403168, "26886": 0.5267143249511719, "27144": 1.0628231763839722, "27295": 0.013579257763922215, "27321": 0.08064348995685577, "27605": 0.7942996621131897, "27781": 0.8083226680755615, "27881": 0.06795065850019455, "28027": 0.08064348995685577, "28873": 0.39893341064453125, "29107": 0.14264501631259918, "29206": 0.38308101892471313, "29290": 0.2659635543823242, "29441": 0.1358480453491211} | 12358173 | Angiogenesis is a recently described prognostic factor in non-small-cell lung cancer. Platelet-derived endothelial cell growth factor (PD-ECGF), shown to be the enzyme thymidine phosphorylase (TP), induces angiogenesis in vitro and in vivo. High intracellular levels of the enzyme are associated with increased chemosensitivity to pyrimidine antimetabolites. PD-ECGF/TP expression was evaluated immunohistochemically in surgically resected specimens from 107 patients with operable non-small-cell lung cancer using the P-GF,44C monoclonal antibody. High expression of PD-ECGF/TP was found in 25% of cases and was associated with high vascular grade (P = 0.01). Fourteen of 32 (44%) high vascular grade tumours showed a positive reactivity for PD-ECGF/TP vs 13/75 (17%) of low/medium vascular grade. Positive expression was observed more frequently in T2-staged cases than in T1 (P = 0.04). While overall survival was not affected (P = 0.09), subset analysis revealed that node-negative patients with positive PD-ECGF/TP expression had a worse prognosis (P = 0.04). The results suggest that PD-ECGF/TP may be an important molecule involved in angiogenesis in non-small-cell lung cancer. Up-regulation of the enzyme defines a more aggressive tumour phenotype in patients with node-negative disease. Assessment of vascular grade and PD-ECGF/TP expression should be taken into account in the design of randomized trials assessing the role of adjuvant chemotherapy in non-small-cell lung cancer. | Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in non-small-cell lung cancer. |
{"1018": 0.6086184978485107, "1041": 0.08603433519601822, "1044": 0.036437395960092545, "1050": 0.12038381397724152, "1061": 0.4512746334075928, "1997": 0.06520967930555344, "1998": 0.14686977863311768, "2029": 0.010684899985790253, "2035": 0.06977381557226181, "2039": 0.009718249551951885, "2043": 0.07341018319129944, "2062": 0.6296497583389282, "2066": 0.16690383851528168, "2090": 0.5607312321662903, "2102": 0.7220231294631958, "2109": 0.36900100111961365, "2111": 0.4855078160762787, "2116": 0.39762192964553833, "2126": 0.2881702482700348, "2129": 0.013579257763922215, "2135": 0.2983669638633728, "2152": 0.861702561378479, "2168": 0.02792670577764511, "2176": 0.823009729385376, "2179": 0.06886265426874161, "2224": 0.417115718126297, "2339": 0.13755162060260773, "2379": 0.12642613053321838, "2389": 0.6369074583053589, "2391": 0.00875066313892603, "2429": 0.4431571960449219, "2433": 0.3353555500507355, "2470": 0.6338034868240356, "2478": 0.2763880789279938, "2485": 0.07341018319129944, "2488": 0.03266380727291107, "2490": 0.4873090982437134, "2494": 0.19782574474811554, "2504": 1.1864371299743652, "2521": 0.48068851232528687, "2522": 0.36967599391937256, "2523": 0.9115922451019287, "2556": 0.18167030811309814, "2558": 0.6441128253936768, "2566": 0.32129061222076416, "2582": 0.030771657824516296, "2591": 0.7115318179130554, "2616": 0.45437926054000854, "2653": 0.045809537172317505, "2659": 0.26296505331993103, "2665": 0.4093637466430664, "2682": 0.3423145115375519, "2687": 0.23556606471538544, "2711": 0.19381128251552582, "2714": 0.6813592314720154, "2773": 0.304147332906723, "2804": 0.011650617234408855, "2812": 0.04767346754670143, "2817": 0.3656192123889923, "2846": 0.012615402229130268, "2896": 0.0797421783208847, "2913": 0.2954642176628113, "2936": 0.03831886500120163, "2944": 0.3297532796859741, "2959": 0.40481385588645935, "3012": 0.5618454217910767, "3020": 0.7647408246994019, "3141": 0.8374842405319214, "3168": 0.022212404757738113, "3215": 0.15526613593101501, "3231": 0.7500885725021362, "3273": 0.11081436276435852, "3276": 0.3269403576850891, "3284": 0.4337083101272583, "3292": 1.278652548789978, "3350": 0.015504186972975731, "3367": 0.6719275116920471, "3378": 0.4487839937210083, "3399": 0.9394577741622925, "3401": 0.5116065740585327, "3408": 0.0029254043474793434, "3445": 0.13414156436920166, "3553": 0.03831886500120163, "3569": 0.35950297117233276, "3579": 0.08692999184131622, "3594": 0.11081436276435852, "3596": 0.29255300760269165, "3618": 0.34370049834251404, "3623": 0.07341018319129944, "3648": 0.29473719000816345, "3686": 0.3283478021621704, "3798": 0.9271688461303711, "3811": 0.14264501631259918, "3818": 0.045809537172317505, "3971": 0.0038986403960734606, "3973": 0.2719337046146393, "4013": 0.5838727951049805, "4045": 0.06795065850019455, "4081": 0.012615402229130268, "4094": 0.3170322775840759, "4106": 0.2034190446138382, "4127": 0.04860413447022438, "4145": 0.14349138736724854, "4237": 0.04394211992621422, "4262": 0.1808556467294693, "4286": 0.06612417846918106, "4340": 0.052318159490823746, "4343": 0.083342544734478, "4402": 0.574020504951477, "4415": 0.05417001247406006, "4489": 0.12470348179340363, "4531": 0.1693800985813141, "4539": 0.8117979168891907, "4598": 0.034552380442619324, "4637": 0.07793712615966797, "4725": 0.03266380727291107, "4839": 0.5640701055526733, "4852": 0.16359257698059082, "4863": 0.0009760859538801014, "4876": 0.14095009863376617, "4928": 0.08961215615272522, "5071": 0.2089812457561493, "5177": 0.13157635927200317, "5443": 0.4974553883075714, "5468": 0.18411032855510712, "5482": 0.1602703034877777, "5531": 0.045809537172317505, "5603": 0.8083226680755615, "5604": 0.5370414853096008, "5622": 0.6709295511245728, "5646": 0.1064341589808464, "5760": 0.4831010699272156, "5761": 0.016465263441205025, "5799": 0.01934296265244484, "5852": 0.4879087805747986, "5919": 0.13157635927200317, "6011": 0.08692999184131622, "6028": 0.016465263441205025, "6123": 0.09938567131757736, "6129": 0.6420594453811646, "6179": 0.07431721687316895, "6180": 0.22704219818115234, "6210": 0.013579257763922215, "6388": 0.46117570996284485, "6428": 0.013579257763922215, "6431": 0.2983669638633728, "6447": 0.05694137513637543, "6526": 0.28743788599967957, "6550": 0.015504186972975731, "6553": 0.006812678650021553, "6660": 0.1011524572968483, "6699": 0.06246116757392883, "6741": 0.15442965924739838, "6747": 0.0354953333735466, "6753": 0.2881702482700348, "6802": 0.512191891670227, "6820": 1.126855492591858, "6825": 1.0437490940093994, "6832": 0.09584271162748337, "6950": 0.15777134895324707, "6958": 0.1889725625514984, "6972": 0.0174254160374403, "6993": 0.2607102394104004, "7189": 0.37035053968429565, "7290": 0.013579257763922215, "7339": 0.12814582884311676, "7372": 0.007782140281051397, "7461": 0.02316705882549286, "7474": 0.18654440343379974, "7551": 0.6492279767990112, "7563": 0.10467668622732162, "7645": 0.48430517315864563, "7667": 0.09317722171545029, "7718": 0.12642613053321838, "7778": 0.04767346754670143, "7868": 0.23556606471538544, "7885": 0.680370569229126, "7889": 0.8500841856002808, "8023": 0.014542185701429844, "8106": 0.7482418417930603, "8290": 0.1930064558982849, "8317": 1.1487655639648438, "8319": 0.10026945173740387, "8663": 0.22548456490039825, "8689": 0.08871890604496002, "8690": 0.10731173306703568, "8736": 0.1384023278951645, "8745": 0.0797421783208847, "8785": 0.05970508232712746, "8787": 0.2478361576795578, "8789": 0.5849615335464478, "8800": 0.26296505331993103, "8924": 0.7610978484153748, "9014": 0.040196798741817474, "9048": 0.8022117614746094, "9067": 0.7076893448829651, "9147": 0.026025565341114998, "9312": 0.28597161173820496, "9366": 0.6441128253936768, "9373": 0.34922540187835693, "9416": 0.15610189735889435, "9420": 0.06520967930555344, "9530": 0.8813109993934631, "9556": 0.5784112811088562, "9570": 0.23092569410800934, "9646": 0.9470623731613159, "9777": 0.20660123229026794, "9812": 0.890972912311554, "9854": 0.011650617234408855, "10039": 0.4067663550376892, "10061": 1.059443712234497, "10091": 0.08782484382390976, "10173": 0.1751343309879303, "10262": 0.2184450328350067, "10580": 0.5033760666847229, "10597": 0.11256109178066254, "10617": 0.06154331564903259, "10629": 0.026976587250828743, "10699": 0.2830325961112976, "10744": 0.43623676896095276, "10753": 0.08244366943836212, "10857": 0.08871890604496002, "10903": 0.2749055027961731, "11100": 0.18004031479358673, "11191": 0.6212902665138245, "11213": 0.755608320236206, "11338": 0.5734702348709106, "11455": 0.13071982562541962, "11507": 0.32553088665008545, "11835": 0.0019512200960889459, "11850": 0.2026219218969345, "12005": 0.022212404757738113, "12064": 0.05139094591140747, "12103": 0.9379299283027649, "12319": 0.2837681770324707, "12435": 0.37907835841178894, "12477": 0.0174254160374403, "12515": 0.0913962796330452, "12631": 0.009718249551951885, "12693": 0.31560876965522766, "12821": 0.9739698171615601, "12837": 0.13499516248703003, "13014": 0.14686977863311768, "13224": 0.3297532796859741, "13247": 0.15610189735889435, "13325": 0.6400018334388733, "13339": 0.1994270235300064, "13530": 0.04860413447022438, "13589": 1.0151457786560059, "14126": 0.12470348179340363, "14260": 0.015504186972975731, "14286": 0.46608972549438477, "14313": 0.2478361576795578, "14358": 0.11691460013389587, "14396": 0.4512746334075928, "14402": 0.5690577030181885, "14623": 0.4158279001712799, "14679": 0.02412080205976963, "14868": 0.2719337046146393, "14966": 0.619189441204071, "15034": 0.6931471824645996, "15142": 0.2749055027961731, "15525": 0.026976587250828743, "15850": 1.0144377946853638, "15963": 0.7182208299636841, "15965": 0.1229778528213501, "15980": 0.056018441915512085, "16014": 0.5151132941246033, "16157": 0.1221139207482338, "16383": 0.09672962874174118, "16416": 0.18411032855510712, "16454": 0.06429435312747955, "16646": 0.1619328260421753, "16691": 0.20818853378295898, "16756": 0.9680526852607727, "16902": 0.4932899475097656, "17158": 0.6543170213699341, "17289": 0.09850110858678818, "17522": 0.17840765416622162, "17537": 0.02792670577764511, "17547": 0.36290550231933594, "17568": 0.46914875507354736, "17635": 0.9394577741622925, "17686": 0.13755162060260773, "17994": 0.11865071207284927, "18224": 0.6466736793518066, "18933": 0.7791815400123596, "19064": 0.05417001247406006, "19141": 0.22626367211341858, "19389": 0.2954642176628113, "19639": 0.23710809648036957, "19817": 0.6265231370925903, "19835": 0.015504186972975731, "20077": 0.1229778528213501, "20086": 0.417115718126297, "20472": 0.0842406153678894, "20515": 0.12038381397724152, "20714": 0.26146242022514343, "20805": 0.08961215615272522, "20932": 0.25467249751091003, "21641": 0.18816383183002472, "21951": 0.06703783571720123, "22915": 0.3956514894962311, "23208": 0.0913962796330452, "23732": 0.0009760859538801014, "23760": 0.29255300760269165, "23900": 0.3757305145263672, "23991": 1.207676887512207, "24241": 0.6112717390060425, "24264": 1.070887804031372, "24344": 0.22859740257263184, "24504": 0.1873544454574585, "24655": 1.004473328590393, "24846": 0.20501139760017395, "24899": 0.1064341589808464, "25301": 0.13071982562541962, "25428": 0.7295845746994019, "25455": 0.025073638185858727, "25613": 0.9084475636482239, "25965": 0.1602703034877777, "26497": 0.10379679501056671, "26836": 0.3443928062915802, "26886": 0.00875066313892603, "27473": 0.03266380727291107, "28081": 0.1221139207482338, "28398": 0.06246116757392883, "28442": 0.52266925573349, "28551": 0.07793712615966797, "28937": 0.05694137513637543, "29333": 1.036847710609436, "29458": 0.6808650493621826} | 12364109 | According to construal level theory (N. Liberman, Y. Trope, & E. Stephan, in press; Y. Trope & N. Liberman, 2003), people use a more abstract, high construal level when judging, perceiving, and predicting more psychologically distal targets, and they judge more abstract targets as being more psychologically distal. The present research demonstrated that associations between more distance and higher level of construal also exist on a pure conceptual level. Eight experiments used the Implicit Association Test (IAT; A. G. Greenwald, D. E. McGhee, & J. L. K. Schwartz, 1998) to demonstrate an association between words related to construal level (low vs. high) and words related to four dimensions of distance (proximal vs. distal): temporal distance, spatial distance, social distance, and hypotheticality. In addition to demonstrating an association between level of construal and psychological distance, these findings also corroborate the assumption that all 4 dimensions of psychological distance are related to level of construal in a similar way and support the notion that they all are forms of psychological distance. | The association between psychological distance and construal level: evidence from an implicit association test. |
{"1037": 0.04487626627087593, "2003": 0.02887592278420925, "2051": 0.5404602885246277, "2063": 0.040196798741817474, "2064": 0.2983669638633728, "2065": 0.06795065850019455, "2071": 0.02887592278420925, "2079": 0.1889725625514984, "2109": 0.06612417846918106, "2121": 0.43244171142578125, "2129": 0.19541899859905243, "2170": 0.1229778528213501, "2179": 0.040196798741817474, "2182": 0.09317722171545029, "2291": 0.15693697333335876, "2302": 0.40871503949165344, "2311": 0.5080875158309937, "2315": 0.25995752215385437, "2335": 0.8272887468338013, "2339": 0.22079704701900482, "2362": 0.0058422754518687725, "2389": 0.05046287178993225, "2397": 0.27342069149017334, "2421": 0.21135559678077698, "2443": 0.2160874605178833, "2491": 0.1332872211933136, "2504": 0.32553088665008545, "2515": 0.2622140049934387, "2535": 0.25088030099868774, "2545": 0.09228714555501938, "2580": 0.037378571927547455, "2587": 0.3930181860923767, "2609": 0.4267219603061676, "2640": 0.6950984001159668, "2794": 0.0009760859538801014, "2804": 0.4145384132862091, "2832": 0.3304552733898163, "2836": 0.755608320236206, "2881": 0.46363574266433716, "2890": 0.21765978634357452, "2891": 0.4926934838294983, "2974": 0.01934296265244484, "3001": 0.09317722171545029, "3020": 0.0752234235405922, "3169": 0.009718249551951885, "3177": 0.4158279001712799, "3208": 0.040196798741817474, "3274": 0.18492233753204346, "3278": 0.022212404757738113, "3294": 0.2719337046146393, "3298": 0.4938860833644867, "3330": 0.22782009840011597, "3365": 0.06337817758321762, "3375": 0.9147270321846008, "3399": 0.06795065850019455, "3433": 0.7791815400123596, "3435": 0.46486347913742065, "3443": 0.44566190242767334, "3466": 0.440646231174469, "3491": 0.029824240133166313, "3526": 0.3601844012737274, "3584": 0.3012613356113434, "3635": 0.08961215615272522, "3638": 0.04113444685935974, "3693": 0.39367714524269104, "3698": 0.22392450273036957, "3710": 0.22782009840011597, "3739": 0.3554046154022217, "3747": 0.006812678650021553, "3754": 0.14686977863311768, "3787": 0.4374985992908478, "3796": 0.8100618124008179, "3798": 0.14602625370025635, "3800": 0.16690383851528168, "3853": 0.6223390698432922, "3857": 0.2689530849456787, "3896": 0.32058215141296387, "3941": 0.021256839856505394, "4030": 0.3870677351951599, "4062": 1.2398450374603271, "4140": 0.34300774335861206, "4162": 0.43623676896095276, "4198": 0.04207121208310127, "4240": 0.25239890813827515, "4245": 0.09584271162748337, "4254": 0.672426164150238, "4325": 0.21687394380569458, "4439": 0.4400174915790558, "4442": 0.3304552733898163, "4526": 0.24401791393756866, "4573": 0.6892333030700684, "4685": 0.18329764902591705, "4730": 0.14433705806732178, "4742": 0.49982786178588867, "4863": 0.021256839856505394, "4957": 0.0174254160374403, "4962": 1.1300151348114014, "4972": 0.40806588530540466, "4984": 1.1610734462738037, "4997": 0.5685047507286072, "5080": 0.9827804565429688, "5098": 0.01934296265244484, "5159": 0.2983669638633728, "5214": 0.2659635543823242, "5241": 0.4709797203540802, "5248": 1.0992631912231445, "5250": 0.5871354341506958, "5320": 0.06520967930555344, "5360": 0.4450363218784332, "5459": 0.23402166366577148, "5514": 0.304147332906723, "5521": 0.5685047507286072, "5533": 0.24325250089168549, "5546": 0.07612881064414978, "5547": 0.1602703034877777, "5617": 0.3464667797088623, "5733": 0.7445381283760071, "5783": 0.3374483287334442, "5799": 0.10379679501056671, "5854": 0.5973974466323853, "5859": 0.22859740257263184, "5915": 0.07068414986133575, "5991": 0.7969439625740051, "6022": 0.5110208988189697, "6064": 0.5562619566917419, "6075": 0.0842406153678894, "6146": 0.890972912311554, "6194": 0.3622259199619293, "6364": 0.05694137513637543, "6377": 0.013579257763922215, "6418": 0.26446542143821716, "6433": 0.15526613593101501, "6481": 0.48670899868011475, "6611": 0.3601844012737274, "6673": 0.11430477350950241, "6681": 0.00875066313892603, "6853": 1.1236859560012817, "6869": 0.37304413318634033, "6887": 0.6492279767990112, "6897": 0.14686977863311768, "6937": 0.9115922451019287, "6958": 0.8169882297515869, "7017": 0.1332872211933136, "7065": 0.02792670577764511, "7170": 1.5221424102783203, "7176": 0.025073638185858727, "7192": 0.21530038118362427, "7292": 0.058784693479537964, "7337": 0.31132611632347107, "7366": 0.32905077934265137, "7403": 1.17624831199646, "7461": 0.7067264318466187, "7507": 0.41195443272590637, "7528": 0.18248429894447327, "7645": 0.4794800877571106, "7711": 0.04953393340110779, "7755": 0.4879087805747986, "7816": 0.37102460861206055, "7885": 0.1011524572968483, "7915": 0.21530038118362427, "7945": 0.04674193635582924, "7953": 0.5914691090583801, "7961": 0.31204116344451904, "7976": 0.016465263441205025, "8031": 0.8813109993934631, "8050": 0.5920094847679138, "8122": 0.13755162060260773, "8139": 0.1994270235300064, "8171": 0.5057345628738403, "8209": 0.6664261221885681, "8223": 0.09938567131757736, "8292": 0.6533012986183167, "8360": 0.32905077934265137, "8394": 0.8013357520103455, "8458": 0.5734702348709106, "8536": 0.9621002674102783, "8552": 0.24859806895256042, "8566": 0.013579257763922215, "8745": 0.8433839678764343, "8783": 0.13071982562541962, "8980": 0.20739519596099854, "8991": 0.25694093108177185, "9005": 0.083342544734478, "9007": 0.29400965571403503, "9015": 0.043007105588912964, "9090": 0.12556517124176025, "9164": 0.6684301495552063, "9165": 0.9842413663864136, "9223": 0.07884006202220917, "9239": 0.6892333030700684, "9289": 1.035461664199829, "9297": 0.4512746334075928, "9319": 0.08244366943836212, "9358": 0.19622190296649933, "9367": 0.0029254043474793434, "9407": 0.175953671336174, "9671": 0.33325836062431335, "9794": 0.28670501708984375, "9839": 0.3141832649707794, "9859": 0.4286321699619293, "9885": 0.5133614540100098, "10210": 0.5936289429664612, "10327": 0.22001366317272186, "10394": 0.18004031479358673, "10408": 0.2830325961112976, "10438": 0.02887592278420925, "10467": 0.11256109178066254, "10502": 0.8805016279220581, "10548": 0.29255300760269165, "10578": 1.1726272106170654, "10580": 0.39696553349494934, "10595": 0.22001366317272186, "10673": 0.6160298585891724, "10738": 0.8161250352859497, "10752": 0.11604541540145874, "10851": 0.28450319170951843, "10859": 0.4126010537147522, "10960": 0.1994270235300064, "11066": 0.846739649772644, "11099": 0.1510767638683319, "11157": 0.02887592278420925, "11336": 1.1281205415725708, "11365": 0.7728893756866455, "11383": 0.015504186972975731, "11477": 0.034552380442619324, "11486": 0.3423145115375519, "11610": 0.09850110858678818, "11619": 0.28670501708984375, "11674": 0.007782140281051397, "11949": 0.14349138736724854, "12033": 0.2493593990802765, "12222": 0.3923587501049042, "12285": 0.13499516248703003, "12381": 0.5551415085792542, "12430": 0.4419025182723999, "12452": 0.20421554148197174, "12473": 0.34023189544677734, "12477": 0.010684899985790253, "12508": 0.14602625370025635, "12553": 1.033379077911377, "12697": 0.42096930742263794, "12702": 0.40871503949165344, "12987": 0.2018241584300995, "13248": 1.0881409645080566, "13308": 0.083342544734478, "13340": 0.20818853378295898, "13369": 0.23864774405956268, "13458": 0.436867892742157, "13531": 0.4709797203540802, "13532": 0.08064348995685577, "13671": 0.304147332906723, "13685": 0.25995752215385437, "13782": 1.0933903455734253, "13909": 1.1444218158721924, "13938": 0.20580662786960602, "14080": 0.2145126610994339, "14120": 0.43938836455345154, "14184": 1.1947507858276367, "14187": 0.28450319170951843, "14193": 0.841701865196228, "14260": 0.6212902665138245, "14313": 0.15693697333335876, "14350": 0.6629094481468201, "14443": 0.13414156436920166, "14471": 0.839173436164856, "14613": 0.0606246218085289, "14670": 0.46853771805763245, "14709": 0.06154331564903259, "14800": 0.2749055027961731, "14828": 0.055094651877880096, "14917": 0.13157635927200317, "15007": 0.4093637466430664, "15115": 0.0354953333735466, "15176": 0.09317722171545029, "15258": 0.02792670577764511, "15316": 0.05046287178993225, "15380": 0.14095009863376617, "15420": 0.22704219818115234, "15492": 0.2317005842924118, "15543": 0.0317181795835495, "15592": 0.5816917419433594, "15643": 0.1619328260421753, "15660": 0.07884006202220917, "15665": 0.8861536383628845, "16012": 0.417115718126297, "16045": 0.06154331564903259, "16221": 0.09761575609445572, "16487": 0.3870677351951599, "16505": 0.10731173306703568, "16582": 0.5021947622299194, "16691": 0.22782009840011597, "16706": 0.06886265426874161, "16913": 0.06520967930555344, "16984": 0.1332872211933136, "17266": 1.0437490940093994, "17372": 0.0009760859538801014, "17468": 0.5893046259880066, "17592": 0.16690383851528168, "17698": 0.06977381557226181, "17913": 0.3297532796859741, "18278": 0.08692999184131622, "18439": 0.09584271162748337, "18478": 0.27342069149017334, "18549": 0.12470348179340363, "18570": 0.26146242022514343, "18639": 0.07884006202220917, "18678": 0.347847044467926, "18757": 0.0842406153678894, "19001": 1.018678069114685, "19160": 0.7647408246994019, "19209": 0.35403475165367126, "19345": 0.6186635494232178, "19762": 0.8583967685699463, "19780": 0.025073638185858727, "20235": 0.9425065517425537, "20353": 0.5822374224662781, "20407": 0.3743882179260254, "20483": 0.1930064558982849, "20600": 0.06795065850019455, "20681": 0.20660123229026794, "20817": 0.26446542143821716, "21162": 0.015504186972975731, "21425": 0.5882205963134766, "21446": 0.9232974052429199, "21485": 0.13755162060260773, "21575": 0.1889725625514984, "21618": 0.3622259199619293, "21716": 0.500420093536377, "21890": 0.23402166366577148, "21957": 0.1734936386346817, "22026": 0.1946154683828354, "22164": 0.42608439922332764, "22747": 0.8450632095336914, "23217": 0.25694093108177185, "23467": 0.18004031479358673, "23468": 0.10731173306703568, "23663": 0.29400965571403503, "23809": 0.01934296265244484, "24038": 0.13243216276168823, "24122": 0.17020416259765625, "24203": 0.1384023278951645, "24251": 0.0606246218085289, "24558": 0.03266380727291107, "25100": 0.2837681770324707, "25524": 0.2223619967699051, "25644": 0.03266380727291107, "26591": 0.08244366943836212, "26651": 0.1994270235300064, "26702": 0.09850110858678818, "26979": 0.03831886500120163, "27441": 0.13071982562541962, "27531": 0.0770333781838417, "27928": 0.03266380727291107, "28433": 0.15442965924739838, "28582": 0.11168810725212097, "28731": 0.7656494975090027, "28732": 0.10906458646059036, "29172": 0.4412745535373688, "29297": 1.1708117723464966, "29391": 0.0019512200960889459, "29494": 0.037378571927547455} | 12370190 | The behavior of gene modules in complex synthetic circuits is often unpredictable. After joining modules to create a circuit, downstream elements (such as binding sites for a regulatory protein) apply a load to upstream modules that can negatively affect circuit function. Here we devised a genetic device named a load driver that mitigates the impact of load on circuit function, and we demonstrate its behavior in Saccharomyces cerevisiae. The load driver implements the design principle of timescale separation: inclusion of the load driver's fast phosphotransfer processes restores the capability of a slower transcriptional circuit to respond to time-varying input signals even in the presence of substantial load. Without the load driver, we observed circuit behavior that suffered from a 76% delay in response time and a 25% decrease in system bandwidth due to load. With the addition of a load driver, circuit performance was almost completely restored. Load drivers will serve as fundamental building blocks in the creation of complex, higher-level genetic circuits. | A load driver device for engineering modularity in biological networks |
{"1011": 0.5215105414390564, "1038": 0.47766464948654175, "1048": 0.21530038118362427, "1055": 0.31204116344451904, "2004": 0.022212404757738113, "2005": 0.5033760666847229, "2012": 0.15275461971759796, "2029": 0.06429435312747955, "2033": 0.4093637466430664, "2063": 0.06703783571720123, "2080": 0.8981585502624512, "2109": 0.2034190446138382, "2143": 0.6446255445480347, "2172": 0.37304413318634033, "2184": 0.5045560002326965, "2303": 0.2145126610994339, "2322": 0.6233867406845093, "2361": 0.31845372915267944, "2489": 0.42353010177612305, "2515": 0.12470348179340363, "2566": 0.006812678650021553, "2571": 0.6096806526184082, "2575": 0.6669275164604187, "2618": 0.1602703034877777, "2632": 0.4734157919883728, "2677": 0.45932671427726746, "2705": 0.08782484382390976, "2721": 0.6634125709533691, "2764": 0.0019512200960889459, "2765": 0.2622140049934387, "2846": 0.034552380442619324, "2856": 0.6603899002075195, "2891": 0.5174443125724792, "2895": 0.20501139760017395, "2896": 0.12642613053321838, "2915": 0.09495500475168228, "2944": 0.3381449282169342, "2951": 0.43244171142578125, "2966": 0.058784693479537964, "2970": 0.5685047507286072, "3081": 0.14349138736724854, "3152": 0.46670228242874146, "3161": 0.06520967930555344, "3185": 0.05694137513637543, "3231": 0.021256839856505394, "3273": 0.03925827145576477, "3351": 0.39762192964553833, "3366": 0.18654440343379974, "3430": 0.669430673122406, "3446": 0.06337817758321762, "3447": 0.613389253616333, "3463": 0.5220900774002075, "3466": 0.5909284353256226, "3491": 0.08244366943836212, "3512": 0.4932899475097656, "3550": 0.2478361576795578, "3593": 0.34922540187835693, "3597": 0.4617912769317627, "3623": 0.15023678541183472, "3630": 0.6911921501159668, "3635": 0.7134475708007812, "3726": 0.6170841455459595, "3798": 0.02792670577764511, "3808": 0.026976587250828743, "3815": 0.026976587250828743, "3893": 0.0770333781838417, "3896": 0.5301685929298401, "3921": 0.5092619061470032, "3949": 0.43244171142578125, "3989": 0.6684301495552063, "4005": 0.15442965924739838, "4022": 1.1469062566757202, "4047": 0.16607704758644104, "4053": 0.22079704701900482, "4118": 0.567397952079773, "4130": 0.23324857652187347, "4168": 0.6613984704017639, "4200": 0.10906458646059036, "4227": 0.25845035910606384, "4275": 0.07612881064414978, "4319": 0.28450319170951843, "4372": 0.5568217039108276, "4383": 0.4879087805747986, "4456": 0.13414156436920166, "4475": 0.7987030148506165, "4523": 0.1913948506116867, "4539": 0.07884006202220917, "4544": 0.7229714393615723, "4621": 0.22626367211341858, "4652": 0.8796916007995605, "4705": 0.8247235417366028, "4725": 0.6704301834106445, "4758": 0.14179791510105133, "4810": 0.6139179468154907, "4862": 1.2244645357131958, "4872": 0.16442140936851501, "4939": 0.5197699069976807, "4971": 0.2539152204990387, "5022": 0.015504186972975731, "5072": 0.3750596046447754, "5114": 0.8408597707748413, "5229": 0.02887592278420925, "5301": 0.42990362644195557, "5335": 0.43244171142578125, "5423": 1.3367470502853394, "5461": 0.2160874605178833, "5505": 0.14518201351165771, "5531": 0.32764431834220886, "5576": 0.04487626627087593, "5591": 0.10026945173740387, "5666": 0.7592713832855225, "5850": 0.43875885009765625, "6026": 0.17020416259765625, "6028": 0.3877306580543518, "6074": 0.25694093108177185, "6178": 0.2667117714881897, "6190": 0.6502478122711182, "6310": 0.018384648486971855, "6361": 0.1401015669107437, "6370": 0.1332872211933136, "6441": 0.5284429788589478, "6444": 0.19541899859905243, "6553": 0.5517725944519043, "6612": 0.25845035910606384, "6614": 0.2478361576795578, "6638": 0.0038986403960734606, "6648": 0.13243216276168823, "6666": 0.16110190749168396, "6693": 0.3241194784641266, "6761": 0.04207121208310127, "6779": 0.0797421783208847, "6887": 0.3464667797088623, "6897": 0.06246116757392883, "6939": 0.05139094591140747, "7028": 0.18654440343379974, "7091": 0.6022219061851501, "7170": 0.36290550231933594, "7242": 0.7601850032806396, "7274": 0.4145384132862091, "7337": 0.015504186972975731, "7356": 0.4891071021556854, "7361": 0.02412080205976963, "7374": 0.31489628553390503, "7438": 0.37304413318634033, "7461": 0.19862671196460724, "7547": 0.371698260307312, "7620": 0.5795059204101562, "7629": 0.025073638185858727, "7632": 0.6853039860725403, "7645": 0.26446542143821716, "7709": 0.08782484382390976, "7834": 0.3526630103588104, "7895": 0.08603433519601822, "8000": 0.9455460906028748, "8029": 0.17922431230545044, "8082": 0.004870930220931768, "8107": 0.43053874373435974, "8197": 0.08154398202896118, "8209": 0.8323994874954224, "8377": 0.3883931338787079, "8449": 0.8408597707748413, "8553": 0.27934664487838745, "8564": 0.5290185213088989, "8700": 0.9432673454284668, "8729": 0.4794800877571106, "8778": 0.018384648486971855, "8803": 0.012615402229130268, "8878": 0.006812678650021553, "8920": 0.06337817758321762, "8948": 0.9628462791442871, "9007": 0.09228714555501938, "9063": 0.0317181795835495, "9229": 0.18004031479358673, "9280": 0.14264501631259918, "9308": 0.0752234235405922, "9312": 0.11865071207284927, "9350": 0.3777405619621277, "9412": 0.6451379656791687, "9416": 0.006812678650021553, "9474": 0.013579257763922215, "9556": 0.09938567131757736, "9560": 0.0606246218085289, "9711": 1.1929750442504883, "9740": 0.4002431631088257, "9754": 0.7629209756851196, "9821": 0.026976587250828743, "9855": 0.07341018319129944, "9859": 0.23710809648036957, "9956": 0.07884006202220917, "9998": 0.6170841455459595, "10003": 0.1751343309879303, "10015": 0.9531047344207764, "10109": 0.0174254160374403, "10572": 0.7683706283569336, "10578": 0.5341835021972656, "10610": 0.1913948506116867, "10673": 0.0842406153678894, "10723": 0.3019835948944092, "10744": 0.08064348995685577, "10769": 0.6107416749000549, "10847": 0.029824240133166313, "10882": 0.8065804839134216, "11087": 0.7163142561912537, "11157": 0.24859806895256042, "11192": 1.141931176185608, "11261": 0.47827014327049255, "11325": 0.7105726003646851, "11432": 0.36290550231933594, "11439": 0.2652147710323334, "11460": 0.7728893756866455, "11508": 0.997294545173645, "11548": 0.2501201331615448, "11598": 0.3141832649707794, "11628": 0.2689530849456787, "11637": 0.28890204429626465, "11733": 0.13157635927200317, "11867": 1.452418565750122, "12123": 0.0058422754518687725, "12154": 0.4764525294303894, "12248": 0.01934296265244484, "12328": 0.9576126337051392, "12353": 0.07793712615966797, "12391": 0.08513788133859634, "12448": 0.083342544734478, "12462": 0.6543170213699341, "12618": 1.117955207824707, "12728": 0.19541899859905243, "12944": 0.4196864068508148, "13004": 0.7201237678527832, "13046": 0.17840765416622162, "13070": 0.030771657824516296, "13102": 0.804835319519043, "13105": 0.02792670577764511, "13186": 0.029824240133166313, "13246": 0.43875885009765625, "13341": 0.3241194784641266, "13494": 0.13071982562541962, "13791": 0.11951763927936554, "13833": 0.6430866718292236, "13859": 0.17267228662967682, "13922": 0.0752234235405922, "14061": 0.25467249751091003, "14192": 0.034552380442619324, "14277": 0.29255300760269165, "14405": 0.5562619566917419, "14604": 0.15943801403045654, "14667": 0.4311734735965729, "14856": 0.8973627090454102, "14887": 0.015504186972975731, "14956": 0.0174254160374403, "15000": 0.12814582884311676, "15238": 0.083342544734478, "15306": 0.512191891670227, "15459": 0.7333439588546753, "15460": 0.2184450328350067, "15596": 0.1064341589808464, "15665": 0.052318159490823746, "15869": 0.6038249135017395, "15871": 0.026025565341114998, "15946": 0.23710809648036957, "16012": 0.5651806592941284, "16134": 0.5209306478500366, "16183": 0.06886265426874161, "16263": 0.4512746334075928, "16275": 0.015504186972975731, "16330": 0.04113444685935974, "16464": 0.16359257698059082, "16519": 0.04674193635582924, "16530": 0.2576959431171417, "16605": 0.21293537318706512, "16913": 0.23864774405956268, "16940": 0.7969439625740051, "17042": 0.14939609169960022, "17261": 0.932563841342926, "17379": 0.11951763927936554, "17468": 0.1710275560617447, "17473": 0.02792670577764511, "17668": 0.009718249551951885, "17695": 0.8608771562576294, "17830": 0.004870930220931768, "18178": 0.1751343309879303, "18468": 0.056018441915512085, "18479": 0.09495500475168228, "18583": 0.030771657824516296, "18585": 1.147526502609253, "18714": 0.15442965924739838, "18715": 0.05970508232712746, "18847": 0.953857421875, "18857": 0.32553088665008545, "19009": 0.02316705882549286, "19101": 0.26446542143821716, "19137": 1.246605634689331, "19314": 0.4812922179698944, "19478": 0.8788808584213257, "19531": 0.11430477350950241, "19570": 0.04394211992621422, "19601": 0.00875066313892603, "19653": 0.5784112811088562, "19872": 0.9900637865066528, "20187": 0.791648268699646, "20194": 0.129004567861557, "20219": 0.16359257698059082, "20228": 0.1685553640127182, "20752": 0.1693800985813141, "20806": 0.6838265657424927, "20828": 0.4462870955467224, "20858": 0.034552380442619324, "20900": 0.3027053773403168, "20906": 0.0317181795835495, "20936": 0.13670019805431366, "20992": 0.27934664487838745, "21150": 0.34922540187835693, "21223": 0.39762192964553833, "21497": 0.18411032855510712, "21656": 0.5957841277122498, "21733": 0.5696102976799011, "21890": 0.6583697199821472, "21908": 0.3601844012737274, "22320": 0.02887592278420925, "22359": 0.05417001247406006, "22415": 0.14518201351165771, "22423": 0.037378571927547455, "22500": 0.2105647772550583, "22597": 0.03831886500120163, "22684": 0.6921701431274414, "22953": 0.036437395960092545, "22991": 0.1677299439907074, "23191": 0.004870930220931768, "23586": 0.23092569410800934, "23692": 0.9470623731613159, "23722": 1.2117549180984497, "23736": 0.04860413447022438, "24054": 0.7665573358535767, "24163": 0.672426164150238, "24269": 0.10026945173740387, "24479": 0.5551415085792542, "24552": 0.04767346754670143, "24556": 0.034552380442619324, "24797": 0.02792670577764511, "24840": 0.14349138736724854, "24848": 0.09406650811433792, "24983": 0.2089812457561493, "25117": 0.029824240133166313, "25407": 0.06337817758321762, "25456": 0.49686139822006226, "25502": 0.9021284580230713, "25525": 0.9209672808647156, "25714": 0.1229778528213501, "25950": 1.1128336191177368, "26180": 0.10818854719400406, "26394": 0.10731173306703568, "26402": 0.2741633653640747, "26591": 0.36358460783958435, "26632": 0.7201237678527832, "27144": 0.23864774405956268, "27292": 0.4831010699272156, "27321": 0.30486753582954407, "27642": 0.6327666640281677, "27833": 0.31204116344451904, "27854": 0.040196798741817474, "28113": 0.42353010177612305, "28156": 0.26146242022514343, "28228": 0.6358738541603088, "28312": 1.133164644241333, "29191": 0.016465263441205025, "29290": 0.04953393340110779, "29361": 0.016465263441205025, "29451": 0.083342544734478} | 12370881 | AIM To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. MATERIALS & METHODS Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. RESULTS Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C(hi) monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. CONCLUSION Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis. | Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice. |
{"1014": 0.255429208278656, "1018": 0.31560876965522766, "1041": 0.11430477350950241, "1045": 0.0029254043474793434, "1048": 0.7827593088150024, "1052": 0.045809537172317505, "2001": 0.16359257698059082, "2011": 0.0606246218085289, "2012": 0.1485546976327896, "2013": 0.3177432417869568, "2020": 0.04953393340110779, "2041": 0.47584590315818787, "2043": 0.2231435477733612, "2064": 0.10203468054533005, "2073": 0.32905077934265137, "2095": 0.06246116757392883, "2106": 0.12384103983640671, "2109": 0.49030399322509766, "2116": 0.23092569410800934, "2129": 0.08782484382390976, "2138": 0.5104349255561829, "2144": 0.11778303235769272, "2152": 0.12384103983640671, "2167": 0.05786345899105072, "2176": 0.08513788133859634, "2179": 0.31132611632347107, "2181": 0.7276995778083801, "2193": 0.32129061222076416, "2220": 0.8641747236251831, "2224": 0.0752234235405922, "2241": 0.2478361576795578, "2259": 0.00875066313892603, "2270": 0.5244048833847046, "2275": 0.018384648486971855, "2313": 1.0257055759429932, "2334": 0.755608320236206, "2339": 0.5751199722290039, "2349": 0.18167030811309814, "2360": 0.22704219818115234, "2382": 0.4709797203540802, "2406": 0.0770333781838417, "2470": 0.31204116344451904, "2478": 0.26446542143821716, "2483": 0.8567397594451904, "2491": 0.4531385898590088, "2492": 1.0207915306091309, "2511": 0.9680526852607727, "2539": 0.04860413447022438, "2550": 0.006812678650021553, "2555": 0.026976587250828743, "2580": 0.272677481174469, "2592": 0.030771657824516296, "2609": 0.5914691090583801, "2650": 0.009718249551951885, "2710": 1.360575795173645, "2740": 0.32199856638908386, "2752": 0.8829278349876404, "2756": 0.33115679025650024, "2764": 0.27342069149017334, "2803": 0.07612881064414978, "2817": 0.5139457583427429, "2846": 0.6563454270362854, "2864": 0.15943801403045654, "2874": 0.28670501708984375, "2901": 0.6260011196136475, "2913": 0.40481385588645935, "2944": 0.6573580503463745, "2951": 0.6064908504486084, "2953": 0.48068851232528687, "3010": 1.1363043785095215, "3012": 0.6006163358688354, "3032": 0.1011524572968483, "3041": 0.3423145115375519, "3073": 0.011650617234408855, "3085": 0.1946154683828354, "3107": 0.23479416966438293, "3114": 0.053244512528181076, "3169": 0.045809537172317505, "3231": 0.004870930220931768, "3273": 0.1384023278951645, "3295": 0.06612417846918106, "3350": 0.018384648486971855, "3433": 0.6441128253936768, "3450": 0.27934664487838745, "3451": 0.07612881064414978, "3479": 0.0009760859538801014, "3498": 0.21214580535888672, "3517": 0.24401791393756866, "3563": 0.6989894509315491, "3570": 0.004870930220931768, "3603": 0.14518201351165771, "3616": 0.09672962874174118, "3618": 0.22392450273036957, "3643": 0.4831010699272156, "3647": 0.009718249551951885, "3800": 0.0058422754518687725, "3818": 0.025073638185858727, "3891": 0.9225212931632996, "3898": 0.03831886500120163, "3921": 0.46117570996284485, "3942": 0.0354953333735466, "3963": 0.09850110858678818, "3965": 0.19541899859905243, "3988": 0.15526613593101501, "3996": 0.015504186972975731, "4023": 0.20580662786960602, "4044": 0.4330752193927765, "4081": 0.5267143249511719, "4094": 0.8550800085067749, "4106": 0.18411032855510712, "4118": 0.4938860833644867, "4187": 0.6218147873878479, "4195": 0.014542185701429844, "4224": 0.03831886500120163, "4228": 0.12038381397724152, "4249": 0.49030399322509766, "4275": 0.417115718126297, "4295": 0.8500841856002808, "4340": 0.04674193635582924, "4358": 0.043007105588912964, "4361": 0.42353010177612305, "4383": 0.08961215615272522, "4423": 0.18167030811309814, "4453": 0.6155022978782654, "4466": 0.4400174915790558, "4483": 0.6838265657424927, "4487": 0.10818854719400406, "4493": 0.2247048318386078, "4539": 0.0354953333735466, "4561": 0.6471850275993347, "4573": 0.8400169610977173, "4647": 0.5313173532485962, "4652": 0.16690383851528168, "4655": 0.24325250089168549, "4716": 0.21530038118362427, "4725": 0.4770587682723999, "4742": 0.6744182109832764, "4743": 0.5773153901100159, "4758": 0.2223619967699051, "4795": 0.015504186972975731, "4848": 0.3012613356113434, "4935": 0.5887627601623535, "4949": 0.9515975713729858, "4975": 0.20421554148197174, "4992": 0.129004567861557, "5002": 0.21372433006763458, "5038": 0.08244366943836212, "5055": 0.7258110046386719, "5067": 0.007782140281051397, "5069": 0.9394577741622925, "5173": 0.49686139822006226, "5204": 0.18329764902591705, "5269": 0.1212492436170578, "5300": 0.2089812457561493, "5320": 0.016465263441205025, "5323": 0.7220231294631958, "5360": 0.15943801403045654, "5425": 0.26146242022514343, "5436": 0.5483922958374023, "5447": 1.2791962623596191, "5452": 0.2749055027961731, "5456": 0.20580662786960602, "5461": 0.04487626627087593, "5468": 0.05139094591140747, "5473": 0.006812678650021553, "5548": 0.6139179468154907, "5604": 0.0842406153678894, "5622": 0.015504186972975731, "5646": 0.09938567131757736, "5668": 0.255429208278656, "5700": 0.4624064862728119, "5748": 0.08064348995685577, "5838": 0.025073638185858727, "5863": 0.010684899985790253, "5901": 0.04394211992621422, "5906": 0.24859806895256042, "5915": 0.4574742913246155, "5950": 0.7239188551902771, "6003": 0.6317287683486938, "6022": 0.4400174915790558, "6028": 0.1994270235300064, "6075": 0.06246116757392883, "6083": 0.33675122261047363, "6086": 0.1384023278951645, "6146": 0.9363996982574463, "6174": 0.17840765416622162, "6179": 0.43875885009765625, "6187": 0.21372433006763458, "6388": 0.04767346754670143, "6413": 0.4531385898590088, "6552": 0.045809537172317505, "6553": 0.5506471395492554, "6592": 0.35334911942481995, "6709": 0.5773153901100159, "6747": 0.018384648486971855, "6805": 0.0317181795835495, "6835": 0.007782140281051397, "6869": 0.3269403576850891, "6930": 0.38905516266822815, "6994": 0.38374659419059753, "7080": 0.8780695199966431, "7246": 0.417115718126297, "7271": 0.083342544734478, "7274": 0.013579257763922215, "7276": 0.08244366943836212, "7282": 0.22079704701900482, "7320": 0.19862671196460724, "7341": 0.812664806842804, "7361": 0.08244366943836212, "7399": 0.8829278349876404, "7411": 0.6960725784301758, "7420": 0.1930064558982849, "7505": 0.5301685929298401, "7521": 0.07341018319129944, "7524": 0.175953671336174, "7528": 0.016465263441205025, "7551": 0.1619328260421753, "7591": 0.5284429788589478, "7649": 0.19381128251552582, "7711": 0.25694093108177185, "7755": 0.46117570996284485, "7778": 0.13243216276168823, "7809": 0.23015019297599792, "7818": 0.27786844968795776, "7864": 0.06795065850019455, "7870": 0.6394867897033691, "7885": 0.12384103983640671, "7934": 1.1437997817993164, "8010": 0.8161250352859497, "8017": 0.18411032855510712, "8040": 0.8821197748184204, "8080": 0.12556517124176025, "8107": 0.24859806895256042, "8166": 0.3318578004837036, "8321": 0.6435998678207397, "8361": 1.252763032913208, "8448": 0.20977331697940826, "8455": 0.18978065252304077, "8483": 0.17020416259765625, "8553": 0.012615402229130268, "8598": 0.417115718126297, "8720": 0.8004589080810547, "8729": 0.043007105588912964, "8767": 0.15526613593101501, "8777": 0.8238670229911804, "8822": 0.472198486328125, "8833": 0.3995884954929352, "8840": 0.07159364968538284, "8890": 0.03831886500120163, "8909": 0.11604541540145874, "8977": 0.04767346754670143, "9016": 0.04674193635582924, "9104": 0.08064348995685577, "9183": 0.906871497631073, "9186": 0.4318077862262726, "9207": 0.861702561378479, "9230": 0.35745587944984436, "9331": 0.9100211262702942, "9398": 0.5640701055526733, "9499": 0.9754437208175659, "9539": 0.4938860833644867, "9651": 0.2089812457561493, "9676": 0.23556606471538544, "9723": 0.13071982562541962, "9740": 0.42735910415649414, "9756": 0.16442140936851501, "9765": 0.2184450328350067, "9867": 1.1671710014343262, "9896": 0.05786345899105072, "9937": 0.04767346754670143, "10003": 0.09850110858678818, "10019": 0.007782140281051397, "10029": 0.07431721687316895, "10056": 0.7454653382301331, "10061": 0.6916812658309937, "10068": 0.23787821829319, "10173": 0.791648268699646, "10197": 0.1485546976327896, "10210": 0.05046287178993225, "10244": 0.8332487344741821, "10357": 0.14433705806732178, "10505": 0.46608972549438477, "10512": 0.2786078155040741, "10640": 0.5838727951049805, "10744": 0.11778303235769272, "10758": 0.00875066313892603, "10788": 1.0533316135406494, "10831": 0.5579402446746826, "10960": 0.41065993905067444, "10992": 0.5427330136299133, "11156": 0.823009729385376, "11158": 0.42608439922332764, "11207": 0.8877626657485962, "11310": 0.23710809648036957, "11326": 0.4932899475097656, "11436": 0.20421554148197174, "11487": 0.8264343738555908, "11568": 0.010684899985790253, "11582": 0.29400965571403503, "11643": 0.45251765847206116, "11703": 0.13925230503082275, "11814": 1.0927356481552124, "11829": 0.22704219818115234, "11860": 0.006812678650021553, "11983": 0.10203468054533005, "12151": 0.5952457785606384, "12231": 0.17431432008743286, "12375": 0.7809720039367676, "12477": 0.13414156436920166, "12504": 0.11778303235769272, "12636": 0.8869584798812866, "12832": 0.056018441915512085, "12883": 0.09938567131757736, "12887": 0.08692999184131622, "13135": 1.1702059507369995, "13368": 0.11691460013389587, "13581": 0.13499516248703003, "13589": 0.2034190446138382, "14053": 0.613389253616333, "14087": 0.20739519596099854, "14120": 0.3554046154022217, "14125": 0.13755162060260773, "14160": 0.0354953333735466, "14211": 0.23556606471538544, "14440": 0.05786345899105072, "14639": 0.8091925978660583, "14658": 0.07431721687316895, "14811": 0.7229714393615723, "14828": 0.1011524572968483, "14847": 0.3127557039260864, "14906": 0.052318159490823746, "15113": 0.004870930220931768, "15157": 0.3615458607673645, "15165": 0.37707099318504333, "15356": 0.013579257763922215, "15424": 0.07793712615966797, "15502": 0.43875885009765625, "15559": 0.02887592278420925, "15900": 0.09317722171545029, "15923": 0.14686977863311768, "15982": 0.17267228662967682, "16014": 0.9951307773590088, "16134": 0.4196864068508148, "16340": 0.13925230503082275, "16356": 1.4900912046432495, "16406": 0.01934296265244484, "16474": 0.09584271162748337, "16485": 0.7629209756851196, "17174": 0.14518201351165771, "17192": 0.8425432443618774, "17208": 0.06337817758321762, "17245": 0.12470348179340363, "17318": 0.034552380442619324, "17338": 0.13925230503082275, "17404": 0.04394211992621422, "17503": 0.2837681770324707, "17547": 1.001607894897461, "17668": 0.77198725938797, "17715": 0.15777134895324707, "17785": 0.18816383183002472, "17844": 0.0770333781838417, "18130": 0.03831886500120163, "18422": 0.10203468054533005, "18547": 0.06246116757392883, "18949": 0.1619328260421753, "18953": 0.07431721687316895, "19019": 0.6244332790374756, "19034": 0.5551415085792542, "19132": 0.42096930742263794, "19188": 0.026025565341114998, "19199": 0.06703783571720123, "19293": 0.13499516248703003, "19391": 0.4794800877571106, "19518": 0.19862671196460724, "19847": 1.1153976917266846, "19939": 0.6813592314720154, "20248": 0.31489628553390503, "20272": 0.960606575012207, "20536": 0.07159364968538284, "20607": 0.1064341589808464, "20731": 0.1358480453491211, "20739": 0.037378571927547455, "20932": 0.8731874823570251, "20969": 0.36290550231933594, "21009": 0.4311734735965729, "21371": 0.034552380442619324, "21425": 0.12038381397724152, "21919": 0.012615402229130268, "21961": 0.04113444685935974, "22010": 0.0354953333735466, "22161": 0.39762192964553833, "22262": 0.8298473954200745, "22311": 0.021256839856505394, "22333": 0.41195443272590637, "22529": 0.4248080551624298, "22769": 0.045809537172317505, "22806": 0.3923587501049042, "22835": 0.4437839686870575, "23041": 0.3547199070453644, "23408": 0.02412080205976963, "24010": 0.022212404757738113, "24155": 0.04207121208310127, "24710": 0.14349138736724854, "25064": 0.15023678541183472, "25169": 0.16442140936851501, "25219": 1.4847954511642456, "25262": 0.2763880789279938, "25331": 0.15693697333335876, "25510": 1.4283655881881714, "25604": 0.7009293437004089, "25952": 0.4831010699272156, "25971": 0.5104349255561829, "26237": 0.9944084882736206, "26629": 0.029824240133166313, "26651": 0.0009760859538801014, "26735": 0.4487839937210083, "26835": 0.20501139760017395, "27354": 0.2317005842924118, "27400": 0.030771657824516296, "27592": 0.2763880789279938, "27627": 0.011650617234408855, "27833": 0.1905880719423294, "28561": 0.13670019805431366, "28603": 0.19541899859905243, "28636": 0.030771657824516296, "29034": 0.3547199070453644, "29299": 0.3949938118457794, "29458": 0.7951818704605103} | 12383365 | ABSTRACT Lyme disease (LD) is emerging in Canada because of the northward expansion of the geographic range of the tick vector Ixodes scapularis (Say). Early detection of emerging areas of LD risk is critical to public health responses, but the methods to do so on a local scale are lacking. Passive tick surveillance has operated in Canada since 1990 but this method lacks specificity for identifying areas where tick populations are established because of dispersion of ticks from established LD risk areas by migratory birds. Using data from 70 field sites in Quebec visited previously, we developed a logistic regression model for estimating the risk of I. scapularis population establishment based on the number of ticks submitted in passive surveillance and a model-derived environmental suitability index. Sensitivity-specificity plots were used to select an optimal threshold value of the linear predictor from the model as the signal for tick population establishment. This value was used to produce an “Alert Map” identifying areas where the passive surveillance data suggested ticks were establishing in Quebec. Alert Map predictions were validated by field surveillance at 76 sites: the prevalence of established I. scapularis populations was significantly greater in areas predicted as high-risk by the Alert map (29 out of 48) than in areas predicted as moderate-risk (4 out of 30) (P < 0.001). This study suggests that Alert Maps created using this approach can provide a usefully rapid and accurate tool for early identification of emerging areas of LD risk at a geographic scale appropriate for local disease control and prevention activities. | Passive Surveillance for I. scapularis Ticks: Enhanced Analysis for Early Detection of Emerging Lyme Disease Risk |
{"1014": 0.43434104323387146, "1052": 0.1930064558982849, "2000": 0.0029254043474793434, "2005": 0.5033760666847229, "2007": 0.08782484382390976, "2011": 0.07884006202220917, "2029": 0.08782484382390976, "2034": 0.4770587682723999, "2039": 0.09228714555501938, "2050": 0.13670019805431366, "2051": 0.1477125883102417, "2062": 0.3177432417869568, "2064": 0.0058422754518687725, "2076": 0.3554046154022217, "2077": 0.7500885725021362, "2078": 0.6358738541603088, "2084": 0.5057345628738403, "2089": 0.052318159490823746, "2090": 0.06246116757392883, "2092": 0.2561853528022766, "2109": 0.3676496744155884, "2114": 0.5640701055526733, "2146": 0.2800849378108978, "2147": 0.15275461971759796, "2181": 0.21372433006763458, "2206": 0.3547199070453644, "2208": 1.0841858386993408, "2229": 0.15023678541183472, "2240": 0.6714286804199219, "2278": 0.3897167444229126, "2319": 0.06246116757392883, "2322": 0.0009760859538801014, "2362": 0.2034190446138382, "2378": 0.28890204429626465, "2399": 0.14349138736724854, "2420": 0.0842406153678894, "2458": 0.04953393340110779, "2470": 0.15860503911972046, "2488": 0.14602625370025635, "2491": 0.09938567131757736, "2512": 0.4286321699619293, "2515": 0.1751343309879303, "2527": 0.5186077356338501, "2535": 0.31560876965522766, "2552": 1.5398868322372437, "2553": 0.175953671336174, "2556": 0.10467668622732162, "2618": 0.42608439922332764, "2625": 0.0174254160374403, "2628": 0.3547199070453644, "2660": 0.2478361576795578, "2696": 0.5914691090583801, "2752": 0.10818854719400406, "2754": 0.7482418417930603, "2764": 0.6583697199821472, "2765": 0.28597161173820496, "2817": 0.06703783571720123, "2827": 0.21372433006763458, "2855": 0.0009760859538801014, "2895": 0.4444103240966797, "2896": 0.11430477350950241, "2913": 0.03831886500120163, "2915": 0.04487626627087593, "2946": 0.3897167444229126, "2951": 0.2659635543823242, "2968": 0.09672962874174118, "3022": 0.6353566646575928, "3025": 0.6522845029830933, "3083": 0.020300358533859253, "3088": 0.07884006202220917, "3102": 0.16276304423809052, "3107": 0.755608320236206, "3112": 0.2018241584300995, "3130": 0.24171993136405945, "3144": 0.28450319170951843, "3170": 0.4624064862728119, "3188": 0.6070231795310974, "3210": 0.2531573474407196, "3265": 0.0317181795835495, "3273": 0.06337817758321762, "3278": 0.6907027959823608, "3348": 0.6064908504486084, "3366": 0.036437395960092545, "3378": 0.6533012986183167, "3406": 0.7755908370018005, "3424": 0.7978238463401794, "3435": 0.2160874605178833, "3446": 0.09317722171545029, "3463": 0.5301685929298401, "3466": 0.6086184978485107, "3478": 0.0842406153678894, "3490": 0.2637155055999756, "3491": 0.022212404757738113, "3497": 0.19782574474811554, "3540": 0.06612417846918106, "3572": 0.4500300884246826, "3582": 0.7510106563568115, "3619": 0.11865071207284927, "3653": 0.6348392367362976, "3659": 0.3464667797088623, "3677": 0.012615402229130268, "3734": 0.058784693479537964, "3739": 0.603290855884552, "3772": 0.42799583077430725, "3798": 0.0019512200960889459, "3816": 0.14686977863311768, "3867": 0.15023678541183472, "3893": 0.8109301924705505, "3896": 0.45499902963638306, "3943": 0.2501201331615448, "3949": 0.9842413663864136, "3979": 0.7454653382301331, "3981": 0.09672962874174118, "4022": 0.6624060273170471, "4076": 0.04674193635582924, "4102": 0.6548244953155518, "4117": 0.46486347913742065, "4118": 0.4177590310573578, "4146": 0.34715715050697327, "4162": 0.021256839856505394, "4200": 0.07431721687316895, "4233": 0.21530038118362427, "4254": 0.8731874823570251, "4281": 0.9013357162475586, "4292": 0.371698260307312, "4295": 0.18329764902591705, "4304": 1.0601204633712769, "4319": 0.14349138736724854, "4358": 0.39893341064453125, "4359": 0.5387523174285889, "4403": 0.1751343309879303, "4424": 0.8829278349876404, "4489": 0.20102575421333313, "4490": 1.0478670597076416, "4503": 0.24631060659885406, "4506": 0.14179791510105133, "4539": 0.1677299439907074, "4621": 0.8091925978660583, "4632": 0.259204238653183, "4652": 0.10203468054533005, "4654": 0.07431721687316895, "4666": 0.1602703034877777, "4710": 0.04767346754670143, "4725": 0.49686139822006226, "4749": 0.4437839686870575, "4800": 0.5506471395492554, "4812": 0.14179791510105133, "4895": 0.1930064558982849, "4942": 0.5865923762321472, "4945": 0.6664261221885681, "4955": 0.21293537318706512, "4975": 0.27342069149017334, "5007": 0.007782140281051397, "5012": 0.15526613593101501, "5022": 0.37974658608436584, "5082": 0.083342544734478, "5257": 1.1456648111343384, "5302": 0.27712854743003845, "5345": 0.9271688461303711, "5360": 0.0058422754518687725, "5393": 0.036437395960092545, "5498": 0.987156867980957, "5514": 0.04113444685935974, "5531": 0.11168810725212097, "5547": 0.6389714479446411, "5576": 0.07431721687316895, "5666": 0.7665573358535767, "5711": 0.4286321699619293, "5717": 0.2034190446138382, "5740": 0.2501201331615448, "5776": 0.2689530849456787, "5845": 0.6533012986183167, "5850": 0.3353555500507355, "5901": 0.30917787551879883, "5915": 0.8450632095336914, "5966": 0.04767346754670143, "6022": 0.846739649772644, "6028": 0.09317722171545029, "6051": 0.007782140281051397, "6074": 0.1332872211933136, "6233": 0.08513788133859634, "6388": 0.42608439922332764, "6428": 0.24171993136405945, "6431": 0.22626367211341858, "6463": 0.8534175157546997, "6464": 0.25845035910606384, "6551": 0.20501139760017395, "6612": 0.09317722171545029, "6666": 0.15442965924739838, "6726": 0.966567873954773, "6761": 0.04860413447022438, "6779": 0.04953393340110779, "6790": 0.025073638185858727, "6839": 0.40220460295677185, "6904": 0.7978238463401794, "6937": 0.17431432008743286, "6939": 0.22079704701900482, "7011": 0.08064348995685577, "7012": 0.8517522215843201, "7017": 0.45870962738990784, "7028": 0.030771657824516296, "7091": 0.472198486328125, "7102": 0.08603433519601822, "7146": 0.32270604372024536, "7242": 0.8315495252609253, "7312": 0.7510106563568115, "7320": 0.06703783571720123, "7337": 0.09406650811433792, "7352": 0.6497380137443542, "7358": 1.0326838493347168, "7438": 0.7969439625740051, "7461": 0.22937409579753876, "7551": 0.4891071021556854, "7629": 0.09850110858678818, "7645": 0.10379679501056671, "7685": 0.03360854089260101, "7709": 0.06520967930555344, "7712": 0.20501139760017395, "7774": 0.7800771594047546, "7778": 0.055094651877880096, "7784": 0.14939609169960022, "7831": 0.5336109399795532, "7870": 0.20580662786960602, "7885": 0.5822374224662781, "7889": 0.11168810725212097, "7895": 0.15860503911972046, "7915": 0.07612881064414978, "7938": 1.0628231763839722, "8058": 0.6369074583053589, "8114": 0.10291612148284912, "8161": 0.23787821829319, "8197": 0.04394211992621422, "8246": 0.17020416259765625, "8387": 0.037378571927547455, "8524": 0.04394211992621422, "8528": 0.0019512200960889459, "8556": 0.10555581003427505, "8563": 0.0029254043474793434, "8729": 0.007782140281051397, "8740": 1.1363043785095215, "8778": 0.09228714555501938, "8805": 0.1905880719423294, "8830": 0.07159364968538284, "8893": 0.19622190296649933, "8970": 0.4203280806541443, "8977": 0.10555581003427505, "8985": 0.6228629946708679, "9006": 0.4349733293056488, "9067": 0.8583967685699463, "9099": 0.007782140281051397, "9207": 0.44691193103790283, "9367": 0.14349138736724854, "9388": 0.0029254043474793434, "9412": 0.4891071021556854, "9526": 0.4311734735965729, "9556": 0.055094651877880096, "9560": 0.10026945173740387, "9626": 0.19220098853111267, "9723": 0.9455460906028748, "9728": 0.1221139207482338, "9742": 0.30486753582954407, "9839": 0.21293537318706512, "9885": 0.20739519596099854, "10003": 0.13670019805431366, "10015": 0.058784693479537964, "10035": 0.25239890813827515, "10077": 0.1808556467294693, "10091": 0.29400965571403503, "10197": 0.0797421783208847, "10210": 0.3601844012737274, "10230": 0.09850110858678818, "10449": 0.1332872211933136, "10450": 0.020300358533859253, "10488": 0.1477125883102417, "10543": 0.436867892742157, "10586": 0.2231435477733612, "10610": 0.23247487843036652, "10631": 0.08603433519601822, "10698": 0.0354953333735466, "10755": 0.6759096384048462, "10847": 0.28082266449928284, "10980": 0.9432673454284668, "11024": 0.27044451236724854, "11119": 0.03360854089260101, "11166": 0.17759032547473907, "11311": 0.16524957120418549, "11363": 0.512191891670227, "11493": 0.0058422754518687725, "11498": 0.7047978043556213, "11506": 0.26146242022514343, "11514": 0.7629209756851196, "11566": 0.42608439922332764, "11598": 0.7057625651359558, "11860": 0.8332487344741821, "11955": 0.25239890813827515, "11958": 0.013579257763922215, "11979": 0.004870930220931768, "12016": 0.2184450328350067, "12099": 0.009718249551951885, "12219": 0.1212492436170578, "12318": 0.5370414853096008, "12353": 0.6563454270362854, "12381": 0.11517547070980072, "12435": 0.1994270235300064, "12517": 0.04674193635582924, "12581": 0.8238670229911804, "12596": 0.04674193635582924, "12637": 0.19622190296649933, "12811": 1.141931176185608, "12826": 0.2837681770324707, "12943": 0.006812678650021553, "13046": 0.8332487344741821, "13070": 0.4400174915790558, "13105": 0.12814582884311676, "13122": 0.006812678650021553, "13341": 0.28670501708984375, "13416": 0.35950297117233276, "13441": 0.8117979168891907, "13463": 0.07793712615966797, "13494": 0.037378571927547455, "13585": 0.22548456490039825, "13599": 0.40806588530540466, "14206": 0.020300358533859253, "14211": 0.2317005842924118, "14455": 0.23247487843036652, "14613": 0.29400965571403503, "14627": 0.11604541540145874, "14667": 0.4311734735965729, "14670": 0.3416208028793335, "14736": 0.02887592278420925, "14756": 0.04207121208310127, "14816": 0.7239188551902771, "14930": 0.8349450826644897, "15053": 0.18004031479358673, "15100": 0.2659635543823242, "15227": 0.2501201331615448, "15245": 0.5127768516540527, "15289": 0.0752234235405922, "15306": 0.45251765847206116, "15308": 0.23864774405956268, "15403": 0.03925827145576477, "15428": 0.04767346754670143, "15459": 0.011650617234408855, "15472": 0.8813109993934631, "15485": 0.19622190296649933, "15596": 0.11430477350950241, "15728": 1.0298984050750732, "15877": 0.02316705882549286, "15900": 0.12814582884311676, "16028": 0.018384648486971855, "16134": 0.4318077862262726, "16253": 0.34715715050697327, "16414": 0.26296505331993103, "16514": 0.46363574266433716, "16593": 0.10993985831737518, "16650": 0.004870930220931768, "16670": 0.4938860833644867, "17250": 0.05694137513637543, "17261": 0.3262358605861664, "17404": 0.46914875507354736, "17577": 0.7898768186569214, "17872": 0.6857960224151611, "18178": 0.18654440343379974, "18231": 0.3554046154022217, "18452": 0.2026219218969345, "18478": 0.12470348179340363, "18595": 0.1619328260421753, "18622": 0.13071982562541962, "18747": 0.5427330136299133, "18847": 0.22392450273036957, "18891": 0.03266380727291107, "18901": 0.11256109178066254, "19063": 1.5373711585998535, "19064": 0.014542185701429844, "19105": 0.0038986403960734606, "19107": 0.6202403903007507, "19132": 1.5913057327270508, "19209": 0.24018502235412598, "19210": 0.8764448165893555, "19388": 0.026976587250828743, "19496": 0.2837681770324707, "19761": 0.14939609169960022, "19791": 0.10467668622732162, "19818": 0.5646255612373352, "20022": 0.11951763927936554, "20226": 0.06703783571720123, "20228": 0.7665573358535767, "20428": 0.6096806526184082, "20657": 0.021256839856505394, "20694": 0.07159364968538284, "20900": 0.46363574266433716, "20936": 0.11343330889940262, "20992": 0.17840765416622162, "21114": 0.014542185701429844, "21124": 0.15275461971759796, "21150": 0.6249561905860901, "21198": 1.0668635368347168, "21261": 0.2470736801624298, "21383": 0.026976587250828743, "21391": 0.34577593207359314, "21639": 0.10731173306703568, "21670": 0.18654440343379974, "21823": 0.05694137513637543, "21879": 0.6296497583389282, "21961": 0.35813871026039124, "22153": 0.10291612148284912, "22260": 0.05417001247406006, "22320": 0.045809537172317505, "22330": 0.10993985831737518, "22415": 0.22157983481884003, "22529": 1.1337933540344238, "22648": 0.0354953333735466, "22769": 0.35813871026039124, "22963": 0.347847044467926, "23041": 0.3601844012737274, "23238": 0.565735399723053, "23306": 0.09317722171545029, "23631": 0.35677260160446167, "23820": 0.18573370575904846, "23900": 0.05046287178993225, "23996": 1.0073304176330566, "24054": 0.1358480453491211, "24198": 0.21687394380569458, "24290": 0.10291612148284912, "24479": 0.20421554148197174, "24759": 0.41065993905067444, "24895": 0.006812678650021553, "25006": 0.3910386264324188, "25022": 0.637939989566803, "25025": 0.7314660549163818, "25027": 0.20660123229026794, "25090": 0.175953671336174, "25353": 0.12986256182193756, "25604": 0.6064908504486084, "25714": 0.06337817758321762, "25969": 0.2954642176628113, "26039": 0.06246116757392883, "26045": 0.7674643993377686, "26163": 0.21135559678077698, "26237": 1.250528335571289, "26402": 0.14686977863311768, "26461": 0.8821197748184204, "26563": 0.07884006202220917, "26591": 0.011650617234408855, "26728": 1.351516842842102, "26835": 0.19622190296649933, "26957": 0.5010119676589966, "27144": 0.4574742913246155, "27321": 0.7809720039367676, "27859": 0.14518201351165771, "28032": 0.6892333030700684, "28173": 0.045809537172317505, "28225": 0.007782140281051397, "28263": 0.12556517124176025, "28369": 0.026976587250828743, "28389": 0.1873544454574585, "28518": 0.2409527748823166, "28739": 0.029824240133166313, "28775": 0.1970241367816925, "28788": 0.09938567131757736, "28896": 0.12986256182193756, "28935": 0.3662964701652527, "29393": 0.25845035910606384, "29596": 0.20580662786960602} | 12409683 | BACKGROUND Artemisinin combination therapies (ACT), which are increasingly being introduced for treatment of Plasmodium falciparum malaria, are more effective against sexual stage parasites (gametocytes) than previous first-line antimalarials and therefore have the potential to reduce parasite transmission. The size of this effect is estimated in symptomatic P. falciparum infections. METHODS Data on 3,174 patients were pooled from six antimalarial trials conducted in The Gambia and Kenya. Multivariable regression was used to investigate the role of ACT versus non-artemisinin antimalarial treatment, treatment failure, presence of pre-treatment gametocytes and submicroscopic gametocytaemia on transmission to mosquitoes and the area under the curve (AUC) of gametocyte density during the 28 days of follow up. RESULTS ACT treatment was associated with a significant reduction in the probability of being gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26), transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means 0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the difference between ACT and non-artemisinin impact. The presence of slide-positive gametocytaemia prior to treatment significantly reduced ACT impact on gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia reduced estimates of ACT impact in a high transmission setting in Kenya, but not in a lower transmission setting in the Gambia. CONCLUSION Treatment with ACT significantly reduces infectiousness of individual patients with uncomplicated falciparum malaria compared to previous first line treatments. Rapid treatment of cases before gametocytaemia is well developed may enhance the impact of ACT on transmission. | Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials |
{"1039": 0.29981520771980286, "1996": 0.15023678541183472, "1999": 0.012615402229130268, "2011": 0.32058215141296387, "2013": 0.6714286804199219, "2015": 0.1212492436170578, "2019": 0.4196864068508148, "2021": 0.2105647772550583, "2026": 1.0655186176300049, "2031": 0.3012613356113434, "2033": 0.5197699069976807, "2038": 0.06977381557226181, "2061": 0.7124901413917542, "2064": 0.0842406153678894, "2073": 0.18411032855510712, "2078": 0.12814582884311676, "2081": 0.22782009840011597, "2089": 0.16359257698059082, "2140": 0.04953393340110779, "2179": 0.2881702482700348, "2203": 0.3170322775840759, "2241": 0.23479416966438293, "2265": 0.053244512528181076, "2272": 0.22626367211341858, "2291": 0.4067663550376892, "2298": 0.2674594223499298, "2310": 0.319873183965683, "2339": 0.026025565341114998, "2367": 0.17759032547473907, "2433": 0.34922540187835693, "2458": 0.2447827309370041, "2512": 0.7352184057235718, "2550": 0.2741633653640747, "2556": 0.6096806526184082, "2649": 0.09584271162748337, "2695": 0.4938860833644867, "2719": 0.3012613356113434, "2754": 0.3077431619167328, "2777": 0.43244171142578125, "2825": 0.3923587501049042, "2828": 0.1751343309879303, "2918": 0.02412080205976963, "3001": 0.19381128251552582, "3067": 0.06154331564903259, "3120": 0.16276304423809052, "3252": 0.503966212272644, "3311": 0.4311734735965729, "3350": 0.011650617234408855, "3370": 0.38174858689308167, "3430": 0.0019512200960889459, "3468": 0.7809720039367676, "3491": 0.0913962796330452, "3526": 0.7942996621131897, "3544": 0.1718502640724182, "3603": 0.06246116757392883, "3670": 0.09938567131757736, "3671": 0.007782140281051397, "3711": 0.35745587944984436, "3732": 0.23710809648036957, "3739": 0.02412080205976963, "3768": 0.5838727951049805, "3922": 0.2026219218969345, "3930": 0.37640097737312317, "3965": 0.28670501708984375, "4013": 0.4950772523880005, "4022": 0.5215105414390564, "4063": 0.87237149477005, "4106": 0.11691460013389587, "4111": 0.19220098853111267, "4176": 0.22392450273036957, "4195": 0.21372433006763458, "4221": 0.9162907600402832, "4245": 0.04767346754670143, "4305": 0.37304413318634033, "4315": 0.13157635927200317, "4340": 0.03266380727291107, "4442": 1.0375399589538574, "4531": 0.24325250089168549, "4541": 0.05970508232712746, "4639": 0.44753631949424744, "4651": 0.05694137513637543, "4663": 0.28082266449928284, "4671": 0.16690383851528168, "4761": 0.7737906575202942, "4765": 0.3910386264324188, "4800": 0.4487839937210083, "4839": 0.026976587250828743, "4863": 0.4349733293056488, "4958": 0.5139457583427429, "4962": 0.11691460013389587, "4982": 0.08244366943836212, "5090": 0.5427330136299133, "5159": 0.11951763927936554, "5173": 1.104454517364502, "5228": 0.4093637466430664, "5258": 0.010684899985790253, "5383": 0.020300358533859253, "5589": 0.1718502640724182, "5643": 0.007782140281051397, "5681": 0.3499138653278351, "5711": 0.29619070887565613, "5769": 0.09050461649894714, "5871": 1.1262223720550537, "5923": 0.34577593207359314, "5944": 0.1889725625514984, "6001": 0.2531573474407196, "6061": 0.3877306580543518, "6064": 0.04767346754670143, "6083": 0.2837681770324707, "6235": 0.1994270235300064, "6310": 0.030771657824516296, "6319": 0.6327666640281677, "6321": 0.006812678650021553, "6459": 0.26146242022514343, "6499": 0.7258110046386719, "6592": 0.25088030099868774, "6622": 0.2667117714881897, "6650": 1.301234245300293, "6740": 1.4696369171142578, "6741": 0.011650617234408855, "6851": 0.1064341589808464, "6855": 0.1384023278951645, "6914": 0.5557019114494324, "7013": 0.43938836455345154, "7137": 0.037378571927547455, "7275": 0.12038381397724152, "7297": 0.12814582884311676, "7321": 0.30558720231056213, "7366": 0.1602703034877777, "7403": 0.3034266233444214, "7526": 0.05139094591140747, "7606": 0.2800849378108978, "7607": 0.17020416259765625, "7616": 0.6476961374282837, "7645": 0.015504186972975731, "7856": 0.8057082891464233, "7872": 0.06886265426874161, "7939": 0.23556606471538544, "7940": 0.21214580535888672, "7964": 0.0770333781838417, "8000": 0.9710156321525574, "8089": 0.46117570996284485, "8138": 0.6064908504486084, "8153": 0.9115922451019287, "8288": 0.04767346754670143, "8332": 0.1401015669107437, "8553": 0.20818853378295898, "8713": 0.5903874635696411, "8939": 0.823009729385376, "9005": 0.04394211992621422, "9031": 0.08244366943836212, "9099": 0.6054253578186035, "9104": 0.1994270235300064, "9287": 0.18573370575904846, "9350": 0.21687394380569458, "9420": 0.6759096384048462, "9513": 0.056018441915512085, "9556": 0.12814582884311676, "9699": 0.6664261221885681, "10077": 0.37974658608436584, "10295": 0.0174254160374403, "10439": 0.42416930198669434, "10497": 0.8143964409828186, "10572": 0.012615402229130268, "10726": 0.6492279767990112, "10744": 0.272677481174469, "10752": 0.0797421783208847, "11008": 0.6950984001159668, "11158": 0.36290550231933594, "11432": 0.030771657824516296, "11498": 0.7333439588546753, "11657": 0.03925827145576477, "11717": 0.2667117714881897, "12115": 0.32553088665008545, "12153": 0.4914994537830353, "12319": 0.015504186972975731, "12328": 0.9186317324638367, "12494": 0.8433839678764343, "12556": 0.03831886500120163, "12562": 0.03831886500120163, "12759": 0.9485763907432556, "13014": 0.08244366943836212, "13103": 0.1685553640127182, "13320": 0.6659244894981384, "13321": 0.011650617234408855, "13336": 0.07884006202220917, "13369": 0.6186635494232178, "13375": 0.09228714555501938, "13472": 0.8682814836502075, "13526": 0.6553317308425903, "13595": 0.016465263441205025, "13819": 0.10291612148284912, "13908": 0.5232481360435486, "13960": 0.010684899985790253, "14079": 0.13071982562541962, "14087": 0.3339579105377197, "14095": 0.7201237678527832, "14494": 0.07250232994556427, "14516": 0.1994270235300064, "14549": 0.7153595685958862, "14573": 0.5540198087692261, "14760": 0.12384103983640671, "14787": 0.9717550277709961, "14800": 0.02316705882549286, "14817": 0.12556517124176025, "15053": 0.11517547070980072, "15067": 0.42225050926208496, "15070": 0.3485364317893982, "15142": 0.3903779089450836, "15286": 0.23402166366577148, "15291": 0.6553317308425903, "15527": 0.5936289429664612, "15596": 0.05694137513637543, "15660": 0.6862877607345581, "15799": 0.08692999184131622, "15826": 0.055094651877880096, "15901": 0.16524957120418549, "15923": 0.043007105588912964, "16026": 0.8195732831954956, "16221": 0.4400174915790558, "16387": 0.41065993905067444, "16463": 0.015504186972975731, "16505": 0.5523349046707153, "16530": 0.16276304423809052, "16745": 0.5506471395492554, "16749": 0.30989447236061096, "16762": 0.07250232994556427, "16882": 0.11343330889940262, "16896": 0.12038381397724152, "17063": 0.22079704701900482, "17598": 0.8821197748184204, "17959": 0.2018241584300995, "18547": 0.823009729385376, "18647": 0.011650617234408855, "18714": 0.3191637098789215, "18856": 0.669430673122406, "18963": 0.7960633039474487, "19009": 0.7537717819213867, "19035": 0.05694137513637543, "19345": 0.13157635927200317, "19421": 0.3877306580543518, "19476": 0.42161011695861816, "19515": 0.00875066313892603, "19660": 0.347847044467926, "19723": 0.6223390698432922, "19731": 1.0326838493347168, "19833": 0.812664806842804, "19852": 0.013579257763922215, "19976": 0.777387797832489, "20045": 0.9531047344207764, "20118": 0.8707374930381775, "20415": 1.581713318824768, "20582": 0.0770333781838417, "20620": 0.0797421783208847, "20679": 0.8074519634246826, "20752": 0.3339579105377197, "20806": 0.20102575421333313, "21376": 0.16442140936851501, "21412": 0.8298473954200745, "21449": 1.035461664199829, "21754": 0.5778634548187256, "22008": 0.7067264318466187, "22160": 0.0019512200960889459, "22291": 0.5209306478500366, "22412": 0.055094651877880096, "22524": 0.05139094591140747, "22694": 0.0058422754518687725, "23212": 0.0770333781838417, "23419": 1.12241530418396, "23420": 0.02887592278420925, "23572": 0.35060185194015503, "23737": 0.4932899475097656, "23892": 0.11951763927936554, "23924": 0.9037119746208191, "24012": 0.1064341589808464, "24203": 0.1619328260421753, "24269": 0.29473719000816345, "24278": 1.3530324697494507, "24418": 0.5110208988189697, "24454": 0.11430477350950241, "24587": 0.7436100244522095, "24755": 0.08961215615272522, "25128": 0.0019512200960889459, "25258": 0.8989537954330444, "25426": 0.7836518287658691, "25517": 0.1994270235300064, "25700": 0.4419025182723999, "25714": 0.846739649772644, "26243": 0.02316705882549286, "26524": 0.23710809648036957, "27287": 0.5920094847679138, "27381": 0.27564704418182373, "28024": 0.16607704758644104, "28086": 1.310758113861084, "28156": 0.2983669638633728, "28297": 0.8349450826644897, "28788": 0.025073638185858727, "28901": 0.2409527748823166, "29280": 0.36494144797325134, "29486": 0.20421554148197174} | 12411274 | Skeletal muscle in vertebrates is derived from somites, epithelial structures of the paraxial mesoderm, yet many unrelated reports describe the occasional appearance of myogenic cells from tissues of nonsomite origin, suggesting either transdifferentiation or the persistence of a multipotent progenitor. Here, we show that clonable skeletal myogenic cells are present in the embryonic dorsal aorta of mouse embryos. This finding is based on a detailed clonal analysis of different tissue anlagen at various developmental stages. In vitro, these myogenic cells show the same morphology as satellite cells derived from adult skeletal muscle, and express a number of myogenic and endothelial markers. Surprisingly, the latter are also expressed by adult satellite cells. Furthermore, it is possible to clone myogenic cells from limbs of mutant c-Met-/- embryos, which lack appendicular muscles, but have a normal vascular system. Upon transplantation, aorta-derived myogenic cells participate in postnatal muscle growth and regeneration, and fuse with resident satellite cells. The potential of the vascular system to generate skeletal muscle cells may explain observations of nonsomite skeletal myogenesis and raises the possibility that a subset of satellite cells may derive from the vascular system. | Skeletal Myogenic Progenitors Originating from Embryonic Dorsal Aorta Coexpress Endothelial and Myogenic Markers and Contribute to Postnatal Muscle Growth and Regeneration |
{"1019": 0.05417001247406006, "1037": 0.02316705882549286, "1040": 0.3034266233444214, "1043": 0.09672962874174118, "1054": 0.08871890604496002, "2004": 0.0038986403960734606, "2006": 0.02412080205976963, "2025": 0.30558720231056213, "2038": 0.0913962796330452, "2042": 0.2674594223499298, "2089": 0.11517547070980072, "2090": 0.1064341589808464, "2094": 0.5489565134048462, "2099": 1.0641717910766602, "2118": 0.045809537172317505, "2135": 0.2231435477733612, "2155": 0.8039615154266357, "2174": 0.13243216276168823, "2177": 0.3554046154022217, "2179": 0.2184450328350067, "2193": 0.15526613593101501, "2229": 0.2145126610994339, "2236": 0.3248254358768463, "2266": 0.11691460013389587, "2321": 0.006812678650021553, "2336": 0.17840765416622162, "2364": 0.053244512528181076, "2372": 0.21214580535888672, "2389": 0.2976420819759369, "2391": 0.5968599319458008, "2403": 0.15526613593101501, "2410": 0.672426164150238, "2433": 0.07793712615966797, "2451": 0.018384648486971855, "2456": 0.21372433006763458, "2470": 0.15359249711036682, "2487": 0.06612417846918106, "2490": 0.5104349255561829, "2504": 0.06154331564903259, "2509": 0.3750596046447754, "2522": 0.5483922958374023, "2555": 0.5947071313858032, "2618": 0.28670501708984375, "2628": 0.14264501631259918, "2640": 0.3262358605861664, "2641": 0.31489628553390503, "2649": 0.12038381397724152, "2685": 0.49982786178588867, "2705": 0.6212902665138245, "2765": 0.2470736801624298, "2775": 0.40481385588645935, "2779": 0.40089741349220276, "2825": 0.01934296265244484, "2828": 0.12384103983640671, "2846": 0.13670019805431366, "2864": 0.23633737862110138, "2869": 0.41001203656196594, "2898": 0.4132472574710846, "2922": 0.06977381557226181, "2944": 0.2561853528022766, "2945": 0.7239188551902771, "2951": 0.6233867406845093, "2967": 0.14349138736724854, "2988": 0.1384023278951645, "3008": 0.2881702482700348, "3025": 0.21922965347766876, "3130": 0.5127768516540527, "3141": 0.20580662786960602, "3189": 0.3283478021621704, "3195": 0.2763880789279938, "3231": 0.16524957120418549, "3265": 0.18248429894447327, "3270": 0.7258110046386719, "3284": 0.1384023278951645, "3350": 0.755608320236206, "3351": 0.5364705324172974, "3366": 0.5871354341506958, "3378": 0.24171993136405945, "3388": 0.45499902963638306, "3426": 0.11865071207284927, "3463": 0.5051454305648804, "3512": 0.11343330889940262, "3556": 1.0298984050750732, "3582": 0.02792670577764511, "3596": 0.1751343309879303, "3618": 0.46670228242874146, "3633": 0.3170322775840759, "3643": 0.02887592278420925, "3653": 0.31845372915267944, "3674": 0.7737906575202942, "3806": 0.9409833550453186, "3809": 0.083342544734478, "3811": 0.029824240133166313, "3818": 0.011650617234408855, "3858": 0.0913962796330452, "3891": 0.02792670577764511, "3935": 0.09938567131757736, "3940": 0.28670501708984375, "3943": 0.08782484382390976, "4081": 0.5590575933456421, "4094": 0.31560876965522766, "4098": 0.5596157908439636, "4103": 0.6793810129165649, "4106": 0.817850649356842, "4146": 0.0058422754518687725, "4160": 0.6911921501159668, "4235": 0.4709797203540802, "4242": 0.3949938118457794, "4270": 0.7408206462860107, "4281": 0.02412080205976963, "4292": 0.2749055027961731, "4295": 0.7201237678527832, "4308": 0.7827593088150024, "4311": 0.29328158497810364, "4328": 0.6487176418304443, "4340": 0.672426164150238, "4453": 0.5805994272232056, "4456": 0.08064348995685577, "4531": 0.10906458646059036, "4555": 0.8893690705299377, "4577": 0.35334911942481995, "4602": 0.07341018319129944, "4637": 0.010684899985790253, "4642": 0.42353010177612305, "4655": 0.5579402446746826, "4663": 0.3519764244556427, "4678": 0.15777134895324707, "4800": 0.8332487344741821, "4949": 0.6233867406845093, "4957": 0.7809720039367676, "4962": 1.1109062433242798, "5022": 0.20501139760017395, "5136": 0.06520967930555344, "5201": 0.3019835948944092, "5240": 0.46486347913742065, "5292": 0.08154398202896118, "5320": 0.13755162060260773, "5360": 0.7737906575202942, "5381": 0.29109421372413635, "5387": 0.045809537172317505, "5388": 0.27564704418182373, "5393": 0.10467668622732162, "5418": 0.7500885725021362, "5468": 0.2749055027961731, "5531": 0.30558720231056213, "5537": 0.0174254160374403, "5542": 0.08603433519601822, "5579": 0.014542185701429844, "5593": 0.25995752215385437, "5604": 0.15359249711036682, "5646": 0.39762192964553833, "5648": 0.037378571927547455, "5729": 1.0933903455734253, "5739": 0.1510767638683319, "5761": 0.2478361576795578, "5769": 0.2852376699447632, "5776": 0.37640097737312317, "5790": 0.11865071207284927, "5799": 0.5668440461158752, "5857": 0.07250232994556427, "5867": 0.6931471824645996, "5876": 0.056018441915512085, "5950": 0.021256839856505394, "6034": 0.3588210940361023, "6064": 0.7258110046386719, "6070": 0.4679262638092041, "6075": 0.043007105588912964, "6083": 0.49864232540130615, "6122": 0.08961215615272522, "6123": 0.8550800085067749, "6177": 0.3353555500507355, "6195": 0.29036402702331543, "6200": 0.05046287178993225, "6592": 0.7872136831283569, "6687": 0.034552380442619324, "6691": 0.1619328260421753, "6709": 0.6139179468154907, "6721": 0.08692999184131622, "6887": 0.46608972549438477, "6914": 0.11081436276435852, "6922": 0.6405166387557983, "6927": 0.5685047507286072, "6971": 0.1718502640724182, "7011": 0.7692760229110718, "7060": 0.6634125709533691, "7091": 0.43875885009765625, "7093": 0.12814582884311676, "7108": 0.129004567861557, "7275": 0.09050461649894714, "7279": 0.757441520690918, "7341": 0.6075552701950073, "7361": 0.35334911942481995, "7403": 1.2387138605117798, "7444": 0.839173436164856, "7461": 0.36967599391937256, "7594": 0.04674193635582924, "7644": 0.7942996621131897, "7645": 0.083342544734478, "7685": 0.3757305145263672, "7689": 0.1751343309879303, "7693": 0.2034190446138382, "7718": 0.052318159490823746, "7784": 0.016465263441205025, "7809": 0.14518201351165771, "7843": 0.33953672647476196, "7863": 0.8989537954330444, "7870": 0.5816917419433594, "7900": 0.8877626657485962, "8020": 0.24018502235412598, "8022": 0.5324648022651672, "8077": 0.02792670577764511, "8285": 0.6482070088386536, "8343": 0.00875066313892603, "8400": 0.6096806526184082, "8486": 0.6160298585891724, "8599": 0.0606246218085289, "8715": 0.3656192123889923, "8761": 0.3070250153541565, "8777": 0.15023678541183472, "8833": 0.45437926054000854, "8840": 1.0001721382141113, "8949": 0.49982786178588867, "8991": 0.5762182474136353, "9002": 0.6410312056541443, "9104": 0.28743788599967957, "9128": 0.7314660549163818, "9165": 0.981317400932312, "9358": 0.7537717819213867, "9389": 0.6989894509315491, "9504": 0.053244512528181076, "9535": 0.2667117714881897, "9551": 0.06429435312747955, "9556": 0.2830325961112976, "9560": 0.5027855634689331, "10109": 0.09317722171545029, "10174": 0.006812678650021553, "10238": 0.9455460906028748, "10256": 0.1734936386346817, "10258": 0.11865071207284927, "10381": 0.11517547070980072, "10440": 0.04394211992621422, "10623": 0.0058422754518687725, "10744": 0.32341301441192627, "10840": 0.13670019805431366, "11100": 0.6000806093215942, "11156": 0.10203468054533005, "11268": 0.27934664487838745, "11383": 0.176772341132164, "11643": 0.20102575421333313, "11644": 0.38905516266822815, "11721": 0.05046287178993225, "11888": 0.6613984704017639, "12115": 0.9271688461303711, "12130": 0.4041621685028076, "12151": 0.3084607720375061, "12171": 0.2516399025917053, "12289": 0.055094651877880096, "12349": 0.7028654217720032, "12375": 0.7537717819213867, "12412": 0.5635144114494324, "12473": 0.04394211992621422, "12514": 0.16359257698059082, "12515": 0.2470736801624298, "12521": 0.40546512603759766, "12540": 0.3723714053630829, "12617": 0.09317722171545029, "12680": 0.05970508232712746, "12702": 0.7105726003646851, "12712": 0.20660123229026794, "12839": 0.9820492267608643, "12941": 0.18816383183002472, "12955": 0.27564704418182373, "13105": 0.3910386264324188, "13181": 0.9348671436309814, "13348": 0.7827593088150024, "13458": 0.8013357520103455, "13553": 0.9005423784255981, "13594": 0.5816917419433594, "13722": 0.24859806895256042, "13767": 0.22548456490039825, "13811": 0.4067663550376892, "13874": 0.75193190574646, "13923": 0.1718502640724182, "14045": 0.1685553640127182, "14155": 0.011650617234408855, "14244": 0.19220098853111267, "14246": 0.1710275560617447, "14440": 0.42225050926208496, "14471": 0.8567397594451904, "14494": 0.34715715050697327, "14536": 0.11430477350950241, "14800": 1.2900071144104004, "14847": 0.2531573474407196, "14859": 0.22392450273036957, "15112": 0.10555581003427505, "15306": 0.5010119676589966, "15527": 0.3141832649707794, "15543": 0.11168810725212097, "15758": 0.17759032547473907, "16014": 0.09938567131757736, "16048": 0.15359249711036682, "16216": 1.3489859104156494, "16221": 0.5882205963134766, "16275": 0.030771657824516296, "16339": 0.6543170213699341, "16344": 0.1710275560617447, "16387": 0.9240728616714478, "16463": 0.43875885009765625, "16478": 0.3269403576850891, "16483": 0.0019512200960889459, "16505": 0.24018502235412598, "16515": 0.8212929964065552, "16576": 0.5478278398513794, "16578": 0.15943801403045654, "16599": 0.04487626627087593, "16605": 0.5301685929298401, "16643": 0.11256109178066254, "16706": 1.0881409645080566, "16846": 0.8877626657485962, "16884": 0.41065993905067444, "16932": 0.7463917136192322, "16998": 0.8699195384979248, "17134": 0.8837352395057678, "17359": 0.006812678650021553, "17421": 0.757441520690918, "17603": 0.8877626657485962, "17655": 0.20501139760017395, "17715": 0.9021284580230713, "17826": 0.0009760859538801014, "17830": 0.20818853378295898, "17886": 0.4537591338157654, "17908": 0.5584990978240967, "18078": 0.7565253376960754, "18211": 0.04207121208310127, "18275": 0.3526630103588104, "18886": 0.27342069149017334, "18949": 0.8281423449516296, "18960": 0.016465263441205025, "18976": 0.75193190574646, "19064": 0.11430477350950241, "19126": 0.2637155055999756, "19345": 0.6165571808815002, "19500": 0.03831886500120163, "19539": 0.6476961374282837, "19652": 0.8039615154266357, "19739": 0.2667117714881897, "19835": 0.755608320236206, "20014": 0.15860503911972046, "20253": 0.10731173306703568, "20272": 0.3141832649707794, "20467": 0.009718249551951885, "20569": 0.021256839856505394, "20662": 0.15023678541183472, "21025": 0.6862877607345581, "21211": 0.09406650811433792, "21262": 0.04487626627087593, "21307": 0.026976587250828743, "21472": 0.08154398202896118, "21486": 0.22937409579753876, "21621": 0.8450632095336914, "21770": 0.06612417846918106, "21877": 0.1905880719423294, "22026": 0.2231435477733612, "22060": 0.010684899985790253, "22107": 0.04487626627087593, "22154": 0.3027053773403168, "22275": 0.732405424118042, "22466": 0.29109421372413635, "22490": 0.3485364317893982, "22571": 0.22782009840011597, "23079": 0.04953393340110779, "23186": 0.0009760859538801014, "23368": 0.03831886500120163, "23614": 1.19888174533844, "23833": 0.981317400932312, "23900": 0.0019512200960889459, "24004": 0.0797421783208847, "24481": 0.05786345899105072, "24552": 0.13755162060260773, "24558": 0.1401015669107437, "24590": 0.2160874605178833, "24665": 0.08064348995685577, "24720": 0.8247235417366028, "24759": 0.27786844968795776, "24921": 0.1905880719423294, "24971": 0.5069117546081543, "25148": 1.4037197828292847, "25206": 1.3321186304092407, "25416": 0.9739698171615601, "25426": 0.7258110046386719, "25469": 0.5284429788589478, "25524": 0.09850110858678818, "25538": 0.19862671196460724, "25817": 0.2223619967699051, "26264": 0.16110190749168396, "26305": 0.7009293437004089, "26572": 0.4794800877571106, "26684": 0.08692999184131622, "26741": 0.3662964701652527, "26871": 0.6348392367362976, "26874": 0.8349450826644897, "27011": 0.0058422754518687725, "27404": 0.2954642176628113, "27441": 0.052318159490823746, "27480": 0.306306391954422, "27642": 0.5517725944519043, "27811": 0.0174254160374403, "27815": 0.38574060797691345, "28290": 0.36358460783958435, "28637": 0.3381449282169342, "29160": 0.2247048318386078, "29562": 0.9348671436309814, "29606": 0.09850110858678818} | 12428137 | CONTEXT Gastroesophageal reflux (GER) has not previously been widely regarded as a hereditary disease. A few reports have suggested, however, that a genetic component may contribute to the incidence of GER, especially in its severe or chronic forms. OBJECTIVE To identify a genetic locus that cosegregates with a severe pediatric GER phenotype in families with multiple affected members. DESIGN A genome-wide scan of families affected by severe pediatric GER using polymorphic microsatellite markers spaced at an average of 8 centimorgans (cM), followed by haplotyping and by pairwise and multipoint linkage analyses. SETTING General US community, with research performed in a university tertiary care hospital. SUBJECTS Affected and unaffected family members from 5 families having multiple individuals affected by severe pediatric GER, identified through a patient support group. MAIN OUTCOME MEASURES Determination of inheritance patterns and linkage of a genetic locus with the severe pediatric GER phenotype by logarithm-of-odds (lod) score analysis, considering a lod score of 3 or greater as evidence of linkage. RESULTS In these families, severe pediatric GER followed an autosomal dominant hereditary pattern with high penetrance. A gene for severe pediatric GER was mapped to a 13-cM region on chromosome 13q between microsatellite markers D13S171 and D13S263. A maximum multifamily 2-point lod score of 5.58 and a maximum multifamily multipoint lod score of 7.15 were obtained for marker D13S1253 at map position 35 cM when presumptively affected persons were modeled as unknown (a maximum multipoint score of 4.88 was obtained when presumptively affected persons were modeled as unaffected). CONCLUSION These data suggest that a gene for severe pediatric GER maps to chromosome 13q14. JAMA. 2000;284:325-334 | Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14. |
{"1014": 0.8212929964065552, "1015": 0.16690383851528168, "1016": 0.20580662786960602, "1038": 0.6296497583389282, "1043": 0.12384103983640671, "1044": 0.0797421783208847, "2000": 0.29255300760269165, "2002": 0.10731173306703568, "2005": 0.07612881064414978, "2011": 0.4203280806541443, "2047": 0.7067264318466187, "2048": 0.4950772523880005, "2051": 0.6070231795310974, "2062": 0.44753631949424744, "2063": 0.053244512528181076, "2077": 0.00875066313892603, "2088": 0.14433705806732178, "2104": 0.4574742913246155, "2116": 0.0354953333735466, "2120": 0.7528522610664368, "2121": 0.1913948506116867, "2152": 0.4067663550376892, "2172": 0.0317181795835495, "2217": 0.32553088665008545, "2236": 0.12642613053321838, "2248": 0.48068851232528687, "2271": 0.27564704418182373, "2289": 0.04487626627087593, "2323": 0.27934664487838745, "2331": 0.026025565341114998, "2334": 0.7295845746994019, "2335": 0.07612881064414978, "2336": 0.38308101892471313, "2339": 0.30558720231056213, "2369": 0.49030399322509766, "2397": 0.15777134895324707, "2406": 0.684319257736206, "2470": 0.22626367211341858, "2474": 0.6989894509315491, "2490": 0.6926587820053101, "2491": 0.18816383183002472, "2497": 0.8195732831954956, "2504": 0.25845035910606384, "2535": 0.5478278398513794, "2545": 0.37371641397476196, "2553": 0.5461324453353882, "2555": 0.4500300884246826, "2556": 0.016465263441205025, "2565": 0.5629584193229675, "2615": 0.083342544734478, "2641": 0.07431721687316895, "2646": 0.20660123229026794, "2689": 0.03266380727291107, "2753": 0.6583697199821472, "2775": 0.4425300657749176, "2787": 0.6461620330810547, "2817": 0.5069117546081543, "2828": 0.46117570996284485, "2859": 0.016465263441205025, "2875": 0.43053874373435974, "2885": 0.083342544734478, "2901": 0.02887592278420925, "2913": 0.4574742913246155, "2915": 0.6107416749000549, "2944": 0.5729197263717651, "2951": 0.2493593990802765, "3020": 0.18248429894447327, "3025": 0.3930181860923767, "3032": 0.7389566898345947, "3097": 0.0354953333735466, "3107": 0.19381128251552582, "3141": 0.5773153901100159, "3164": 0.24325250089168549, "3171": 0.7124901413917542, "3176": 0.011650617234408855, "3177": 0.5607312321662903, "3247": 1.184049129486084, "3259": 0.22079704701900482, "3273": 0.10379679501056671, "3278": 0.574020504951477, "3284": 0.013579257763922215, "3318": 0.4512746334075928, "3343": 0.8238670229911804, "3350": 0.6813592314720154, "3357": 0.37907835841178894, "3378": 0.7592713832855225, "3445": 0.2990913391113281, "3446": 0.3850763738155365, "3454": 0.4891071021556854, "3463": 0.03266380727291107, "3465": 0.7172679901123047, "3466": 0.1685553640127182, "3478": 0.010684899985790253, "3517": 0.06154331564903259, "3550": 0.00875066313892603, "3567": 0.0913962796330452, "3569": 0.5174443125724792, "3572": 0.2447827309370041, "3591": 0.151916041970253, "3601": 0.2881702482700348, "3623": 0.4450363218784332, "3674": 0.0029254043474793434, "3739": 0.5045560002326965, "3741": 0.17840765416622162, "3747": 0.6813592314720154, "3795": 0.9100211262702942, "3805": 0.19381128251552582, "3811": 0.27786844968795776, "3818": 0.23633737862110138, "3842": 0.25845035910606384, "3867": 0.17267228662967682, "3891": 0.12470348179340363, "3921": 0.5255602598190308, "3935": 0.0019512200960889459, "3943": 0.3070250153541565, "3970": 0.24325250089168549, "3976": 0.6482070088386536, "3989": 0.66441810131073, "4030": 0.15777134895324707, "4041": 0.23015019297599792, "4072": 0.012615402229130268, "4081": 0.37707099318504333, "4084": 0.37304413318634033, "4106": 0.619189441204071, "4108": 0.026025565341114998, "4118": 0.20501139760017395, "4127": 0.10026945173740387, "4146": 0.03925827145576477, "4233": 1.1089750528335571, "4254": 0.20501139760017395, "4275": 0.4462870955467224, "4281": 1.0735615491867065, "4293": 0.012615402229130268, "4295": 0.37102460861206055, "4328": 0.3883931338787079, "4340": 0.1693800985813141, "4395": 0.30989447236061096, "4397": 0.053244512528181076, "4425": 0.44753631949424744, "4453": 0.1229778528213501, "4541": 0.27712854743003845, "4610": 0.3423145115375519, "4637": 0.45994341373443604, "4655": 0.30558720231056213, "4707": 0.9944084882736206, "4725": 0.3283478021621704, "4730": 0.175953671336174, "4746": 0.2674594223499298, "4800": 0.3084607720375061, "4804": 0.24325250089168549, "4844": 0.05139094591140747, "4852": 0.24171993136405945, "4863": 0.4574742913246155, "4942": 0.34922540187835693, "4945": 0.7276995778083801, "4958": 0.3163207769393921, "4969": 0.31560876965522766, "4975": 0.010684899985790253, "4989": 0.034552380442619324, "5084": 0.3339579105377197, "5105": 0.38308101892471313, "5136": 0.3005385100841522, "5138": 0.25088030099868774, "5150": 0.11604541540145874, "5157": 0.6892333030700684, "5178": 0.46363574266433716, "5292": 0.7426811456680298, "5333": 0.03831886500120163, "5345": 0.9485763907432556, "5366": 0.18492233753204346, "5386": 0.129004567861557, "5387": 0.8925741910934448, "5514": 0.24018502235412598, "5516": 0.33115679025650024, "5531": 0.18329764902591705, "5543": 0.5472630262374878, "5547": 0.3374483287334442, "5555": 0.058784693479537964, "5593": 0.22157983481884003, "5630": 0.5461324453353882, "5635": 0.05417001247406006, "5656": 0.20660123229026794, "5717": 0.7239188551902771, "5737": 1.024303913116455, "5769": 0.04207121208310127, "5840": 0.1384023278951645, "5876": 0.8442239761352539, "5915": 0.4203280806541443, "5967": 0.19782574474811554, "6022": 0.1401015669107437, "6026": 0.10993985831737518, "6043": 0.4734157919883728, "6083": 0.39762192964553833, "6094": 0.06337817758321762, "6110": 0.1332872211933136, "6146": 0.12814582884311676, "6165": 0.07612881064414978, "6185": 0.3615458607673645, "6191": 0.36900100111961365, "6195": 0.24401791393756866, "6226": 0.1229778528213501, "6303": 0.12986256182193756, "6378": 0.011650617234408855, "6383": 0.25694093108177185, "6450": 0.10026945173740387, "6463": 0.1889725625514984, "6485": 0.14939609169960022, "6567": 0.9710156321525574, "6592": 0.5069117546081543, "6633": 0.15275461971759796, "6648": 0.7674643993377686, "6727": 0.1808556467294693, "6749": 0.42990362644195557, "6753": 0.3560888469219208, "6787": 0.0058422754518687725, "6789": 0.1751343309879303, "6827": 0.19541899859905243, "6873": 0.07068414986133575, "6937": 0.04953393340110779, "7012": 0.0770333781838417, "7017": 0.42096930742263794, "7065": 0.12814582884311676, "7091": 0.4132472574710846, "7171": 0.6466736793518066, "7197": 0.16524957120418549, "7246": 0.4374985992908478, "7288": 0.3662964701652527, "7312": 0.15526613593101501, "7361": 0.29619070887565613, "7375": 0.11256109178066254, "7387": 0.030771657824516296, "7457": 0.2689530849456787, "7461": 0.20739519596099854, "7528": 0.09050461649894714, "7587": 0.18329764902591705, "7597": 0.3374483287334442, "7607": 0.05417001247406006, "7632": 1.0416836738586426, "7654": 0.021256839856505394, "7670": 0.06246116757392883, "7784": 0.28450319170951843, "7792": 0.39893341064453125, "7870": 0.26146242022514343, "7882": 0.14518201351165771, "7915": 0.2034190446138382, "7977": 0.23864774405956268, "8010": 0.11865071207284927, "8092": 0.3676496744155884, "8107": 0.5590575933456421, "8127": 0.09584271162748337, "8161": 0.34508460760116577, "8246": 0.2689530849456787, "8394": 1.0444365739822388, "8497": 0.3339579105377197, "8507": 0.02887592278420925, "8536": 0.9710156321525574, "8553": 0.04207121208310127, "8569": 0.01934296265244484, "8581": 1.0158531665802002, "8824": 0.06520967930555344, "8970": 0.20739519596099854, "9104": 0.6254787445068359, "9128": 0.3949938118457794, "9312": 0.05786345899105072, "9323": 0.7276995778083801, "9355": 0.1619328260421753, "9455": 0.045809537172317505, "9470": 0.21922965347766876, "9513": 0.16276304423809052, "9556": 0.6249561905860901, "9582": 0.32270604372024536, "9584": 0.3304552733898163, "9632": 0.674915611743927, "9662": 0.00875066313892603, "9694": 0.009718249551951885, "9804": 0.09761575609445572, "9886": 1.1935672760009766, "9920": 0.10555581003427505, "9990": 0.10731173306703568, "10047": 0.5707147121429443, "10091": 0.1994270235300064, "10342": 0.28670501708984375, "10408": 0.056018441915512085, "10449": 0.23092569410800934, "10460": 0.33115679025650024, "10527": 0.02887592278420925, "10549": 0.13925230503082275, "10561": 0.5324648022651672, "10638": 0.22548456490039825, "10711": 0.7426811456680298, "10744": 0.021256839856505394, "10755": 0.42096930742263794, "10857": 0.22079704701900482, "10859": 0.8013357520103455, "10898": 0.07431721687316895, "10915": 0.015504186972975731, "11092": 1.130645751953125, "11162": 0.025073638185858727, "11343": 0.083342544734478, "11365": 0.04674193635582924, "11395": 0.5370414853096008, "11429": 0.6233867406845093, "11433": 0.6823468804359436, "11436": 0.16607704758644104, "11553": 0.06246116757392883, "11643": 0.4462870955467224, "11709": 0.1930064558982849, "11721": 1.0855059623718262, "11896": 0.011650617234408855, "12132": 0.06520967930555344, "12353": 0.03831886500120163, "12360": 0.04860413447022438, "12503": 0.175953671336174, "12504": 0.12384103983640671, "12637": 0.007782140281051397, "12644": 0.28743788599967957, "12693": 0.7115318179130554, "12832": 0.7701805830001831, "12941": 0.022212404757738113, "13075": 0.06886265426874161, "13105": 0.14349138736724854, "13341": 0.41065993905067444, "13356": 0.7352184057235718, "13494": 0.052318159490823746, "13543": 0.07431721687316895, "13562": 0.0029254043474793434, "13732": 0.007782140281051397, "13827": 0.018384648486971855, "14218": 0.08692999184131622, "14350": 0.9798521995544434, "14475": 0.3949938118457794, "14613": 1.2819099426269531, "14693": 1.1281205415725708, "14751": 0.12642613053321838, "14754": 0.3304552733898163, "14949": 0.07159364968538284, "14972": 0.29328158497810364, "15306": 0.6553317308425903, "15318": 0.319873183965683, "15403": 0.15610189735889435, "15406": 0.1905880719423294, "15428": 0.0770333781838417, "15581": 0.26146242022514343, "15843": 0.16110190749168396, "15877": 0.3883931338787079, "16014": 0.06886265426874161, "16026": 0.045809537172317505, "16134": 0.3930181860923767, "16151": 0.9115922451019287, "16216": 0.025073638185858727, "16264": 0.8065804839134216, "16269": 0.05046287178993225, "16381": 0.0019512200960889459, "16408": 0.14179791510105133, "16452": 0.7342816591262817, "16478": 0.021256839856505394, "16599": 0.030771657824516296, "16731": 0.009718249551951885, "16755": 0.3297532796859741, "16852": 0.1905880719423294, "16887": 0.22782009840011597, "16989": 0.08603433519601822, "17024": 0.045809537172317505, "17060": 0.045809537172317505, "17208": 0.05786345899105072, "17258": 0.10555581003427505, "17404": 1.3454316854476929, "17908": 0.21530038118362427, "17959": 0.14264501631259918, "18583": 0.2652147710323334, "18730": 0.28963330388069153, "18876": 0.013579257763922215, "18891": 0.009718249551951885, "19064": 0.05046287178993225, "19132": 0.01934296265244484, "19199": 0.07884006202220917, "19209": 0.07250232994556427, "19210": 0.7701805830001831, "19293": 0.09584271162748337, "19466": 1.0073304176330566, "19518": 0.18573370575904846, "19601": 0.16524957120418549, "19761": 0.08961215615272522, "19857": 0.8195732831954956, "20065": 0.42544642090797424, "20141": 0.04487626627087593, "20253": 0.012615402229130268, "20502": 0.04674193635582924, "20536": 0.020300358533859253, "20874": 0.3269403576850891, "21125": 0.04953393340110779, "21277": 0.5925496220588684, "21485": 0.45623743534088135, "21663": 0.03925827145576477, "21791": 0.129004567861557, "21823": 0.7163142561912537, "22318": 0.32764431834220886, "22574": 0.04767346754670143, "22623": 0.05694137513637543, "22731": 0.39762192964553833, "23035": 0.1212492436170578, "23041": 1.0001721382141113, "23306": 0.8805016279220581, "23468": 0.440646231174469, "23614": 0.01934296265244484, "23854": 0.27934664487838745, "23900": 0.24401791393756866, "24010": 0.1384023278951645, "24306": 0.6254787445068359, "24370": 0.3127557039260864, "24442": 1.0907690525054932, "24576": 0.037378571927547455, "24710": 0.2026219218969345, "24748": 0.2763880789279938, "24755": 0.15442965924739838, "24787": 0.31845372915267944, "25022": 0.5104349255561829, "25095": 0.0752234235405922, "25434": 0.10291612148284912, "25765": 0.2607102394104004, "25870": 0.2184450328350067, "26163": 0.2018241584300995, "26835": 0.06886265426874161, "27258": 0.3339579105377197, "28258": 0.18978065252304077, "28277": 0.026976587250828743, "28389": 0.0029254043474793434, "28436": 0.029824240133166313, "28748": 0.14518201351165771, "28809": 0.013579257763922215, "28896": 1.2953691482543945, "28931": 0.777387797832489, "29073": 0.2881702482700348, "29391": 0.43244171142578125, "29491": 0.04674193635582924, "29494": 1.0051883459091187, "29513": 0.0752234235405922} | 12428497 | BACKGROUND Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance). METHODS AND FINDINGS Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18-0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33-0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00-1.04). Global recommendations and local studies were not associated with time to decision. CONCLUSIONS This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors. | Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis |
{"1020": 0.6212902665138245, "1044": 0.39367714524269104, "1056": 0.6872705817222595, "2002": 0.7009293437004089, "2007": 0.0770333781838417, "2008": 0.03831886500120163, "2011": 0.5483922958374023, "2015": 0.02792670577764511, "2029": 0.16359257698059082, "2046": 0.5415972471237183, "2063": 0.07341018319129944, "2075": 0.1477125883102417, "2090": 0.5690577030181885, "2098": 0.678390383720398, "2291": 0.8433839678764343, "2361": 1.059443712234497, "2378": 0.57457035779953, "2416": 0.7314660549163818, "2426": 0.5816917419433594, "2465": 0.3622259199619293, "2522": 0.22157983481884003, "2535": 0.10379679501056671, "2537": 0.021256839856505394, "2575": 1.147526502609253, "2618": 0.23787821829319, "2649": 0.04953393340110779, "2828": 0.5506471395492554, "2865": 0.7105726003646851, "2913": 0.07068414986133575, "2944": 0.3864043951034546, "2953": 1.141931176185608, "3001": 0.762009859085083, "3031": 0.11865071207284927, "3223": 0.4494072198867798, "3252": 0.21922965347766876, "3258": 1.0389231443405151, "3273": 0.0009760859538801014, "3302": 0.5784112811088562, "3366": 0.07431721687316895, "3370": 0.09050461649894714, "3375": 0.48670899868011475, "3436": 0.39762192964553833, "3466": 1.0430610179901123, "3526": 0.567397952079773, "3563": 0.1485546976327896, "3595": 1.2666174173355103, "3614": 0.8374842405319214, "3686": 0.07884006202220917, "3736": 0.1751343309879303, "3800": 0.0019512200960889459, "3853": 0.5483922958374023, "3858": 0.6149744987487793, "3896": 0.3339579105377197, "3936": 0.037378571927547455, "4072": 0.04113444685935974, "4106": 0.37102460861206055, "4127": 0.34922540187835693, "4130": 0.2674594223499298, "4135": 0.48008447885513306, "4183": 0.6332852244377136, "4235": 0.10731173306703568, "4275": 0.34370049834251404, "4280": 0.319873183965683, "4310": 0.6471850275993347, "4338": 0.5116065740585327, "4369": 0.3662964701652527, "4372": 0.18573370575904846, "4383": 0.9485763907432556, "4442": 0.6430866718292236, "4453": 0.03266380727291107, "4523": 0.34023189544677734, "4539": 0.8633513450622559, "4563": 1.2307592630386353, "4668": 0.06337817758321762, "4747": 0.7889899015426636, "4757": 1.0881409645080566, "4770": 0.6950984001159668, "4842": 0.659380316734314, "4919": 0.5427330136299133, "4962": 0.06429435312747955, "4972": 0.42161011695861816, "4997": 0.8332487344741821, "5017": 1.0409941673278809, "5038": 0.8600510358810425, "5044": 0.6989894509315491, "5072": 0.10993985831737518, "5110": 0.10906458646059036, "5182": 0.004870930220931768, "5250": 1.086165428161621, "5292": 0.8600510358810425, "5387": 0.36967599391937256, "5391": 0.5979346632957458, "5393": 0.18167030811309814, "5416": 0.06429435312747955, "5449": 0.25845035910606384, "5478": 0.472198486328125, "5579": 0.06886265426874161, "5643": 0.812664806842804, "5668": 1.0894558429718018, "5740": 0.817850649356842, "5769": 0.3170322775840759, "5847": 0.11430477350950241, "5860": 0.49626702070236206, "5876": 0.5016035437583923, "5918": 0.3949938118457794, "5921": 0.25088030099868774, "5942": 0.3897167444229126, "5966": 0.30558720231056213, "6146": 0.056018441915512085, "6327": 0.08961215615272522, "6370": 0.026976587250828743, "6459": 0.04113444685935974, "6522": 0.10993985831737518, "6565": 0.5209306478500366, "6633": 0.48430517315864563, "6807": 0.4980490207672119, "6819": 1.04512357711792, "6897": 0.10026945173740387, "6923": 0.574020504951477, "7127": 0.020300358533859253, "7274": 0.9827804565429688, "7337": 1.04512357711792, "7356": 0.7445381283760071, "7366": 0.36426326632499695, "7461": 0.3163207769393921, "7578": 0.6275664567947388, "7635": 0.6059582233428955, "7645": 0.3615458607673645, "7712": 0.32058215141296387, "7800": 0.13670019805431366, "7843": 0.3346569836139679, "7883": 0.026976587250828743, "7889": 0.7201237678527832, "7925": 0.05694137513637543, "8031": 0.5080875158309937, "8050": 0.8013357520103455, "8153": 0.0029254043474793434, "8171": 1.0087559223175049, "8281": 0.04860413447022438, "8290": 0.5893046259880066, "8360": 0.17020416259765625, "8382": 0.08692999184131622, "8496": 0.6212902665138245, "8523": 0.8366385698318481, "8566": 0.8315495252609253, "8803": 0.08692999184131622, "8890": 0.5010119676589966, "8906": 0.05139094591140747, "9007": 0.6793810129165649, "9034": 0.10906458646059036, "9095": 0.2667117714881897, "9096": 0.8699195384979248, "9099": 0.8315495252609253, "9147": 0.6202403903007507, "9167": 1.0795515775680542, "9416": 0.35950297117233276, "9513": 0.06977381557226181, "9530": 0.5021947622299194, "9547": 0.16607704758644104, "9937": 0.20421554148197174, "9972": 0.35950297117233276, "10253": 1.0101795196533203, "10266": 0.45499902963638306, "10327": 1.19829261302948, "10466": 0.3949938118457794, "10496": 0.7408206462860107, "10595": 0.8893690705299377, "10719": 0.6892333030700684, "10737": 0.6394867897033691, "10763": 0.9754437208175659, "10769": 0.6664261221885681, "10788": 0.08692999184131622, "11022": 0.14518201351165771, "11211": 0.11081436276435852, "11234": 0.0752234235405922, "11548": 0.32129061222076416, "11637": 0.35334911942481995, "11643": 0.16442140936851501, "11767": 0.28890204429626465, "11835": 0.3318578004837036, "12228": 0.029824240133166313, "12477": 0.0354953333735466, "12644": 0.4093637466430664, "12679": 0.5215105414390564, "12681": 0.4177590310573578, "12702": 0.6808650493621826, "12732": 0.9798521995544434, "12758": 0.05417001247406006, "12762": 0.2749055027961731, "12921": 0.25694093108177185, "12944": 0.6038249135017395, "12987": 0.021256839856505394, "13250": 1.034073829650879, "13523": 0.04767346754670143, "13791": 0.07431721687316895, "13827": 0.0019512200960889459, "13833": 0.6466736793518066, "13922": 0.5191890001296997, "13974": 0.14179791510105133, "13978": 0.05046287178993225, "14049": 0.23247487843036652, "14126": 0.2659635543823242, "14187": 0.5903874635696411, "14338": 0.6430866718292236, "14399": 0.7969439625740051, "14442": 0.0019512200960889459, "14600": 0.5795059204101562, "14622": 0.5033760666847229, "14774": 0.09228714555501938, "14776": 0.6233867406845093, "14828": 0.07341018319129944, "15185": 0.10731173306703568, "15370": 0.12986256182193756, "15420": 0.15359249711036682, "15612": 0.7057625651359558, "15775": 0.8298473954200745, "15923": 0.15526613593101501, "16086": 0.06977381557226181, "16280": 0.9628462791442871, "16285": 0.49982786178588867, "16305": 1.2117549180984497, "16690": 0.18654440343379974, "16731": 1.1822543144226074, "16748": 0.3005385100841522, "16771": 0.27342069149017334, "16862": 0.6389714479446411, "16910": 0.9371650815010071, "16989": 1.1911962032318115, "17341": 0.9987343549728394, "17379": 0.012615402229130268, "17614": 0.21687394380569458, "17908": 0.21530038118362427, "18252": 0.3615458607673645, "18404": 0.46853771805763245, "18479": 0.6970458030700684, "18499": 0.9225212931632996, "18684": 0.6970458030700684, "18771": 0.0606246218085289, "19107": 0.06795065850019455, "19129": 0.47766464948654175, "19185": 0.30917787551879883, "19476": 0.012615402229130268, "19601": 0.04113444685935974, "19610": 0.11343330889940262, "19780": 0.07068414986133575, "19798": 0.11691460013389587, "19872": 0.42416930198669434, "20026": 0.7755908370018005, "20582": 0.21214580535888672, "20655": 0.13414156436920166, "20766": 0.040196798741817474, "20817": 0.7827593088150024, "21102": 0.1485546976327896, "21162": 0.7124901413917542, "21685": 0.36494144797325134, "21781": 0.8143964409828186, "21821": 0.3443928062915802, "21996": 0.043007105588912964, "22330": 0.6139179468154907, "22476": 0.026025565341114998, "22625": 0.9425065517425537, "22694": 0.11778303235769272, "23191": 0.08244366943836212, "23340": 0.1994270235300064, "23725": 1.0855059623718262, "23758": 0.04953393340110779, "24024": 0.46853771805763245, "24054": 0.0174254160374403, "24312": 0.04207121208310127, "24345": 0.04674193635582924, "24382": 0.13414156436920166, "24529": 0.08871890604496002, "24635": 0.6202403903007507, "24848": 1.2753846645355225, "25117": 0.2990913391113281, "25181": 0.175953671336174, "25281": 0.11691460013389587, "25352": 0.0913962796330452, "25458": 0.08603433519601822, "26236": 0.0354953333735466, "26244": 0.030771657824516296, "26282": 0.3304552733898163, "26396": 0.13755162060260773, "26435": 0.13755162060260773, "26549": 0.9084475636482239, "26591": 0.3318578004837036, "26775": 0.018384648486971855, "26835": 0.28963330388069153, "27846": 0.0058422754518687725, "27854": 0.10467668622732162, "28041": 0.13499516248703003, "28184": 0.3409265875816345, "28498": 0.08782484382390976, "29105": 0.6931471824645996, "29347": 0.16524957120418549, "29390": 0.04674193635582924} | 12428814 | Secretion systems require high-fidelity mechanisms to discriminate substrates among the vast cytoplasmic pool of proteins. Factors mediating substrate recognition by the type VI secretion system (T6SS) of Gram-negative bacteria, a widespread pathway that translocates effector proteins into target bacterial cells, have not been defined. We report that haemolysin coregulated protein (Hcp), a ring-shaped hexamer secreted by all characterized T6SSs, binds specifically to cognate effector molecules. Electron microscopy analysis of an Hcp-effector complex from Pseudomonas aeruginosa revealed the effector bound to the inner surface of Hcp. Further studies demonstrated that interaction with the Hcp pore is a general requirement for secretion of diverse effectors encompassing several enzymatic classes. Though previous models depict Hcp as a static conduit, our data indicate it is a chaperone and receptor of substrates. These unique functions of a secreted protein highlight fundamental differences between the export mechanism of T6 and other characterized secretory pathways. | Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates. |
{"1014": 0.4400174915790558, "1019": 0.37102460861206055, "1022": 0.1485546976327896, "1023": 0.2493593990802765, "1051": 0.5370414853096008, "1062": 0.06703783571720123, "2001": 0.1332872211933136, "2007": 0.18248429894447327, "2014": 0.09495500475168228, "2020": 0.014542185701429844, "2039": 0.21687394380569458, "2042": 0.1510767638683319, "2043": 0.15777134895324707, "2044": 0.5816917419433594, "2051": 0.2089812457561493, "2053": 0.3012613356113434, "2067": 0.06337817758321762, "2076": 0.2800849378108978, "2077": 0.03266380727291107, "2078": 0.5438674688339233, "2080": 0.04207121208310127, "2084": 0.176772341132164, "2086": 0.7565253376960754, "2088": 0.15693697333335876, "2095": 0.42608439922332764, "2101": 0.33675122261047363, "2102": 0.24401791393756866, "2106": 0.02887592278420925, "2109": 0.04860413447022438, "2114": 0.503966212272644, "2116": 0.2105647772550583, "2117": 0.36967599391937256, "2128": 0.2470736801624298, "2145": 0.32905077934265137, "2146": 0.7537717819213867, "2151": 0.08782484382390976, "2166": 0.6512666940689087, "2184": 0.7408206462860107, "2193": 0.6128603219985962, "2197": 0.31560876965522766, "2203": 0.2667117714881897, "2204": 0.0058422754518687725, "2206": 0.2983669638633728, "2217": 0.5882205963134766, "2220": 0.6543170213699341, "2260": 0.006812678650021553, "2274": 0.14433705806732178, "2287": 0.42608439922332764, "2294": 0.10818854719400406, "2308": 0.8349450826644897, "2313": 0.06246116757392883, "2321": 0.14095009863376617, "2324": 0.02412080205976963, "2331": 0.7951818704605103, "2351": 0.23864774405956268, "2384": 0.5127768516540527, "2397": 0.045809537172317505, "2403": 0.19622190296649933, "2411": 0.13925230503082275, "2426": 0.4400174915790558, "2430": 0.5433003902435303, "2432": 0.15777134895324707, "2450": 0.6149744987487793, "2460": 0.004870930220931768, "2470": 0.2837681770324707, "2491": 0.803087055683136, "2501": 0.015504186972975731, "2506": 0.6989894509315491, "2515": 0.018384648486971855, "2527": 0.09672962874174118, "2538": 0.10291612148284912, "2581": 0.020300358533859253, "2582": 0.6950984001159668, "2595": 0.14686977863311768, "2620": 0.23324857652187347, "2625": 0.029824240133166313, "2628": 0.4374985992908478, "2644": 0.7295845746994019, "2680": 0.18654440343379974, "2702": 0.49626702070236206, "2727": 0.8039615154266357, "2744": 0.9576126337051392, "2765": 0.21765978634357452, "2786": 0.175953671336174, "2802": 0.009718249551951885, "2807": 0.08244366943836212, "2817": 0.6160298585891724, "2871": 0.029824240133166313, "2902": 0.6578640341758728, "2913": 0.46486347913742065, "2931": 0.45251765847206116, "2936": 0.37035053968429565, "2949": 0.2852376699447632, "2951": 0.0354953333735466, "2988": 0.20580662786960602, "2994": 0.053244512528181076, "3025": 0.04860413447022438, "3030": 0.5540198087692261, "3041": 0.18816383183002472, "3091": 0.16607704758644104, "3092": 0.09938567131757736, "3112": 0.36358460783958435, "3126": 0.6170841455459595, "3144": 0.17840765416622162, "3189": 0.5528968572616577, "3247": 0.09406650811433792, "3268": 0.1693800985813141, "3273": 0.29473719000816345, "3274": 0.34508460760116577, "3278": 0.16442140936851501, "3280": 0.2763880789279938, "3283": 0.09761575609445572, "3296": 0.037378571927547455, "3370": 0.18411032855510712, "3378": 0.08603433519601822, "3408": 0.1710275560617447, "3439": 0.04487626627087593, "3446": 0.7454653382301331, "3452": 0.6165571808815002, "3463": 0.25995752215385437, "3466": 0.6400018334388733, "3479": 0.23402166366577148, "3540": 0.1011524572968483, "3556": 0.06246116757392883, "3570": 0.9287132620811462, "3582": 0.817850649356842, "3588": 0.1751343309879303, "3613": 0.6931471824645996, "3616": 0.31489628553390503, "3695": 0.04487626627087593, "3795": 0.2918238639831543, "3801": 0.29109421372413635, "3807": 0.020300358533859253, "3808": 0.1889725625514984, "3867": 0.10818854719400406, "3891": 0.848413348197937, "3893": 0.9100211262702942, "3896": 0.6573580503463745, "3938": 0.5618454217910767, "3949": 0.630689799785614, "3961": 0.14179791510105133, "3979": 0.6394867897033691, "4015": 0.20580662786960602, "4076": 0.16276304423809052, "4090": 0.5495203733444214, "4102": 0.304147332906723, "4106": 0.026025565341114998, "4118": 0.3141832649707794, "4137": 0.5197699069976807, "4236": 0.2652147710323334, "4242": 0.5601736903190613, "4247": 0.4891071021556854, "4254": 0.07431721687316895, "4281": 0.8997484445571899, "4295": 0.6296497583389282, "4311": 0.1602703034877777, "4328": 0.055094651877880096, "4355": 0.567397952079773, "4359": 0.5215105414390564, "4443": 0.16276304423809052, "4456": 1.301234245300293, "4464": 0.2719337046146393, "4531": 0.007782140281051397, "4566": 0.24859806895256042, "4568": 0.07431721687316895, "4621": 0.30486753582954407, "4651": 0.06612417846918106, "4725": 0.3883931338787079, "4748": 0.35060185194015503, "4758": 0.7295845746994019, "4914": 0.4568560719490051, "4948": 0.030771657824516296, "4958": 0.0752234235405922, "4969": 0.7791815400123596, "4997": 0.7827593088150024, "5003": 0.06703783571720123, "5012": 0.055094651877880096, "5022": 0.28670501708984375, "5068": 0.7445381283760071, "5082": 0.12642613053321838, "5345": 0.5466978549957275, "5360": 0.10993985831737518, "5388": 0.38174858689308167, "5443": 0.48430517315864563, "5486": 0.18248429894447327, "5547": 0.4512746334075928, "5567": 0.13670019805431366, "5574": 0.12814582884311676, "5643": 0.06154331564903259, "5700": 0.15442965924739838, "5717": 0.23092569410800934, "5719": 0.812664806842804, "5776": 0.2954642176628113, "5786": 0.11168810725212097, "5790": 0.04394211992621422, "5824": 0.07431721687316895, "5845": 0.5461324453353882, "5939": 0.010684899985790253, "5996": 0.0770333781838417, "6022": 0.6664261221885681, "6034": 0.28743788599967957, "6070": 0.17840765416622162, "6075": 0.2954642176628113, "6165": 0.6054253578186035, "6191": 0.19622190296649933, "6245": 0.013579257763922215, "6273": 0.2749055027961731, "6390": 0.6533012986183167, "6431": 0.4764525294303894, "6449": 0.23247487843036652, "6463": 0.817850649356842, "6480": 0.13414156436920166, "6503": 0.05417001247406006, "6535": 0.4512746334075928, "6540": 0.22157983481884003, "6551": 0.2018241584300995, "6612": 0.18978065252304077, "6677": 0.6064908504486084, "6721": 0.7229714393615723, "6747": 0.31560876965522766, "6762": 0.3588210940361023, "6937": 0.45499902963638306, "6939": 0.10291612148284912, "7012": 0.5957841277122498, "7017": 0.42225050926208496, "7023": 0.018384648486971855, "7065": 0.3554046154022217, "7142": 0.33115679025650024, "7163": 0.472198486328125, "7242": 0.2223619967699051, "7312": 0.7537717819213867, "7316": 0.1930064558982849, "7382": 0.25467249751091003, "7388": 1.2059240341186523, "7422": 0.11081436276435852, "7438": 0.30558720231056213, "7458": 0.8764448165893555, "7461": 0.22937409579753876, "7552": 0.36494144797325134, "7588": 0.151916041970253, "7619": 0.8383291959762573, "7667": 0.2447827309370041, "7691": 0.7220231294631958, "7711": 0.7009293437004089, "7778": 0.021256839856505394, "7820": 0.3560888469219208, "7831": 0.3554046154022217, "7870": 0.29981520771980286, "7987": 0.32199856638908386, "8046": 0.3034266233444214, "8161": 0.15610189735889435, "8302": 0.175953671336174, "8323": 0.30558720231056213, "8449": 0.03925827145576477, "8553": 0.05970508232712746, "8599": 0.020300358533859253, "8729": 0.040196798741817474, "8775": 0.026976587250828743, "8819": 0.17922431230545044, "8944": 0.7220231294631958, "8977": 0.06977381557226181, "9031": 0.1064341589808464, "9103": 0.8281423449516296, "9190": 0.09228714555501938, "9211": 0.022212404757738113, "9235": 0.02792670577764511, "9236": 0.1693800985813141, "9253": 0.12986256182193756, "9336": 0.28597161173820496, "9367": 0.6543170213699341, "9377": 0.32341301441192627, "9398": 0.11430477350950241, "9413": 1.0151457786560059, "9556": 0.6149744987487793, "9560": 0.8289952278137207, "9614": 0.07612881064414978, "9626": 0.10906458646059036, "9634": 0.6853039860725403, "9756": 0.4093637466430664, "9765": 0.4158279001712799, "9839": 0.2983669638633728, "9867": 0.04674193635582924, "9879": 0.38041436672210693, "9885": 0.07159364968538284, "9915": 0.029824240133166313, "10238": 0.09672962874174118, "10534": 0.02792670577764511, "10611": 0.3560888469219208, "10694": 0.1913948506116867, "10722": 0.05417001247406006, "10755": 0.40806588530540466, "10769": 0.8845420479774475, "10790": 0.25239890813827515, "10831": 0.42608439922332764, "11095": 1.1115491390228271, "11119": 0.0913962796330452, "11231": 0.12556517124176025, "11441": 0.32199856638908386, "11568": 1.086165428161621, "11616": 0.45994341373443604, "11620": 0.13755162060260773, "11636": 0.7500885725021362, "11656": 0.21135559678077698, "11674": 0.08244366943836212, "11709": 0.07250232994556427, "11890": 0.8315495252609253, "12098": 0.004870930220931768, "12142": 0.07341018319129944, "12173": 0.28082266449928284, "12353": 0.26146242022514343, "12380": 0.0842406153678894, "12381": 0.7755908370018005, "12654": 0.10993985831737518, "12682": 0.6405166387557983, "12763": 0.129004567861557, "13070": 0.28082266449928284, "13105": 0.9440274834632874, "13341": 0.015504186972975731, "13356": 1.0437490940093994, "13412": 0.23710809648036957, "13416": 0.18654440343379974, "13441": 0.28670501708984375, "13633": 0.42735910415649414, "13656": 0.5438674688339233, "13833": 0.8109301924705505, "14155": 0.42608439922332764, "14267": 0.1946154683828354, "14298": 0.03925827145576477, "14358": 0.42735910415649414, "14667": 0.12728634476661682, "15192": 0.004870930220931768, "15258": 0.058784693479537964, "15306": 0.04860413447022438, "15316": 0.8349450826644897, "15330": 0.12986256182193756, "15354": 0.38374659419059753, "15429": 0.055094651877880096, "15509": 0.16110190749168396, "15584": 0.23092569410800934, "15630": 0.6332852244377136, "15643": 0.09406650811433792, "15928": 0.00875066313892603, "16007": 0.3297532796859741, "16026": 0.18978065252304077, "16134": 0.5010119676589966, "16147": 0.1485546976327896, "16169": 1.3398208618164062, "16330": 0.08154398202896118, "16452": 0.2822965085506439, "16483": 0.3757305145263672, "16515": 0.0009760859538801014, "16670": 0.2918238639831543, "16677": 0.06886265426874161, "16778": 0.15023678541183472, "16983": 0.043007105588912964, "17060": 0.12038381397724152, "17214": 1.216973900794983, "17473": 0.02412080205976963, "17503": 0.16690383851528168, "17927": 0.013579257763922215, "18154": 0.5805994272232056, "18178": 0.020300358533859253, "18684": 0.32199856638908386, "18687": 0.0913962796330452, "18714": 0.6212902665138245, "18941": 0.9650808572769165, "18949": 0.4311734735965729, "18992": 0.2394166737794876, "19064": 0.23092569410800934, "19188": 0.1229778528213501, "19362": 0.0058422754518687725, "19824": 0.42096930742263794, "19982": 0.1477125883102417, "20162": 0.06154331564903259, "20247": 0.4770587682723999, "20272": 0.004870930220931768, "20360": 0.018384648486971855, "20752": 0.46486347913742065, "20996": 0.16276304423809052, "21081": 0.6327666640281677, "21150": 0.40806588530540466, "21261": 0.040196798741817474, "21371": 0.009718249551951885, "21391": 0.2516399025917053, "21434": 0.4419025182723999, "21472": 0.8143964409828186, "21557": 0.05417001247406006, "21879": 0.6054253578186035, "21961": 0.25995752215385437, "22394": 0.401551216840744, "22407": 0.812664806842804, "22500": 0.2689530849456787, "22935": 0.052318159490823746, "22991": 1.0979610681533813, "23086": 0.09938567131757736, "23163": 0.11081436276435852, "23260": 1.1369311809539795, "23552": 0.043007105588912964, "23833": 0.7124901413917542, "23911": 0.38574060797691345, "24413": 0.950843095779419, "24755": 0.8332487344741821, "24759": 0.4337083101272583, "25006": 0.757441520690918, "25022": 0.25088030099868774, "25269": 1.004473328590393, "25409": 0.8550800085067749, "25481": 0.040196798741817474, "25778": 0.08244366943836212, "25937": 0.10818854719400406, "26163": 0.35745587944984436, "26187": 0.06703783571720123, "26462": 0.5784112811088562, "26745": 0.2145126610994339, "26897": 0.058784693479537964, "26906": 0.30989447236061096, "26914": 0.18167030811309814, "27006": 0.0029254043474793434, "27144": 0.45994341373443604, "27483": 0.25995752215385437, "27794": 0.0174254160374403, "28207": 0.22392450273036957, "28225": 0.12814582884311676, "28358": 0.3930181860923767, "28474": 0.03925827145576477, "28517": 0.0606246218085289, "28667": 0.9115922451019287, "28687": 0.31204116344451904, "28732": 0.09850110858678818, "28977": 0.12470348179340363, "29251": 0.28963330388069153, "29264": 0.36900100111961365, "29323": 0.9958525896072388, "29486": 0.0770333781838417} | 12438901 | BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed. | Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial |
{"2004": 0.026025565341114998, "2005": 0.06429435312747955, "2008": 0.04860413447022438, "2011": 0.014542185701429844, "2012": 0.11168810725212097, "2015": 0.5318912267684937, "2024": 0.07884006202220917, "2037": 0.1064341589808464, "2050": 0.14518201351165771, "2054": 0.014542185701429844, "2064": 0.058784693479537964, "2070": 0.18329764902591705, "2076": 0.11778303235769272, "2078": 0.5461324453353882, "2079": 0.4624064862728119, "2089": 0.12642613053321838, "2109": 0.40351006388664246, "2128": 0.11691460013389587, "2166": 0.01934296265244484, "2193": 0.04860413447022438, "2224": 0.3269403576850891, "2239": 0.26146242022514343, "2291": 0.791648268699646, "2339": 0.28890204429626465, "2393": 0.630689799785614, "2426": 0.04113444685935974, "2458": 0.3615458607673645, "2490": 0.22782009840011597, "2491": 0.2493593990802765, "2515": 0.2918238639831543, "2532": 1.12938392162323, "2535": 0.7863243818283081, "2545": 0.0317181795835495, "2566": 0.07431721687316895, "2590": 0.5466978549957275, "2695": 0.7629209756851196, "2742": 0.41195443272590637, "2750": 0.06612417846918106, "2791": 0.2034190446138382, "2832": 0.4041621685028076, "2897": 0.6921701431274414, "2953": 0.6291293501853943, "3001": 0.8780695199966431, "3022": 0.10818854719400406, "3271": 0.09938567131757736, "3350": 0.5990082025527954, "3450": 0.5021947622299194, "3454": 0.10818854719400406, "3466": 0.1930064558982849, "3526": 0.15860503911972046, "3594": 0.3084607720375061, "3619": 0.38441169261932373, "3625": 0.15777134895324707, "3654": 0.35813871026039124, "3670": 0.8796916007995605, "3671": 0.29255300760269165, "3698": 0.04767346754670143, "3800": 0.40546512603759766, "3853": 0.6950984001159668, "3896": 0.21922965347766876, "4023": 0.4041621685028076, "4044": 0.5370414853096008, "4072": 0.1602703034877777, "4081": 0.175953671336174, "4111": 0.48430517315864563, "4176": 0.46486347913742065, "4254": 0.22704219818115234, "4263": 0.055094651877880096, "4286": 0.11168810725212097, "4295": 0.2990913391113281, "4395": 0.6353566646575928, "4483": 0.6517757177352905, "4506": 0.13925230503082275, "4539": 0.0606246218085289, "4671": 0.15359249711036682, "4730": 0.20977331697940826, "4809": 0.28670501708984375, "4962": 1.0560526847839355, "4972": 0.5914691090583801, "4973": 0.4286321699619293, "4975": 0.06520967930555344, "5017": 0.013579257763922215, "5094": 0.16359257698059082, "5162": 0.018384648486971855, "5197": 0.32553088665008545, "5201": 0.20580662786960602, "5214": 0.11517547070980072, "5224": 0.371698260307312, "5228": 0.3339579105377197, "5250": 0.06886265426874161, "5335": 0.06612417846918106, "5441": 0.6270449161529541, "5449": 0.401551216840744, "5537": 0.021256839856505394, "5668": 0.8877626657485962, "5682": 0.03831886500120163, "5769": 0.037378571927547455, "5770": 0.22079704701900482, "5802": 0.09850110858678818, "5857": 0.255429208278656, "5991": 0.026025565341114998, "6032": 0.4145384132862091, "6064": 0.4673144817352295, "6083": 0.5016035437583923, "6100": 0.44753631949424744, "6123": 0.4537591338157654, "6125": 0.45870962738990784, "6129": 0.1873544454574585, "6179": 0.24171993136405945, "6194": 0.5540198087692261, "6364": 0.18492233753204346, "6481": 0.4196864068508148, "6494": 0.6286086440086365, "6509": 0.1913948506116867, "6528": 0.736154317855835, "6591": 0.40806588530540466, "6592": 0.3381449282169342, "6622": 0.4831010699272156, "6666": 0.35745587944984436, "6691": 0.4132472574710846, "6721": 0.6456501483917236, "6897": 1.1864371299743652, "6911": 0.18573370575904846, "6936": 0.04207121208310127, "6958": 0.5209306478500366, "7011": 0.03360854089260101, "7065": 0.14939609169960022, "7077": 0.22079704701900482, "7126": 0.41647201776504517, "7163": 0.05139094591140747, "7197": 0.07612881064414978, "7229": 0.21372433006763458, "7337": 0.823009729385376, "7366": 1.0437490940093994, "7403": 0.8450632095336914, "7461": 0.1358480453491211, "7512": 0.7845434546470642, "7711": 0.2674594223499298, "7784": 0.015504186972975731, "7816": 0.26146242022514343, "7856": 0.12642613053321838, "7895": 0.08782484382390976, "7908": 0.0029254043474793434, "7949": 0.3127557039260864, "7976": 0.09850110858678818, "8010": 0.09850110858678818, "8020": 0.11865071207284927, "8092": 0.013579257763922215, "8171": 0.1358480453491211, "8303": 1.1363043785095215, "8360": 0.3170322775840759, "8386": 0.13414156436920166, "8456": 0.10379679501056671, "8465": 0.41195443272590637, "8498": 0.3784096837043762, "8553": 0.12986256182193756, "8840": 0.013579257763922215, "8991": 0.15943801403045654, "9002": 0.6212902665138245, "9007": 0.1913948506116867, "9099": 0.06886265426874161, "9165": 0.9440274834632874, "9211": 0.06246116757392883, "9279": 0.022212404757738113, "9319": 0.5640701055526733, "9398": 0.16690383851528168, "9509": 0.21214580535888672, "9516": 0.0019512200960889459, "9521": 0.12470348179340363, "9530": 0.1751343309879303, "9585": 0.11865071207284927, "10058": 0.15860503911972046, "10071": 0.17922431230545044, "10266": 0.06977381557226181, "10394": 0.11081436276435852, "10595": 0.8500841856002808, "10673": 0.04860413447022438, "10737": 0.11604541540145874, "10738": 0.1751343309879303, "10744": 0.06246116757392883, "10956": 0.0317181795835495, "11013": 0.14686977863311768, "11160": 0.04394211992621422, "11307": 0.030771657824516296, "11423": 0.4764525294303894, "11598": 0.20977331697940826, "11619": 0.045809537172317505, "11649": 1.426491141319275, "11767": 0.2223619967699051, "11981": 0.14518201351165771, "12067": 0.011650617234408855, "12115": 0.09672962874174118, "12130": 0.31132611632347107, "12222": 0.0317181795835495, "12285": 0.056018441915512085, "12562": 0.18654440343379974, "12637": 0.05694137513637543, "12702": 1.2341761589050293, "12761": 0.2317005842924118, "12789": 1.6470046043395996, "12987": 1.2375813722610474, "13248": 0.09050461649894714, "13348": 0.2674594223499298, "13458": 0.4462870955467224, "13494": 0.4909018874168396, "13712": 0.472198486328125, "13833": 0.27786844968795776, "13908": 0.26296505331993103, "13955": 0.021256839856505394, "14026": 0.05417001247406006, "14044": 0.14349138736724854, "14048": 0.6451379656791687, "14080": 0.13414156436920166, "14163": 0.1064341589808464, "14193": 0.9754437208175659, "14262": 0.23633737862110138, "14471": 0.567951500415802, "14505": 0.15023678541183472, "14670": 0.23247487843036652, "14719": 1.5841201543807983, "14800": 0.04860413447022438, "14828": 0.043007105588912964, "14863": 0.5461324453353882, "15115": 0.12642613053321838, "15176": 0.1751343309879303, "15186": 0.4330752193927765, "15189": 0.16524957120418549, "15543": 0.06795065850019455, "15723": 0.34023189544677734, "15770": 0.13499516248703003, "15826": 0.21687394380569458, "15873": 1.0914250612258911, "15923": 0.3519764244556427, "15932": 0.08692999184131622, "16012": 1.0874829292297363, "16069": 0.6043586730957031, "16081": 0.8813109993934631, "16118": 0.1685553640127182, "16119": 0.567397952079773, "16127": 0.5618454217910767, "16221": 0.05046287178993225, "16275": 0.45623743534088135, "16285": 0.09228714555501938, "16341": 0.6476961374282837, "16360": 0.8400169610977173, "16387": 0.06977381557226181, "16416": 0.14349138736724854, "16453": 0.1229778528213501, "16605": 0.44691193103790283, "16884": 0.2786078155040741, "16927": 0.13071982562541962, "16984": 0.02792670577764511, "17235": 0.020300358533859253, "17341": 0.06977381557226181, "17452": 0.06886265426874161, "17592": 0.3409265875816345, "17666": 0.029824240133166313, "17698": 0.0058422754518687725, "17824": 0.255429208278656, "18046": 0.3464667797088623, "18062": 0.32129061222076416, "18154": 0.3560888469219208, "18357": 0.32058215141296387, "18612": 0.02887592278420925, "18906": 0.1011524572968483, "18920": 0.0797421783208847, "19222": 0.13414156436920166, "19293": 0.2317005842924118, "19301": 0.8332487344741821, "19309": 0.0009760859538801014, "19345": 0.28597161173820496, "19389": 0.40741631388664246, "19563": 0.24248650670051575, "19811": 0.26446542143821716, "19833": 0.1970241367816925, "19852": 0.08603433519601822, "20001": 0.21372433006763458, "20110": 0.22937409579753876, "20353": 0.678390383720398, "20440": 0.02887592278420925, "20503": 0.07431721687316895, "20598": 0.21687394380569458, "20689": 0.935633659362793, "20906": 0.472198486328125, "20909": 0.053244512528181076, "21442": 0.06246116757392883, "21446": 0.0913962796330452, "21477": 0.6011518239974976, "21575": 0.037378571927547455, "21618": 0.32764431834220886, "21685": 0.4654768109321594, "21709": 0.04394211992621422, "21781": 0.1808556467294693, "22026": 0.025073638185858727, "22419": 0.11604541540145874, "22422": 0.5255602598190308, "22483": 0.026976587250828743, "22822": 0.00875066313892603, "22993": 0.19381128251552582, "23217": 0.12728634476661682, "23235": 0.817850649356842, "23563": 0.04860413447022438, "23757": 0.7352184057235718, "24051": 0.8583967685699463, "24133": 0.6322478652000427, "24269": 0.04674193635582924, "24328": 0.15860503911972046, "24396": 0.6244332790374756, "24501": 0.12556517124176025, "24714": 0.1384023278951645, "24731": 0.32129061222076416, "24908": 0.24171993136405945, "25175": 0.32341301441192627, "25262": 0.21922965347766876, "25323": 0.011650617234408855, "25416": 0.011650617234408855, "25502": 0.11256109178066254, "25524": 0.2561853528022766, "25644": 0.24325250089168549, "25932": 0.6070231795310974, "26282": 0.4190443754196167, "26288": 0.029824240133166313, "26356": 0.043007105588912964, "26358": 0.176772341132164, "26402": 0.2954642176628113, "26520": 0.0752234235405922, "26524": 0.3241194784641266, "26651": 0.06520967930555344, "26773": 0.07250232994556427, "26835": 0.0058422754518687725, "27287": 0.07884006202220917, "27617": 0.09317722171545029, "27788": 0.5607312321662903, "28327": 0.8475768566131592, "28436": 0.42735910415649414, "28848": 0.38174858689308167, "28892": 0.7528522610664368, "29278": 0.6882523894309998, "29390": 0.2719337046146393, "29533": 0.16690383851528168, "29602": 0.053244512528181076} | 12440953 | Biological systems use a variety of mechanisms to maintain their functions in the face of environmental and genetic perturbations. Increasing evidence suggests that, among their roles as posttranscriptional repressors of gene expression, microRNAs (miRNAs) help to confer robustness to biological processes by reinforcing transcriptional programs and attenuating aberrant transcripts, and they may in some network contexts help suppress random fluctuations in transcript copy number. These activities have important consequences for normal development and physiology, disease, and evolution. Here, we will discuss examples and principles of miRNAs that contribute to robustness in animal systems. | Roles for MicroRNAs in Conferring Robustness to Biological Processes |
{"1011": 0.2561853528022766, "1040": 0.2741633653640747, "1998": 0.05694137513637543, "2001": 0.2689530849456787, "2005": 0.08603433519601822, "2007": 0.14349138736724854, "2013": 0.02887592278420925, "2018": 0.04953393340110779, "2020": 0.1913948506116867, "2038": 0.3485364317893982, "2042": 0.5584990978240967, "2043": 0.28450319170951843, "2044": 0.030771657824516296, "2057": 0.5381823778152466, "2058": 0.04487626627087593, "2060": 0.5370414853096008, "2063": 0.16110190749168396, "2064": 0.03360854089260101, "2076": 0.13755162060260773, "2080": 0.007782140281051397, "2084": 0.16690383851528168, "2086": 0.18167030811309814, "2095": 0.3325583338737488, "2100": 0.46424978971481323, "2106": 0.40220460295677185, "2109": 0.38441169261932373, "2111": 0.045809537172317505, "2116": 0.34508460760116577, "2120": 0.15526613593101501, "2125": 0.24859806895256042, "2140": 0.6892333030700684, "2144": 0.0752234235405922, "2166": 0.1873544454574585, "2186": 0.2763880789279938, "2193": 0.32129061222076416, "2206": 0.015504186972975731, "2207": 0.2852376699447632, "2213": 0.25088030099868774, "2217": 0.17020416259765625, "2230": 0.46363574266433716, "2235": 0.013579257763922215, "2241": 0.1229778528213501, "2263": 0.7969439625740051, "2289": 0.7009293437004089, "2290": 0.13243216276168823, "2294": 0.2954642176628113, "2302": 0.18978065252304077, "2309": 0.6149744987487793, "2329": 0.0174254160374403, "2330": 0.1873544454574585, "2331": 0.8666408061981201, "2339": 0.07793712615966797, "2350": 0.4203280806541443, "2351": 0.6921701431274414, "2362": 0.1873544454574585, "2381": 0.24018502235412598, "2384": 0.8625272512435913, "2414": 0.2531573474407196, "2432": 0.7827593088150024, "2439": 0.08961215615272522, "2440": 0.13157635927200317, "2443": 0.1710275560617447, "2470": 0.21922965347766876, "2494": 0.20421554148197174, "2515": 0.1685553640127182, "2522": 0.7791815400123596, "2523": 0.35403475165367126, "2563": 0.7537717819213867, "2566": 0.19782574474811554, "2579": 0.06886265426874161, "2592": 0.030771657824516296, "2594": 0.34370049834251404, "2595": 0.4337083101272583, "2687": 0.6629094481468201, "2689": 0.09672962874174118, "2714": 0.02412080205976963, "2730": 0.6931471824645996, "2740": 0.306306391954422, "2750": 0.16690383851528168, "2757": 0.22548456490039825, "2803": 0.1734936386346817, "2817": 0.45870962738990784, "2825": 0.04207121208310127, "2866": 1.013020396232605, "2885": 0.2447827309370041, "2894": 0.14433705806732178, "2904": 0.371698260307312, "2913": 0.3995884954929352, "2920": 0.8281423449516296, "2951": 0.2223619967699051, "2983": 0.2447827309370041, "2988": 0.06154331564903259, "2999": 0.11168810725212097, "3030": 0.0770333781838417, "3032": 0.0752234235405922, "3047": 0.21765978634357452, "3089": 0.4248080551624298, "3102": 0.11517547070980072, "3163": 0.004870930220931768, "3170": 0.3325583338737488, "3217": 0.30558720231056213, "3268": 0.31845372915267944, "3273": 0.30486753582954407, "3278": 0.6144463419914246, "3280": 0.681853175163269, "3283": 0.3676496744155884, "3303": 0.2749055027961731, "3333": 0.011650617234408855, "3344": 0.6613984704017639, "3351": 0.1913948506116867, "3378": 0.5833279490470886, "3401": 0.5882205963134766, "3426": 0.4311734735965729, "3431": 0.22079704701900482, "3445": 0.43812891840934753, "3466": 0.38905516266822815, "3575": 1.0236024856567383, "3597": 0.8022117614746094, "3603": 0.012615402229130268, "3616": 0.3423145115375519, "3623": 0.4673144817352295, "3642": 0.6265231370925903, "3647": 0.7314660549163818, "3653": 0.7028654217720032, "3695": 0.23710809648036957, "3725": 0.5267143249511719, "3808": 0.7629209756851196, "3816": 0.007782140281051397, "3885": 0.2478361576795578, "3896": 0.5551415085792542, "3929": 0.0174254160374403, "4013": 1.0151457786560059, "4014": 0.03266380727291107, "4090": 0.036437395960092545, "4102": 0.6286086440086365, "4106": 0.5267143249511719, "4115": 0.026025565341114998, "4117": 0.48430517315864563, "4200": 0.14939609169960022, "4235": 0.5685047507286072, "4237": 0.23864774405956268, "4256": 0.4568560719490051, "4281": 0.823009729385376, "4284": 0.6149744987487793, "4287": 0.20501139760017395, "4288": 0.15526613593101501, "4319": 0.6492279767990112, "4340": 0.05046287178993225, "4358": 0.1212492436170578, "4359": 0.16359257698059082, "4593": 0.004870930220931768, "4621": 0.5506471395492554, "4747": 0.9194108247756958, "4758": 0.2470736801624298, "4795": 0.5816917419433594, "4852": 0.25239890813827515, "4887": 0.20102575421333313, "4926": 0.25694093108177185, "4986": 0.1930064558982849, "5043": 0.10467668622732162, "5142": 0.512191891670227, "5159": 0.04113444685935974, "5162": 0.6389714479446411, "5174": 0.12556517124176025, "5257": 0.8699195384979248, "5280": 0.8212929964065552, "5302": 1.0788878202438354, "5320": 0.14349138736724854, "5345": 0.48430517315864563, "5360": 0.2531573474407196, "5386": 0.1946154683828354, "5547": 0.14939609169960022, "5598": 0.0354953333735466, "5642": 0.6128603219985962, "5787": 0.14686977863311768, "5794": 0.175953671336174, "5799": 0.15275461971759796, "5826": 0.22626367211341858, "5842": 0.0174254160374403, "5850": 0.7267557382583618, "5920": 1.0506030321121216, "5936": 0.5701626539230347, "5939": 0.3353555500507355, "5994": 0.3141832649707794, "5996": 0.14264501631259918, "6022": 0.4067663550376892, "6110": 0.23092569410800934, "6124": 0.4412745535373688, "6151": 0.06703783571720123, "6165": 0.026976587250828743, "6337": 0.42544642090797424, "6359": 0.034552380442619324, "6419": 0.015504186972975731, "6444": 0.6471850275993347, "6537": 0.1905880719423294, "6558": 0.4286321699619293, "6677": 0.9178520441055298, "6728": 0.3163207769393921, "6747": 0.678885817527771, "6801": 0.045809537172317505, "6820": 0.33675122261047363, "6835": 0.472198486328125, "6844": 0.19220098853111267, "6873": 0.680370569229126, "6923": 0.4974553883075714, "6937": 0.06520967930555344, "7012": 0.2105647772550583, "7017": 0.23864774405956268, "7146": 0.07159364968538284, "7153": 0.0913962796330452, "7274": 0.12556517124176025, "7312": 0.6603899002075195, "7336": 0.011650617234408855, "7383": 0.18248429894447327, "7386": 0.1693800985813141, "7420": 0.056018441915512085, "7457": 0.36358460783958435, "7458": 0.175953671336174, "7461": 0.07431721687316895, "7551": 0.0842406153678894, "7681": 0.22782009840011597, "7704": 0.46302130818367004, "7712": 0.16607704758644104, "7716": 0.0354953333735466, "7728": 0.12470348179340363, "7778": 0.13755162060260773, "7784": 0.06337817758321762, "7831": 0.3743882179260254, "7863": 0.777387797832489, "7885": 0.045809537172317505, "7917": 0.27342069149017334, "8046": 0.02792670577764511, "8067": 0.18573370575904846, "8077": 0.012615402229130268, "8161": 0.10203468054533005, "8289": 0.045809537172317505, "8449": 1.1971133947372437, "8458": 0.45994341373443604, "8516": 0.1332872211933136, "8563": 0.3956514894962311, "8585": 0.14518201351165771, "8625": 0.6244332790374756, "8664": 0.2786078155040741, "8729": 0.10818854719400406, "8780": 0.24631060659885406, "8902": 0.14939609169960022, "8924": 0.02412080205976963, "8944": 0.3810817003250122, "9048": 0.24631060659885406, "9078": 0.16276304423809052, "9125": 0.33953672647476196, "9252": 0.6471850275993347, "9363": 0.11951763927936554, "9365": 0.8674615025520325, "9469": 0.11517547070980072, "9537": 0.2478361576795578, "9554": 0.35745587944984436, "9556": 0.13670019805431366, "9574": 0.3897167444229126, "9582": 0.07068414986133575, "9633": 0.2223619967699051, "9915": 0.13755162060260773, "9947": 1.0326838493347168, "9997": 0.13157635927200317, "10035": 0.09406650811433792, "10111": 0.0029254043474793434, "10149": 0.1485546976327896, "10472": 0.42096930742263794, "10534": 1.0855059623718262, "10611": 1.013020396232605, "10632": 0.637939989566803, "10847": 0.12728634476661682, "10967": 0.35677260160446167, "10975": 0.0606246218085289, "11020": 0.650757372379303, "11031": 0.2637155055999756, "11100": 0.31489628553390503, "11498": 0.9021284580230713, "11566": 0.1734936386346817, "11636": 0.05694137513637543, "11704": 0.777387797832489, "12174": 0.052318159490823746, "12248": 0.129004567861557, "12269": 0.2018241584300995, "12333": 0.32553088665008545, "12353": 0.7683706283569336, "12435": 0.2223619967699051, "12503": 0.05694137513637543, "12517": 0.8567397594451904, "12546": 0.567397952079773, "12673": 0.1946154683828354, "12765": 0.7942996621131897, "12826": 0.11951763927936554, "13070": 0.09495500475168228, "13105": 0.06612417846918106, "13143": 0.4926934838294983, "13181": 0.7445381283760071, "13186": 0.1751343309879303, "13356": 0.5822374224662781, "13436": 0.043007105588912964, "13599": 0.12814582884311676, "13726": 0.3262358605861664, "13749": 0.24325250089168549, "14155": 0.3877306580543518, "14392": 0.49686139822006226, "14604": 0.1710275560617447, "14667": 0.5612884759902954, "14930": 0.47158926725387573, "14956": 0.020300358533859253, "15141": 0.6170841455459595, "15306": 0.2990913391113281, "15316": 0.13157635927200317, "15345": 0.10731173306703568, "15453": 0.8534175157546997, "15464": 0.9650808572769165, "15472": 0.037378571927547455, "15482": 0.09050461649894714, "15530": 0.5450005531311035, "15559": 0.021256839856505394, "15596": 0.004870930220931768, "15725": 0.04487626627087593, "15779": 0.0797421783208847, "15872": 0.39762192964553833, "16102": 0.10731173306703568, "16118": 0.007782140281051397, "16149": 1.262204885482788, "16161": 0.08244366943836212, "16211": 0.8065804839134216, "16250": 0.417115718126297, "16311": 0.07159364968538284, "16339": 0.07341018319129944, "16351": 0.20102575421333313, "16505": 0.0009760859538801014, "16796": 0.15359249711036682, "17128": 1.0389231443405151, "17237": 0.969535231590271, "17311": 0.6989894509315491, "17316": 0.5534584522247314, "17357": 0.05786345899105072, "17631": 0.3757305145263672, "17672": 0.6233867406845093, "17678": 0.0317181795835495, "17722": 0.10993985831737518, "17760": 0.12986256182193756, "17879": 0.24171993136405945, "18037": 0.7086513638496399, "18098": 0.025073638185858727, "18178": 0.07068414986133575, "18538": 0.06795065850019455, "18647": 0.021256839856505394, "18684": 1.15000319480896, "18938": 0.18816383183002472, "18949": 0.26446542143821716, "18992": 0.18978065252304077, "19001": 0.40285754203796387, "19269": 0.09938567131757736, "19429": 0.9702757596969604, "19450": 0.07250232994556427, "19565": 0.02412080205976963, "19690": 0.38174858689308167, "19817": 0.0058422754518687725, "20010": 0.18411032855510712, "20201": 0.055094651877880096, "20255": 0.09050461649894714, "20302": 0.8039615154266357, "20303": 0.21922965347766876, "20422": 0.08244366943836212, "20467": 0.53589928150177, "20647": 0.9287132620811462, "20694": 0.2561853528022766, "20738": 1.022197961807251, "20754": 0.3346569836139679, "20871": 0.5789587497711182, "20885": 0.7925328612327576, "20992": 0.25995752215385437, "21075": 0.13414156436920166, "21081": 0.20102575421333313, "21150": 0.47766464948654175, "21382": 0.012615402229130268, "21572": 0.8195732831954956, "21604": 0.1602703034877777, "21779": 0.5092619061470032, "21800": 0.33675122261047363, "21890": 0.04394211992621422, "21891": 0.2034190446138382, "22330": 0.6654226183891296, "22402": 0.14602625370025635, "22423": 0.6583697199821472, "22499": 0.07159364968538284, "22500": 0.3325583338737488, "22591": 1.1406835317611694, "22641": 0.8083226680755615, "22684": 0.3381449282169342, "22718": 0.5209306478500366, "22822": 0.7482418417930603, "22835": 0.11951763927936554, "22963": 0.1229778528213501, "23060": 0.890972912311554, "23320": 0.05417001247406006, "23681": 0.2478361576795578, "23971": 0.19782574474811554, "24155": 0.23479416966438293, "24198": 0.15777134895324707, "24284": 0.045809537172317505, "24755": 0.0009760859538801014, "24873": 0.0058422754518687725, "25006": 0.5255602598190308, "25015": 0.06795065850019455, "25022": 0.1930064558982849, "25025": 0.4891071021556854, "25089": 0.3810817003250122, "25121": 0.0797421783208847, "25135": 0.3409265875816345, "25344": 0.41001203656196594, "25500": 0.07612881064414978, "25688": 0.804835319519043, "25855": 0.25845035910606384, "26094": 0.9886114001274109, "26163": 0.010684899985790253, "26292": 0.29109421372413635, "26319": 0.2674594223499298, "26563": 0.05786345899105072, "26641": 0.6394867897033691, "26855": 0.14433705806732178, "26877": 0.058784693479537964, "27290": 0.259204238653183, "27896": 0.129004567861557, "28093": 0.3519764244556427, "28139": 0.13755162060260773, "28155": 0.043007105588912964, "28687": 0.3560888469219208, "29090": 0.23402166366577148, "29234": 0.3499138653278351, "29361": 0.0029254043474793434, "29461": 0.06429435312747955, "29477": 0.011650617234408855, "29566": 0.48008447885513306, "29596": 0.08782484382390976} | 12442311 | BACKGROUND The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005-2010 compared with 1998-2004, including estimation of possible substitution effects by other analgesics. METHODS AND FINDINGS We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005-2010 compared with 1998-2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of -21 deaths (95% CI -34 to -8) per quarter, equating to approximately 500 fewer suicide deaths (-61%) over the 6 years 2005-2010, and -25 deaths (95% CI -38 to -12) per quarter, equating to 600 fewer deaths (-62%) when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed. CONCLUSIONS During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics. | Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study |
{"1014": 0.1718502640724182, "1017": 0.07250232994556427, "1018": 0.029824240133166313, "1022": 0.04860413447022438, "1039": 0.17922431230545044, "1041": 0.7067264318466187, "1052": 0.16524957120418549, "1056": 0.20501139760017395, "1177": 0.613389253616333, "2007": 0.11343330889940262, "2012": 0.0752234235405922, "2015": 0.12556517124176025, "2020": 0.013579257763922215, "2029": 0.15526613593101501, "2035": 0.6144463419914246, "2052": 0.18248429894447327, "2062": 0.3656192123889923, "2063": 0.06886265426874161, "2080": 0.3269403576850891, "2090": 0.6270449161529541, "2093": 0.20580662786960602, "2094": 0.36290550231933594, "2116": 0.020300358533859253, "2118": 0.5903874635696411, "2121": 0.1212492436170578, "2132": 0.2763880789279938, "2136": 0.1677299439907074, "2177": 0.04207121208310127, "2179": 0.058784693479537964, "2184": 0.11256109178066254, "2193": 0.1873544454574585, "2229": 0.030771657824516296, "2267": 0.8941729068756104, "2275": 0.1889725625514984, "2290": 0.1677299439907074, "2308": 0.3554046154022217, "2313": 0.15693697333335876, "2335": 0.469759464263916, "2362": 0.026025565341114998, "2364": 0.11778303235769272, "2374": 0.8238670229911804, "2381": 0.7665573358535767, "2383": 0.2145126610994339, "2426": 0.2763880789279938, "2447": 0.09850110858678818, "2450": 0.05046287178993225, "2470": 0.6405166387557983, "2475": 0.520350456237793, "2512": 0.5021947622299194, "2523": 1.0030416250228882, "2549": 0.839173436164856, "2556": 0.025073638185858727, "2572": 0.05046287178993225, "2606": 0.10555581003427505, "2611": 0.11081436276435852, "2620": 0.151916041970253, "2640": 0.6527929902076721, "2765": 0.45499902963638306, "2809": 0.03266380727291107, "2817": 0.7782850861549377, "2825": 0.09938567131757736, "2828": 0.009718249551951885, "2867": 0.3084607720375061, "2879": 0.03360854089260101, "2881": 0.022212404757738113, "2892": 0.6327666640281677, "2906": 0.3485364317893982, "2913": 0.6118015646934509, "2920": 0.18411032855510712, "2931": 0.5116065740585327, "2944": 0.15359249711036682, "2951": 0.11691460013389587, "2969": 0.30558720231056213, "2988": 0.5690577030181885, "2998": 0.6096806526184082, "3025": 0.6793810129165649, "3053": 0.3777405619621277, "3057": 0.16110190749168396, "3130": 0.17020416259765625, "3141": 0.10555581003427505, "3160": 0.5104349255561829, "3188": 0.1905880719423294, "3189": 0.6838265657424927, "3231": 0.272677481174469, "3265": 0.19622190296649933, "3273": 0.3910386264324188, "3276": 0.2447827309370041, "3278": 0.7898768186569214, "3287": 0.3662964701652527, "3337": 0.026976587250828743, "3344": 0.46363574266433716, "3378": 0.6833335757255554, "3382": 0.09317722171545029, "3426": 0.15275461971759796, "3439": 0.3723714053630829, "3445": 0.025073638185858727, "3455": 0.3499138653278351, "3463": 0.6358738541603088, "3497": 0.8057082891464233, "3517": 0.14602625370025635, "3550": 0.4002431631088257, "3556": 0.13071982562541962, "3576": 1.039613962173462, "3598": 0.13755162060260773, "3618": 0.5607312321662903, "3633": 0.4177590310573578, "3634": 0.043007105588912964, "3643": 0.1384023278951645, "3670": 0.12556517124176025, "3674": 0.8877626657485962, "3767": 0.16359257698059082, "3801": 0.3750596046447754, "3873": 0.2954642176628113, "3891": 0.7445381283760071, "3943": 0.24018502235412598, "3979": 0.21687394380569458, "3980": 0.0354953333735466, "3989": 0.0029254043474793434, "4018": 0.08244366943836212, "4043": 0.026025565341114998, "4102": 0.04487626627087593, "4106": 0.31204116344451904, "4128": 0.5898461937904358, "4140": 0.46853771805763245, "4146": 0.09406650811433792, "4167": 0.10906458646059036, "4254": 0.055094651877880096, "4287": 0.5347557663917542, "4292": 0.5057345628738403, "4295": 0.20421554148197174, "4311": 0.36290550231933594, "4322": 0.39762192964553833, "4340": 0.0797421783208847, "4362": 0.029824240133166313, "4368": 0.3784096837043762, "4402": 0.33953672647476196, "4531": 0.2034190446138382, "4544": 0.06154331564903259, "4632": 0.04394211992621422, "4678": 1.1653456687927246, "4697": 0.01934296265244484, "4715": 1.1076855659484863, "4745": 0.07159364968538284, "4755": 0.7286425232887268, "4800": 0.524982750415802, "4843": 0.0009760859538801014, "4926": 0.026025565341114998, "4962": 0.7987030148506165, "5002": 0.10731173306703568, "5022": 0.026025565341114998, "5093": 0.02412080205976963, "5188": 0.9037119746208191, "5250": 0.3191637098789215, "5281": 0.11081436276435852, "5292": 0.052318159490823746, "5387": 0.2539152204990387, "5468": 0.3084607720375061, "5486": 0.08154398202896118, "5531": 0.04953393340110779, "5534": 0.10291612148284912, "5604": 0.14349138736724854, "5617": 0.2145126610994339, "5646": 0.1808556467294693, "5666": 0.25995752215385437, "5709": 0.04953393340110779, "5739": 0.1602703034877777, "5761": 0.2576959431171417, "5799": 0.1011524572968483, "5823": 0.11778303235769272, "5840": 0.1477125883102417, "5852": 0.07159364968538284, "5876": 0.11691460013389587, "5907": 0.10291612148284912, "5922": 0.14939609169960022, "5986": 0.4831010699272156, "5997": 0.15693697333335876, "6022": 0.20580662786960602, "6030": 0.0752234235405922, "6064": 0.5833279490470886, "6075": 0.13157635927200317, "6337": 0.036437395960092545, "6388": 0.3877306580543518, "6431": 0.4709797203540802, "6445": 0.36290550231933594, "6459": 0.09761575609445572, "6463": 0.8400169610977173, "6482": 0.6107416749000549, "6667": 0.25995752215385437, "6721": 0.3757305145263672, "6806": 0.07612881064414978, "6818": 0.7163142561912537, "6839": 0.8772575259208679, "6845": 0.10993985831737518, "6864": 0.09406650811433792, "6873": 0.3897167444229126, "6909": 0.021256839856505394, "6951": 0.2918238639831543, "7012": 0.2105647772550583, "7069": 0.025073638185858727, "7091": 0.21293537318706512, "7099": 0.4462870955467224, "7275": 0.0019512200960889459, "7314": 0.5562619566917419, "7316": 0.5376120805740356, "7361": 0.01934296265244484, "7403": 0.7995813488960266, "7419": 0.28155985474586487, "7454": 0.12642613053321838, "7485": 0.20421554148197174, "7551": 0.5427330136299133, "7576": 1.0008903741836548, "7594": 0.030771657824516296, "7644": 0.04394211992621422, "7645": 0.1718502640724182, "7667": 0.23864774405956268, "7718": 0.08871890604496002, "7784": 0.40806588530540466, "7831": 0.16110190749168396, "7863": 0.9225212931632996, "7883": 0.4425300657749176, "7885": 0.40741631388664246, "7900": 0.3601844012737274, "8168": 0.6639154553413391, "8171": 0.022212404757738113, "8247": 0.0009760859538801014, "8258": 0.9115922451019287, "8290": 0.4158279001712799, "8522": 0.036437395960092545, "8715": 0.3956514894962311, "8830": 0.567397952079773, "8832": 0.4812922179698944, "8913": 1.5297857522964478, "8924": 0.8195732831954956, "8991": 0.7182208299636841, "9007": 0.13071982562541962, "9096": 0.15693697333335876, "9165": 0.6244332790374756, "9232": 0.1734936386346817, "9234": 0.2719337046146393, "9312": 0.6149744987487793, "9358": 0.014542185701429844, "9420": 0.0009760859538801014, "9532": 0.03831886500120163, "9556": 0.31845372915267944, "9560": 0.6533012986183167, "9592": 0.2969166338443756, "9706": 1.160461664199829, "9723": 0.5220900774002075, "9896": 0.1384023278951645, "10010": 0.8247235417366028, "10173": 0.0058422754518687725, "10238": 1.179255723953247, "10266": 0.15777134895324707, "10285": 0.13243216276168823, "10441": 0.18573370575904846, "10448": 0.4617912769317627, "10452": 0.006812678650021553, "10488": 0.045809537172317505, "10669": 0.16359257698059082, "10744": 0.4462870955467224, "10831": 0.3027053773403168, "10857": 0.02792670577764511, "10893": 0.8682814836502075, "10943": 0.7124901413917542, "11100": 0.7009293437004089, "11229": 0.12470348179340363, "11363": 0.9240728616714478, "11628": 0.12384103983640671, "11710": 0.11778303235769272, "12098": 0.6202403903007507, "12115": 0.06612417846918106, "12260": 1.0927356481552124, "12377": 0.6160298585891724, "12603": 0.3084607720375061, "12697": 0.20102575421333313, "12701": 0.1229778528213501, "12839": 0.1685553640127182, "12955": 0.03925827145576477, "12987": 0.045809537172317505, "13013": 0.9827804565429688, "13105": 0.5444341897964478, "13180": 0.4412745535373688, "13191": 0.1619328260421753, "13417": 0.06337817758321762, "13458": 0.26446542143821716, "13488": 0.36086538434028625, "13599": 0.020300358533859253, "13625": 0.06977381557226181, "13765": 0.21530038118362427, "13827": 0.016465263441205025, "13874": 0.4537591338157654, "14002": 0.12728634476661682, "14039": 0.30989447236061096, "14155": 0.5849615335464478, "14358": 0.29473719000816345, "14382": 0.4926934838294983, "14405": 0.021256839856505394, "14471": 0.30486753582954407, "14494": 0.4132472574710846, "14526": 0.5718178153038025, "14573": 0.535327672958374, "14800": 0.41065993905067444, "14978": 0.3656192123889923, "15112": 0.020300358533859253, "15215": 0.44691193103790283, "15306": 0.5800528526306152, "15527": 0.14518201351165771, "15543": 1.2364475727081299, "15596": 0.37707099318504333, "16014": 0.40351006388664246, "16048": 0.1229778528213501, "16068": 0.5968599319458008, "16157": 0.5573811531066895, "16221": 0.5811457633972168, "16227": 0.176772341132164, "16252": 1.211173415184021, "16275": 0.1011524572968483, "16330": 0.574020504951477, "16335": 0.3995884954929352, "16340": 0.8780695199966431, "16458": 0.12038381397724152, "16463": 0.0009760859538801014, "16483": 0.2145126610994339, "16505": 0.1905880719423294, "16515": 0.6674286723136902, "16530": 0.4462870955467224, "16557": 0.07612881064414978, "16593": 0.14939609169960022, "16706": 0.2837681770324707, "16902": 0.4709797203540802, "16923": 0.011650617234408855, "17338": 0.22626367211341858, "17547": 0.029824240133166313, "17867": 0.6813592314720154, "17908": 0.17267228662967682, "18120": 0.014542185701429844, "18260": 0.016465263441205025, "18275": 0.2516399025917053, "18464": 0.5495203733444214, "18949": 0.08692999184131622, "19064": 0.21530038118362427, "19235": 0.09672962874174118, "19317": 0.14518201351165771, "19345": 0.2223619967699051, "19388": 0.7342816591262817, "19465": 0.052318159490823746, "19478": 0.04487626627087593, "19500": 0.07884006202220917, "19539": 1.0066169500350952, "19653": 0.0174254160374403, "19686": 0.4349733293056488, "19711": 0.02316705882549286, "19804": 0.09672962874174118, "19938": 0.0029254043474793434, "20155": 0.1808556467294693, "20240": 0.020300358533859253, "20272": 0.2478361576795578, "20589": 0.8517522215843201, "20636": 1.057410478591919, "20806": 0.1751343309879303, "20905": 0.09850110858678818, "21539": 0.09406650811433792, "21709": 0.638455867767334, "21879": 0.6517757177352905, "21996": 0.07068414986133575, "22107": 0.24554696679115295, "22275": 0.045809537172317505, "22330": 0.47584590315818787, "22461": 0.0752234235405922, "22504": 0.8281423449516296, "22571": 0.823009729385376, "23159": 1.5801056623458862, "23208": 0.28963330388069153, "23368": 0.33953672647476196, "23407": 0.052318159490823746, "23799": 0.18167030811309814, "23900": 0.19862671196460724, "24004": 0.1808556467294693, "24547": 1.2158164978027344, "25055": 0.3656192123889923, "25206": 0.4462870955467224, "25426": 0.05417001247406006, "25721": 0.2983669638633728, "26305": 1.1160377264022827, "26308": 1.0822023153305054, "26512": 1.0229004621505737, "26534": 0.11951763927936554, "26572": 0.6916812658309937, "26741": 1.1695996522903442, "26874": 0.16359257698059082, "26994": 0.09850110858678818, "27197": 0.8788808584213257, "27354": 0.1401015669107437, "27480": 0.00875066313892603, "27606": 0.0029254043474793434, "27710": 0.0174254160374403, "27784": 0.3084607720375061, "27794": 0.08782484382390976, "28038": 0.05046287178993225, "28290": 0.3824150264263153, "28436": 0.04767346754670143, "28873": 0.3683255612850189, "29206": 0.11691460013389587, "29458": 0.13243216276168823} | 12443371 | OBJECTIVE To evaluate the association between apolipoprotein E (APOE) polymorphisms (E2, C/T Arg158Cys; E4, T/C Cys112Arg; and promoter, g-219t) and the history of concussion in college athletes. We hypothesized that carrying 1 or more APOE rare (or minor) allele assessed in this study would be associated with having a history of 1 or more concussions. DESIGN Multicenter cross-sectional study. SETTING University athletic facilities. PARTICIPANTS One hundred ninety-six male football (n = 163) and female soccer (n = 33) college athletes volunteered. INTERVENTIONS Written concussion history questionnaire and saliva samples for genotyping. MAIN OUTCOME MEASURES Self-reported history of a documented concussion and rare APOE genotype (E2, E4, promoter). RESULTS There was a significant association (Wald χ² = 3.82; P = 0.05; odds ratio = 9.8) between carrying all APOE rare alleles and the history of a previous concussion. There was also a significant association (Wald χ² = 3.96, P = 0.04, odds ratio = 8.4) between carrying the APOE promoter minor allele and experiencing 2 or more concussions. CONCLUSIONS Carriers of all 3 APOE rare (or minor) alleles assessed in this study were nearly 10 times more likely to report a previous concussion and may be at a greater risk of concussion versus noncarriers. Promoter minor allele carriers were 8.4 times more likely to report multiple concussions and may be at a greater risk of multiple concussions versus noncarriers. Research involving larger samples of individuals with multiple concussions and carriers of multiple APOE rare alleles is warranted. | Apolipoprotein E genotype and concussion in college athletes. |
{"1011": 0.056018441915512085, "1017": 0.20739519596099854, "1044": 0.8004589080810547, "1050": 0.03925827145576477, "2007": 0.04767346754670143, "2012": 0.3723714053630829, "2019": 1.0423725843429565, "2029": 0.1011524572968483, "2039": 0.1358480453491211, "2052": 0.014542185701429844, "2071": 0.03831886500120163, "2076": 0.021256839856505394, "2093": 0.21372433006763458, "2102": 0.12470348179340363, "2110": 0.3870677351951599, "2117": 0.5215105414390564, "2152": 0.5936289429664612, "2163": 0.319873183965683, "2177": 0.5893046259880066, "2232": 0.13755162060260773, "2300": 0.5685047507286072, "2308": 0.5696102976799011, "2322": 0.18411032855510712, "2353": 0.7239188551902771, "2361": 0.9084475636482239, "2368": 0.42096930742263794, "2378": 0.02792670577764511, "2383": 0.25845035910606384, "2450": 0.3191637098789215, "2470": 0.26146242022514343, "2491": 0.5952457785606384, "2504": 0.28597161173820496, "2522": 0.9052929878234863, "2546": 0.020300358533859253, "2558": 0.06886265426874161, "2640": 0.3750596046447754, "2668": 0.8255793452262878, "2682": 0.013579257763922215, "2695": 0.4764525294303894, "2765": 0.2160874605178833, "2812": 0.0058422754518687725, "2817": 0.5301685929298401, "2846": 0.07250232994556427, "2901": 0.39696553349494934, "2913": 0.49626702070236206, "2920": 0.6358738541603088, "2931": 0.6011518239974976, "2967": 0.38308101892471313, "3020": 0.4419025182723999, "3057": 0.04953393340110779, "3089": 0.5427330136299133, "3161": 0.4831010699272156, "3174": 0.5381823778152466, "3231": 0.40351006388664246, "3273": 0.3269403576850891, "3278": 0.029824240133166313, "3284": 0.24631060659885406, "3303": 0.09317722171545029, "3336": 0.3409265875816345, "3378": 0.06337817758321762, "3391": 0.05046287178993225, "3399": 0.6363908052444458, "3416": 0.16607704758644104, "3426": 0.26296505331993103, "3445": 0.35950297117233276, "3449": 0.053244512528181076, "3461": 0.2539152204990387, "3463": 0.40806588530540466, "3466": 0.056018441915512085, "3491": 0.20977331697940826, "3512": 0.25995752215385437, "3623": 0.24018502235412598, "3625": 0.7583568692207336, "3643": 0.6165571808815002, "3653": 0.7105726003646851, "3662": 0.08692999184131622, "3778": 0.9922385215759277, "3798": 0.36358460783958435, "3801": 0.7182208299636841, "3822": 0.3601844012737274, "3896": 0.13243216276168823, "3938": 1.1236859560012817, "4013": 0.8780695199966431, "4102": 0.48610860109329224, "4125": 0.04860413447022438, "4146": 0.0913962796330452, "4168": 0.2837681770324707, "4182": 0.2741633653640747, "4228": 0.16524957120418549, "4340": 0.3381449282169342, "4450": 0.22157983481884003, "4502": 0.037378571927547455, "4523": 0.058784693479537964, "4588": 0.1677299439907074, "4651": 0.03360854089260101, "4742": 0.4132472574710846, "4758": 0.5590575933456421, "4812": 0.16607704758644104, "4991": 0.2822965085506439, "5022": 0.2223619967699051, "5067": 0.17840765416622162, "5072": 0.16524957120418549, "5292": 0.14264501631259918, "5300": 0.57457035779953, "5320": 0.19381128251552582, "5333": 0.16524957120418549, "5387": 0.15359249711036682, "5397": 0.8829278349876404, "5468": 0.6862877607345581, "5474": 0.8925741910934448, "5531": 0.1994270235300064, "5536": 0.7755908370018005, "5604": 0.16690383851528168, "5617": 0.06429435312747955, "5646": 0.20818853378295898, "5659": 0.04207121208310127, "5761": 0.3916989266872406, "5776": 0.5336109399795532, "5809": 0.27564704418182373, "5818": 0.7182208299636841, "5850": 0.09672962874174118, "5852": 0.12470348179340363, "5876": 0.030771657824516296, "5986": 0.23479416966438293, "5994": 0.026976587250828743, "6022": 0.5596157908439636, "6025": 0.3388410806655884, "6074": 0.030771657824516296, "6114": 0.21530038118362427, "6193": 0.016465263441205025, "6279": 0.0752234235405922, "6351": 0.1751343309879303, "6370": 0.036437395960092545, "6388": 0.13157635927200317, "6461": 0.10467668622732162, "6564": 0.016465263441205025, "6657": 1.154322862625122, "6678": 0.058784693479537964, "6693": 0.02792670577764511, "6875": 1.4469189643859863, "7012": 0.05139094591140747, "7091": 0.15860503911972046, "7099": 0.2637155055999756, "7274": 0.5461324453353882, "7277": 0.02887592278420925, "7336": 0.24859806895256042, "7337": 0.21530038118362427, "7382": 0.5021947622299194, "7457": 0.15023678541183472, "7461": 0.0752234235405922, "7505": 0.02316705882549286, "7551": 0.32129061222076416, "7584": 0.52266925573349, "7594": 0.49626702070236206, "7632": 0.04394211992621422, "7645": 0.1889725625514984, "7711": 0.6011518239974976, "7718": 0.2539152204990387, "7755": 0.27044451236724854, "7831": 0.3526630103588104, "7863": 0.9287132620811462, "7885": 0.34300774335861206, "7959": 0.013579257763922215, "8080": 0.011650617234408855, "8106": 0.6823468804359436, "8168": 0.4512746334075928, "8314": 0.27786844968795776, "8319": 0.45994341373443604, "8442": 0.7086513638496399, "8574": 0.8901712894439697, "8822": 0.016465263441205025, "8878": 0.1710275560617447, "8898": 0.11517547070980072, "9006": 0.3923587501049042, "9007": 0.672426164150238, "9015": 0.23556606471538544, "9096": 0.960606575012207, "9125": 0.2231435477733612, "9128": 0.35060185194015503, "9152": 0.13499516248703003, "9279": 0.5341835021972656, "9373": 0.05139094591140747, "9488": 0.0009760859538801014, "9530": 0.1946154683828354, "9556": 0.22548456490039825, "9574": 0.018384648486971855, "9617": 0.4624064862728119, "9756": 0.25239890813827515, "9854": 0.08513788133859634, "9869": 0.46608972549438477, "10032": 1.5448994636535645, "10047": 0.3464667797088623, "10216": 0.043007105588912964, "10280": 0.20501139760017395, "10441": 0.5180262327194214, "10463": 0.6492279767990112, "10572": 1.0688776969909668, "10595": 0.09761575609445572, "10744": 0.43623676896095276, "10768": 0.21530038118362427, "10769": 0.6233867406845093, "10847": 0.14686977863311768, "10903": 0.2969166338443756, "10924": 0.2516399025917053, "11022": 0.7782850861549377, "11100": 0.5472630262374878, "11156": 0.11430477350950241, "11324": 0.08961215615272522, "11355": 0.007782140281051397, "11375": 0.0019512200960889459, "11467": 0.22626367211341858, "11487": 0.06612417846918106, "11488": 0.7818660736083984, "11709": 0.5860490798950195, "11796": 0.03925827145576477, "11816": 0.020300358533859253, "11944": 0.014542185701429844, "12021": 0.022212404757738113, "12044": 0.18248429894447327, "12123": 1.0519683361053467, "12184": 0.2607102394104004, "12241": 0.6704301834106445, "12380": 0.0770333781838417, "12435": 0.06520967930555344, "12823": 0.45870962738990784, "12826": 0.21214580535888672, "12943": 0.23787821829319, "13120": 0.0770333781838417, "13153": 0.013579257763922215, "13181": 0.11951763927936554, "13331": 0.27342069149017334, "13365": 0.28963330388069153, "13599": 0.2918238639831543, "13791": 0.04113444685935974, "13833": 0.6754127144813538, "13922": 0.029824240133166313, "14017": 0.1477125883102417, "14085": 0.8433839678764343, "14155": 0.1751343309879303, "14358": 0.06795065850019455, "14482": 1.034073829650879, "14545": 0.04113444685935974, "14828": 0.7629209756851196, "14900": 0.4311734735965729, "14945": 0.026025565341114998, "15306": 0.5278670787811279, "15316": 0.012615402229130268, "15399": 0.037378571927547455, "15758": 0.28450319170951843, "15869": 0.5668440461158752, "15946": 0.46424978971481323, "16012": 0.2160874605178833, "16014": 0.013579257763922215, "16183": 0.19622190296649933, "16216": 0.24554696679115295, "16231": 0.11691460013389587, "16285": 0.5162794589996338, "16381": 0.28082266449928284, "16401": 0.12556517124176025, "16463": 0.18654440343379974, "16505": 0.14433705806732178, "16731": 0.2822965085506439, "16952": 0.5495203733444214, "16989": 0.49626702070236206, "17076": 0.11256109178066254, "17531": 0.9379299283027649, "17643": 0.5301685929298401, "17703": 0.08692999184131622, "17785": 0.1970241367816925, "17819": 0.06703783571720123, "17996": 0.7482418417930603, "18260": 0.39762192964553833, "18419": 0.6563454270362854, "18647": 0.10379679501056671, "18714": 0.5104349255561829, "18969": 0.503966212272644, "19009": 0.7220231294631958, "19610": 0.00875066313892603, "19620": 0.09406650811433792, "19653": 0.9131608605384827, "19833": 0.37035053968429565, "19872": 0.04113444685935974, "20100": 0.9209672808647156, "20125": 0.9747070074081421, "20194": 0.3012613356113434, "20350": 0.02412080205976963, "20367": 0.9455460906028748, "20467": 0.07612881064414978, "20576": 0.0019512200960889459, "20652": 0.3864043951034546, "20752": 0.46853771805763245, "21057": 0.1970241367816925, "21122": 0.07884006202220917, "21262": 0.732405424118042, "21371": 0.1602703034877777, "21449": 0.1913948506116867, "21539": 0.4286321699619293, "21557": 0.053244512528181076, "21919": 0.472198486328125, "21969": 0.02316705882549286, "22419": 0.02887592278420925, "22571": 0.45870962738990784, "22930": 0.18167030811309814, "22963": 0.17922431230545044, "23041": 0.3982778787612915, "23480": 0.5450005531311035, "23592": 0.3248254358768463, "23676": 0.5045560002326965, "23737": 0.052318159490823746, "23760": 1.076228141784668, "23900": 0.16690383851528168, "23961": 1.0326838493347168, "24054": 0.12384103983640671, "24241": 0.0009760859538801014, "24278": 0.06977381557226181, "24345": 1.0285027027130127, "25032": 0.23710809648036957, "25117": 0.9576126337051392, "25451": 0.5968599319458008, "25619": 0.8247235417366028, "25808": 1.068206787109375, "25817": 0.12814582884311676, "25972": 0.4349733293056488, "26578": 0.11343330889940262, "26835": 0.804835319519043, "28155": 0.1384023278951645, "28207": 0.3743882179260254, "28413": 0.2160874605178833, "28691": 1.309704303741455, "28699": 0.7057625651359558, "28828": 0.06246116757392883, "28835": 0.004870930220931768, "29048": 1.1929750442504883, "29290": 0.5762182474136353, "29454": 0.0317181795835495, "29477": 0.1011524572968483} | 12451492 | OBJECTIVE One of the theories involved in the pathogenesis of pregnancy induced hypertension involves salt and water retention. We aimed to measure the proenzyme convertase corin, responsible for pro-atrial natriuretic peptide (ANP) cleavage to active ANP, in plasma of hypertensive pregnant females. STUDY DESIGN Sixty pregnant females suffering from pregnancy induced hypertension in second and third trimesters of pregnancy were compared to twenty eight healthy pregnant females of the same gestational period. Concomitant urine and plasma samples were collected for the determination of some biochemical parameters. Plasma soluble corin and N-terminal (NT) pro-ANP (1-98) values were determined in both groups using enzyme immunoassays. RESULTS Plasma soluble corin mean value was significantly higher in the patient group compared to the control group. Upon dividing the patient group according to blood pressure, plasma NT pro-ANP showed significantly higher mean value in the group with blood pressure⩾140/90mmHg compared to the group with blood pressure<140/90mmHg and control group. CONCLUSIONS High plasma soluble corin and NT pro-ANP values in hypertensive pregnant females particularly those with blood pressure⩾140/90mmHg speculates an ANP receptor/ post receptor signaling defect, which would aggravate the pregnancy induced hypertensive state. | Plasma soluble corin and N-terminal pro-atrial natriuretic peptide levels in pregnancy induced hypertension. |
{"1011": 0.2969166338443756, "1017": 0.3519764244556427, "1018": 0.38441169261932373, "1020": 0.6000806093215942, "1039": 0.07793712615966797, "1043": 0.5080875158309937, "1044": 0.06337817758321762, "1045": 0.23710809648036957, "1048": 0.30558720231056213, "1050": 0.5523349046707153, "1052": 0.680370569229126, "2005": 0.0317181795835495, "2007": 0.4349733293056488, "2008": 0.06977381557226181, "2011": 0.37707099318504333, "2012": 0.4512746334075928, "2025": 0.3547199070453644, "2029": 0.3743882179260254, "2030": 0.18411032855510712, "2034": 0.03831886500120163, "2043": 0.009718249551951885, "2050": 0.3519764244556427, "2063": 0.10379679501056671, "2072": 0.22001366317272186, "2075": 0.0913962796330452, "2090": 0.4879087805747986, "2091": 0.23633737862110138, "2093": 0.10818854719400406, "2099": 0.36290550231933594, "2102": 0.0770333781838417, "2106": 0.03831886500120163, "2135": 0.14433705806732178, "2139": 0.10818854719400406, "2173": 0.5393219590187073, "2175": 0.13755162060260773, "2176": 0.129004567861557, "2179": 0.05694137513637543, "2239": 0.21687394380569458, "2278": 0.06977381557226181, "2290": 0.30989447236061096, "2302": 0.2830325961112976, "2322": 0.03360854089260101, "2353": 0.03925827145576477, "2389": 0.40351006388664246, "2416": 0.5238267183303833, "2421": 0.05694137513637543, "2426": 0.2501201331615448, "2427": 0.5685047507286072, "2443": 0.06703783571720123, "2458": 0.3485364317893982, "2459": 0.6853039860725403, "2461": 0.08782484382390976, "2487": 0.5472630262374878, "2509": 0.6754127144813538, "2515": 0.02316705882549286, "2522": 0.15777134895324707, "2529": 0.6075552701950073, "2546": 0.1970241367816925, "2549": 0.5010119676589966, "2560": 0.02412080205976963, "2575": 0.4337083101272583, "2581": 0.004870930220931768, "2609": 0.7491656541824341, "2620": 0.35403475165367126, "2629": 0.5255602598190308, "2692": 0.4770587682723999, "2696": 1.154322862625122, "2753": 0.5860490798950195, "2756": 0.06703783571720123, "2766": 0.11691460013389587, "2810": 0.02887592278420925, "2890": 0.3877306580543518, "2920": 0.3070250153541565, "2959": 0.1946154683828354, "2981": 0.09495500475168228, "3022": 0.3656192123889923, "3148": 0.10379679501056671, "3161": 0.33675122261047363, "3231": 0.20739519596099854, "3283": 0.1808556467294693, "3334": 0.029824240133166313, "3366": 0.6466736793518066, "3370": 0.4914994537830353, "3378": 0.25995752215385437, "3406": 0.5104349255561829, "3409": 1.0073304176330566, "3429": 0.17922431230545044, "3445": 0.5612884759902954, "3450": 0.5876781344413757, "3466": 0.03831886500120163, "3491": 0.2231435477733612, "3526": 0.5751199722290039, "3563": 0.6654226183891296, "3623": 0.4349733293056488, "3670": 0.9240728616714478, "3833": 0.16276304423809052, "4015": 0.28963330388069153, "4023": 0.7610978484153748, "4048": 0.5596157908439636, "4072": 0.08064348995685577, "4081": 0.034552380442619324, "4108": 0.38905516266822815, "4139": 0.5573811531066895, "4158": 0.09938567131757736, "4167": 0.043007105588912964, "4185": 0.3930181860923767, "4254": 0.02792670577764511, "4286": 0.47036975622177124, "4340": 0.06337817758321762, "4369": 0.21530038118362427, "4442": 0.7463917136192322, "4453": 0.6441128253936768, "4484": 0.5336109399795532, "4517": 0.7370892763137817, "4539": 0.24018502235412598, "4573": 0.7746911644935608, "4632": 0.7258110046386719, "4651": 0.6327666640281677, "4668": 0.16442140936851501, "4671": 0.47584590315818787, "4710": 0.5472630262374878, "4748": 0.16690383851528168, "4758": 0.08871890604496002, "4815": 0.18654440343379974, "4937": 0.4450363218784332, "4962": 1.0702182054519653, "5072": 0.15359249711036682, "5228": 0.53589928150177, "5250": 0.3262358605861664, "5258": 0.23710809648036957, "5383": 0.01934296265244484, "5387": 0.757441520690918, "5388": 0.7201237678527832, "5393": 0.018384648486971855, "5449": 0.25088030099868774, "5521": 0.681853175163269, "5537": 0.1710275560617447, "5550": 0.013579257763922215, "5604": 0.10026945173740387, "5643": 0.5696102976799011, "5714": 0.3750596046447754, "5876": 0.5925496220588684, "5946": 0.1685553640127182, "5994": 0.06337817758321762, "6064": 0.9687942266464233, "6083": 0.02412080205976963, "6388": 0.1401015669107437, "6592": 0.10291612148284912, "6709": 0.36900100111961365, "6790": 0.41840189695358276, "6827": 0.40351006388664246, "6895": 0.3877306580543518, "6897": 0.06795065850019455, "7231": 0.11865071207284927, "7275": 0.0009760859538801014, "7297": 0.022212404757738113, "7337": 0.18004031479358673, "7361": 0.41195443272590637, "7366": 0.17759032547473907, "7389": 0.7629209756851196, "7403": 0.7665573358535767, "7457": 0.3464667797088623, "7461": 0.12986256182193756, "7473": 0.6096806526184082, "7551": 0.24325250089168549, "7630": 0.512191891670227, "7645": 0.5805994272232056, "7711": 0.00875066313892603, "7790": 0.9531047344207764, "7816": 0.083342544734478, "7861": 0.08871890604496002, "7885": 0.5080875158309937, "7958": 0.13755162060260773, "8000": 0.2786078155040741, "8031": 1.0298984050750732, "8137": 0.23092569410800934, "8153": 0.7009293437004089, "8171": 0.03266380727291107, "8290": 1.049919843673706, "8507": 0.12384103983640671, "8524": 0.05694137513637543, "8878": 0.9440274834632874, "8991": 0.2034190446138382, "9007": 0.8374842405319214, "9096": 0.029824240133166313, "9099": 0.5495203733444214, "9104": 0.151916041970253, "9165": 0.935633659362793, "9171": 0.3339579105377197, "9207": 0.8633513450622559, "9284": 0.1873544454574585, "9350": 0.09406650811433792, "9416": 0.16442140936851501, "9426": 0.09406650811433792, "9495": 0.0752234235405922, "9570": 0.6420594453811646, "9597": 0.15860503911972046, "9783": 0.28890204429626465, "9885": 0.34508460760116577, "10032": 0.18329764902591705, "10047": 0.613389253616333, "10210": 0.007782140281051397, "10230": 0.5729197263717651, "10232": 0.3027053773403168, "10266": 0.9271688461303711, "10381": 0.4196864068508148, "10465": 0.9029204845428467, "10509": 0.20022670924663544, "10548": 0.5398913025856018, "10572": 0.7592713832855225, "10708": 0.2247048318386078, "10738": 0.021256839856505394, "10889": 0.056018441915512085, "11022": 0.5773153901100159, "11156": 0.11691460013389587, "11254": 0.4419025182723999, "11423": 0.25845035910606384, "11598": 0.010684899985790253, "11636": 0.40871503949165344, "11721": 1.3474642038345337, "11816": 0.2089812457561493, "11835": 0.7546905279159546, "11867": 0.960606575012207, "12205": 0.3012613356113434, "12210": 0.3339579105377197, "12322": 0.7942996621131897, "12328": 0.41195443272590637, "12376": 0.00875066313892603, "12380": 0.6054253578186035, "12530": 0.3141832649707794, "12541": 0.5116065740585327, "12644": 0.09938567131757736, "12649": 0.08782484382390976, "12732": 0.025073638185858727, "12776": 0.9650808572769165, "12987": 0.4425300657749176, "13091": 0.14349138736724854, "13316": 0.6950984001159668, "13330": 0.12642613053321838, "13458": 0.36967599391937256, "13490": 0.040196798741817474, "13502": 0.17759032547473907, "13656": 0.00875066313892603, "13791": 0.7665573358535767, "13908": 0.7601850032806396, "13922": 0.19220098853111267, "13964": 0.007782140281051397, "14026": 0.40220460295677185, "14080": 0.02792670577764511, "14095": 0.4537591338157654, "14187": 0.5773153901100159, "14193": 1.0326838493347168, "14194": 0.7951818704605103, "14471": 0.30917787551879883, "14494": 0.7755908370018005, "14828": 0.07431721687316895, "14847": 0.22859740257263184, "14949": 0.2637155055999756, "14956": 0.11517547070980072, "14993": 0.02792670577764511, "15115": 0.26146242022514343, "15136": 0.06337817758321762, "15191": 0.9761797785758972, "15210": 0.04394211992621422, "15333": 0.9348671436309814, "15425": 0.02412080205976963, "15527": 0.6848117709159851, "15543": 1.018678069114685, "15663": 0.3923587501049042, "15758": 0.8989537954330444, "15869": 0.08064348995685577, "15874": 0.5301685929298401, "15946": 0.24325250089168549, "16048": 0.5662899017333984, "16068": 0.10906458646059036, "16221": 0.9769153594970703, "16238": 0.1677299439907074, "16285": 0.6553317308425903, "16303": 1.036847710609436, "16305": 0.11778303235769272, "16351": 0.07884006202220917, "16389": 0.09050461649894714, "16420": 0.5833279490470886, "16505": 0.3982778787612915, "16515": 0.24631060659885406, "16576": 0.8893690705299377, "16706": 0.33325836062431335, "16730": 0.07884006202220917, "16771": 0.4400174915790558, "16923": 0.21687394380569458, "16984": 0.7942996621131897, "17379": 0.08871890604496002, "17441": 0.5562619566917419, "17531": 0.2501201331615448, "17613": 0.2223619967699051, "17913": 0.33325836062431335, "18037": 0.6911921501159668, "18089": 0.2711893916130066, "18118": 0.0797421783208847, "18260": 0.4734157919883728, "18479": 0.7047978043556213, "18491": 0.75193190574646, "18561": 0.12814582884311676, "18595": 0.040196798741817474, "18596": 0.045809537172317505, "18647": 0.03266380727291107, "18714": 0.3676496744155884, "18715": 0.22079704701900482, "19015": 0.10467668622732162, "19019": 0.6022219061851501, "19121": 0.9115922451019287, "19289": 0.15359249711036682, "19387": 0.6533012986183167, "19446": 0.15275461971759796, "19481": 0.2223619967699051, "19539": 0.21687394380569458, "19653": 0.7047978043556213, "19681": 0.07431721687316895, "19687": 0.09495500475168228, "19738": 0.6764062643051147, "19871": 0.012615402229130268, "19872": 0.24554696679115295, "19955": 0.20102575421333313, "19961": 1.1798561811447144, "20035": 0.5168620347976685, "20119": 0.1994270235300064, "20363": 0.8715548515319824, "20366": 1.1363043785095215, "20500": 0.5573811531066895, "20544": 0.7018978595733643, "20752": 0.2622140049934387, "20766": 0.9194108247756958, "20817": 0.6669275164604187, "20958": 0.05786345899105072, "21025": 0.12642613053321838, "21035": 0.4500300884246826, "21104": 0.08513788133859634, "21114": 0.18329764902591705, "21252": 0.030771657824516296, "21453": 0.015504186972975731, "21466": 0.25845035910606384, "21472": 0.45499902963638306, "21489": 1.1726272106170654, "21618": 0.006812678650021553, "21647": 0.06886265426874161, "21716": 0.8550800085067749, "21821": 0.1946154683828354, "21890": 0.7951818704605103, "21903": 0.678885817527771, "21935": 0.4481603503227234, "21967": 0.2247048318386078, "22022": 0.006812678650021553, "22025": 0.015504186972975731, "22238": 0.7124901413917542, "22330": 0.7845434546470642, "22407": 0.29255300760269165, "22597": 0.0019512200960889459, "22747": 0.8169882297515869, "22907": 0.3070250153541565, "22916": 0.7692760229110718, "22931": 0.32270604372024536, "22932": 0.35813871026039124, "22943": 0.8022117614746094, "22991": 0.0913962796330452, "23041": 0.8091925978660583, "23079": 0.23402166366577148, "23150": 0.058784693479537964, "23212": 0.0038986403960734606, "23216": 0.176772341132164, "23270": 0.6338034868240356, "23283": 0.2394166737794876, "23586": 0.4113073945045471, "23737": 0.2822965085506439, "23767": 0.18248429894447327, "23777": 0.37035053968429565, "23833": 0.018384648486971855, "23892": 0.3723714053630829, "23924": 0.3141832649707794, "24054": 0.3005385100841522, "24226": 0.040196798741817474, "24269": 0.06886265426874161, "24278": 1.12241530418396, "24319": 0.8853482007980347, "24594": 0.9170717000961304, "24629": 0.42735910415649414, "24848": 0.13755162060260773, "24958": 1.0471819639205933, "25002": 0.8109301924705505, "25015": 0.05046287178993225, "25152": 0.052318159490823746, "25194": 0.28670501708984375, "25206": 0.2763880789279938, "25714": 0.2470736801624298, "25761": 0.2247048318386078, "25937": 0.12038381397724152, "25969": 0.7683706283569336, "25972": 0.10026945173740387, "26046": 1.0815403461456299, "26083": 0.19381128251552582, "26187": 0.12556517124176025, "26243": 0.09495500475168228, "26244": 0.3777405619621277, "26261": 0.9987343549728394, "26305": 0.176772341132164, "26402": 0.42990362644195557, "26512": 0.820433497428894, "26524": 0.17922431230545044, "26534": 0.2145126610994339, "26601": 0.27044451236724854, "26702": 0.18816383183002472, "26775": 0.13670019805431366, "26874": 0.004870930220931768, "27531": 0.052318159490823746, "27781": 0.175953671336174, "27854": 0.034552380442619324, "28086": 0.1212492436170578, "28177": 0.13755162060260773, "28691": 0.14686977863311768, "28833": 0.4818955361843109, "28835": 0.2652147710323334, "28873": 0.13499516248703003, "29031": 0.9005423784255981, "29107": 0.0354953333735466, "29206": 0.1970241367816925, "29290": 0.3127557039260864, "29336": 0.5612884759902954, "29490": 0.29109421372413635, "29514": 0.5220900774002075, "29533": 0.06154331564903259, "29610": 0.4512746334075928} | 12462961 | Cytochrome P450c17 catalyzes steroidogenic 17alpha-hydroxylase and 17,20 lyase activities. Expression of the gene for P450c17 is cAMP dependent, tissue specific, developmentally programmed, and varies among species. Binding of Sp1, Sp3, and NF1-C (nuclear factor 1-C) to the first 227 bp of 5'flanking DNA (-227/LUC) is crucial for basal transcription in human NCI-H295A adrenal cells. Human placental JEG-3 cells contain Sp1, Sp3, and NF1, but do not express -227/LUC, even when transfected with a vector expressing steroidogenic factor 1 (SF-1). Therefore, other factors are essential for basal expression of P450c17. Deoxyribonuclease I footprinting and EMSAs identified a GATA consensus site at -64/-58 and an SF-1 site at -58/-50. RT-PCR identified GATA-4, GATA-6, and SF-1 in NCI-H295A cells and GATA-2 and GATA-3, but not GATA-4, GATA-6, or SF-1 in JEG-3 cells. Cotransfection of either GATA-4 or GATA-6 without SF-1 activated -227/LUC in JEG-3 cells, but cotransfection of GATA-2 or GATA-3 with or without SF-1 did not. Surprisingly, mutation of the GATA binding site in -227/LUC increased GATA-4 or GATA-6 induced activity, whereas mutation of the Sp1/Sp3 site decreased it. Furthermore, promoter constructs including the GATA site, but excluding the Sp1/Sp3 site at -196/-188, were not activated by GATA-4 or GATA-6, suggesting an interaction between Sp1/Sp3 and GATA-4 or GATA-6. Glutathione-S-transferase pull-down experiments and coimmunoprecipitation demonstrated interaction between GATA-4 or GATA-6 and Sp1, but not Sp3. Chromatin immunoprecipitation assays confirmed that this GATA-4/6 interaction with Sp1 occurred at the Sp site in the P450c17 promoter in NCI-H295A cells. Demethylation with 5-aza-2-deoxycytidine permitted JEG-3 cells to express endogenous P450c17, SF-1, GATA-4, GATA-6, and transfected -227/LUC. Thus, GATA-4 or GATA-6 and Sp1 together regulate expression of P450c17 in adrenal NCI-H295A cells and methylation of P450c17, GATA-4 and GATA-6 silence the expression of P450c17 in placental JEG-3 cells. | GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1. |
{"1011": 0.47827014327049255, "1020": 1.0229004621505737, "1048": 1.0158531665802002, "1053": 0.2786078155040741, "1055": 0.42225050926208496, "2001": 0.02412080205976963, "2003": 0.0058422754518687725, "2005": 0.15023678541183472, "2012": 0.6970458030700684, "2015": 0.9531047344207764, "2040": 0.055094651877880096, "2053": 0.020300358533859253, "2064": 0.04767346754670143, "2078": 0.9178520441055298, "2093": 0.20580662786960602, "2109": 0.567397952079773, "2111": 0.3850763738155365, "2120": 0.5255602598190308, "2155": 0.9100211262702942, "2177": 0.08871890604496002, "2204": 0.3339579105377197, "2214": 0.32905077934265137, "2222": 0.15860503911972046, "2224": 0.19622190296649933, "2239": 0.22937409579753876, "2241": 0.29981520771980286, "2287": 0.4624064862728119, "2313": 0.5116065740585327, "2321": 0.26146242022514343, "2322": 0.16690383851528168, "2323": 0.2719337046146393, "2342": 0.11951763927936554, "2391": 0.4891071021556854, "2406": 0.0913962796330452, "2408": 0.13071982562541962, "2414": 0.757441520690918, "2416": 0.9500881433486938, "2417": 0.45499902963638306, "2421": 0.18248429894447327, "2426": 0.42608439922332764, "2443": 0.21687394380569458, "2451": 0.7018978595733643, "2460": 0.9115922451019287, "2470": 0.36086538434028625, "2478": 0.009718249551951885, "2490": 0.7827593088150024, "2504": 0.11691460013389587, "2523": 0.12470348179340363, "2544": 0.35745587944984436, "2554": 0.5461324453353882, "2556": 0.3723714053630829, "2575": 0.9333322048187256, "2591": 1.2985725402832031, "2592": 0.41840189695358276, "2605": 0.07250232994556427, "2640": 0.5404602885246277, "2641": 0.43623676896095276, "2647": 0.8074519634246826, "2685": 0.6176109313964844, "2705": 0.24248650670051575, "2711": 0.6144463419914246, "2762": 0.12556517124176025, "2764": 0.07341018319129944, "2767": 0.8559102416038513, "2814": 1.0116009712219238, "2817": 0.5607312321662903, "2827": 0.11081436276435852, "2836": 0.47584590315818787, "2864": 0.14095009863376617, "2866": 0.19782574474811554, "2869": 0.20739519596099854, "2881": 0.30917787551879883, "2885": 0.7389566898345947, "2892": 0.8247235417366028, "2897": 1.0894558429718018, "2913": 0.36967599391937256, "2944": 0.37304413318634033, "2945": 0.4311734735965729, "2951": 0.31560876965522766, "2967": 0.0029254043474793434, "3013": 0.8559102416038513, "3026": 0.8272887468338013, "3032": 0.45437926054000854, "3036": 0.08782484382390976, "3080": 1.0546929836273193, "3176": 0.21372433006763458, "3189": 0.10291612148284912, "3218": 0.6970458030700684, "3226": 0.2674594223499298, "3231": 0.4794800877571106, "3252": 0.16110190749168396, "3265": 0.015504186972975731, "3273": 0.1401015669107437, "3319": 0.052318159490823746, "3372": 0.3662964701652527, "3385": 0.026025565341114998, "3393": 0.1734936386346817, "3394": 0.07250232994556427, "3406": 0.5162794589996338, "3445": 0.7665573358535767, "3451": 0.7096124291419983, "3463": 0.2607102394104004, "3556": 0.5773153901100159, "3569": 0.42161011695861816, "3570": 0.21372433006763458, "3591": 0.09495500475168228, "3594": 0.0354953333735466, "3618": 0.037378571927547455, "3619": 1.498855471611023, "3623": 0.4437839686870575, "3633": 0.4126010537147522, "3640": 0.0606246218085289, "3647": 0.025073638185858727, "3673": 0.0058422754518687725, "3725": 0.2822965085506439, "3768": 0.13414156436920166, "3798": 0.2105647772550583, "3800": 0.7352184057235718, "3818": 0.32129061222076416, "3891": 1.1425544023513794, "3898": 0.9092346429824829, "3920": 0.08513788133859634, "3948": 0.8756314516067505, "3979": 0.0009760859538801014, "4068": 0.02316705882549286, "4081": 0.02316705882549286, "4094": 1.2975058555603027, "4106": 0.28597161173820496, "4118": 0.3676496744155884, "4145": 0.2145126610994339, "4146": 0.083342544734478, "4244": 0.14179791510105133, "4254": 0.11256109178066254, "4262": 0.06520967930555344, "4279": 0.3949938118457794, "4369": 0.5893046259880066, "4434": 0.2516399025917053, "4453": 0.2231435477733612, "4468": 0.02792670577764511, "4539": 0.4831010699272156, "4577": 0.1751343309879303, "4587": 0.22157983481884003, "4617": 0.1401015669107437, "4637": 0.5045560002326965, "4639": 0.6149744987487793, "4701": 0.13243216276168823, "4722": 0.16524957120418549, "4725": 0.5318912267684937, "4757": 0.15693697333335876, "4766": 0.0752234235405922, "4793": 0.37907835841178894, "4852": 0.28670501708984375, "4877": 0.0317181795835495, "4942": 0.22079704701900482, "4948": 1.2969720363616943, "5002": 0.46363574266433716, "5054": 0.07068414986133575, "5075": 0.1930064558982849, "5079": 0.47584590315818787, "5090": 0.2089812457561493, "5136": 0.08692999184131622, "5177": 0.010684899985790253, "5267": 0.17431432008743286, "5288": 1.0087559223175049, "5351": 0.14602625370025635, "5364": 0.7463917136192322, "5381": 0.8281423449516296, "5387": 0.2763880789279938, "5459": 0.18004031479358673, "5468": 0.4574742913246155, "5473": 0.02887592278420925, "5495": 0.6659244894981384, "5531": 0.4926934838294983, "5579": 0.15943801403045654, "5604": 0.3870677351951599, "5617": 0.10467668622732162, "5622": 0.037378571927547455, "5643": 0.09672962874174118, "5644": 0.32905077934265137, "5646": 0.2447827309370041, "5658": 0.09584271162748337, "5682": 0.3916989266872406, "5761": 0.347847044467926, "5770": 0.34023189544677734, "5790": 0.2089812457561493, "5852": 0.22001366317272186, "5876": 0.2470736801624298, "5950": 0.1994270235300064, "5995": 0.6286086440086365, "5997": 0.08692999184131622, "6001": 0.6744182109832764, "6078": 0.42096930742263794, "6125": 0.823009729385376, "6132": 0.02887592278420925, "6179": 0.3084607720375061, "6180": 0.3656192123889923, "6219": 0.05046287178993225, "6276": 0.42096930742263794, "6378": 0.029824240133166313, "6412": 0.01934296265244484, "6422": 0.6704301834106445, "6483": 0.083342544734478, "6540": 0.5381823778152466, "6550": 0.08064348995685577, "6612": 0.8161250352859497, "6666": 0.30917787551879883, "6709": 0.23710809648036957, "6747": 0.34715715050697327, "6753": 0.7398891448974609, "6825": 0.1889725625514984, "6826": 0.05417001247406006, "6860": 1.19888174533844, "6962": 0.08513788133859634, "6994": 0.09406650811433792, "7012": 0.0317181795835495, "7017": 0.12556517124176025, "7020": 0.319873183965683, "7080": 0.48430517315864563, "7091": 0.20977331697940826, "7099": 0.25845035910606384, "7159": 0.4419025182723999, "7197": 0.24631060659885406, "7208": 1.0868242979049683, "7243": 0.1384023278951645, "7264": 0.6086184978485107, "7274": 0.2145126610994339, "7275": 1.1153976917266846, "7316": 0.021256839856505394, "7327": 0.3170322775840759, "7367": 0.06429435312747955, "7457": 0.1751343309879303, "7551": 0.10555581003427505, "7644": 0.35060185194015503, "7645": 0.2711893916130066, "7659": 0.04113444685935974, "7667": 1.0326838493347168, "7713": 0.15442965924739838, "7718": 0.1401015669107437, "7778": 0.34370049834251404, "7784": 0.12038381397724152, "7809": 0.10026945173740387, "7863": 0.08064348995685577, "7885": 0.04674193635582924, "7889": 0.41065993905067444, "8023": 0.47827014327049255, "8152": 0.34300774335861206, "8168": 0.3850763738155365, "8290": 0.0354953333735466, "8317": 0.4764525294303894, "8318": 0.014542185701429844, "8319": 0.33675122261047363, "8332": 0.22157983481884003, "8335": 0.304147332906723, "8339": 0.0606246218085289, "8357": 0.1718502640724182, "8400": 0.14264501631259918, "8553": 0.14349138736724854, "8578": 0.17020416259765625, "8713": 0.040196798741817474, "8719": 0.9348671436309814, "8745": 0.06246116757392883, "8778": 0.8845420479774475, "8803": 0.1221139207482338, "8822": 0.03925827145576477, "8830": 0.5127768516540527, "8977": 0.11778303235769272, "9132": 0.20421554148197174, "9147": 0.009718249551951885, "9181": 0.5086748600006104, "9211": 0.36358460783958435, "9312": 0.8788808584213257, "9349": 0.32270604372024536, "9398": 0.7389566898345947, "9407": 0.4512746334075928, "9416": 0.619189441204071, "9479": 0.29255300760269165, "9539": 1.2244645357131958, "9547": 0.05694137513637543, "9556": 0.06246116757392883, "9582": 0.19381128251552582, "9584": 0.014542185701429844, "9750": 1.0437490940093994, "9895": 0.13499516248703003, "9896": 0.021256839856505394, "9966": 0.6128603219985962, "10174": 0.020300358533859253, "10196": 0.01934296265244484, "10204": 0.28890204429626465, "10266": 0.25467249751091003, "10342": 0.10291612148284912, "10502": 0.8877626657485962, "10539": 0.7408206462860107, "10640": 0.08244366943836212, "10744": 0.12814582884311676, "10765": 0.1734936386346817, "10788": 0.10555581003427505, "10831": 0.6317287683486938, "10857": 0.6059582233428955, "11163": 0.3262358605861664, "11207": 0.02887592278420925, "11320": 1.1592369079589844, "11326": 1.167778730392456, "11487": 0.05139094591140747, "11507": 0.5347557663917542, "11550": 0.06703783571720123, "11649": 0.6202403903007507, "11709": 0.13157635927200317, "11883": 0.24859806895256042, "11946": 0.03831886500120163, "12066": 0.678885817527771, "12117": 0.4512746334075928, "12151": 0.18492233753204346, "12238": 0.8212929964065552, "12265": 0.3084607720375061, "12353": 0.0174254160374403, "12358": 0.26820653676986694, "12421": 0.1913948506116867, "12477": 1.4432357549667358, "12515": 0.083342544734478, "12520": 0.6022219061851501, "12631": 0.1064341589808464, "12690": 0.15442965924739838, "12693": 0.040196798741817474, "12697": 0.14518201351165771, "12746": 0.1401015669107437, "12857": 0.14095009863376617, "12874": 0.02316705882549286, "13045": 0.10555581003427505, "13153": 0.1718502640724182, "13160": 0.7809720039367676, "13376": 0.7629209756851196, "13481": 0.21687394380569458, "13494": 0.8281423449516296, "13500": 0.32270604372024536, "13594": 0.15442965924739838, "14048": 0.9724938273429871, "14126": 0.304147332906723, "14155": 0.6170841455459595, "14164": 0.13414156436920166, "14286": 0.9621002674102783, "14287": 0.7239188551902771, "14348": 0.20818853378295898, "14358": 0.839173436164856, "14617": 0.7710843086242676, "14657": 0.08961215615272522, "14730": 0.04207121208310127, "14847": 0.21765978634357452, "15034": 0.20580662786960602, "15258": 0.7105726003646851, "15306": 0.2516399025917053, "15354": 0.045809537172317505, "15460": 0.1602703034877777, "15782": 0.45623743534088135, "15873": 0.03360854089260101, "15945": 0.6517757177352905, "15982": 0.24859806895256042, "15995": 0.7352184057235718, "16134": 0.4932899475097656, "16157": 0.3163207769393921, "16216": 0.9680526852607727, "16228": 0.04394211992621422, "16330": 0.47827014327049255, "16335": 0.06612417846918106, "16343": 0.14602625370025635, "16367": 0.1358480453491211, "16406": 1.0423725843429565, "16408": 0.5045560002326965, "16519": 0.29400965571403503, "16599": 0.16607704758644104, "16744": 0.8748174905776978, "16846": 0.08603433519601822, "16902": 0.7124901413917542, "17237": 0.08064348995685577, "17245": 0.2145126610994339, "17522": 0.7398891448974609, "17606": 0.1212492436170578, "17660": 0.0174254160374403, "18130": 0.10993985831737518, "18160": 0.05970508232712746, "18182": 0.26146242022514343, "18249": 0.04394211992621422, "18363": 0.5033760666847229, "18426": 0.9162907600402832, "18486": 0.14602625370025635, "18678": 0.4151833653450012, "18700": 0.7863243818283081, "18742": 0.6654226183891296, "18953": 0.3346569836139679, "19064": 0.20022670924663544, "19143": 0.6482070088386536, "19188": 0.2539152204990387, "19229": 0.603290855884552, "19388": 0.6233867406845093, "19465": 0.0009760859538801014, "19473": 1.360074758529663, "20047": 0.0354953333735466, "20077": 0.5415972471237183, "20137": 0.12642613053321838, "20155": 1.0868242979049683, "20272": 0.30486753582954407, "20334": 0.42225050926208496, "20486": 0.012615402229130268, "20547": 0.4734157919883728, "20589": 0.32341301441192627, "20793": 0.24248650670051575, "20794": 0.7163142561912537, "21106": 0.09317722171545029, "21150": 0.3526630103588104, "21707": 0.25694093108177185, "21821": 0.08603433519601822, "21901": 0.5127768516540527, "22248": 0.6739205718040466, "22498": 0.5427330136299133, "22568": 0.05970508232712746, "22616": 0.05046287178993225, "22781": 0.06429435312747955, "22942": 0.04394211992621422, "23208": 0.1221139207482338, "23329": 0.14518201351165771, "23382": 0.006812678650021553, "23386": 0.06703783571720123, "23411": 0.018384648486971855, "23579": 0.0019512200960889459, "23900": 0.3601844012737274, "24110": 0.6960725784301758, "24209": 0.4196864068508148, "24339": 0.08154398202896118, "24340": 0.07250232994556427, "24410": 0.3777405619621277, "24846": 0.1905880719423294, "24978": 0.2247048318386078, "24992": 0.06612417846918106, "25094": 0.11778303235769272, "25121": 0.07159364968538284, "25169": 0.4914994537830353, "25323": 0.2800849378108978, "25430": 0.22626367211341858, "25437": 0.5427330136299133, "25472": 0.1808556467294693, "25494": 0.15442965924739838, "25947": 0.09228714555501938, "26237": 0.029824240133166313, "26264": 0.0913962796330452, "26453": 0.053244512528181076, "26521": 0.03831886500120163, "26814": 0.007782140281051397, "26886": 0.014542185701429844, "27084": 0.45870962738990784, "27135": 0.0029254043474793434, "27152": 1.138809084892273, "27296": 0.14179791510105133, "27354": 0.6451379656791687, "27453": 0.24859806895256042, "27698": 0.31489628553390503, "27794": 0.0009760859538801014, "27866": 0.11865071207284927, "28212": 0.6170841455459595, "28314": 1.013020396232605, "28321": 0.15359249711036682, "28767": 0.28670501708984375, "28823": 0.020300358533859253, "28857": 0.2659635543823242, "28956": 0.6233867406845093, "29174": 0.2018241584300995, "29409": 0.43875885009765625, "29415": 0.21687394380569458} | 12470783 | PURPOSE There is a need for valid and reliable short scales that can be used to assess social networks and social supports and to screen for social isolation in older persons. DESIGN AND METHODS The present study is a cross-national and cross-cultural evaluation of the performance of an abbreviated version of the Lubben Social Network Scale (LSNS-6), which was used to screen for social isolation among community-dwelling older adult populations in three European countries. Based on the concept of lack of redundancy of social ties we defined clinical cut-points of the LSNS-6 for identifying persons deemed at risk for social isolation. RESULTS Among all three samples, the LSNS-6 and two subscales (Family and Friends) demonstrated high levels of internal consistency, stable factor structures, and high correlations with criterion variables. The proposed clinical cut-points showed good convergent validity, and classified 20% of the respondents in Hamburg, 11% of those in Solothurn (Switzerland), and 15% of those in London as at risk for social isolation. IMPLICATIONS We conclude that abbreviated scales such as the LSNS-6 should be considered for inclusion in practice protocols of gerontological practitioners. Screening older persons based on the LSNS-6 provides quantitative information on their family and friendship ties, and identifies persons at increased risk for social isolation who might benefit from in-depth assessment and targeted interventions. | Performance of an abbreviated version of the Lubben Social Network Scale among three European community-dwelling older adult populations. |
{"1003": 0.2659635543823242, "1022": 0.053244512528181076, "1028": 0.1229778528213501, "1052": 1.0444365739822388, "1609": 0.37707099318504333, "2003": 0.034552380442619324, "2020": 0.07612881064414978, "2035": 0.3560888469219208, "2042": 0.15610189735889435, "2047": 0.13414156436920166, "2075": 0.6980181336402893, "2080": 0.08961215615272522, "2109": 0.34508460760116577, "2116": 0.4849066734313965, "2152": 0.6170841455459595, "2169": 0.1221139207482338, "2177": 0.06977381557226181, "2179": 0.009718249551951885, "2190": 0.3676496744155884, "2193": 0.2689530849456787, "2265": 0.012615402229130268, "2274": 0.05786345899105072, "2313": 0.619189441204071, "2321": 0.16110190749168396, "2327": 0.49864232540130615, "2336": 0.4734157919883728, "2350": 0.39696553349494934, "2358": 0.0009760859538801014, "2361": 0.2741633653640747, "2367": 0.5186077356338501, "2389": 0.13670019805431366, "2421": 0.20660123229026794, "2443": 0.37907835841178894, "2470": 0.5244048833847046, "2492": 0.9987343549728394, "2504": 0.1889725625514984, "2511": 0.5914691090583801, "2531": 0.822151780128479, "2532": 0.18004031479358673, "2583": 0.13670019805431366, "2595": 0.28743788599967957, "2615": 1.0158531665802002, "2622": 0.5427330136299133, "2638": 1.0236024856567383, "2659": 0.14433705806732178, "2691": 0.4248080551624298, "2764": 0.40546512603759766, "2765": 0.32129061222076416, "2775": 0.34023189544677734, "2800": 0.26446542143821716, "2809": 0.0009760859538801014, "2817": 0.6853039860725403, "2819": 0.8057082891464233, "2828": 0.013579257763922215, "2836": 0.23247487843036652, "2846": 0.6902132034301758, "2864": 0.38041436672210693, "2906": 0.567951500415802, "2913": 0.6773988008499146, "2915": 0.27044451236724854, "2925": 0.3601844012737274, "2951": 0.4349733293056488, "2967": 0.1064341589808464, "3020": 0.20421554148197174, "3032": 0.39893341064453125, "3078": 0.7220231294631958, "3112": 0.14686977863311768, "3132": 0.14179791510105133, "3144": 0.21765978634357452, "3151": 0.5607312321662903, "3174": 0.1873544454574585, "3226": 0.5795059204101562, "3231": 0.9005423784255981, "3273": 0.45437926054000854, "3284": 0.5618454217910767, "3305": 0.4113073945045471, "3318": 0.14518201351165771, "3344": 0.2719337046146393, "3351": 0.42926809191703796, "3357": 0.20421554148197174, "3395": 0.007782140281051397, "3433": 0.013579257763922215, "3445": 0.10203468054533005, "3446": 0.2711893916130066, "3452": 0.777387797832489, "3463": 0.6016870141029358, "3464": 0.23710809648036957, "3484": 0.15693697333335876, "3490": 0.1751343309879303, "3491": 0.022212404757738113, "3512": 0.4909018874168396, "3517": 0.08692999184131622, "3556": 0.2881702482700348, "3563": 0.04674193635582924, "3576": 0.7314660549163818, "3634": 0.06337817758321762, "3643": 0.7163142561912537, "3665": 0.304147332906723, "3669": 0.2561853528022766, "3674": 0.9732321500778198, "3680": 0.08154398202896118, "3798": 0.06429435312747955, "3867": 0.4431571960449219, "3893": 0.8625272512435913, "3898": 0.1751343309879303, "3917": 0.0317181795835495, "3934": 0.17759032547473907, "3938": 0.20022670924663544, "3963": 0.11256109178066254, "3979": 0.17020416259765625, "4084": 0.18004031479358673, "4094": 0.10379679501056671, "4098": 0.034552380442619324, "4102": 0.4794800877571106, "4106": 0.1718502640724182, "4118": 0.8074519634246826, "4140": 0.75193190574646, "4146": 0.19220098853111267, "4249": 0.4437839686870575, "4254": 0.9900637865066528, "4270": 0.5174443125724792, "4281": 0.9994535446166992, "4287": 0.11430477350950241, "4292": 0.20022670924663544, "4295": 0.4318077862262726, "4340": 0.47584590315818787, "4431": 0.8813109993934631, "4453": 0.17431432008743286, "4488": 0.3409265875816345, "4492": 0.13670019805431366, "4520": 0.056018441915512085, "4522": 0.5421652793884277, "4555": 0.259204238653183, "4632": 0.07612881064414978, "4710": 0.2918238639831543, "4725": 0.9271688461303711, "4755": 0.04394211992621422, "4800": 0.347847044467926, "4810": 0.08871890604496002, "4824": 0.791648268699646, "4839": 0.38174858689308167, "4903": 1.076228141784668, "5012": 0.2539152204990387, "5067": 0.45251765847206116, "5109": 0.036437395960092545, "5147": 0.034552380442619324, "5267": 0.37707099318504333, "5300": 0.45994341373443604, "5323": 0.09050461649894714, "5345": 0.6451379656791687, "5417": 0.3084607720375061, "5461": 0.44566190242767334, "5476": 0.29473719000816345, "5500": 0.272677481174469, "5531": 0.0797421783208847, "5585": 0.6877616047859192, "5593": 0.11517547070980072, "5604": 0.7701805830001831, "5643": 0.0913962796330452, "5646": 0.11691460013389587, "5657": 0.034552380442619324, "5677": 0.05139094591140747, "5701": 0.45994341373443604, "5787": 0.32764431834220886, "5790": 0.0009760859538801014, "5818": 0.7144040465354919, "5852": 0.5364705324172974, "5911": 0.6684301495552063, "5986": 0.5104349255561829, "5989": 0.025073638185858727, "5997": 0.058784693479537964, "6022": 0.08513788133859634, "6028": 0.32905077934265137, "6038": 0.8459017872810364, "6064": 0.0797421783208847, "6090": 0.02792670577764511, "6109": 0.6739205718040466, "6282": 0.11343330889940262, "6352": 0.04860413447022438, "6356": 0.46424978971481323, "6365": 0.04487626627087593, "6388": 0.1619328260421753, "6397": 0.4709797203540802, "6445": 0.22392450273036957, "6459": 0.1358480453491211, "6463": 0.10026945173740387, "6537": 0.21214580535888672, "6564": 0.012615402229130268, "6585": 0.6086184978485107, "6612": 0.10906458646059036, "6643": 0.17020416259765625, "6709": 0.259204238653183, "6767": 0.09672962874174118, "6827": 0.18573370575904846, "6845": 0.5517725944519043, "6873": 0.31845372915267944, "6887": 0.10993985831737518, "7012": 0.33675122261047363, "7017": 0.6086184978485107, "7080": 0.6149744987487793, "7091": 0.2976420819759369, "7099": 0.6244332790374756, "7125": 0.020300358533859253, "7159": 0.0770333781838417, "7170": 0.04767346754670143, "7171": 0.26296505331993103, "7275": 0.07793712615966797, "7361": 0.5805994272232056, "7393": 0.053244512528181076, "7403": 0.4002431631088257, "7444": 0.8731874823570251, "7461": 0.1751343309879303, "7478": 0.3241194784641266, "7551": 0.27934664487838745, "7578": 0.7647408246994019, "7591": 1.039613962173462, "7594": 0.020300358533859253, "7604": 0.45437926054000854, "7645": 0.0797421783208847, "7667": 0.09584271162748337, "7709": 0.009718249551951885, "7718": 0.5696102976799011, "7721": 0.8169882297515869, "7730": 0.2531573474407196, "7831": 0.5590575933456421, "7865": 0.4419025182723999, "7870": 0.3170322775840759, "7885": 0.2822965085506439, "7975": 0.13670019805431366, "8167": 0.8135309815406799, "8168": 0.66441810131073, "8270": 0.036437395960092545, "8304": 0.09050461649894714, "8319": 0.29036402702331543, "8321": 0.10818854719400406, "8355": 0.7047978043556213, "8462": 0.5261374711990356, "8483": 0.32129061222076416, "8578": 0.5267143249511719, "8625": 0.34370049834251404, "8720": 0.3777405619621277, "8778": 0.14179791510105133, "8827": 0.27044451236724854, "8906": 0.3810817003250122, "8985": 0.41065993905067444, "9118": 1.4180124998092651, "9128": 0.02887592278420925, "9152": 0.05139094591140747, "9197": 0.2160874605178833, "9312": 0.7987030148506165, "9323": 0.22079704701900482, "9398": 0.0019512200960889459, "9426": 0.06337817758321762, "9447": 0.9100211262702942, "9513": 0.16442140936851501, "9532": 0.029824240133166313, "9556": 0.4673144817352295, "9560": 0.014542185701429844, "9723": 0.10291612148284912, "9820": 0.35060185194015503, "9896": 0.030771657824516296, "9908": 0.20977331697940826, "9997": 0.822151780128479, "10173": 0.35813871026039124, "10174": 0.08064348995685577, "10318": 0.053244512528181076, "10327": 0.7220231294631958, "10441": 0.07341018319129944, "10509": 0.19862671196460724, "10539": 0.016465263441205025, "10640": 0.2822965085506439, "10788": 0.6461620330810547, "10803": 0.4574742913246155, "10847": 0.040196798741817474, "10859": 1.1160377264022827, "10906": 0.2719337046146393, "11156": 0.6634125709533691, "11192": 0.026025565341114998, "11265": 0.21530038118362427, "11326": 0.3012613356113434, "11343": 0.05786345899105072, "11375": 0.36494144797325134, "11487": 0.803087055683136, "11629": 0.006812678650021553, "11709": 0.2711893916130066, "11923": 0.06337817758321762, "12030": 0.1485546976327896, "12151": 0.16442140936851501, "12184": 0.0009760859538801014, "12353": 0.1602703034877777, "12367": 0.4734157919883728, "12411": 0.3870677351951599, "12435": 0.2741633653640747, "12477": 0.08961215615272522, "12546": 0.7701805830001831, "12596": 0.12728634476661682, "12654": 0.11256109178066254, "12702": 0.6410312056541443, "12826": 0.2637155055999756, "12868": 0.1677299439907074, "12996": 0.07068414986133575, "13070": 0.5092619061470032, "13075": 0.10731173306703568, "13105": 0.026025565341114998, "13186": 0.083342544734478, "13341": 0.025073638185858727, "13433": 0.23402166366577148, "13434": 0.15023678541183472, "13464": 0.13925230503082275, "13494": 0.045809537172317505, "13599": 0.48068851232528687, "13625": 0.2317005842924118, "13683": 0.026976587250828743, "13706": 0.11778303235769272, "13811": 0.45932671427726746, "13874": 0.47036975622177124, "13923": 0.020300358533859253, "13988": 0.8821197748184204, "13990": 0.03266380727291107, "14084": 0.009718249551951885, "14155": 0.28597161173820496, "14198": 0.09761575609445572, "14262": 0.9724938273429871, "14358": 0.24018502235412598, "14639": 1.252763032913208, "14670": 0.38041436672210693, "14693": 0.8949713706970215, "15088": 0.2018241584300995, "15245": 0.1602703034877777, "15258": 0.013579257763922215, "15286": 0.013579257763922215, "15306": 0.6038249135017395, "15403": 0.18411032855510712, "15406": 0.129004567861557, "15502": 0.056018441915512085, "15844": 0.846739649772644, "15873": 0.026025565341114998, "15877": 0.46486347913742065, "15923": 0.10291612148284912, "15955": 0.026976587250828743, "16014": 0.8893690705299377, "16134": 0.6348392367362976, "16157": 0.35677260160446167, "16221": 0.07884006202220917, "16227": 0.10906458646059036, "16330": 0.5033760666847229, "16405": 0.17922431230545044, "16463": 0.1221139207482338, "16483": 0.18978065252304077, "16515": 0.36967599391937256, "16665": 0.8408597707748413, "16744": 0.09584271162748337, "16839": 0.13243216276168823, "17198": 0.42735910415649414, "17235": 0.9186317324638367, "17341": 0.43623676896095276, "17404": 1.0641717910766602, "17547": 0.574020504951477, "17744": 0.42608439922332764, "18002": 0.2830325961112976, "18100": 0.7656494975090027, "18111": 1.12432062625885, "18130": 0.07341018319129944, "18163": 0.12470348179340363, "18191": 0.15275461971759796, "18464": 0.1602703034877777, "18539": 0.1485546976327896, "18583": 0.9724938273429871, "18613": 0.12470348179340363, "18752": 0.417115718126297, "18863": 0.07250232994556427, "18891": 0.0752234235405922, "18925": 0.04674193635582924, "19064": 0.12986256182193756, "19209": 0.3784096837043762, "19547": 0.5347557663917542, "19709": 0.2822965085506439, "19761": 0.25694093108177185, "19841": 0.5990082025527954, "20077": 0.004870930220931768, "20155": 0.3409265875816345, "20159": 0.371698260307312, "20228": 0.3560888469219208, "20272": 0.1510767638683319, "20641": 0.7220231294631958, "20932": 0.16110190749168396, "21150": 0.319873183965683, "21162": 0.5186077356338501, "21210": 0.05046287178993225, "21325": 0.16524957120418549, "21425": 0.012615402229130268, "21685": 0.10379679501056671, "21759": 0.022212404757738113, "21770": 0.06886265426874161, "21778": 0.018384648486971855, "21781": 0.052318159490823746, "21877": 0.09228714555501938, "22084": 0.10203468054533005, "22107": 0.037378571927547455, "22199": 0.15359249711036682, "22248": 0.03266380727291107, "22571": 0.9139442443847656, "22643": 0.06795065850019455, "22718": 0.9470623731613159, "22851": 0.043007105588912964, "22916": 0.09050461649894714, "22931": 0.07793712615966797, "22963": 0.22782009840011597, "23041": 0.6674286723136902, "23208": 0.39367714524269104, "23350": 0.33953672647476196, "23446": 0.5244048833847046, "23614": 0.1808556467294693, "23713": 0.2822965085506439, "24024": 0.16110190749168396, "24163": 1.0822023153305054, "24442": 0.05417001247406006, "24479": 0.021256839856505394, "25362": 1.0298984050750732, "25473": 0.09406650811433792, "25714": 0.18329764902591705, "25765": 0.3750596046447754, "25952": 0.4537591338157654, "26013": 0.22001366317272186, "26163": 0.3547199070453644, "26189": 0.15526613593101501, "26290": 0.14349138736724854, "26305": 1.160461664199829, "26572": 0.18167030811309814, "26591": 0.09584271162748337, "26651": 0.06429435312747955, "26835": 1.0815403461456299, "26994": 0.08603433519601822, "27152": 0.16359257698059082, "27354": 0.27786844968795776, "27441": 0.2696990668773651, "27631": 1.0641717910766602, "28389": 0.2145126610994339, "28689": 0.08064348995685577, "28873": 0.4002431631088257, "28896": 1.0312920808792114, "29107": 0.36290550231933594, "29207": 0.17020416259765625, "29458": 0.6128603219985962, "29490": 0.21135559678077698, "29587": 0.12814582884311676} | 12471115 | BACKGROUND The pneumococcus is a diverse pathogen whose primary niche is the nasopharynx. Over 90 different serotypes exist, and nasopharyngeal carriage of multiple serotypes is common. Understanding pneumococcal carriage is essential for evaluating the impact of pneumococcal vaccines. Traditional serotyping methods are cumbersome and insufficient for detecting multiple serotype carriage, and there are few data comparing the new methods that have been developed over the past decade. We established the PneuCarriage project, a large, international multi-centre study dedicated to the identification of the best pneumococcal serotyping methods for carriage studies. METHODS AND FINDINGS Reference sample sets were distributed to 15 research groups for blinded testing. Twenty pneumococcal serotyping methods were used to test 81 laboratory-prepared (spiked) samples. The five top-performing methods were used to test 260 nasopharyngeal (field) samples collected from children in six high-burden countries. Sensitivity and positive predictive value (PPV) were determined for the test methods and the reference method (traditional serotyping of >100 colonies from each sample). For the alternate serotyping methods, the overall sensitivity ranged from 1% to 99% (reference method 98%), and PPV from 8% to 100% (reference method 100%), when testing the spiked samples. Fifteen methods had ≥70% sensitivity to detect the dominant (major) serotype, whilst only eight methods had ≥70% sensitivity to detect minor serotypes. For the field samples, the overall sensitivity ranged from 74.2% to 95.8% (reference method 93.8%), and PPV from 82.2% to 96.4% (reference method 99.6%). The microarray had the highest sensitivity (95.8%) and high PPV (93.7%). The major limitation of this study is that not all of the available alternative serotyping methods were included. CONCLUSIONS Most methods were able to detect the dominant serotype in a sample, but many performed poorly in detecting the minor serotype populations. Microarray with a culture amplification step was the top-performing method. Results from this comprehensive evaluation will inform future vaccine evaluation and impact studies, particularly in low-income settings, where pneumococcal disease burden remains high. | The PneuCarriage Project: A Multi-Centre Comparative Study to Identify the Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies |
{"1048": 0.8861536383628845, "1054": 1.151856780052185, "1996": 0.2105647772550583, "2008": 0.045809537172317505, "2015": 0.01934296265244484, "2029": 0.2478361576795578, "2038": 0.040196798741817474, "2047": 0.020300358533859253, "2075": 0.4286321699619293, "2076": 0.1718502640724182, "2089": 0.10379679501056671, "2128": 0.1946154683828354, "2179": 0.18492233753204346, "2182": 0.2409527748823166, "2188": 0.7629209756851196, "2306": 0.23247487843036652, "2310": 0.47584590315818787, "2339": 0.045809537172317505, "2361": 0.822151780128479, "2389": 0.23402166366577148, "2458": 0.5404602885246277, "2491": 0.755608320236206, "2515": 0.09050461649894714, "2535": 0.12986256182193756, "2549": 0.08871890604496002, "2555": 0.17840765416622162, "2649": 0.011650617234408855, "2683": 0.4067663550376892, "2738": 0.22157983481884003, "2764": 0.0029254043474793434, "2828": 0.052318159490823746, "2920": 0.010684899985790253, "2951": 0.0029254043474793434, "3012": 0.35677260160446167, "3161": 0.040196798741817474, "3252": 0.06154331564903259, "3265": 0.347847044467926, "3279": 0.41065993905067444, "3375": 1.0601204633712769, "3393": 0.013579257763922215, "3450": 0.29981520771980286, "3491": 0.06246116757392883, "3526": 0.06520967930555344, "3563": 0.6624060273170471, "3603": 0.17922431230545044, "3670": 0.9100211262702942, "3770": 0.16359257698059082, "3795": 0.7592713832855225, "3811": 0.8877626657485962, "3853": 0.3084607720375061, "3898": 0.1619328260421753, "3936": 0.23402166366577148, "3977": 0.6568518877029419, "4023": 0.6533012986183167, "4081": 0.21530038118362427, "4168": 0.6764062643051147, "4195": 0.6070231795310974, "4229": 0.8013357520103455, "4260": 0.14095009863376617, "4453": 0.49864232540130615, "4503": 0.07250232994556427, "4523": 0.9886114001274109, "4527": 0.23787821829319, "4531": 0.040196798741817474, "4655": 0.44753631949424744, "4671": 0.21687394380569458, "4758": 0.7601850032806396, "4919": 0.014542185701429844, "4962": 1.181056022644043, "4972": 0.034552380442619324, "4975": 0.02412080205976963, "5014": 0.20580662786960602, "5158": 0.27786844968795776, "5186": 0.10906458646059036, "5214": 0.17267228662967682, "5228": 0.39762192964553833, "5250": 1.0894558429718018, "5258": 0.42225050926208496, "5393": 0.07884006202220917, "5418": 0.8550800085067749, "5421": 0.3262358605861664, "5449": 1.0966572761535645, "5456": 0.0317181795835495, "5537": 0.0038986403960734606, "5546": 0.04207121208310127, "5716": 0.030771657824516296, "5769": 0.31845372915267944, "5812": 0.07159364968538284, "5866": 0.11778303235769272, "6022": 0.3269403576850891, "6024": 0.4950772523880005, "6064": 0.48068851232528687, "6083": 0.43053874373435974, "6177": 0.17840765416622162, "6310": 0.10291612148284912, "6551": 0.08513788133859634, "6564": 0.1229778528213501, "6592": 0.5483922958374023, "6622": 0.08961215615272522, "6709": 0.42096930742263794, "6741": 0.6011518239974976, "6887": 0.25467249751091003, "6897": 0.052318159490823746, "6922": 0.4412745535373688, "7021": 0.12642613053321838, "7040": 0.2089812457561493, "7060": 0.6502478122711182, "7127": 0.052318159490823746, "7145": 0.39762192964553833, "7276": 0.27044451236724854, "7337": 0.16442140936851501, "7366": 0.22392450273036957, "7403": 0.8383291959762573, "7487": 0.3283478021621704, "7512": 0.07612881064414978, "7645": 0.13755162060260773, "7657": 0.36697331070899963, "7711": 0.7210738658905029, "7816": 0.9131608605384827, "7834": 0.4437839686870575, "8000": 0.9500881433486938, "8077": 0.07159364968538284, "8123": 0.14939609169960022, "8153": 0.57457035779953, "8171": 0.9005423784255981, "8176": 0.1718502640724182, "8270": 0.19622190296649933, "8288": 0.007782140281051397, "8327": 0.2184450328350067, "8349": 0.0019512200960889459, "8360": 0.018384648486971855, "8445": 0.4824984669685364, "8469": 0.38041436672210693, "8525": 0.5220900774002075, "8552": 0.2674594223499298, "8590": 0.20501139760017395, "8651": 0.5197699069976807, "8790": 0.9485763907432556, "8793": 0.46853771805763245, "8991": 0.255429208278656, "9007": 0.2394166737794876, "9014": 0.5301685929298401, "9067": 0.05970508232712746, "9099": 0.4837033152580261, "9104": 0.1970241367816925, "9165": 1.005902886390686, "9223": 0.2969166338443756, "9350": 0.3810817003250122, "9412": 0.2409527748823166, "9530": 0.43875885009765625, "9556": 0.5968599319458008, "9756": 0.35060185194015503, "9839": 0.1913948506116867, "9859": 0.11951763927936554, "10109": 0.2749055027961731, "10335": 0.87237149477005, "10637": 0.0174254160374403, "10673": 0.22157983481884003, "10697": 0.0038986403960734606, "10738": 1.0874829292297363, "10744": 0.15023678541183472, "10752": 0.7683706283569336, "10769": 0.1064341589808464, "10889": 0.04113444685935974, "10938": 0.3485364317893982, "10949": 0.5795059204101562, "10956": 0.5174443125724792, "10958": 0.31132611632347107, "11156": 0.151916041970253, "11326": 0.043007105588912964, "11341": 0.6522845029830933, "11369": 0.1970241367816925, "11403": 0.21765978634357452, "11423": 0.38308101892471313, "11432": 0.4248080551624298, "11486": 0.10291612148284912, "11487": 0.0019512200960889459, "11598": 0.09406650811433792, "11619": 0.2763880789279938, "11636": 0.47584590315818787, "11657": 0.10203468054533005, "11913": 0.040196798741817474, "11993": 0.3127557039260864, "12222": 1.0933903455734253, "12328": 1.2324692010879517, "12359": 0.06703783571720123, "12516": 0.06246116757392883, "12650": 0.19622190296649933, "12667": 0.2711893916130066, "12740": 0.25467249751091003, "12939": 0.02412080205976963, "12987": 1.033379077911377, "13369": 0.10203468054533005, "13458": 0.3963087201118469, "13526": 0.6857960224151611, "13643": 0.03360854089260101, "13685": 0.0174254160374403, "13769": 0.08782484382390976, "13833": 0.21530038118362427, "13874": 0.4537591338157654, "13908": 0.5472630262374878, "14026": 0.06612417846918106, "14080": 0.35128939151763916, "14095": 0.31560876965522766, "14142": 0.04674193635582924, "14153": 0.5590575933456421, "14163": 0.5267143249511719, "14193": 0.4914994537830353, "14258": 0.0913962796330452, "14471": 0.37640097737312317, "14494": 1.1561684608459473, "14774": 0.24859806895256042, "14786": 0.04487626627087593, "14800": 0.08782484382390976, "14828": 0.12384103983640671, "14847": 0.18329764902591705, "15042": 0.07341018319129944, "15053": 0.255429208278656, "15176": 0.7417513132095337, "15286": 0.2223619967699051, "15420": 0.5495203733444214, "15527": 1.0560526847839355, "15543": 0.20818853378295898, "15704": 0.8349450826644897, "16002": 0.8143964409828186, "16086": 0.06429435312747955, "16221": 1.250528335571289, "16238": 0.6254787445068359, "16429": 0.659380316734314, "16452": 0.1913948506116867, "16515": 0.8212929964065552, "16599": 0.006812678650021553, "16643": 0.7258110046386719, "16705": 0.04207121208310127, "16706": 0.7818660736083984, "16745": 0.37640097737312317, "16840": 0.27044451236724854, "16880": 0.14349138736724854, "16984": 0.02887592278420925, "17014": 0.04953393340110779, "17431": 0.18167030811309814, "17637": 0.17759032547473907, "17727": 0.5707147121429443, "17785": 0.1011524572968483, "17914": 0.2231435477733612, "18139": 0.06520967930555344, "18153": 0.8869584798812866, "18419": 1.001607894897461, "19137": 1.0512858629226685, "19293": 0.5092619061470032, "19345": 0.13925230503082275, "19387": 0.09495500475168228, "19395": 1.4487555027008057, "19470": 0.06520967930555344, "19481": 0.053244512528181076, "19601": 0.46853771805763245, "19653": 0.04860413447022438, "19723": 0.19782574474811554, "19731": 1.0748957395553589, "19817": 0.06246116757392883, "19968": 0.09672962874174118, "20214": 0.8641747236251831, "20415": 0.6218147873878479, "20467": 0.052318159490823746, "20591": 0.1485546976327896, "20689": 1.057410478591919, "20752": 0.0009760859538801014, "20842": 0.2501201331615448, "20996": 0.07793712615966797, "21057": 0.10731173306703568, "21144": 0.14518201351165771, "21157": 0.319873183965683, "21262": 0.9100211262702942, "21425": 0.02792670577764511, "21472": 0.3519764244556427, "21575": 0.5506471395492554, "21618": 0.5284429788589478, "21619": 0.2089812457561493, "21743": 0.09050461649894714, "21865": 0.755608320236206, "21903": 0.22392450273036957, "22008": 0.996573805809021, "22022": 0.4337083101272583, "22025": 1.6817586421966553, "22026": 0.23324857652187347, "22110": 0.03266380727291107, "22275": 0.21922965347766876, "22394": 0.417115718126297, "22407": 0.3949938118457794, "22422": 0.13499516248703003, "22694": 0.05139094591140747, "22869": 0.19381128251552582, "22907": 0.12556517124176025, "22922": 0.42990362644195557, "23079": 0.2749055027961731, "23150": 0.06886265426874161, "23233": 0.004870930220931768, "23277": 0.3027053773403168, "23499": 0.7047978043556213, "23572": 0.4487839937210083, "23758": 0.27564704418182373, "23777": 0.41840189695358276, "23833": 0.1221139207482338, "23892": 0.5438674688339233, "24051": 0.1905880719423294, "24203": 0.47827014327049255, "24269": 0.17431432008743286, "24365": 0.28082266449928284, "24434": 0.5701626539230347, "24501": 0.09850110858678818, "24759": 0.9576126337051392, "24848": 0.11256109178066254, "25202": 0.6970458030700684, "25206": 0.043007105588912964, "25219": 0.9842413663864136, "25258": 0.8004589080810547, "25269": 0.3019835948944092, "25336": 0.1677299439907074, "25476": 0.052318159490823746, "25505": 0.1212492436170578, "25517": 0.18654440343379974, "25644": 0.3127557039260864, "25700": 0.3163207769393921, "26305": 0.06246116757392883, "26402": 0.06337817758321762, "26524": 0.7258110046386719, "26534": 0.1994270235300064, "26601": 0.3241194784641266, "26773": 0.7683706283569336, "26775": 0.01934296265244484, "26819": 1.0144377946853638, "26874": 0.26820653676986694, "27009": 0.34577593207359314, "27226": 0.5398913025856018, "27381": 0.06886265426874161, "27642": 1.160461664199829, "27690": 0.319873183965683, "27777": 0.66441810131073, "27814": 0.45870962738990784, "28086": 1.475906491279602, "28156": 0.4673144817352295, "28353": 0.10026945173740387, "28828": 0.2976420819759369, "28829": 0.1485546976327896, "28848": 1.029200792312622, "29295": 0.6338034868240356, "29300": 0.2493593990802765, "29537": 0.2607102394104004} | 12486491 | Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than regulatory capacity in mRNA translation. Here we identify mutations of the Ribosomal Protein L38 (Rpl38) gene in mice exhibiting surprising tissue-specific patterning defects, including pronounced homeotic transformations of the axial skeleton. In Rpl38 mutant embryos, global protein synthesis is unchanged; however the translation of a select subset of Homeobox mRNAs is perturbed. Our data reveal that RPL38 facilitates 80S complex formation on these mRNAs as a regulatory component of the ribosome to confer transcript-specific translational control. We further show that Rpl38 expression is markedly enriched in regions of the embryo where loss-of-function phenotypes occur. Unexpectedly, a ribosomal protein (RP) expression screen reveals dynamic regulation of individual RPs within the vertebrate embryo. Collectively, these findings suggest that RP activity may be highly regulated to impart a new layer of specificity in the control of gene expression and mammalian development. | Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning |
{"1020": 0.022212404757738113, "1999": 0.16359257698059082, "2001": 0.1693800985813141, "2004": 0.1710275560617447, "2008": 0.053244512528181076, "2020": 0.3177432417869568, "2029": 0.09317722171545029, "2030": 0.650757372379303, "2034": 0.04487626627087593, "2041": 0.011650617234408855, "2046": 0.7057625651359558, "2069": 0.05139094591140747, "2073": 0.04487626627087593, "2078": 0.06337817758321762, "2079": 0.029824240133166313, "2090": 0.319873183965683, "2093": 0.3897167444229126, "2098": 0.13499516248703003, "2106": 0.3339579105377197, "2109": 0.27044451236724854, "2116": 0.09495500475168228, "2129": 0.11430477350950241, "2135": 0.20977331697940826, "2158": 0.12728634476661682, "2162": 0.12470348179340363, "2166": 0.3262358605861664, "2176": 0.16607704758644104, "2179": 0.4673144817352295, "2203": 0.48430517315864563, "2227": 0.4926934838294983, "2240": 0.26146242022514343, "2247": 0.6358738541603088, "2302": 0.175953671336174, "2339": 0.058784693479537964, "2350": 0.14349138736724854, "2416": 0.3141832649707794, "2433": 0.151916041970253, "2458": 0.15943801403045654, "2470": 0.14179791510105133, "2503": 0.13670019805431366, "2515": 0.04953393340110779, "2529": 0.953857421875, "2535": 0.0354953333735466, "2580": 0.1011524572968483, "2668": 0.2478361576795578, "2698": 0.04674193635582924, "2705": 0.8143964409828186, "2764": 0.6684301495552063, "2817": 0.25467249751091003, "2828": 0.01934296265244484, "2832": 0.05417001247406006, "2863": 0.956112265586853, "2864": 0.11778303235769272, "2872": 0.06612417846918106, "2881": 0.015504186972975731, "2886": 0.3464667797088623, "2891": 0.0019512200960889459, "2913": 0.07250232994556427, "2915": 0.2786078155040741, "2920": 0.08961215615272522, "2944": 0.9732321500778198, "3022": 0.04767346754670143, "3031": 0.31132611632347107, "3064": 0.3297532796859741, "3096": 1.1947507858276367, "3133": 0.013579257763922215, "3210": 0.5579402446746826, "3215": 0.13071982562541962, "3231": 0.09228714555501938, "3273": 0.2976420819759369, "3344": 0.16359257698059082, "3350": 0.11168810725212097, "3362": 0.06886265426874161, "3365": 0.16110190749168396, "3399": 0.04767346754670143, "3431": 0.2652147710323334, "3436": 0.03360854089260101, "3466": 0.17759032547473907, "3473": 0.7610978484153748, "3526": 0.8780695199966431, "3560": 0.14264501631259918, "3572": 0.0009760859538801014, "3603": 0.25088030099868774, "3652": 0.5466978549957275, "3659": 0.5512100458145142, "3671": 0.4425300657749176, "3674": 0.6327666640281677, "3695": 0.38574060797691345, "3800": 0.06703783571720123, "3930": 0.4944818615913391, "3935": 0.0770333781838417, "3973": 0.06977381557226181, "4013": 0.5973974466323853, "4069": 0.46853771805763245, "4072": 0.09761575609445572, "4102": 0.14095009863376617, "4127": 0.1905880719423294, "4146": 0.1718502640724182, "4176": 0.32553088665008545, "4275": 0.8658194541931152, "4286": 0.8780695199966431, "4294": 0.5027855634689331, "4315": 0.8715548515319824, "4340": 0.2317005842924118, "4406": 0.0174254160374403, "4423": 0.5651806592941284, "4442": 1.0560526847839355, "4456": 1.1249549388885498, "4457": 0.3526630103588104, "4489": 0.3662964701652527, "4491": 0.15693697333335876, "4503": 0.4132472574710846, "4588": 0.030771657824516296, "4607": 0.4228905141353607, "4649": 0.42799583077430725, "4663": 0.040196798741817474, "4725": 0.14602625370025635, "4935": 0.6249561905860901, "4944": 0.1946154683828354, "4961": 0.5596157908439636, "4975": 0.1718502640724182, "4982": 0.8925741910934448, "5051": 0.1693800985813141, "5173": 0.012615402229130268, "5274": 1.034073829650879, "5320": 0.0019512200960889459, "5332": 0.5255602598190308, "5418": 0.5301685929298401, "5422": 0.3949938118457794, "5461": 0.07884006202220917, "5646": 0.28082266449928284, "5688": 0.29981520771980286, "5740": 0.030771657824516296, "5769": 0.10203468054533005, "5966": 0.3304552733898163, "5967": 0.08603433519601822, "5970": 0.23092569410800934, "6028": 0.23864774405956268, "6083": 0.14518201351165771, "6101": 0.02887592278420925, "6179": 0.3777405619621277, "6258": 0.6064908504486084, "6388": 0.043007105588912964, "6459": 0.5318912267684937, "6470": 0.9084475636482239, "6529": 0.043007105588912964, "6549": 0.7665573358535767, "6592": 0.15860503911972046, "6761": 1.2330384254455566, "6955": 0.10818854719400406, "7060": 0.6487176418304443, "7096": 0.0174254160374403, "7171": 0.0058422754518687725, "7293": 0.890972912311554, "7337": 0.11256109178066254, "7356": 0.2983669638633728, "7366": 0.0019512200960889459, "7502": 0.7144040465354919, "7516": 0.17840765416622162, "7551": 0.27342069149017334, "7645": 0.1930064558982849, "7685": 0.04860413447022438, "7709": 0.0842406153678894, "7712": 0.20421554148197174, "7718": 0.14686977863311768, "7818": 0.77198725938797, "7831": 0.14433705806732178, "7865": 0.0019512200960889459, "7866": 0.16524957120418549, "7872": 0.026976587250828743, "7885": 0.42096930742263794, "7949": 0.22079704701900482, "7976": 0.11691460013389587, "8000": 1.2883929014205933, "8039": 0.16442140936851501, "8153": 0.5751199722290039, "8156": 0.17759032547473907, "8160": 0.10203468054533005, "8168": 0.034552380442619324, "8278": 0.04487626627087593, "8281": 0.6249561905860901, "8290": 0.5957841277122498, "8402": 0.022212404757738113, "8469": 0.47158926725387573, "8523": 0.04953393340110779, "8826": 0.12986256182193756, "8873": 0.3191637098789215, "8898": 0.9052929878234863, "8902": 0.6950984001159668, "8948": 0.7951818704605103, "9067": 0.27564704418182373, "9104": 0.15526613593101501, "9153": 0.5909284353256226, "9186": 0.9131608605384827, "9250": 0.77198725938797, "9253": 0.47463157773017883, "9307": 0.5415972471237183, "9335": 0.6773988008499146, "9350": 0.630689799785614, "9359": 0.10818854719400406, "9416": 0.2837681770324707, "9513": 0.6689305305480957, "9607": 0.2954642176628113, "9626": 0.5021947622299194, "9869": 0.7546905279159546, "10085": 0.7201237678527832, "10199": 0.28082266449928284, "10266": 0.8057082891464233, "10572": 0.18167030811309814, "10641": 0.0038986403960734606, "10744": 0.11430477350950241, "10760": 0.07068414986133575, "10836": 1.2284748554229736, "10847": 0.11517547070980072, "10924": 0.6107416749000549, "11156": 0.04487626627087593, "11192": 0.66441810131073, "11234": 0.12728634476661682, "11432": 0.6892333030700684, "11439": 1.0920805931091309, "11463": 1.1312761306762695, "11467": 0.4794800877571106, "11487": 0.04487626627087593, "11494": 0.2394166737794876, "11514": 0.11778303235769272, "11643": 0.7408206462860107, "11657": 0.4734157919883728, "11707": 0.006812678650021553, "11791": 0.15023678541183472, "11835": 0.5523349046707153, "11917": 0.5398913025856018, "12319": 0.1913948506116867, "12326": 0.24018502235412598, "12328": 1.3274686336517334, "12504": 0.40546512603759766, "12562": 0.18411032855510712, "12889": 0.21214580535888672, "12898": 0.1710275560617447, "12955": 0.0058422754518687725, "13228": 0.015504186972975731, "13268": 0.20022670924663544, "13341": 0.8674615025520325, "13369": 0.15023678541183472, "13656": 0.906871497631073, "14081": 0.3248254358768463, "14095": 0.272677481174469, "14163": 0.4145384132862091, "14164": 0.18248429894447327, "14440": 0.4337083101272583, "14573": 0.7370892763137817, "14795": 0.058784693479537964, "14874": 0.06520967930555344, "15059": 0.11604541540145874, "15070": 0.4794800877571106, "15172": 0.1873544454574585, "15287": 0.7445381283760071, "15509": 0.8600510358810425, "15630": 0.6931471824645996, "15923": 0.14179791510105133, "16007": 1.0165601968765259, "16014": 0.13499516248703003, "16098": 0.2089812457561493, "16134": 0.010684899985790253, "16186": 0.12642613053321838, "16221": 0.058784693479537964, "16307": 0.12038381397724152, "16308": 0.8255793452262878, "16453": 0.22937409579753876, "16463": 0.2830325961112976, "16505": 0.8247235417366028, "16596": 0.8195732831954956, "16662": 0.6989894509315491, "16677": 0.12728634476661682, "16709": 0.2881702482700348, "16844": 0.272677481174469, "17059": 0.27786844968795776, "17076": 0.6102113127708435, "17191": 0.38174858689308167, "17287": 0.0752234235405922, "17347": 0.6054253578186035, "17503": 0.6533012986183167, "17598": 0.38574060797691345, "17643": 0.026025565341114998, "17657": 0.8349450826644897, "17695": 0.05139094591140747, "18075": 0.1477125883102417, "18077": 0.02316705882549286, "18191": 0.08871890604496002, "18445": 1.1549384593963623, "18647": 0.04394211992621422, "18804": 0.7463917136192322, "18900": 0.1212492436170578, "18969": 0.3304552733898163, "19136": 0.5957841277122498, "19155": 0.13071982562541962, "19241": 0.29473719000816345, "19274": 0.15526613593101501, "19518": 0.3381449282169342, "19653": 0.03831886500120163, "19737": 0.966567873954773, "20063": 0.1602703034877777, "20214": 0.06429435312747955, "20250": 0.12814582884311676, "20350": 0.23015019297599792, "20360": 0.3318578004837036, "20582": 0.011650617234408855, "20614": 0.609149694442749, "20679": 0.9455460906028748, "20746": 0.18329764902591705, "20806": 0.02887592278420925, "20861": 0.10906458646059036, "20875": 0.28670501708984375, "20900": 0.009718249551951885, "20918": 0.010684899985790253, "20962": 0.33675122261047363, "21049": 0.2622140049934387, "21081": 0.5404602885246277, "21434": 0.7951818704605103, "21449": 0.34922540187835693, "21653": 0.28082266449928284, "21928": 1.12241530418396, "21935": 0.14686977863311768, "22160": 1.3331490755081177, "22291": 0.8925741910934448, "22391": 0.23864774405956268, "22471": 0.1808556467294693, "22520": 0.3547199070453644, "22963": 0.1384023278951645, "23150": 0.27044451236724854, "23275": 0.13157635927200317, "23536": 0.5596157908439636, "23599": 0.04113444685935974, "23737": 0.33675122261047363, "24269": 0.9710156321525574, "24278": 0.4624064862728119, "24330": 1.134421706199646, "24545": 0.43434104323387146, "24554": 0.3777405619621277, "24587": 0.66441810131073, "24672": 0.5433003902435303, "24710": 0.42735910415649414, "24755": 0.08603433519601822, "24759": 0.44691193103790283, "24895": 0.0797421783208847, "25145": 0.3656192123889923, "25336": 0.10818854719400406, "25409": 0.6317287683486938, "25468": 0.13414156436920166, "25537": 0.02792670577764511, "25690": 0.03360854089260101, "25714": 0.5057345628738403, "26461": 0.37035053968429565, "26524": 0.06337817758321762, "26633": 0.14179791510105133, "27159": 0.20102575421333313, "27263": 0.012615402229130268, "27343": 0.15693697333335876, "27528": 0.6144463419914246, "27881": 1.0030416250228882, "28024": 0.1384023278951645, "28086": 0.31489628553390503, "28105": 0.8583967685699463, "28156": 0.7239188551902771, "28207": 0.04860413447022438, "28644": 0.10906458646059036, "28674": 0.2881702482700348, "28736": 0.0019512200960889459, "28915": 0.13925230503082275, "29543": 0.47766464948654175} | 12489130 | An orthotopic model of human melanoma was developed in which malignant cells were injected into human skin grafted to nude and SCID mice. Melanoma cells proliferated and invaded the human skin grafts with characteristic patterns. Three of six melanomas grew as multiple nodules and infiltered the grafts without major architectural changes in the dermis, whereas the others invaded the dermis along collagen fibers with prominent endothelial vessels. By contrast, melanoma cells inoculated into mouse skin grew as diffusely expanding nodules that did not invade the murine dermis. In human skin grafts, human melanoma cells were angiogenic for human blood vessels, and murine vessels were only found at the periphery of grafts. Tumor cells invaded the human vessels, and four out of seven cell lines metastasized to lungs, suggesting that this model is useful to determine in vivo the interactions between normal and malignant human cells. | Growth and invasion of human melanomas in human skin grafted to immunodeficient mice. |
{"1011": 0.13157635927200317, "1044": 0.5601736903190613, "1051": 0.0174254160374403, "1052": 0.03266380727291107, "1996": 0.0606246218085289, "1997": 0.016465263441205025, "1999": 0.22859740257263184, "2011": 0.4709797203540802, "2015": 0.2652147710323334, "2024": 0.09672962874174118, "2026": 0.5162794589996338, "2029": 0.036437395960092545, "2037": 0.19862671196460724, "2046": 0.2852376699447632, "2076": 0.469759464263916, "2078": 0.11081436276435852, "2079": 0.28963330388069153, "2080": 1.1469062566757202, "2089": 0.020300358533859253, "2099": 0.17840765416622162, "2139": 0.4531385898590088, "2140": 0.1384023278951645, "2207": 0.8195732831954956, "2291": 0.8682814836502075, "2309": 0.29109421372413635, "2331": 0.46302130818367004, "2339": 0.037378571927547455, "2377": 0.2018241584300995, "2426": 0.22548456490039825, "2427": 0.2231435477733612, "2433": 0.3070250153541565, "2475": 0.7969439625740051, "2515": 0.1477125883102417, "2535": 0.8383291959762573, "2550": 0.3318578004837036, "2566": 0.4752389192581177, "2569": 0.043007105588912964, "2590": 0.4932899475097656, "2594": 0.4950772523880005, "2618": 0.14686977863311768, "2648": 0.6548244953155518, "2668": 0.06429435312747955, "2713": 0.6212902665138245, "2719": 0.6317287683486938, "2730": 0.004870930220931768, "2804": 0.0770333781838417, "2832": 0.3923587501049042, "2886": 0.5773153901100159, "2891": 0.6980181336402893, "2895": 0.040196798741817474, "2920": 0.3949938118457794, "2947": 0.006812678650021553, "2981": 0.9425065517425537, "3001": 0.7182208299636841, "3078": 0.6512666940689087, "3102": 0.08603433519601822, "3120": 0.27342069149017334, "3161": 0.42799583077430725, "3170": 0.27342069149017334, "3217": 0.8100618124008179, "3227": 0.26820653676986694, "3248": 0.39762192964553833, "3252": 0.058784693479537964, "3278": 0.01934296265244484, "3302": 0.5063233375549316, "3319": 0.417115718126297, "3322": 0.2990913391113281, "3350": 0.3923587501049042, "3366": 0.5151132941246033, "3378": 0.10467668622732162, "3393": 0.8074519634246826, "3424": 0.8500841856002808, "3433": 0.10555581003427505, "3450": 0.39762192964553833, "3466": 0.16607704758644104, "3508": 0.4624064862728119, "3525": 0.24401791393756866, "3526": 0.6833335757255554, "3560": 0.4500300884246826, "3563": 0.255429208278656, "3567": 0.5220900774002075, "3582": 0.04394211992621422, "3596": 0.2478361576795578, "3619": 0.38308101892471313, "3625": 0.3615458607673645, "3671": 0.18654440343379974, "3688": 0.5127768516540527, "3774": 0.24325250089168549, "3800": 0.2652147710323334, "3811": 0.6543170213699341, "3818": 0.0029254043474793434, "3853": 0.7528522610664368, "3896": 0.11604541540145874, "3908": 0.29328158497810364, "3952": 0.12814582884311676, "3988": 0.7295845746994019, "4005": 0.6038249135017395, "4022": 0.6543170213699341, "4023": 0.7746911644935608, "4031": 0.4145384132862091, "4053": 0.3547199070453644, "4072": 0.09050461649894714, "4076": 0.3547199070453644, "4195": 0.6369074583053589, "4216": 0.21765978634357452, "4230": 0.022212404757738113, "4254": 0.045809537172317505, "4288": 0.026025565341114998, "4295": 0.3963087201118469, "4336": 0.02887592278420925, "4395": 0.6773988008499146, "4442": 0.6394867897033691, "4457": 0.23479416966438293, "4491": 0.3982778787612915, "4544": 0.5778634548187256, "4668": 0.10993985831737518, "4745": 0.3170322775840759, "4842": 0.44753631949424744, "4904": 0.8989537954330444, "4972": 0.6027565002441406, "5072": 0.23787821829319, "5100": 0.42735910415649414, "5158": 0.3409265875816345, "5178": 0.7105726003646851, "5197": 0.3084607720375061, "5201": 0.1384023278951645, "5250": 0.006812678650021553, "5258": 0.33953672647476196, "5292": 0.09584271162748337, "5302": 0.6343214511871338, "5320": 0.12556517124176025, "5391": 0.09938567131757736, "5398": 0.27934664487838745, "5435": 0.36967599391937256, "5505": 0.25467249751091003, "5531": 0.4624064862728119, "5576": 0.030771657824516296, "5591": 0.19862671196460724, "5648": 0.6170841455459595, "5658": 0.06612417846918106, "5666": 0.7276995778083801, "5716": 0.1221139207482338, "5857": 0.07250232994556427, "6033": 0.5450005531311035, "6074": 0.6764062643051147, "6131": 1.240975022315979, "6194": 0.23247487843036652, "6215": 0.8780695199966431, "6327": 0.016465263441205025, "6370": 0.045809537172317505, "6377": 0.09050461649894714, "6441": 0.4190443754196167, "6459": 0.1808556467294693, "6491": 0.13414156436920166, "6499": 0.20022670924663544, "6532": 1.1469062566757202, "6624": 0.6254787445068359, "6691": 0.2493593990802765, "6728": 0.4267219603061676, "6806": 0.2160874605178833, "6873": 0.26296505331993103, "6887": 0.8682814836502075, "6897": 0.06977381557226181, "6968": 0.8821197748184204, "7085": 0.48970574140548706, "7088": 0.1602703034877777, "7108": 0.010684899985790253, "7337": 0.33675122261047363, "7356": 0.11081436276435852, "7366": 0.3547199070453644, "7461": 0.1401015669107437, "7485": 0.1064341589808464, "7490": 0.890972912311554, "7610": 0.04860413447022438, "7712": 0.5045560002326965, "7722": 1.108330488204956, "7738": 0.2516399025917053, "7772": 0.8100618124008179, "7784": 0.10731173306703568, "7790": 0.08782484382390976, "7866": 0.1889725625514984, "7870": 0.24401791393756866, "8020": 0.12814582884311676, "8031": 0.6613984704017639, "8071": 0.06703783571720123, "8153": 0.680370569229126, "8171": 0.15943801403045654, "8281": 0.011650617234408855, "8287": 0.1930064558982849, "8360": 0.19782574474811554, "8381": 0.7638313174247742, "8417": 0.21135559678077698, "8449": 0.045809537172317505, "8462": 0.1212492436170578, "8523": 0.8829278349876404, "8524": 0.7352184057235718, "8578": 0.036437395960092545, "8621": 0.2478361576795578, "8676": 0.3750596046447754, "8681": 0.05046287178993225, "8747": 1.0828639268875122, "8878": 0.053244512528181076, "9002": 0.5116065740585327, "9007": 0.3084607720375061, "9063": 0.04860413447022438, "9113": 0.21765978634357452, "9125": 0.036437395960092545, "9174": 0.31489628553390503, "9307": 0.6212902665138245, "9513": 0.07884006202220917, "9597": 0.13243216276168823, "9732": 0.9240728616714478, "9846": 0.22392450273036957, "9947": 0.018384648486971855, "9972": 0.26446542143821716, "10016": 0.1734936386346817, "10163": 0.05970508232712746, "10202": 0.4093637466430664, "10327": 0.5914691090583801, "10381": 0.5979346632957458, "10448": 0.2247048318386078, "10509": 0.1212492436170578, "10595": 0.02412080205976963, "10610": 0.21530038118362427, "10626": 1.0768938064575195, "10698": 1.2347444295883179, "10737": 0.10818854719400406, "10744": 0.2231435477733612, "10769": 0.5690577030181885, "10804": 0.7314660549163818, "11085": 1.1530905961990356, "11231": 0.9225212931632996, "11265": 1.068206787109375, "11311": 0.18654440343379974, "11439": 0.009718249551951885, "11528": 0.32341301441192627, "11631": 0.40806588530540466, "11636": 0.574020504951477, "11663": 0.9485763907432556, "11704": 0.9005423784255981, "11767": 0.5651806592941284, "11889": 0.6027565002441406, "12123": 0.24631060659885406, "12130": 0.1485546976327896, "12141": 0.10555581003427505, "12374": 0.25467249751091003, "12510": 0.09228714555501938, "12562": 0.10731173306703568, "12604": 0.8264343738555908, "12616": 0.6000806093215942, "12649": 0.013579257763922215, "12681": 0.38905516266822815, "12702": 1.0815403461456299, "12737": 0.42990362644195557, "12765": 0.12038381397724152, "12902": 0.02792670577764511, "13221": 0.053244512528181076, "13265": 0.2501201331615448, "13490": 0.8731874823570251, "13543": 0.1751343309879303, "13592": 1.0298984050750732, "13595": 0.020300358533859253, "13711": 0.9371650815010071, "13749": 0.5822374224662781, "13833": 0.8633513450622559, "13922": 0.15442965924739838, "14045": 1.022197961807251, "14095": 0.4512746334075928, "14187": 0.8039615154266357, "14194": 0.7746911644935608, "14228": 0.1229778528213501, "14374": 0.3777405619621277, "14384": 0.5209306478500366, "14399": 0.8074519634246826, "14536": 0.7182208299636841, "14715": 0.00875066313892603, "14774": 0.12642613053321838, "14949": 0.025073638185858727, "15026": 0.9842413663864136, "15044": 0.2852376699447632, "15596": 0.09850110858678818, "15615": 0.5882205963134766, "15695": 0.07884006202220917, "15772": 0.37907835841178894, "15900": 0.13414156436920166, "15923": 0.5244048833847046, "16012": 0.0019512200960889459, "16149": 0.04487626627087593, "16285": 0.15359249711036682, "16308": 0.8143964409828186, "16371": 0.0174254160374403, "16389": 0.0797421783208847, "16446": 0.14349138736724854, "16464": 0.8272887468338013, "16585": 0.18573370575904846, "16605": 0.4891071021556854, "16627": 0.15442965924739838, "16678": 0.21530038118362427, "16731": 0.2674594223499298, "16781": 0.43875885009765625, "16882": 0.8022117614746094, "16884": 0.25995752215385437, "16935": 0.6872705817222595, "16975": 1.0087559223175049, "17009": 0.5540198087692261, "17201": 0.28155985474586487, "17250": 0.8074519634246826, "17287": 0.06429435312747955, "17341": 0.3910386264324188, "17379": 0.05694137513637543, "17631": 0.1970241367816925, "17643": 0.9621002674102783, "17760": 0.07068414986133575, "17782": 0.1685553640127182, "17926": 0.006812678650021553, "17944": 0.6833335757255554, "18037": 0.791648268699646, "18089": 0.01934296265244484, "18349": 1.0312920808792114, "18384": 0.006812678650021553, "18479": 0.841701865196228, "18595": 0.10818854719400406, "18699": 0.08871890604496002, "18715": 0.10467668622732162, "18845": 0.045809537172317505, "18856": 0.13157635927200317, "18898": 0.7286425232887268, "18903": 0.11865071207284927, "18981": 1.1063944101333618, "19009": 0.5936289429664612, "19057": 1.1185935735702515, "19098": 0.015504186972975731, "19137": 0.034552380442619324, "19230": 0.37371641397476196, "19239": 0.7342816591262817, "19359": 0.4267219603061676, "19466": 1.2851567268371582, "19491": 0.18004031479358673, "19531": 0.07612881064414978, "19577": 0.06703783571720123, "19738": 0.8433839678764343, "19825": 0.32270604372024536, "19915": 1.0101795196533203, "20049": 0.15359249711036682, "20228": 0.04674193635582924, "20582": 0.0058422754518687725, "20606": 0.0174254160374403, "20728": 0.0842406153678894, "20735": 0.46363574266433716, "20752": 0.011650617234408855, "20817": 0.7800771594047546, "20876": 0.9747070074081421, "21053": 0.10906458646059036, "21102": 0.861702561378479, "21162": 0.1913948506116867, "21252": 0.14095009863376617, "21305": 0.9256220459938049, "21685": 0.3353555500507355, "21759": 0.8550800085067749, "21781": 0.20421554148197174, "21823": 0.13071982562541962, "21890": 0.006812678650021553, "22330": 0.6338034868240356, "22423": 0.6950984001159668, "22571": 0.8796916007995605, "22641": 0.4132472574710846, "22643": 0.6181373596191406, "22931": 0.7445381283760071, "23060": 0.08064348995685577, "23079": 0.083342544734478, "23092": 1.0927356481552124, "23130": 0.16359257698059082, "23212": 0.38441169261932373, "23618": 1.0907690525054932, "23692": 1.3170573711395264, "23924": 0.053244512528181076, "24054": 0.08064348995685577, "24098": 0.06154331564903259, "24171": 0.49923527240753174, "24501": 0.15275461971759796, "24532": 0.011650617234408855, "24848": 0.07612881064414978, "24972": 0.5278670787811279, "25426": 0.15777134895324707, "25610": 0.1477125883102417, "25874": 0.1685553640127182, "25950": 0.8933739066123962, "26189": 0.04953393340110779, "26282": 0.3982778787612915, "26394": 0.1718502640724182, "26396": 0.34508460760116577, "26402": 0.015504186972975731, "26443": 1.2059240341186523, "26572": 1.0841858386993408, "26591": 0.19862671196460724, "26721": 0.77198725938797, "26773": 0.0029254043474793434, "26835": 0.9131608605384827, "27287": 0.026025565341114998, "27321": 0.9936857223510742, "27583": 0.052318159490823746, "27781": 0.7656494975090027, "27891": 0.06977381557226181, "28031": 0.3464667797088623, "28479": 1.2610986232757568, "28691": 0.04860413447022438, "28788": 1.018678069114685, "28873": 0.1011524572968483, "29090": 0.6921701431274414} | 12489688 | Neutrophilic polymorphonuclear leukocytes (neutrophils) are highly specialized for their primary function, the phagocytosis and destruction of microorganisms. When coated with opsonins (generally complement and/or antibody), microorganisms bind to specific receptors on the surface of the phagocyte and invagination of the cell membrane occurs with the incorporation of the microorganism into an intracellular phagosome. There follows a burst of oxygen consumption, and much, if not all, of the extra oxygen consumed is converted to highly reactive oxygen species. In addition, the cytoplasmic granules discharge their contents into the phagosome, and death of the ingested microorganism soon follows. Among the antimicrobial systems formed in the phagosome is one consisting of myeloperoxidase (MPO), released into the phagosome during the degranulation process, hydrogen peroxide (H2O2), formed by the respiratory burst and a halide, particularly chloride. The initial product of the MPO-H2O2-chloride system is hypochlorous acid, and subsequent formation of chlorine, chloramines, hydroxyl radicals, singlet oxygen, and ozone has been proposed. These same toxic agents can be released to the outside of the cell, where they may attack normal tissue and thus contribute to the pathogenesis of disease. This review will consider the potential sources of H2O2 for the MPO-H2O2-halide system; the toxic products of the MPO system; the evidence for MPO involvement in the microbicidal activity of neutrophils; the involvement of MPO-independent antimicrobial systems; and the role of the MPO system in tissue injury. It is concluded that the MPO system plays an important role in the microbicidal activity of phagocytes. | Myeloperoxidase: friend and foe. |
{"1011": 0.3683255612850189, "1015": 0.4794800877571106, "1041": 0.8357921838760376, "1059": 0.5909284353256226, "1156": 0.17020416259765625, "1999": 0.04953393340110779, "2004": 0.10993985831737518, "2007": 0.12814582884311676, "2011": 0.2822965085506439, "2015": 0.14264501631259918, "2028": 0.18329764902591705, "2029": 0.2667117714881897, "2051": 0.14686977863311768, "2063": 0.8057082891464233, "2076": 0.10379679501056671, "2099": 0.2493593990802765, "2102": 0.6265231370925903, "2109": 0.2409527748823166, "2140": 0.22157983481884003, "2174": 0.020300358533859253, "2229": 0.7656494975090027, "2290": 0.2918238639831543, "2378": 0.5734702348709106, "2389": 0.3127557039260864, "2397": 0.1693800985813141, "2483": 0.18004031479358673, "2487": 0.5045560002326965, "2504": 0.3519764244556427, "2515": 0.16359257698059082, "2531": 0.5751199722290039, "2535": 0.7818660736083984, "2550": 0.036437395960092545, "2556": 0.4400174915790558, "2590": 0.5063233375549316, "2613": 0.4041621685028076, "2724": 0.16276304423809052, "2752": 0.12814582884311676, "2765": 0.3019835948944092, "2824": 0.46486347913742065, "2828": 0.2317005842924118, "2832": 0.2954642176628113, "2861": 0.1332872211933136, "2920": 0.3339579105377197, "2944": 0.05694137513637543, "2988": 0.026025565341114998, "3189": 0.24171993136405945, "3215": 0.2852376699447632, "3231": 0.3127557039260864, "3248": 0.2637155055999756, "3273": 0.13755162060260773, "3278": 0.24554696679115295, "3283": 0.06886265426874161, "3303": 0.1477125883102417, "3351": 0.7592713832855225, "3367": 0.40351006388664246, "3378": 0.0606246218085289, "3426": 0.12384103983640671, "3433": 0.0317181795835495, "3445": 0.04953393340110779, "3463": 0.5080875158309937, "3466": 0.22859740257263184, "3491": 0.22626367211341858, "3512": 0.2184450328350067, "3623": 0.23324857652187347, "3625": 0.15777134895324707, "3652": 0.0606246218085289, "3670": 0.19622190296649933, "3671": 0.5267143249511719, "3695": 0.755608320236206, "3726": 0.2409527748823166, "3729": 0.5844172835350037, "3748": 0.6317287683486938, "3798": 0.4909018874168396, "3806": 0.6512666940689087, "3853": 0.27934664487838745, "3896": 0.05417001247406006, "3930": 0.920189380645752, "3937": 0.2822965085506439, "3949": 0.10818854719400406, "4013": 0.9209672808647156, "4022": 0.12470348179340363, "4030": 0.1212492436170578, "4072": 0.22548456490039825, "4081": 0.05139094591140747, "4102": 0.603290855884552, "4127": 0.025073638185858727, "4130": 0.7333439588546753, "4146": 0.05970508232712746, "4162": 0.3903779089450836, "4176": 0.1677299439907074, "4195": 0.04674193635582924, "4304": 0.9076598286628723, "4308": 1.0526502132415771, "4340": 0.520350456237793, "4358": 0.5255602598190308, "4359": 0.5540198087692261, "4395": 0.6016870141029358, "4442": 0.11865071207284927, "4453": 0.05970508232712746, "4539": 0.04953393340110779, "4588": 0.47402387857437134, "4646": 0.15693697333335876, "4668": 0.11778303235769272, "4758": 0.05694137513637543, "4824": 0.3304552733898163, "4962": 0.5822374224662781, "4982": 0.24171993136405945, "5022": 0.20421554148197174, "5072": 0.045809537172317505, "5114": 0.010684899985790253, "5173": 0.056018441915512085, "5197": 0.5427330136299133, "5228": 0.055094651877880096, "5250": 0.2447827309370041, "5267": 0.02316705882549286, "5301": 0.12384103983640671, "5335": 0.17020416259765625, "5387": 0.7881022095680237, "5393": 0.030771657824516296, "5449": 0.1212492436170578, "5468": 0.42416930198669434, "5547": 0.4286321699619293, "5603": 0.004870930220931768, "5604": 0.1808556467294693, "5642": 0.6343214511871338, "5646": 0.07068414986133575, "5648": 0.7960633039474487, "5654": 1.1115491390228271, "5685": 0.8837352395057678, "5761": 0.25239890813827515, "5769": 0.055094651877880096, "5776": 0.03831886500120163, "5852": 0.13157635927200317, "5876": 0.7076893448829651, "6022": 0.8212929964065552, "6064": 0.01934296265244484, "6083": 0.02792670577764511, "6131": 1.2158164978027344, "6194": 0.33115679025650024, "6357": 0.5021947622299194, "6388": 0.19862671196460724, "6483": 0.18329764902591705, "6551": 0.20421554148197174, "6592": 0.32270604372024536, "6789": 0.07159364968538284, "6914": 0.11951763927936554, "6961": 0.6882523894309998, "7017": 0.03360854089260101, "7031": 0.013579257763922215, "7176": 0.07884006202220917, "7192": 0.37035053968429565, "7242": 0.0842406153678894, "7312": 0.2719337046146393, "7337": 0.2447827309370041, "7361": 0.1946154683828354, "7380": 0.28963330388069153, "7438": 0.1619328260421753, "7461": 0.1751343309879303, "7473": 0.7610978484153748, "7531": 0.03360854089260101, "7532": 0.7491656541824341, "7551": 0.2763880789279938, "7594": 0.5596157908439636, "7629": 0.11604541540145874, "7645": 0.3141832649707794, "7711": 0.09050461649894714, "7718": 0.347847044467926, "7784": 0.4487839937210083, "7816": 0.04953393340110779, "7831": 0.39762192964553833, "7882": 0.34922540187835693, "7885": 0.2918238639831543, "7949": 0.11256109178066254, "7971": 1.19888174533844, "8000": 0.996573805809021, "8153": 0.9900637865066528, "8161": 0.19220098853111267, "8171": 0.0606246218085289, "8247": 0.26296505331993103, "8290": 0.0019512200960889459, "8360": 0.8764448165893555, "8394": 0.9958525896072388, "8449": 1.20884370803833, "8469": 0.2247048318386078, "8536": 0.7220231294631958, "8590": 0.23864774405956268, "8651": 0.4374985992908478, "8710": 0.5080875158309937, "8820": 0.812664806842804, "8878": 0.20102575421333313, "8898": 0.46608972549438477, "8907": 1.0621482133865356, "8980": 0.07068414986133575, "9007": 0.8442239761352539, "9078": 0.8731874823570251, "9096": 0.021256839856505394, "9153": 0.7370892763137817, "9165": 0.23092569410800934, "9350": 0.46853771805763245, "9412": 0.6254787445068359, "9513": 1.1437997817993164, "9526": 0.18167030811309814, "9535": 0.2983669638633728, "9541": 0.5307431221008301, "9556": 0.07250232994556427, "9597": 0.14602625370025635, "9742": 0.3012613356113434, "9784": 0.045809537172317505, "9839": 0.1994270235300064, "9869": 0.5104349255561829, "9885": 0.08871890604496002, "9966": 0.37974658608436584, "10197": 0.034552380442619324, "10548": 0.14433705806732178, "10556": 0.09672962874174118, "10572": 1.1530905961990356, "10744": 0.08513788133859634, "10752": 0.8517522215843201, "10882": 0.35060185194015503, "10903": 0.16276304423809052, "10924": 0.5341835021972656, "10938": 0.5540198087692261, "10975": 0.14095009863376617, "11005": 0.9084475636482239, "11022": 0.7942996621131897, "11156": 0.0019512200960889459, "11246": 0.6603899002075195, "11369": 1.072893738746643, "11432": 0.5098485946655273, "11598": 0.8837352395057678, "11709": 0.10906458646059036, "11835": 0.013579257763922215, "11837": 0.6027565002441406, "12099": 0.025073638185858727, "12328": 1.3017656803131104, "12349": 0.1332872211933136, "12381": 0.22157983481884003, "12412": 0.9217445850372314, "12435": 0.255429208278656, "12604": 0.9710156321525574, "12616": 0.5267143249511719, "12618": 0.757441520690918, "12673": 0.20739519596099854, "12702": 0.8450632095336914, "12732": 0.35128939151763916, "12737": 0.5517725944519043, "12826": 0.19862671196460724, "12837": 0.14349138736724854, "12849": 1.0437490940093994, "12943": 0.07793712615966797, "12987": 0.8057082891464233, "13096": 0.1358480453491211, "13185": 0.029824240133166313, "13228": 0.9302552938461304, "13330": 0.0354953333735466, "13341": 0.02792670577764511, "13416": 0.2231435477733612, "13494": 0.37035053968429565, "13512": 0.043007105588912964, "13599": 0.3554046154022217, "13637": 0.1889725625514984, "13671": 0.2800849378108978, "13791": 0.09406650811433792, "13878": 0.28670501708984375, "13922": 0.09672962874174118, "14095": 0.8813109993934631, "14142": 0.25694093108177185, "14155": 0.06977381557226181, "14193": 0.026976587250828743, "14262": 0.5255602598190308, "14350": 0.5045560002326965, "14475": 0.05046287178993225, "14562": 0.26820653676986694, "14613": 0.26446542143821716, "14828": 0.12642613053321838, "14925": 0.0029254043474793434, "15027": 0.5838727951049805, "15053": 0.0009760859538801014, "15384": 0.09584271162748337, "15527": 0.1332872211933136, "15543": 0.11951763927936554, "15869": 0.13925230503082275, "15946": 0.39762192964553833, "16014": 0.006812678650021553, "16127": 0.1510767638683319, "16221": 0.04394211992621422, "16285": 0.6583697199821472, "16463": 0.2160874605178833, "16505": 0.9076598286628723, "16523": 0.05139094591140747, "16703": 0.07884006202220917, "16910": 0.11430477350950241, "17059": 0.02887592278420925, "17076": 0.9470623731613159, "17119": 0.9857001900672913, "17338": 0.26446542143821716, "17359": 1.2797396183013916, "17379": 0.3547199070453644, "17663": 0.4624064862728119, "17785": 0.055094651877880096, "17820": 0.20580662786960602, "17886": 0.29036402702331543, "17903": 0.7067264318466187, "18037": 0.5822374224662781, "18089": 0.07431721687316895, "18260": 0.5080875158309937, "18714": 0.5882205963134766, "18720": 1.190008521080017, "18804": 0.03831886500120163, "19126": 0.29109421372413635, "19150": 0.5860490798950195, "19335": 0.15275461971759796, "19357": 0.4462870955467224, "19362": 0.030771657824516296, "19389": 0.7710843086242676, "19653": 1.0601204633712769, "19872": 0.1602703034877777, "20045": 0.3519764244556427, "20226": 0.28597161173820496, "20228": 0.1677299439907074, "20232": 0.15023678541183472, "20250": 0.045809537172317505, "20350": 0.42353010177612305, "20464": 0.6011518239974976, "20544": 0.037378571927547455, "20679": 0.09584271162748337, "20752": 0.3877306580543518, "20763": 0.7389566898345947, "21025": 0.19782574474811554, "21150": 0.17922431230545044, "21252": 0.07431721687316895, "21281": 0.022212404757738113, "21391": 0.09317722171545029, "21419": 0.27712854743003845, "21486": 1.156782865524292, "21618": 0.14686977863311768, "21628": 0.02792670577764511, "21743": 0.07431721687316895, "21800": 0.1064341589808464, "21903": 0.5045560002326965, "21923": 0.7153595685958862, "22211": 0.22937409579753876, "22330": 0.567951500415802, "22415": 0.42096930742263794, "22597": 0.10993985831737518, "22802": 0.11951763927936554, "22931": 0.09584271162748337, "22963": 0.304147332906723, "23216": 0.176772341132164, "23296": 1.0553730726242065, "23306": 0.10379679501056671, "23316": 0.10993985831737518, "23572": 0.7951818704605103, "23586": 0.5579402446746826, "23737": 1.1798561811447144, "23833": 0.2018241584300995, "23900": 0.20739519596099854, "23924": 0.3170322775840759, "24054": 1.0519683361053467, "24155": 0.06246116757392883, "24171": 0.669430673122406, "24203": 1.1444218158721924, "24269": 1.0668635368347168, "24278": 0.4879087805747986, "24279": 0.037378571927547455, "24312": 0.09761575609445572, "24454": 0.040196798741817474, "24587": 0.026976587250828743, "24848": 0.1751343309879303, "25002": 0.009718249551951885, "25006": 0.0752234235405922, "25117": 0.3127557039260864, "25194": 0.11081436276435852, "25426": 0.7969439625740051, "25456": 0.8400169610977173, "25708": 0.40806588530540466, "25714": 0.6165571808815002, "26243": 0.04113444685935974, "26244": 0.04113444685935974, "26296": 0.18978065252304077, "26402": 0.6583697199821472, "26520": 0.00875066313892603, "26636": 0.5151132941246033, "27233": 0.0913962796330452, "27427": 0.4728073179721832, "27781": 0.006812678650021553, "27854": 0.09584271162748337, "28038": 0.15693697333335876, "28156": 0.5232481360435486, "28522": 0.8901712894439697, "28691": 0.07431721687316895, "28835": 0.9139442443847656, "28848": 0.8715548515319824, "29206": 0.12814582884311676, "29290": 0.6989894509315491, "29295": 0.04674193635582924, "29391": 0.1332872211933136, "29560": 0.20818853378295898} | 12513042 | The importance of prostaglandin E(2) in various pathophysiological events emphasizes the necessity of understanding the role of PGE synthases (PGESs) in vivo. However, there has been no report on the functional relevance of microsomal PGES-1 (mPGES-1) to the physiological healing processes of gastric ulcers, or to angiogenesis, which is indispensable to the healing processes. In this report, we tested whether mPGES-1 plays a role in the healing of gastric ulcers and in the enhancement of angiogenesis using mPGES-1 knockout mice (mPGES-1 KO mice) and their wild-type (WT) counterparts. Gastric ulcers were induced by the serosal application of 100% acetic acid, and the areas of the ulcers were measured thereafter. mPGES-1 together with cyclooxygenase-2 were induced in the granulation tissues compared with normal stomach tissues. The healing of acetic acid-induced ulcers was significantly delayed in mPGES-1 KO mice compared with WT. This was accompanied with reduced angiogenesis in ulcer granulation tissues, as estimated by CD31 mRNA levels determined by real-time PCR and the microvessel density in granulation tissues. The mRNA levels of proangiogenic growth factors, such as transforming growth factor-β, basic fibroblast growth factor, and connective tissue growth factor in ulcer granulation tissues determined were reduced in mPGES-1 KO mice compared with WT. The present results suggest that mPGES-1 enhances the ulcer-healing processes and the angiogenesis indispensable to ulcer healing, and that a selective mPGES-1 inhibitor should be used with care in patients with gastric ulcers. | Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers. |
{"1011": 0.1358480453491211, "1014": 0.401551216840744, "1051": 0.06429435312747955, "1052": 0.6233867406845093, "1609": 0.5789587497711182, "1998": 0.0797421783208847, "2007": 0.32764431834220886, "2015": 0.27712854743003845, "2019": 0.9209672808647156, "2020": 0.053244512528181076, "2028": 0.11865071207284927, "2029": 0.08961215615272522, "2044": 0.10379679501056671, "2048": 0.11430477350950241, "2062": 0.5232481360435486, "2084": 0.4673144817352295, "2086": 0.25467249751091003, "2090": 0.1994270235300064, "2094": 0.5696102976799011, "2116": 0.1718502640724182, "2132": 0.13157635927200317, "2146": 0.020300358533859253, "2168": 0.10203468054533005, "2177": 0.7220231294631958, "2179": 0.009718249551951885, "2182": 0.011650617234408855, "2193": 0.28670501708984375, "2213": 0.46853771805763245, "2214": 0.11430477350950241, "2230": 0.24859806895256042, "2235": 0.35334911942481995, "2236": 0.3916989266872406, "2263": 0.5506471395492554, "2287": 0.8187123537063599, "2312": 0.4494072198867798, "2313": 0.45437926054000854, "2465": 0.176772341132164, "2512": 0.7258110046386719, "2522": 0.08154398202896118, "2540": 0.5947071313858032, "2549": 0.1685553640127182, "2560": 0.567951500415802, "2581": 0.5712664127349854, "2641": 0.22001366317272186, "2649": 0.0606246218085289, "2683": 0.11604541540145874, "2691": 0.7370892763137817, "2714": 0.6389714479446411, "2717": 0.05970508232712746, "2765": 0.3141832649707794, "2813": 0.817850649356842, "2817": 0.010684899985790253, "2825": 0.10993985831737518, "2828": 0.15275461971759796, "2902": 0.19381128251552582, "2913": 0.040196798741817474, "2920": 0.05046287178993225, "2922": 0.15777134895324707, "2946": 0.6275664567947388, "2967": 0.45623743534088135, "2968": 0.23402166366577148, "3020": 0.2719337046146393, "3056": 0.05970508232712746, "3080": 0.1221139207482338, "3141": 0.4158279001712799, "3231": 0.13071982562541962, "3264": 0.02887592278420925, "3278": 0.3656192123889923, "3348": 0.20818853378295898, "3365": 0.4462870955467224, "3378": 0.6654226183891296, "3426": 0.06612417846918106, "3445": 0.0317181795835495, "3461": 0.4518963396549225, "3463": 0.4487839937210083, "3469": 0.33675122261047363, "3491": 0.06703783571720123, "3497": 0.5849615335464478, "3526": 0.44753631949424744, "3556": 0.14686977863311768, "3570": 0.5816917419433594, "3588": 0.1751343309879303, "3618": 0.21687394380569458, "3635": 0.5267143249511719, "3643": 0.20501139760017395, "3674": 0.8877626657485962, "3681": 0.4093637466430664, "3695": 0.39893341064453125, "3745": 0.42990362644195557, "3760": 0.004870930220931768, "3778": 0.2830325961112976, "3935": 0.02316705882549286, "3989": 0.4437839686870575, "4003": 0.35060185194015503, "4069": 0.29109421372413635, "4081": 0.10379679501056671, "4094": 0.015504186972975731, "4102": 0.5104349255561829, "4106": 0.6573580503463745, "4118": 0.17759032547473907, "4125": 0.6086184978485107, "4127": 0.0019512200960889459, "4130": 0.7872136831283569, "4141": 0.13925230503082275, "4167": 0.5080875158309937, "4198": 0.02316705882549286, "4206": 0.32129061222076416, "4207": 0.2822965085506439, "4281": 0.997294545173645, "4295": 0.20580662786960602, "4442": 0.42926809191703796, "4484": 0.38574060797691345, "4489": 0.12986256182193756, "4531": 0.07250232994556427, "4544": 0.07431721687316895, "4578": 0.6369074583053589, "4583": 0.5381823778152466, "4654": 0.08513788133859634, "4678": 0.07159364968538284, "4696": 0.06612417846918106, "4703": 0.06703783571720123, "4722": 0.14602625370025635, "4725": 0.304147332906723, "4761": 0.3956514894962311, "4793": 0.6931471824645996, "4800": 0.4444103240966797, "4803": 0.14939609169960022, "4866": 0.11778303235769272, "4895": 0.3170322775840759, "4914": 0.7827593088150024, "4921": 0.417115718126297, "5022": 0.6202403903007507, "5070": 0.10379679501056671, "5213": 0.1401015669107437, "5244": 0.45994341373443604, "5297": 0.14179791510105133, "5300": 0.037378571927547455, "5320": 0.11343330889940262, "5333": 0.04207121208310127, "5339": 0.8332487344741821, "5393": 0.15693697333335876, "5397": 0.011650617234408855, "5400": 0.35060185194015503, "5468": 0.4437839686870575, "5486": 0.8152611255645752, "5531": 0.129004567861557, "5535": 0.06246116757392883, "5546": 0.10291612148284912, "5579": 0.6144463419914246, "5610": 0.034552380442619324, "5646": 0.09228714555501938, "5714": 0.07159364968538284, "5761": 0.2026219218969345, "5769": 0.21530038118362427, "5776": 0.6312094330787659, "5799": 0.0797421783208847, "5907": 0.09850110858678818, "5947": 0.18573370575904846, "5966": 0.04953393340110779, "5994": 0.04487626627087593, "6022": 0.9900637865066528, "6061": 0.11951763927936554, "6083": 0.34023189544677734, "6147": 0.45994341373443604, "6219": 0.6338034868240356, "6258": 0.03925827145576477, "6428": 0.056018441915512085, "6431": 0.08692999184131622, "6449": 0.16524957120418549, "6470": 0.052318159490823746, "6483": 0.41840189695358276, "6496": 0.9680526852607727, "6551": 0.2763880789279938, "6592": 0.4425300657749176, "6612": 0.6892333030700684, "6660": 0.06246116757392883, "6678": 0.09938567131757736, "6705": 0.06977381557226181, "6893": 0.8780695199966431, "6909": 0.9546096324920654, "6923": 0.07250232994556427, "6937": 0.04860413447022438, "6970": 0.1510767638683319, "6976": 0.15777134895324707, "7080": 0.16110190749168396, "7088": 0.1401015669107437, "7091": 0.22937409579753876, "7117": 0.9417452812194824, "7127": 0.007782140281051397, "7176": 0.10555581003427505, "7192": 0.025073638185858727, "7274": 1.0298984050750732, "7275": 0.9447870850563049, "7356": 0.09050461649894714, "7361": 0.33953672647476196, "7412": 0.08782484382390976, "7440": 0.20977331697940826, "7535": 0.1384023278951645, "7594": 0.5903874635696411, "7645": 0.0770333781838417, "7831": 0.4574742913246155, "7861": 0.39696553349494934, "7874": 0.7086513638496399, "8302": 0.26146242022514343, "8319": 0.11168810725212097, "8343": 0.026976587250828743, "8715": 0.3127557039260864, "8740": 0.02412080205976963, "8761": 0.02792670577764511, "8789": 0.20580662786960602, "8800": 0.01934296265244484, "9052": 1.0874829292297363, "9104": 0.35677260160446167, "9113": 0.35403475165367126, "9141": 0.02887592278420925, "9181": 0.0058422754518687725, "9197": 0.11081436276435852, "9324": 0.11691460013389587, "9342": 0.15610189735889435, "9422": 0.4145384132862091, "9445": 0.1602703034877777, "9466": 0.16690383851528168, "9488": 0.07341018319129944, "9556": 0.5618454217910767, "9575": 0.7934166193008423, "9601": 0.29619070887565613, "9617": 0.5421652793884277, "9634": 0.417115718126297, "9646": 0.6853039860725403, "9723": 0.06246116757392883, "9750": 0.28597161173820496, "9779": 0.011650617234408855, "9812": 0.7755908370018005, "9839": 0.3784096837043762, "9932": 0.05694137513637543, "10225": 0.07431721687316895, "10318": 0.23247487843036652, "10426": 0.4734157919883728, "10488": 0.22392450273036957, "10536": 0.06886265426874161, "10755": 0.5860490798950195, "10764": 0.9379299283027649, "10826": 0.3297532796859741, "10903": 0.2749055027961731, "11146": 1.2682671546936035, "11156": 0.175953671336174, "11179": 0.0174254160374403, "11209": 0.09495500475168228, "11234": 0.03831886500120163, "11236": 1.2059240341186523, "11244": 0.6778947114944458, "11265": 0.15275461971759796, "11325": 0.4849066734313965, "11383": 0.23247487843036652, "11522": 0.6000806093215942, "11616": 0.2089812457561493, "11792": 0.058784693479537964, "11890": 0.6729245185852051, "12044": 0.18411032855510712, "12098": 1.1864371299743652, "12099": 0.04860413447022438, "12126": 0.12986256182193756, "12165": 0.27342069149017334, "12170": 0.757441520690918, "12210": 0.3656192123889923, "12319": 0.3601844012737274, "12381": 0.40285754203796387, "12435": 0.35745587944984436, "12477": 0.7086513638496399, "12516": 0.8965662121772766, "12520": 0.5168620347976685, "12596": 0.0752234235405922, "12732": 0.18978065252304077, "12826": 0.24859806895256042, "12990": 0.18248429894447327, "12997": 0.15359249711036682, "13113": 0.3877306580543518, "13212": 0.2749055027961731, "13320": 0.7610978484153748, "13352": 0.6312094330787659, "13360": 0.2749055027961731, "13594": 0.06520967930555344, "13595": 0.09672962874174118, "13599": 0.34922540187835693, "13692": 0.6553317308425903, "13705": 0.03831886500120163, "13876": 0.40285754203796387, "14155": 0.26820653676986694, "14171": 0.3339579105377197, "14267": 0.15023678541183472, "14348": 0.0058422754518687725, "14358": 0.0174254160374403, "14396": 0.004870930220931768, "14402": 0.48430517315864563, "14482": 0.11430477350950241, "14573": 0.2531573474407196, "14773": 0.8238670229911804, "14900": 0.012615402229130268, "14956": 0.6533012986183167, "14971": 0.1970241367816925, "15050": 0.32553088665008545, "15157": 0.9394577741622925, "15306": 0.5162794589996338, "15476": 0.022212404757738113, "15596": 0.17759032547473907, "15698": 0.02792670577764511, "15756": 0.7463917136192322, "16096": 0.29036402702331543, "16134": 0.2539152204990387, "16185": 0.46117570996284485, "16330": 0.09228714555501938, "16478": 0.06154331564903259, "16483": 0.1221139207482338, "16492": 0.0009760859538801014, "16578": 0.24171993136405945, "16749": 0.5651806592941284, "16902": 0.06977381557226181, "16921": 0.854249119758606, "17042": 0.2622140049934387, "17076": 0.8813109993934631, "17080": 0.026025565341114998, "17085": 1.0001721382141113, "17355": 0.7258110046386719, "17503": 0.04207121208310127, "17659": 0.022212404757738113, "17724": 0.07250232994556427, "17876": 0.1332872211933136, "17908": 0.347847044467926, "17928": 0.09850110858678818, "18080": 1.439538836479187, "18419": 0.8074519634246826, "18439": 0.46117570996284485, "18647": 0.20660123229026794, "18691": 0.08064348995685577, "19027": 0.08513788133859634, "19037": 0.817850649356842, "19064": 0.05046287178993225, "19124": 0.15023678541183472, "19158": 0.20022670924663544, "19210": 0.8366385698318481, "19262": 0.7665573358535767, "19314": 0.015504186972975731, "19335": 0.07250232994556427, "19386": 0.06337817758321762, "19470": 0.1994270235300064, "19841": 0.08064348995685577, "19900": 0.2478361576795578, "20014": 0.23864774405956268, "20118": 1.0416836738586426, "20166": 0.02316705882549286, "20247": 0.24325250089168549, "20272": 0.7047978043556213, "20427": 0.26296505331993103, "20567": 0.00875066313892603, "20569": 0.3547199070453644, "20576": 0.8366385698318481, "20763": 0.755608320236206, "20770": 0.01934296265244484, "20868": 0.21530038118362427, "21047": 0.17020416259765625, "21065": 0.045809537172317505, "21120": 0.025073638185858727, "21217": 0.45437926054000854, "21262": 0.9217445850372314, "21274": 0.03925827145576477, "21449": 0.33115679025650024, "21531": 0.8805016279220581, "21639": 0.05694137513637543, "21754": 0.04207121208310127, "21766": 0.7978238463401794, "21976": 0.026025565341114998, "22461": 0.4944818615913391, "22571": 0.36426326632499695, "22662": 0.14939609169960022, "22834": 0.24631060659885406, "22963": 0.1946154683828354, "23130": 0.28963330388069153, "23223": 0.012615402229130268, "23267": 0.8238670229911804, "23693": 0.21214580535888672, "23760": 0.6931471824645996, "23807": 1.151856780052185, "23900": 0.14433705806732178, "23969": 0.16524957120418549, "24081": 0.5433003902435303, "24174": 0.05139094591140747, "24264": 1.4944828748703003, "24552": 0.23556606471538544, "24582": 0.3897167444229126, "24714": 0.272677481174469, "24848": 0.3353555500507355, "24969": 0.018384648486971855, "25032": 0.0606246218085289, "25354": 0.1384023278951645, "25413": 0.3601844012737274, "25543": 0.1905880719423294, "25808": 0.21687394380569458, "25817": 0.23092569410800934, "26163": 0.4412745535373688, "26210": 0.27786844968795776, "26268": 0.3588210940361023, "26404": 0.1401015669107437, "26445": 0.030771657824516296, "26535": 0.6446255445480347, "26721": 1.117955207824707, "26757": 0.03831886500120163, "26775": 0.5461324453353882, "26819": 0.2026219218969345, "26837": 0.036437395960092545, "26886": 0.04860413447022438, "26994": 0.09584271162748337, "27011": 0.1718502640724182, "27109": 0.09761575609445572, "27152": 0.5596157908439636, "27213": 0.1401015669107437, "27312": 0.3784096837043762, "27339": 0.3339579105377197, "27480": 0.02316705882549286, "27532": 1.2948341369628906, "27550": 0.006812678650021553, "27811": 0.07612881064414978, "28155": 0.8022117614746094, "28228": 0.8408597707748413, "28436": 0.11691460013389587, "28498": 0.22079704701900482, "28685": 0.3141832649707794, "28697": 0.08513788133859634, "28828": 0.30486753582954407, "28829": 0.0058422754518687725, "28915": 0.2516399025917053, "29048": 0.7610978484153748, "29295": 0.2223619967699051, "29347": 0.3499138653278351, "29393": 0.15359249711036682, "29477": 0.932563841342926} | 12513972 | BACKGROUND Intracranial aneurysm (IA) is significantly more prevalent in patients with coarctation of the aorta or bicuspid aortic valve than in the general population, suggesting a common pathophysiology connecting IA and aortopathy. Here, we analyzed echocardiographic aortic root dimension (ARD) in patients with IA to confirm this possibility. METHODS From January 2008 to December 2010, 260 consecutive patients with IA who were admitted to our institution for coil embolization or for acute stroke management and who also underwent echocardiography were enrolled. We hypothesized that patients with large, ruptured, or multiple IAs are more likely to harbor co-prevalent aortopathy as measured by ARD compared to patients with small, isolated, unruptured IAs. Eccentric group was defined as patients aged <55 years with at least one ruptured aneurysm, an aneurysm ≥7 mm in size, or multiple aneurysms; the remainder was classified into a non-eccentric group. Clinical, angiographic, and echocardiographic findings of the two groups were compared. RESULTS ARD was significantly larger in the eccentric group than in the non-eccentric group (P = 0.049), and the difference was confirmed by multivariable analysis (P = 0.02). Subgroup analysis of patients aged <55 years showed similar result for ARD (P = 0.03), whereas hypertension was more associated with the non-eccentric group (P = 0.01). In addition, height was inversely related to aneurysm size after adjustment for age, sex, weight, ARD, smoking status, and number of aneurysms (P = 0.004). CONCLUSIONS A certain group of IA patients share a common intrinsic wall defect with aortopathy. Shared neural crest cell origin may give rise to this phenomenon. | Echocardiographic Evidence of Innate Aortopathy in the Human Intracranial Aneurysm |
{"1009": 0.304147332906723, "1014": 0.3662964701652527, "1020": 0.23787821829319, "1022": 0.0317181795835495, "1023": 0.24631060659885406, "1044": 0.20501139760017395, "1052": 0.935633659362793, "1058": 0.21530038118362427, "1059": 0.14686977863311768, "1060": 0.38374659419059753, "2001": 0.0038986403960734606, "2012": 0.02316705882549286, "2029": 0.13071982562541962, "2039": 0.004870930220931768, "2084": 0.29400965571403503, "2116": 0.012615402229130268, "2119": 0.08961215615272522, "2157": 0.5584990978240967, "2168": 0.13071982562541962, "2179": 0.22626367211341858, "2199": 0.052318159490823746, "2217": 0.1889725625514984, "2250": 0.06977381557226181, "2278": 0.20022670924663544, "2287": 0.8074519634246826, "2290": 0.38441169261932373, "2312": 0.29255300760269165, "2313": 0.2105647772550583, "2385": 0.18978065252304077, "2403": 0.2689530849456787, "2443": 0.09938567131757736, "2459": 0.3262358605861664, "2487": 0.1970241367816925, "2491": 0.6970458030700684, "2502": 0.025073638185858727, "2504": 0.06246116757392883, "2539": 0.14095009863376617, "2540": 0.732405424118042, "2556": 0.10203468054533005, "2557": 0.0029254043474793434, "2570": 0.35060185194015503, "2571": 0.37371641397476196, "2575": 0.2145126610994339, "2581": 0.27564704418182373, "2608": 0.5461324453353882, "2615": 1.039613962173462, "2616": 0.2478361576795578, "2625": 0.14264501631259918, "2654": 0.09406650811433792, "2668": 0.8195732831954956, "2683": 0.14602625370025635, "2689": 0.3443928062915802, "2714": 0.7333439588546753, "2765": 0.2881702482700348, "2812": 0.0009760859538801014, "2813": 0.7398891448974609, "2817": 0.058784693479537964, "2846": 0.3325583338737488, "2849": 0.7009293437004089, "2860": 1.0688776969909668, "2898": 0.0058422754518687725, "2902": 0.02412080205976963, "2904": 0.05970508232712746, "2920": 0.05694137513637543, "2922": 0.1401015669107437, "2946": 0.5016035437583923, "2966": 0.11256109178066254, "2970": 0.17840765416622162, "2988": 0.00875066313892603, "3091": 0.020300358533859253, "3108": 0.20660123229026794, "3141": 0.5010119676589966, "3177": 0.5528968572616577, "3231": 0.33325836062431335, "3264": 0.055094651877880096, "3276": 0.6202403903007507, "3278": 0.24018502235412598, "3378": 0.30558720231056213, "3395": 0.1873544454574585, "3431": 0.32764431834220886, "3445": 0.7182208299636841, "3446": 0.25995752215385437, "3456": 0.6558387279510498, "3461": 0.436867892742157, "3463": 0.48970574140548706, "3466": 0.030771657824516296, "3469": 0.39433568716049194, "3491": 0.24859806895256042, "3495": 0.5712664127349854, "3556": 0.21687394380569458, "3567": 0.15777134895324707, "3590": 0.14095009863376617, "3593": 0.42225050926208496, "3618": 0.23787821829319, "3621": 0.2531573474407196, "3622": 0.08603433519601822, "3623": 0.7342816591262817, "3643": 0.36967599391937256, "3662": 0.0797421783208847, "3671": 0.24248650670051575, "3675": 0.8442239761352539, "3681": 0.4425300657749176, "3739": 0.48068851232528687, "3778": 1.0116009712219238, "3798": 0.0752234235405922, "3872": 0.06429435312747955, "3893": 0.009718249551951885, "3935": 0.0038986403960734606, "3938": 0.5729197263717651, "4002": 0.15693697333335876, "4003": 0.2637155055999756, "4094": 0.151916041970253, "4097": 0.5461324453353882, "4102": 0.42799583077430725, "4106": 0.1064341589808464, "4125": 0.1229778528213501, "4179": 0.5080875158309937, "4190": 0.755608320236206, "4213": 0.006812678650021553, "4308": 0.08961215615272522, "4317": 0.029824240133166313, "4400": 1.1786550283432007, "4487": 0.3897167444229126, "4489": 0.22157983481884003, "4525": 0.1332872211933136, "4578": 0.1685553640127182, "4642": 0.42990362644195557, "4758": 0.40285754203796387, "4818": 0.36290550231933594, "4834": 0.18411032855510712, "4852": 0.25845035910606384, "4877": 0.6348392367362976, "4903": 0.07159364968538284, "4949": 0.8247235417366028, "4997": 0.010684899985790253, "5022": 0.5244048833847046, "5072": 0.5822374224662781, "5159": 0.029824240133166313, "5228": 0.02792670577764511, "5278": 0.04394211992621422, "5300": 0.20102575421333313, "5333": 0.31489628553390503, "5360": 0.08692999184131622, "5393": 0.19541899859905243, "5423": 0.8877626657485962, "5443": 0.2763880789279938, "5468": 0.7220231294631958, "5539": 0.4437839686870575, "5709": 0.1221139207482338, "5717": 0.1510767638683319, "5739": 0.6911921501159668, "5757": 0.18492233753204346, "5761": 0.47584590315818787, "5769": 0.28597161173820496, "5776": 0.6011518239974976, "5813": 0.13925230503082275, "5903": 0.036437395960092545, "5966": 0.1011524572968483, "5970": 0.0354953333735466, "5975": 1.061472773551941, "5986": 0.3777405619621277, "5995": 0.08154398202896118, "6020": 0.08244366943836212, "6022": 0.8074519634246826, "6075": 0.3070250153541565, "6146": 0.48068851232528687, "6147": 0.2667117714881897, "6177": 0.19782574474811554, "6181": 0.3409265875816345, "6191": 0.5021947622299194, "6227": 0.49982786178588867, "6258": 0.08154398202896118, "6370": 0.812664806842804, "6431": 0.14349138736724854, "6463": 0.07341018319129944, "6470": 0.13670019805431366, "6522": 0.03266380727291107, "6551": 0.1946154683828354, "6612": 0.07793712615966797, "6643": 0.13670019805431366, "6645": 0.04207121208310127, "6660": 0.13243216276168823, "6678": 0.5220900774002075, "6705": 0.8877626657485962, "6767": 0.32764431834220886, "6887": 0.004870930220931768, "6895": 0.5979346632957458, "6909": 0.1677299439907074, "6922": 0.4450363218784332, "7080": 0.12986256182193756, "7117": 0.7665573358535767, "7189": 0.29473719000816345, "7287": 0.5307431221008301, "7341": 0.5438674688339233, "7457": 0.5324648022651672, "7461": 0.10291612148284912, "7594": 0.8592242002487183, "7645": 0.1619328260421753, "7667": 0.11517547070980072, "7711": 0.5646255612373352, "7716": 0.5116065740585327, "7718": 0.06246116757392883, "7722": 0.18004031479358673, "7831": 0.7172679901123047, "7978": 0.053244512528181076, "8015": 0.08513788133859634, "8023": 0.0913962796330452, "8187": 1.2566616535186768, "8319": 0.5110208988189697, "8522": 0.06977381557226181, "8612": 0.0606246218085289, "8789": 0.006812678650021553, "8995": 0.31132611632347107, "9052": 0.9568626880645752, "9078": 0.0606246218085289, "9141": 0.1930064558982849, "9312": 0.40546512603759766, "9328": 0.0019512200960889459, "9333": 0.24018502235412598, "9381": 0.2800849378108978, "9447": 0.34508460760116577, "9556": 0.18167030811309814, "9646": 0.7436100244522095, "9756": 0.23092569410800934, "9812": 0.45437926054000854, "9821": 0.48068851232528687, "9839": 0.1913948506116867, "9854": 0.14686977863311768, "9885": 0.3554046154022217, "9888": 0.20102575421333313, "9938": 0.2539152204990387, "10061": 0.6476961374282837, "10120": 0.33675122261047363, "10146": 1.1070401668548584, "10173": 0.0029254043474793434, "10174": 0.20501139760017395, "10216": 0.05139094591140747, "10250": 0.7995813488960266, "10426": 0.018384648486971855, "10450": 0.7333439588546753, "10451": 0.3084607720375061, "10548": 0.6064908504486084, "10550": 0.05139094591140747, "10719": 0.9225212931632996, "10751": 1.2204381227493286, "10768": 0.6543170213699341, "10792": 0.11256109178066254, "10803": 0.9673105478286743, "10819": 0.5045560002326965, "10826": 0.1384023278951645, "10898": 0.22157983481884003, "10903": 0.49864232540130615, "10949": 0.18978065252304077, "11071": 0.1710275560617447, "11118": 0.27564704418182373, "11156": 0.21687394380569458, "11176": 0.13925230503082275, "11192": 0.06154331564903259, "11236": 0.3339579105377197, "11487": 0.009718249551951885, "11498": 0.045809537172317505, "11518": 0.6538092494010925, "11655": 0.7951818704605103, "11702": 0.22782009840011597, "11709": 0.09406650811433792, "11792": 0.1221139207482338, "12031": 0.16524957120418549, "12044": 0.35060185194015503, "12126": 0.37640097737312317, "12141": 0.14264501631259918, "12170": 0.6107416749000549, "12177": 0.30989447236061096, "12251": 0.28597161173820496, "12319": 0.436867892742157, "12375": 0.5489565134048462, "12381": 0.13243216276168823, "12407": 0.021256839856505394, "12435": 0.46608972549438477, "12520": 0.04487626627087593, "12565": 0.40806588530540466, "12596": 0.014542185701429844, "12646": 0.8383291959762573, "12826": 0.29981520771980286, "12921": 0.28963330388069153, "13113": 0.25088030099868774, "13212": 0.2830325961112976, "13320": 1.0986123085021973, "13331": 0.3903779089450836, "13360": 0.01934296265244484, "13433": 0.0770333781838417, "13483": 0.006812678650021553, "13508": 0.09761575609445572, "13594": 0.21372433006763458, "13599": 0.40871503949165344, "13705": 0.14179791510105133, "13806": 0.01934296265244484, "13853": 0.10203468054533005, "13878": 0.5963221788406372, "14037": 0.4113073945045471, "14116": 0.0606246218085289, "14155": 0.2983669638633728, "14213": 0.012615402229130268, "14234": 0.2105647772550583, "14267": 0.4248080551624298, "14358": 0.18978065252304077, "14396": 0.16607704758644104, "14402": 0.5427330136299133, "14413": 0.2409527748823166, "14613": 0.030771657824516296, "14623": 0.05694137513637543, "14639": 0.0797421783208847, "14773": 0.7881022095680237, "14982": 0.06337817758321762, "14983": 0.27712854743003845, "15000": 0.009718249551951885, "15050": 0.4752389192581177, "15088": 0.38574060797691345, "15291": 0.08782484382390976, "15321": 0.020300358533859253, "15399": 0.2983669638633728, "15525": 0.029824240133166313, "15535": 0.09050461649894714, "15536": 0.23324857652187347, "15869": 0.2749055027961731, "15977": 0.07612881064414978, "16157": 0.3526630103588104, "16173": 0.9302552938461304, "16185": 0.5336109399795532, "16264": 0.32058215141296387, "16330": 0.5330380201339722, "16405": 0.6989894509315491, "16480": 0.0058422754518687725, "16492": 0.055094651877880096, "16535": 0.7352184057235718, "16749": 0.791648268699646, "16902": 0.5313173532485962, "17076": 0.27564704418182373, "17221": 0.0009760859538801014, "17531": 0.7987030148506165, "17715": 0.25845035910606384, "17785": 0.06703783571720123, "17876": 0.05970508232712746, "17880": 0.1751343309879303, "17913": 0.2247048318386078, "18119": 0.38374659419059753, "18133": 0.020300358533859253, "18422": 0.03266380727291107, "18439": 0.18248429894447327, "18539": 0.1384023278951645, "18585": 0.28155985474586487, "19037": 0.18978065252304077, "19064": 0.3409265875816345, "19134": 0.1401015669107437, "19198": 0.053244512528181076, "19452": 0.05417001247406006, "19610": 0.619189441204071, "19630": 0.07793712615966797, "20116": 0.7934166193008423, "20118": 1.1255888938903809, "20201": 0.030771657824516296, "20294": 0.3723714053630829, "20469": 0.22079704701900482, "20504": 0.14095009863376617, "20567": 0.011650617234408855, "20569": 0.09406650811433792, "20881": 0.6931471824645996, "20960": 0.9225212931632996, "21419": 0.8212929964065552, "21449": 0.40285754203796387, "21887": 0.04767346754670143, "21908": 0.10818854719400406, "22049": 0.9455460906028748, "22084": 0.06977381557226181, "22096": 0.07159364968538284, "22261": 0.10555581003427505, "22419": 0.025073638185858727, "22524": 0.011650617234408855, "22755": 0.04207121208310127, "22793": 0.10291612148284912, "22935": 0.38574060797691345, "22963": 0.22157983481884003, "23139": 0.3283478021621704, "23150": 0.04767346754670143, "23284": 0.018384648486971855, "23389": 0.05786345899105072, "23758": 0.22157983481884003, "23894": 0.7764897346496582, "23900": 0.4228905141353607, "24107": 0.16607704758644104, "24327": 0.022212404757738113, "24577": 0.39367714524269104, "24714": 0.053244512528181076, "25449": 1.1363043785095215, "25465": 0.05139094591140747, "25473": 0.11343330889940262, "25543": 0.9131608605384827, "25604": 0.503966212272644, "26189": 0.1710275560617447, "26462": 0.026976587250828743, "26499": 0.34715715050697327, "26535": 0.18004031479358673, "26677": 0.03360854089260101, "26986": 0.05694137513637543, "27011": 0.15860503911972046, "27312": 0.4568560719490051, "27341": 0.15693697333335876, "27694": 0.0913962796330452, "27833": 0.1011524572968483, "27942": 0.9409833550453186, "28196": 0.23633737862110138, "28228": 0.9317949414253235, "28255": 0.890972912311554, "28277": 0.13670019805431366, "28329": 0.13755162060260773, "28436": 0.2034190446138382, "28714": 0.5500838756561279, "28915": 0.5483922958374023, "29048": 0.43244171142578125, "29295": 0.15023678541183472} | 12549585 | Pulse wave velocity (PWV) was measured in the aorta, right leg and arm of 90 control subjects (CS) and 92 hemodialysis patients (HD) of the same age and mean arterial pressure (MAP). Blood chemistry, including blood lipids, and echographic dimensions of the aorta, were measured in all subjects. Presence of aortic calcification was evaluated by abdominal X-ray and echography. Whereas femoral and brachial PWV were only slightly increased in HD (P less than 0.05), the aortic PWV was significantly elevated (1113 +/- 319 cm/sec) in comparison with CS (965 +/- 216 cm/sec; P = 0.0016). Aortic diameters were larger in HD, both at the root of aorta (32.7 +/- 4 vs. 28.2 +/- 2.8 mm; P less than 0.0001) and aortic bifurcation (16.9 +/- 3.1 vs. 14.6 +/- 2.2 mm; P less than 0.0001). Although the MAP was similar in HD (109.9 +/- 19.3 mm Hg) and CS (110.2 +/- 17.2 mm Hg), the pulse pressure was significantly increased in HD patients (76.6 +/- 23.7 vs. 63.9 +/- 22 mm Hg; P = 0.007). In the two populations, aortic PWV was found to increase with age (P less than 0.0001) and MAP (P less than 0.0001). The presence of aortic calcification showed only a borderline relationship with the increase in aortic PWV (P = 0.050 in CS and P = 0.069 in HD). As change in PWV is directly related to change in distensibility, and the aortic diameters were increased in HD, these results indicate that aortic wall compliance is decreased in HD, resulting in an increase in the pulsatile component of arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS) | Aortic and large artery compliance in end-stage renal failure. |
{"1011": 0.14095009863376617, "1048": 0.20739519596099854, "1052": 0.5596157908439636, "1165": 1.1756457090377808, "2003": 0.2741633653640747, "2008": 0.13670019805431366, "2011": 0.34508460760116577, "2024": 0.043007105588912964, "2029": 0.36697331070899963, "2063": 0.02792670577764511, "2076": 0.012615402229130268, "2078": 0.36358460783958435, "2079": 0.2394166737794876, "2140": 0.7827593088150024, "2203": 0.48430517315864563, "2222": 0.04394211992621422, "2239": 0.2493593990802765, "2433": 0.07884006202220917, "2490": 0.14264501631259918, "2497": 0.7105726003646851, "2504": 0.21372433006763458, "2512": 0.2741633653640747, "2515": 0.21293537318706512, "2535": 0.30917787551879883, "2557": 0.3106105625629425, "2571": 0.3723714053630829, "2587": 0.6212902665138245, "2714": 0.18248429894447327, "2721": 0.4500300884246826, "2824": 0.2105647772550583, "2828": 0.021256839856505394, "2884": 0.3423145115375519, "2920": 0.2231435477733612, "3081": 0.17020416259765625, "3161": 0.014542185701429844, "3223": 0.09850110858678818, "3313": 0.8989537954330444, "3338": 0.48670899868011475, "3366": 0.3519764244556427, "3378": 0.40741631388664246, "3433": 0.7314660549163818, "3445": 0.0752234235405922, "3491": 0.07068414986133575, "3508": 0.2652147710323334, "3522": 0.12384103983640671, "3526": 0.49864232540130615, "3560": 0.053244512528181076, "3596": 0.13499516248703003, "3625": 0.18167030811309814, "3669": 0.5898461937904358, "3670": 0.6583697199821472, "3693": 0.5596157908439636, "3714": 0.3662964701652527, "3728": 0.5021947622299194, "3853": 0.5855054259300232, "3972": 0.5267143249511719, "3973": 0.22937409579753876, "3989": 0.3622259199619293, "4013": 0.11168810725212097, "4014": 0.06429435312747955, "4135": 0.15359249711036682, "4395": 0.037378571927547455, "4442": 0.4203280806541443, "4453": 0.38905516266822815, "4515": 0.19220098853111267, "4668": 0.18329764902591705, "4911": 0.12986256182193756, "4962": 0.7314660549163818, "4972": 0.319873183965683, "5072": 0.022212404757738113, "5228": 0.25467249751091003, "5241": 0.4831010699272156, "5250": 0.33115679025650024, "5313": 0.09317722171545029, "5360": 0.2184450328350067, "5441": 0.1212492436170578, "5449": 0.5162794589996338, "5589": 0.33675122261047363, "5591": 0.016465263441205025, "5622": 0.022212404757738113, "5644": 0.18816383183002472, "6026": 0.34508460760116577, "6032": 0.5662899017333984, "6064": 1.5663347244262695, "6075": 0.4938860833644867, "6123": 0.4568560719490051, "6216": 0.27564704418182373, "6460": 0.16524957120418549, "6540": 0.6714286804199219, "6845": 0.012615402229130268, "6856": 0.2837681770324707, "6869": 0.24171993136405945, "6897": 0.2749055027961731, "7192": 0.9798521995544434, "7297": 0.10731173306703568, "7337": 0.23710809648036957, "7366": 0.40871503949165344, "7403": 0.8264343738555908, "7461": 0.09761575609445572, "7561": 0.06246116757392883, "7591": 0.010684899985790253, "7645": 0.021256839856505394, "7807": 0.6669275164604187, "8018": 0.9409833550453186, "8020": 0.0354953333735466, "8031": 0.10555581003427505, "8040": 0.3191637098789215, "8081": 0.0913962796330452, "8171": 0.05694137513637543, "8247": 0.22392450273036957, "8249": 0.659380316734314, "8327": 0.10993985831737518, "8360": 0.22392450273036957, "8382": 0.4512746334075928, "8498": 0.0019512200960889459, "8516": 0.10993985831737518, "8878": 0.32341301441192627, "8991": 0.5427330136299133, "9002": 0.06795065850019455, "9007": 1.0855059623718262, "9067": 0.04860413447022438, "9096": 0.17759032547473907, "9099": 0.0009760859538801014, "9165": 0.47036975622177124, "9211": 0.9944084882736206, "9319": 0.23324857652187347, "9597": 0.04767346754670143, "9794": 0.3423145115375519, "9884": 0.3346569836139679, "9885": 0.11691460013389587, "9890": 0.045809537172317505, "10163": 0.4891071021556854, "10315": 0.5903874635696411, "10341": 0.09317722171545029, "10381": 0.24171993136405945, "10509": 0.10731173306703568, "10548": 0.11430477350950241, "10572": 0.6911921501159668, "10737": 0.09672962874174118, "10752": 0.31845372915267944, "10893": 0.5936289429664612, "10960": 0.1994270235300064, "11022": 1.2471669912338257, "11085": 0.012615402229130268, "11109": 0.018384648486971855, "11226": 0.6911921501159668, "11374": 0.0770333781838417, "11981": 0.02316705882549286, "11993": 0.03925827145576477, "12260": 0.2622140049934387, "12411": 0.5651806592941284, "12439": 0.39762192964553833, "12562": 0.5729197263717651, "12638": 0.45994341373443604, "12732": 0.6823468804359436, "12745": 0.004870930220931768, "12942": 0.304147332906723, "12987": 0.3554046154022217, "13139": 0.10379679501056671, "13153": 0.04860413447022438, "13451": 0.06429435312747955, "13458": 0.25694093108177185, "13671": 0.8366385698318481, "13791": 0.07884006202220917, "13837": 0.2231435477733612, "13922": 0.30989447236061096, "14026": 0.26296505331993103, "14119": 0.40285754203796387, "14120": 0.28670501708984375, "14193": 0.6456501483917236, "14397": 0.00875066313892603, "14431": 0.02316705882549286, "14471": 0.38041436672210693, "14480": 0.40481385588645935, "14494": 0.10906458646059036, "14765": 0.18816383183002472, "14800": 0.07884006202220917, "14955": 1.6015946865081787, "15113": 0.06520967930555344, "15472": 0.35950297117233276, "15492": 0.4879087805747986, "15527": 0.19782574474811554, "15543": 0.24171993136405945, "15577": 0.11168810725212097, "15663": 1.0748957395553589, "15956": 0.052318159490823746, "16000": 0.7144040465354919, "16221": 0.44691193103790283, "16233": 1.1629066467285156, "16285": 0.8853482007980347, "16389": 0.9409833550453186, "16558": 0.3297532796859741, "16605": 0.23556606471538544, "16627": 0.05694137513637543, "16706": 0.6813592314720154, "16745": 0.2501201331615448, "16771": 0.23092569410800934, "16910": 0.46117570996284485, "16991": 0.14433705806732178, "17257": 0.46363574266433716, "17707": 0.10379679501056671, "17782": 1.3940764665603638, "17913": 0.2607102394104004, "18155": 0.5255602598190308, "18260": 0.4067663550376892, "18419": 0.6950984001159668, "18499": 0.1693800985813141, "18549": 0.791648268699646, "18592": 0.19220098853111267, "18622": 0.175953671336174, "18699": 0.9739698171615601, "19470": 0.03360854089260101, "19601": 0.09317722171545029, "19653": 0.44753631949424744, "19872": 0.8298473954200745, "20228": 0.7665573358535767, "20329": 0.5295937061309814, "20518": 1.2146576642990112, "20554": 0.020300358533859253, "20624": 0.5795059204101562, "20766": 0.06703783571720123, "20850": 0.2852376699447632, "20897": 0.04113444685935974, "21114": 0.0009760859538801014, "21197": 0.4400174915790558, "21262": 0.7629209756851196, "21273": 0.37707099318504333, "21348": 0.18004031479358673, "21360": 0.058784693479537964, "21466": 0.06520967930555344, "21595": 0.07793712615966797, "21618": 0.07612881064414978, "21647": 0.6186635494232178, "21716": 0.4500300884246826, "21877": 0.25995752215385437, "21903": 0.11081436276435852, "21967": 0.5133614540100098, "22026": 0.6363908052444458, "22170": 0.0009760859538801014, "22498": 0.0038986403960734606, "22694": 0.05786345899105072, "22794": 0.14349138736724854, "23057": 0.27044451236724854, "23079": 0.1229778528213501, "23296": 0.13414156436920166, "23375": 1.8187360763549805, "23797": 0.4932899475097656, "24004": 0.6502478122711182, "24054": 0.18329764902591705, "24184": 0.12814582884311676, "24203": 0.15526613593101501, "24277": 0.4855078160762787, "25002": 0.34577593207359314, "25016": 0.05046287178993225, "25039": 0.12384103983640671, "25524": 0.18816383183002472, "25761": 0.5968599319458008, "26244": 0.8731874823570251, "26296": 0.8715548515319824, "26402": 0.11951763927936554, "26475": 1.034073829650879, "26520": 0.03266380727291107, "26524": 0.669430673122406, "26534": 0.14264501631259918, "26572": 0.5685047507286072, "26757": 0.018384648486971855, "26874": 0.24859806895256042, "27216": 0.7463917136192322, "27642": 0.5506471395492554, "27790": 0.2837681770324707, "28032": 0.7086513638496399, "28038": 0.04207121208310127, "28424": 0.14939609169960022, "28715": 0.06520967930555344, "28828": 0.03925827145576477, "28829": 0.619189441204071, "28927": 0.2990913391113281, "29290": 0.10203468054533005, "29436": 0.37640097737312317, "29720": 0.684319257736206, "29727": 1.2041680812835693, "29799": 0.3027053773403168} | 12552297 | DNA polymerase lambda (polλ) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that polλ participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. The expression of a catalytically inactive form of polλ (polλDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polβ and polμ do not. Only events requiring DNA end processing before ligation are affected; this defect is associated with large deletions arising in the vicinity of the induced DSB. Furthermore, polλDN-expressing cells exhibit increased sensitization and genomic instability in response to ionizing radiation similar to that of NHEJ-defective cells. Our data support a requirement for polλ in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway. | The DNA polymerase λ is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells |
{"1014": 0.4518963396549225, "1052": 0.495672345161438, "1054": 0.055094651877880096, "2007": 0.5707147121429443, "2015": 0.7809720039367676, "2018": 0.15943801403045654, "2020": 0.026976587250828743, "2021": 0.083342544734478, "2022": 0.18004031479358673, "2031": 0.05970508232712746, "2051": 0.16276304423809052, "2053": 0.04394211992621422, "2062": 0.4855078160762787, "2067": 0.0317181795835495, "2077": 0.11778303235769272, "2084": 0.46117570996284485, "2094": 0.4673144817352295, "2095": 0.1693800985813141, "2109": 0.020300358533859253, "2128": 0.8442239761352539, "2146": 0.30558720231056213, "2152": 0.27786844968795776, "2153": 0.0797421783208847, "2158": 0.47766464948654175, "2179": 0.02412080205976963, "2241": 0.38041436672210693, "2273": 0.8600510358810425, "2287": 0.21765978634357452, "2308": 1.0992631912231445, "2313": 0.5461324453353882, "2324": 0.2145126610994339, "2329": 0.7229714393615723, "2331": 0.1677299439907074, "2335": 0.304147332906723, "2351": 0.16442140936851501, "2367": 0.15023678541183472, "2383": 0.16524957120418549, "2403": 0.02887592278420925, "2411": 0.021256839856505394, "2420": 0.34370049834251404, "2426": 0.5640701055526733, "2450": 0.9754437208175659, "2465": 0.7333439588546753, "2470": 0.35334911942481995, "2506": 0.2478361576795578, "2512": 0.953857421875, "2513": 0.014542185701429844, "2515": 0.07884006202220917, "2529": 0.07612881064414978, "2532": 0.0797421783208847, "2539": 0.012615402229130268, "2540": 1.020087480545044, "2554": 0.6980181336402893, "2556": 0.4093637466430664, "2591": 0.4914994537830353, "2641": 0.16442140936851501, "2660": 0.12556517124176025, "2676": 0.06977381557226181, "2709": 0.026976587250828743, "2710": 1.0841858386993408, "2714": 0.08871890604496002, "2765": 0.1913948506116867, "2817": 0.7426811456680298, "2854": 0.24248650670051575, "2864": 0.10993985831737518, "2866": 0.02316705882549286, "2902": 0.8143964409828186, "2913": 0.6410312056541443, "2931": 0.9021284580230713, "2936": 0.045809537172317505, "2951": 0.48430517315864563, "3010": 0.8813109993934631, "3012": 0.5795059204101562, "3020": 0.5057345628738403, "3025": 0.4512746334075928, "3057": 0.25088030099868774, "3064": 0.037378571927547455, "3080": 0.33605360984802246, "3108": 0.983511209487915, "3130": 0.12642613053321838, "3151": 0.4518963396549225, "3171": 0.6664261221885681, "3188": 0.7537717819213867, "3191": 0.4580921530723572, "3223": 0.129004567861557, "3231": 0.04953393340110779, "3255": 0.6275664567947388, "3273": 0.3949938118457794, "3278": 0.26296505331993103, "3280": 0.06337817758321762, "3287": 0.5871354341506958, "3348": 0.8600510358810425, "3367": 0.0770333781838417, "3378": 0.36426326632499695, "3426": 0.09317722171545029, "3445": 0.2089812457561493, "3446": 0.6400018334388733, "3463": 0.4512746334075928, "3466": 0.030771657824516296, "3480": 0.06520967930555344, "3491": 0.14095009863376617, "3497": 0.6228629946708679, "3517": 0.1212492436170578, "3525": 0.4041621685028076, "3540": 0.14349138736724854, "3549": 0.12728634476661682, "3563": 0.7124901413917542, "3591": 0.1905880719423294, "3618": 0.16442140936851501, "3643": 0.03266380727291107, "3653": 0.09850110858678818, "3671": 0.7163142561912537, "3695": 0.46302130818367004, "3725": 0.14179791510105133, "3752": 0.22001366317272186, "3767": 0.46608972549438477, "3778": 0.19541899859905243, "3801": 0.7755908370018005, "3807": 0.10993985831737518, "3824": 0.6394867897033691, "3867": 0.29981520771980286, "3891": 0.24018502235412598, "3893": 0.08782484382390976, "3938": 0.00875066313892603, "3973": 0.3346569836139679, "3979": 0.0913962796330452, "3981": 0.3897167444229126, "3989": 0.11951763927936554, "3996": 0.960606575012207, "4003": 0.5500838756561279, "4102": 0.6096806526184082, "4106": 0.0029254043474793434, "4118": 0.3084607720375061, "4146": 0.09584271162748337, "4192": 0.10026945173740387, "4280": 0.4349733293056488, "4281": 0.6223390698432922, "4295": 0.757441520690918, "4361": 0.04487626627087593, "4424": 0.3318578004837036, "4489": 0.29109421372413635, "4531": 0.4926934838294983, "4561": 0.255429208278656, "4610": 0.30558720231056213, "4647": 0.8433839678764343, "4649": 0.18411032855510712, "4650": 0.04113444685935974, "4725": 0.4450363218784332, "4745": 0.5186077356338501, "4757": 0.05786345899105072, "4812": 0.5381823778152466, "4937": 0.7925328612327576, "4945": 0.10731173306703568, "5002": 0.09938567131757736, "5022": 0.5540198087692261, "5067": 0.3027053773403168, "5134": 0.5629584193229675, "5143": 0.05694137513637543, "5159": 0.48670899868011475, "5345": 0.5662899017333984, "5393": 0.11081436276435852, "5400": 0.22079704701900482, "5403": 0.8877626657485962, "5443": 0.17840765416622162, "5447": 0.20022670924663544, "5478": 0.22937409579753876, "5514": 0.15777134895324707, "5531": 0.055094651877880096, "5543": 0.3810817003250122, "5548": 0.11343330889940262, "5567": 0.6902132034301758, "5579": 0.27712854743003845, "5719": 0.037378571927547455, "5769": 0.13670019805431366, "5776": 0.6244332790374756, "5794": 0.0317181795835495, "5907": 0.8022117614746094, "5966": 0.3499138653278351, "5970": 0.36086538434028625, "6022": 0.6989894509315491, "6028": 0.04113444685935974, "6075": 0.20501139760017395, "6083": 0.20818853378295898, "6165": 0.4462870955467224, "6205": 0.08064348995685577, "6289": 0.09672962874174118, "6305": 0.11951763927936554, "6388": 0.006812678650021553, "6393": 0.02792670577764511, "6413": 0.1718502640724182, "6431": 0.4654768109321594, "6456": 0.19782574474811554, "6470": 0.12384103983640671, "6592": 0.22859740257263184, "6612": 0.66441810131073, "6615": 0.053244512528181076, "6721": 0.1602703034877777, "6747": 0.14602625370025635, "6801": 0.08513788133859634, "6820": 0.5596157908439636, "6878": 0.6476961374282837, "6909": 0.997294545173645, "6930": 0.4879087805747986, "6976": 0.11430477350950241, "7012": 0.24554696679115295, "7017": 0.5278670787811279, "7065": 0.29400965571403503, "7080": 0.23092569410800934, "7091": 0.30558720231056213, "7127": 0.011650617234408855, "7388": 0.02887592278420925, "7461": 0.12728634476661682, "7507": 0.35745587944984436, "7551": 0.22859740257263184, "7645": 0.47827014327049255, "7649": 0.28890204429626465, "7666": 0.05970508232712746, "7691": 0.058784693479537964, "7709": 0.151916041970253, "7712": 0.35334911942481995, "7778": 0.0842406153678894, "7831": 0.5893046259880066, "7870": 0.5278670787811279, "7885": 0.11256109178066254, "7987": 0.02887592278420925, "8023": 0.016465263441205025, "8072": 0.03831886500120163, "8089": 0.007782140281051397, "8137": 0.3346569836139679, "8323": 0.4950772523880005, "8343": 0.3923587501049042, "8380": 0.8332487344741821, "8384": 0.42608439922332764, "8385": 0.15526613593101501, "8556": 0.06977381557226181, "8715": 0.7436100244522095, "8830": 0.20421554148197174, "8853": 0.05970508232712746, "9034": 0.3757305145263672, "9078": 0.10291612148284912, "9145": 0.21687394380569458, "9276": 0.6603899002075195, "9312": 0.5947071313858032, "9353": 1.068206787109375, "9363": 0.09406650811433792, "9367": 0.2800849378108978, "9377": 0.8559102416038513, "9556": 0.40741631388664246, "9560": 0.06703783571720123, "9654": 0.037378571927547455, "9662": 0.22392450273036957, "9723": 0.040196798741817474, "9750": 0.29109421372413635, "9751": 0.40285754203796387, "9779": 0.08244366943836212, "9839": 0.0009760859538801014, "9888": 0.10731173306703568, "10068": 0.22782009840011597, "10092": 0.5512100458145142, "10112": 0.0913962796330452, "10381": 0.37371641397476196, "10426": 0.6573580503463745, "10507": 0.10993985831737518, "10512": 0.013579257763922215, "10580": 0.058784693479537964, "10599": 0.6291293501853943, "10694": 0.6911921501159668, "10744": 0.04860413447022438, "10847": 0.42096930742263794, "10886": 0.20102575421333313, "10928": 0.37707099318504333, "11003": 0.12986256182193756, "11124": 0.75193190574646, "11192": 0.26446542143821716, "11234": 0.2478361576795578, "11325": 0.6624060273170471, "11326": 0.22782009840011597, "11441": 0.04767346754670143, "11475": 0.5925496220588684, "11500": 0.006812678650021553, "11522": 0.3283478021621704, "11538": 0.2026219218969345, "11616": 0.34577593207359314, "11674": 0.08782484382390976, "11706": 0.015504186972975731, "11707": 0.00875066313892603, "11826": 0.27712854743003845, "11888": 0.7370892763137817, "11890": 0.0354953333735466, "11949": 0.15023678541183472, "12044": 0.6212902665138245, "12126": 0.08692999184131622, "12273": 0.053244512528181076, "12435": 0.38174858689308167, "12565": 0.06337817758321762, "12581": 0.12038381397724152, "12596": 0.04207121208310127, "12763": 0.05417001247406006, "12818": 0.02316705882549286, "12826": 0.28082266449928284, "12943": 0.2089812457561493, "13105": 0.20102575421333313, "13113": 0.5827828645706177, "13356": 0.12728634476661682, "13494": 0.674915611743927, "13581": 0.16276304423809052, "13594": 0.1994270235300064, "13599": 0.42608439922332764, "13633": 0.0019512200960889459, "13692": 0.7201237678527832, "13705": 0.2659635543823242, "14040": 0.10379679501056671, "14155": 0.18492233753204346, "14171": 0.10291612148284912, "14286": 0.1229778528213501, "14343": 0.01934296265244484, "14773": 0.8633513450622559, "14971": 0.33115679025650024, "15006": 1.0973093509674072, "15050": 1.0066169500350952, "15192": 0.5387523174285889, "15277": 0.7009293437004089, "15306": 0.6022219061851501, "15318": 0.35060185194015503, "15354": 1.0927356481552124, "15502": 0.5629584193229675, "15596": 0.1212492436170578, "15689": 0.0019512200960889459, "15712": 0.1873544454574585, "15965": 0.7827593088150024, "15982": 0.02887592278420925, "16134": 0.3897167444229126, "16157": 0.014542185701429844, "16185": 0.4764525294303894, "16330": 0.4041621685028076, "16360": 0.3283478021621704, "16429": 0.6343214511871338, "16474": 0.6128603219985962, "16485": 0.6892333030700684, "16515": 0.06520967930555344, "16691": 0.06337817758321762, "16749": 0.5244048833847046, "16824": 0.27934664487838745, "16902": 0.036437395960092545, "17062": 0.0752234235405922, "17076": 1.216395378112793, "17080": 0.2622140049934387, "17464": 0.6624060273170471, "17503": 0.22001366317272186, "17531": 0.0019512200960889459, "17917": 0.040196798741817474, "17993": 0.40285754203796387, "18133": 0.09228714555501938, "18539": 0.10818854719400406, "18949": 0.2501201331615448, "19037": 0.4228905141353607, "19064": 0.08064348995685577, "19158": 0.06612417846918106, "19723": 0.006812678650021553, "20050": 0.02316705882549286, "20118": 0.006812678650021553, "20134": 0.053244512528181076, "20155": 0.056018441915512085, "20272": 0.10731173306703568, "20282": 0.0174254160374403, "20350": 0.0606246218085289, "20398": 0.10555581003427505, "20569": 0.5540198087692261, "20576": 0.17431432008743286, "21024": 0.14095009863376617, "21150": 0.151916041970253, "21449": 0.9583619832992554, "21557": 0.08782484382390976, "21791": 0.03831886500120163, "21887": 1.2324692010879517, "21908": 0.6332852244377136, "22110": 0.0009760859538801014, "22930": 0.49626702070236206, "22935": 0.9178520441055298, "22945": 0.012615402229130268, "22953": 0.10731173306703568, "22963": 0.21214580535888672, "22991": 0.1401015669107437, "23163": 0.03831886500120163, "23270": 0.7665573358535767, "23284": 0.06977381557226181, "23318": 0.015504186972975731, "23563": 0.17267228662967682, "23760": 0.5086748600006104, "23851": 0.083342544734478, "23900": 0.11168810725212097, "23969": 0.15359249711036682, "24004": 0.06795065850019455, "24081": 0.09406650811433792, "24413": 0.020300358533859253, "24501": 0.32553088665008545, "24714": 0.3381449282169342, "24735": 0.11691460013389587, "24755": 0.020300358533859253, "24869": 0.030771657824516296, "24895": 0.02316705882549286, "24964": 0.26296505331993103, "24978": 0.27564704418182373, "25022": 0.30917787551879883, "25032": 0.14433705806732178, "25070": 0.37371641397476196, "25141": 0.021256839856505394, "25269": 0.08154398202896118, "25323": 0.2607102394104004, "25481": 0.9776504039764404, "25604": 0.7018978595733643, "25808": 0.16359257698059082, "25937": 0.15693697333335876, "26206": 0.012615402229130268, "26226": 0.319873183965683, "26261": 0.2447827309370041, "26266": 0.016465263441205025, "26535": 0.7951818704605103, "26563": 0.011650617234408855, "26745": 0.3134697377681732, "26837": 0.1485546976327896, "26897": 0.12470348179340363, "27011": 0.045809537172317505, "27065": 1.1063944101333618, "27339": 0.2881702482700348, "27788": 0.1510767638683319, "27794": 1.024303913116455, "27885": 0.6260011196136475, "28093": 0.0029254043474793434, "28297": 0.07068414986133575, "28353": 0.5364705324172974, "28413": 0.06154331564903259, "28436": 0.3012613356113434, "28591": 0.026976587250828743, "28667": 0.6327666640281677, "28697": 0.09761575609445572, "28915": 0.30989447236061096, "29048": 0.6764062643051147, "29264": 0.777387797832489} | 12561083 | BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with "angiographically normal" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women. | Angina with "normal" coronary arteries: sex differences in outcomes. |
{"1011": 0.06246116757392883, "1043": 0.4709797203540802, "1044": 0.09584271162748337, "1047": 1.072225570678711, "1050": 0.4926934838294983, "1164": 0.6343214511871338, "2005": 0.06154331564903259, "2029": 0.3106105625629425, "2039": 0.3381449282169342, "2063": 1.1211429834365845, "2076": 0.05046287178993225, "2179": 0.15275461971759796, "2193": 0.034552380442619324, "2229": 0.255429208278656, "2239": 0.1930064558982849, "2247": 0.1485546976327896, "2250": 1.6078741550445557, "2358": 0.030771657824516296, "2378": 0.6999598741531372, "2385": 0.0009760859538801014, "2389": 0.16276304423809052, "2459": 1.2284748554229736, "2475": 0.5816917419433594, "2497": 0.28670501708984375, "2529": 0.4512746334075928, "2535": 0.11343330889940262, "2546": 0.2184450328350067, "2550": 0.23787821829319, "2555": 0.2719337046146393, "2571": 0.40285754203796387, "2581": 0.35677260160446167, "2606": 0.05970508232712746, "2890": 0.37102460861206055, "2920": 0.07612881064414978, "3096": 1.0775588750839233, "3223": 0.3297532796859741, "3286": 0.47827014327049255, "3351": 0.17922431230545044, "3378": 0.08154398202896118, "3433": 0.7220231294631958, "3457": 0.20660123229026794, "3526": 0.40611594915390015, "3563": 0.41195443272590637, "3642": 0.03266380727291107, "3669": 0.8366385698318481, "3670": 0.981317400932312, "3775": 0.11256109178066254, "3794": 0.083342544734478, "3802": 0.1011524572968483, "3853": 0.469759464263916, "3930": 0.272677481174469, "3978": 0.5290185213088989, "4013": 0.5444341897964478, "4072": 0.14939609169960022, "4176": 0.045809537172317505, "4286": 0.41195443272590637, "4295": 0.6000806093215942, "4315": 0.2990913391113281, "4383": 0.3750596046447754, "4442": 0.5033760666847229, "4456": 0.77198725938797, "4517": 0.42926809191703796, "4539": 0.011650617234408855, "4649": 0.08513788133859634, "4655": 0.3588210940361023, "4668": 0.02412080205976963, "4671": 0.36086538434028625, "4758": 0.1064341589808464, "4761": 0.06246116757392883, "4765": 0.8567397594451904, "4958": 0.7028654217720032, "4962": 0.9333322048187256, "4972": 0.19862671196460724, "5072": 0.06337817758321762, "5228": 0.9425065517425537, "5250": 1.035461664199829, "5387": 0.6502478122711182, "5391": 0.2983669638633728, "5449": 0.33115679025650024, "5450": 0.10379679501056671, "5537": 0.6583697199821472, "5550": 0.21135559678077698, "5666": 0.011650617234408855, "5714": 0.6149744987487793, "5740": 0.7755908370018005, "5876": 0.29619070887565613, "5942": 0.006812678650021553, "6022": 0.026025565341114998, "6064": 0.3870677351951599, "6119": 0.3325583338737488, "6761": 0.1384023278951645, "6827": 0.1994270235300064, "6869": 0.1751343309879303, "6914": 0.22704219818115234, "6970": 0.1734936386346817, "7028": 0.2696990668773651, "7076": 0.05046287178993225, "7096": 0.11604541540145874, "7337": 0.07341018319129944, "7361": 0.2622140049934387, "7366": 0.10203468054533005, "7403": 0.6128603219985962, "7591": 0.09761575609445572, "7711": 0.11604541540145874, "7783": 1.3575652837753296, "7790": 1.0037577152252197, "7810": 0.5696102976799011, "7816": 0.7105726003646851, "7870": 0.47036975622177124, "7882": 0.10818854719400406, "7883": 0.07793712615966797, "7940": 0.06612417846918106, "8000": 0.9732321500778198, "8031": 0.06795065850019455, "8153": 0.4203280806541443, "8171": 0.8997484445571899, "8197": 0.10555581003427505, "8285": 0.8567397594451904, "8290": 0.42353010177612305, "8360": 0.4673144817352295, "8382": 0.6522845029830933, "8469": 0.011650617234408855, "8582": 0.05139094591140747, "8609": 1.1647365093231201, "8878": 0.2105647772550583, "8902": 0.5685047507286072, "8939": 0.8748174905776978, "9007": 0.5596157908439636, "9014": 0.0029254043474793434, "9031": 0.4286321699619293, "9041": 0.05139094591140747, "9099": 0.10467668622732162, "9165": 0.8957691192626953, "9171": 0.9598589539527893, "9253": 0.2881702482700348, "9350": 0.27564704418182373, "9556": 0.5376120805740356, "9597": 0.11865071207284927, "9626": 0.08513788133859634, "10071": 0.30917787551879883, "10253": 0.6613984704017639, "10258": 0.46363574266433716, "10266": 0.32764431834220886, "10278": 1.200058937072754, "10451": 0.6149744987487793, "10465": 0.8264343738555908, "10509": 0.016465263441205025, "10556": 0.37035053968429565, "10572": 0.839173436164856, "10737": 0.129004567861557, "10738": 0.6317287683486938, "10769": 0.03360854089260101, "10803": 0.9178520441055298, "10882": 0.8264343738555908, "10960": 0.5116065740585327, "11187": 0.35128939151763916, "11254": 0.24554696679115295, "11311": 0.8500841856002808, "11382": 0.35334911942481995, "11423": 0.28743788599967957, "11432": 0.34922540187835693, "11835": 0.18816383183002472, "12031": 0.10203468054533005, "12115": 0.14349138736724854, "12222": 0.6583697199821472, "12328": 1.1038070917129517, "12359": 0.15359249711036682, "12369": 0.6348392367362976, "12377": 0.4248080551624298, "12530": 0.16524957120418549, "12987": 0.8583967685699463, "13047": 0.6603899002075195, "13070": 0.11951763927936554, "13330": 0.06520967930555344, "13464": 0.176772341132164, "13502": 0.36900100111961365, "13656": 0.9470623731613159, "13791": 0.14686977863311768, "13833": 0.24631060659885406, "13902": 0.823009729385376, "13922": 0.2983669638633728, "14026": 0.34300774335861206, "14095": 0.13925230503082275, "14114": 0.08064348995685577, "14120": 0.1751343309879303, "14193": 1.12241530418396, "14194": 0.7408206462860107, "14369": 0.45499902963638306, "14447": 0.6882523894309998, "14471": 0.0029254043474793434, "14526": 0.2576959431171417, "14769": 0.47584590315818787, "14802": 0.25845035910606384, "14828": 0.22079704701900482, "14863": 0.12470348179340363, "15136": 0.14686977863311768, "15176": 0.4512746334075928, "15403": 0.34508460760116577, "15425": 0.10291612148284912, "15527": 0.13414156436920166, "15543": 0.9987343549728394, "15873": 0.7163142561912537, "15946": 0.9363996982574463, "16000": 0.37371641397476196, "16007": 0.28670501708984375, "16048": 0.7951818704605103, "16068": 0.1619328260421753, "16118": 1.0587663650512695, "16147": 0.2990913391113281, "16221": 0.22001366317272186, "16275": 0.7528522610664368, "16285": 0.19381128251552582, "16576": 1.3695534467697144, "16745": 0.46853771805763245, "16783": 0.14686977863311768, "16896": 0.06154331564903259, "16932": 0.33953672647476196, "16983": 0.19782574474811554, "17134": 0.319873183965683, "17191": 0.052318159490823746, "17296": 0.9379299283027649, "17379": 0.18654440343379974, "17707": 0.037378571927547455, "17710": 1.1249549388885498, "17820": 0.2034190446138382, "17890": 0.09761575609445572, "18118": 0.1064341589808464, "18178": 0.05046287178993225, "18404": 0.7872136831283569, "18440": 0.08871890604496002, "18688": 0.16442140936851501, "18714": 0.2837681770324707, "18715": 0.16524957120418549, "18900": 0.6853039860725403, "19009": 0.5968599319458008, "19395": 0.6649205088615417, "19653": 0.8039615154266357, "19872": 0.10906458646059036, "20062": 0.3339579105377197, "20187": 1.0179725885391235, "20250": 0.013579257763922215, "20360": 0.2089812457561493, "20528": 0.7333439588546753, "20544": 0.03831886500120163, "20752": 0.18492233753204346, "20806": 0.4286321699619293, "20817": 0.08244366943836212, "21081": 0.32341301441192627, "21358": 0.18573370575904846, "21434": 0.8813109993934631, "21575": 0.47827014327049255, "21618": 1.20182204246521, "21709": 0.8264343738555908, "21733": 0.75193190574646, "21754": 0.35334911942481995, "21770": 0.27564704418182373, "21903": 0.45932671427726746, "22694": 0.24554696679115295, "22907": 0.5336109399795532, "22931": 0.36426326632499695, "23041": 0.9155091643333435, "23216": 0.05139094591140747, "23259": 0.4450363218784332, "23713": 0.8837352395057678, "23737": 0.23247487843036652, "23767": 0.06886265426874161, "23777": 0.17759032547473907, "24051": 0.11430477350950241, "24054": 0.058784693479537964, "24269": 0.0174254160374403, "24587": 0.5209306478500366, "24755": 0.6353566646575928, "24848": 1.0953518152236938, "25117": 0.23633737862110138, "25409": 0.3883931338787079, "25644": 0.9363996982574463, "26243": 0.08603433519601822, "26512": 0.7610978484153748, "26534": 0.10555581003427505, "26651": 0.07612881064414978, "26773": 0.5914691090583801, "26775": 0.09495500475168228, "26835": 0.07341018319129944, "26986": 0.2018241584300995, "27321": 0.567397952079773, "27427": 0.5483922958374023, "27781": 0.2719337046146393, "27854": 0.010684899985790253, "28156": 0.39433568716049194, "28488": 0.02792670577764511, "28848": 0.9987343549728394, "28873": 0.19381128251552582, "29206": 0.8109301924705505, "29290": 0.46670228242874146} | 12580014 | Expression of the intermediate filament protein keratin 17 (K17) is robustly upregulated in inflammatory skin diseases and in many tumors originating in stratified and pseudostratified epithelia. We report that autoimmune regulator (Aire), a transcriptional regulator, is inducibly expressed in human and mouse tumor keratinocytes in a K17-dependent manner and is required for timely onset of Gli2-induced skin tumorigenesis in mice. The induction of Aire mRNA in keratinocytes depends on a functional interaction between K17 and the heterogeneous nuclear ribonucleoprotein hnRNP K. Further, K17 colocalizes with Aire protein in the nucleus of tumor-prone keratinocytes, and each factor is bound to a specific promoter region featuring an NF-κB consensus sequence in a relevant subset of K17- and Aire-dependent proinflammatory genes. These findings provide radically new insight into keratin intermediate filament and Aire function, along with a molecular basis for the K17-dependent amplification of inflammatory and immune responses in diseased epithelia. | Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes |
{"1011": 0.2539152204990387, "1016": 0.1332872211933136, "1047": 1.018678069114685, "2005": 0.07250232994556427, "2007": 0.025073638185858727, "2008": 0.20739519596099854, "2011": 0.3554046154022217, "2012": 0.5370414853096008, "2015": 0.18573370575904846, "2024": 0.15023678541183472, "2029": 0.25088030099868774, "2039": 0.306306391954422, "2050": 0.47827014327049255, "2058": 0.49864232540130615, "2066": 0.28670501708984375, "2071": 0.06520967930555344, "2078": 0.21135559678077698, "2080": 0.39433568716049194, "2084": 0.14349138736724854, "2091": 0.46670228242874146, "2099": 0.21135559678077698, "2179": 0.2317005842924118, "2188": 0.4654768109321594, "2203": 1.0051883459091187, "2235": 0.6176109313964844, "2475": 0.7276995778083801, "2482": 0.5827828645706177, "2487": 0.020300358533859253, "2504": 0.5461324453353882, "2512": 0.5729197263717651, "2515": 0.1221139207482338, "2529": 0.4158279001712799, "2532": 0.7500885725021362, "2535": 0.5232481360435486, "2555": 0.38441169261932373, "2571": 0.4794800877571106, "2613": 0.3824150264263153, "2695": 0.637939989566803, "2765": 0.1384023278951645, "2817": 0.2034190446138382, "2826": 0.7276995778083801, "2890": 0.4849066734313965, "2896": 0.3170322775840759, "2913": 0.43623676896095276, "2920": 0.22001366317272186, "3258": 0.4944818615913391, "3273": 0.1485546976327896, "3283": 0.4831010699272156, "3370": 0.47036975622177124, "3378": 0.043007105588912964, "3424": 0.4419025182723999, "3433": 0.7898768186569214, "3445": 0.7191727757453918, "3457": 0.03266380727291107, "3463": 0.3297532796859741, "3466": 0.21372433006763458, "3491": 0.11865071207284927, "3512": 0.4356052577495575, "3526": 0.46486347913742065, "3593": 0.5718178153038025, "3597": 0.3622259199619293, "3619": 0.3519764244556427, "3623": 0.6813592314720154, "3625": 0.037378571927547455, "3670": 0.9886114001274109, "3760": 0.13071982562541962, "3798": 0.5925496220588684, "3853": 0.5330380201339722, "3936": 0.4177590310573578, "3981": 0.48970574140548706, "4072": 0.0038986403960734606, "4106": 0.4788752794265747, "4115": 0.6286086440086365, "4118": 0.09584271162748337, "4140": 0.5427330136299133, "4195": 0.10026945173740387, "4281": 0.822151780128479, "4286": 0.26296505331993103, "4305": 0.7009293437004089, "4359": 0.47463157773017883, "4383": 0.2478361576795578, "4395": 0.3949938118457794, "4442": 0.7057625651359558, "4515": 0.06977381557226181, "4531": 0.47584590315818787, "4539": 0.5827828645706177, "4566": 0.129004567861557, "4571": 0.565735399723053, "4655": 0.4450363218784332, "4667": 0.791648268699646, "4668": 0.4518963396549225, "4671": 0.09495500475168228, "4677": 0.7333439588546753, "4725": 0.28670501708984375, "4745": 0.05046287178993225, "4758": 0.32553088665008545, "4812": 0.012615402229130268, "4834": 1.154322862625122, "4852": 0.17759032547473907, "4877": 0.5936289429664612, "4895": 0.18654440343379974, "4909": 0.1734936386346817, "4962": 0.9225212931632996, "4972": 0.23247487843036652, "5092": 0.791648268699646, "5224": 0.3810817003250122, "5228": 0.42544642090797424, "5250": 0.6853039860725403, "5302": 0.4654768109321594, "5333": 0.18816383183002472, "5387": 0.9194108247756958, "5402": 0.0770333781838417, "5418": 0.3084607720375061, "5441": 0.6476961374282837, "5449": 0.17759032547473907, "5456": 0.10555581003427505, "5531": 0.14179791510105133, "5547": 0.1510767638683319, "5876": 0.5849615335464478, "5886": 0.8323994874954224, "5986": 0.2231435477733612, "6032": 0.3883931338787079, "6064": 0.23402166366577148, "6072": 0.02792670577764511, "6086": 0.4450363218784332, "6190": 0.469759464263916, "6223": 0.6699305176734924, "6227": 1.486563801765442, "6245": 0.14349138736724854, "6258": 0.0174254160374403, "6470": 0.2969166338443756, "6494": 0.5816917419433594, "6499": 0.8340972661972046, "6573": 0.5197699069976807, "6693": 0.04207121208310127, "6869": 0.2034190446138382, "6895": 0.2026219218969345, "7060": 0.3676496744155884, "7062": 0.5540198087692261, "7297": 0.09850110858678818, "7324": 0.9732321500778198, "7337": 0.27934664487838745, "7361": 0.5272908806800842, "7366": 0.0354953333735466, "7403": 0.4487839937210083, "7457": 0.6064908504486084, "7461": 0.319873183965683, "7476": 0.5734702348709106, "7485": 0.10906458646059036, "7487": 0.21922965347766876, "7645": 0.1485546976327896, "7657": 0.2689530849456787, "7698": 0.6118015646934509, "7711": 0.4891071021556854, "7816": 0.6096806526184082, "7885": 0.1751343309879303, "7889": 0.5033760666847229, "8000": 1.071556806564331, "8031": 0.672426164150238, "8153": 0.28963330388069153, "8171": 0.5450005531311035, "8176": 0.3485364317893982, "8290": 0.015504186972975731, "8303": 0.21293537318706512, "8319": 0.3374483287334442, "8327": 0.3070250153541565, "8335": 0.3127557039260864, "8360": 0.6931471824645996, "8469": 0.06246116757392883, "8498": 0.6714286804199219, "8529": 0.7782850861549377, "8566": 0.6249561905860901, "8577": 0.19782574474811554, "8776": 0.25845035910606384, "8859": 0.21530038118362427, "8878": 0.14686977863311768, "8920": 0.1384023278951645, "9007": 0.6709295511245728, "9033": 0.6435998678207397, "9141": 0.15860503911972046, "9152": 0.8641747236251831, "9165": 0.7683706283569336, "9319": 0.5751199722290039, "9350": 0.2976420819759369, "9412": 0.1994270235300064, "9416": 0.49030399322509766, "9556": 0.4938860833644867, "9597": 0.32270604372024536, "9607": 0.8682814836502075, "9808": 0.4437839686870575, "9821": 0.175953671336174, "9885": 0.6338034868240356, "10047": 0.40546512603759766, "10173": 0.5762182474136353, "10232": 0.23864774405956268, "10253": 0.6149744987487793, "10266": 0.15275461971759796, "10270": 1.468738079071045, "10288": 0.6461620330810547, "10415": 0.846739649772644, "10450": 0.8550800085067749, "10479": 0.16524957120418549, "10509": 0.05417001247406006, "10548": 0.7537717819213867, "10556": 0.48430517315864563, "10572": 0.7454653382301331, "10591": 0.46853771805763245, "10708": 0.014542185701429844, "10737": 0.05694137513637543, "10738": 0.46608972549438477, "10744": 0.15943801403045654, "10752": 0.6476961374282837, "10847": 0.13670019805431366, "10960": 0.30558720231056213, "11022": 0.6548244953155518, "11211": 0.7352184057235718, "11369": 0.4849066734313965, "11382": 0.20022670924663544, "11423": 0.36426326632499695, "11432": 0.20102575421333313, "11598": 0.22782009840011597, "11649": 1.1994705200195312, "11835": 0.06246116757392883, "11880": 1.0907690525054932, "12044": 0.010684899985790253, "12222": 1.0264055728912354, "12314": 0.5209306478500366, "12328": 1.0416836738586426, "12412": 0.6674286723136902, "12436": 0.6181373596191406, "12702": 1.1076855659484863, "12789": 1.4151703119277954, "12818": 1.0512858629226685, "12868": 0.03266380727291107, "12879": 0.00875066313892603, "12987": 1.2192846536636353, "13331": 0.06703783571720123, "13416": 0.09761575609445572, "13458": 0.0354953333735466, "13490": 0.13157635927200317, "13711": 0.6793810129165649, "13776": 0.42161011695861816, "13791": 0.23633737862110138, "13833": 0.10731173306703568, "13922": 0.1229778528213501, "13970": 0.07068414986133575, "14026": 0.037378571927547455, "14120": 0.36290550231933594, "14126": 0.5186077356338501, "14187": 0.8091925978660583, "14193": 1.0907690525054932, "14296": 0.022212404757738113, "14454": 0.7960633039474487, "14573": 0.9546096324920654, "14613": 0.053244512528181076, "14719": 1.611778974533081, "14828": 0.2749055027961731, "14971": 0.07793712615966797, "14988": 1.1012130975723267, "15115": 0.06977381557226181, "15176": 0.8796916007995605, "15306": 0.3662964701652527, "15543": 0.31204116344451904, "15663": 0.11168810725212097, "15772": 0.9798521995544434, "15946": 0.009718249551951885, "16014": 0.5590575933456421, "16069": 0.2659635543823242, "16134": 0.0606246218085289, "16185": 0.18978065252304077, "16215": 0.6011518239974976, "16285": 0.38574060797691345, "16405": 0.7370892763137817, "16749": 0.6301699280738831, "16882": 0.04674193635582924, "16922": 0.040196798741817474, "16983": 1.0229004621505737, "17063": 0.19541899859905243, "17076": 0.23402166366577148, "17379": 0.5330380201339722, "17547": 0.5080875158309937, "17710": 0.2478361576795578, "17782": 0.8340972661972046, "17908": 0.1693800985813141, "17913": 0.4818955361843109, "18062": 0.10026945173740387, "18231": 0.19541899859905243, "18234": 0.9225212931632996, "18260": 0.08961215615272522, "18330": 1.2862366437911987, "18674": 0.14686977863311768, "18714": 0.18329764902591705, "18740": 1.1586239337921143, "18941": 0.15610189735889435, "19301": 0.7500885725021362, "19653": 0.8957691192626953, "19780": 0.38308101892471313, "19811": 0.02792670577764511, "19939": 0.18329764902591705, "20051": 0.9470623731613159, "20110": 0.8893690705299377, "20382": 0.02887592278420925, "20544": 0.08064348995685577, "20752": 0.11168810725212097, "20793": 0.812664806842804, "20806": 0.4909018874168396, "20817": 0.6435998678207397, "20932": 0.26446542143821716, "21053": 1.0144377946853638, "21112": 0.010684899985790253, "21325": 0.1946154683828354, "21449": 0.5347557663917542, "21531": 1.02149498462677, "21575": 0.45623743534088135, "21618": 0.36967599391937256, "21709": 0.9658246636390686, "21716": 0.8682814836502075, "21903": 0.4349733293056488, "22471": 0.8400169610977173, "22694": 0.036437395960092545, "23041": 0.6270449161529541, "23191": 0.021256839856505394, "23216": 0.2983669638633728, "23235": 0.7791815400123596, "23270": 0.5762182474136353, "23572": 0.33605360984802246, "23586": 0.6902132034301758, "23900": 0.1905880719423294, "23993": 0.08961215615272522, "24054": 1.2336074113845825, "24203": 1.0933903455734253, "24328": 0.04860413447022438, "24412": 0.2089812457561493, "24587": 1.013020396232605, "24848": 1.1236859560012817, "25172": 0.6538092494010925, "25456": 1.0478670597076416, "25644": 0.1221139207482338, "25714": 0.014542185701429844, "26014": 0.0354953333735466, "26163": 0.12728634476661682, "26402": 0.7951818704605103, "26512": 0.009718249551951885, "26520": 0.13414156436920166, "26534": 0.12728634476661682, "26773": 0.9155091643333435, "26775": 0.13157635927200317, "27216": 0.2800849378108978, "27854": 0.09584271162748337, "28156": 0.30917787551879883, "28696": 1.2041680812835693, "28848": 0.8074519634246826, "28915": 0.6492279767990112, "29166": 0.06703783571720123, "29290": 0.3824150264263153, "29458": 0.5489565134048462} | 12582729 | BACKGROUND Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis. | Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a. |
{"1014": 0.5762182474136353, "1015": 0.27786844968795776, "1016": 0.9162907600402832, "1017": 0.6149744987487793, "1018": 0.009718249551951885, "1020": 0.36358460783958435, "1043": 0.33675122261047363, "1044": 0.7692760229110718, "1053": 0.44566190242767334, "1997": 0.32764431834220886, "2001": 0.025073638185858727, "2002": 0.2160874605178833, "2007": 0.24325250089168549, "2020": 0.176772341132164, "2025": 0.045809537172317505, "2028": 0.10203468054533005, "2039": 0.3923587501049042, "2044": 0.3262358605861664, "2047": 0.2516399025917053, "2048": 0.42926809191703796, "2051": 0.10467668622732162, "2053": 0.04394211992621422, "2055": 0.07341018319129944, "2078": 0.15275461971759796, "2086": 0.6853039860725403, "2093": 0.6054253578186035, "2095": 0.29400965571403503, "2102": 0.26446542143821716, "2106": 0.12038381397724152, "2109": 0.21922965347766876, "2111": 0.4145384132862091, "2116": 0.14349138736724854, "2119": 0.4311734735965729, "2135": 0.06246116757392883, "2139": 0.11343330889940262, "2142": 0.083342544734478, "2145": 0.030771657824516296, "2146": 0.6420594453811646, "2166": 1.013020396232605, "2176": 0.11081436276435852, "2177": 0.46363574266433716, "2206": 0.28963330388069153, "2224": 0.23787821829319, "2236": 0.5838727951049805, "2241": 0.026976587250828743, "2245": 0.08871890604496002, "2260": 0.1677299439907074, "2271": 0.38574060797691345, "2275": 0.3134697377681732, "2278": 0.684319257736206, "2287": 0.1401015669107437, "2309": 0.9084475636482239, "2313": 0.1734936386346817, "2353": 0.31560876965522766, "2364": 0.24018502235412598, "2367": 0.3339579105377197, "2408": 0.32905077934265137, "2410": 0.10818854719400406, "2411": 0.02316705882549286, "2414": 0.18411032855510712, "2416": 0.42161011695861816, "2434": 0.34370049834251404, "2443": 0.25088030099868774, "2444": 0.06977381557226181, "2451": 0.6043586730957031, "2462": 0.31132611632347107, "2464": 0.45251765847206116, "2470": 0.5914691090583801, "2475": 0.8281423449516296, "2478": 0.11778303235769272, "2487": 0.0354953333735466, "2491": 0.6075552701950073, "2495": 0.7755908370018005, "2497": 0.03266380727291107, "2504": 0.5495203733444214, "2506": 0.3601844012737274, "2549": 0.5278670787811279, "2563": 0.4580921530723572, "2565": 0.5057345628738403, "2575": 0.037378571927547455, "2609": 0.26446542143821716, "2628": 0.34370049834251404, "2640": 0.8109301924705505, "2658": 0.38308101892471313, "2660": 0.09672962874174118, "2668": 0.5186077356338501, "2706": 0.3588210940361023, "2729": 0.7333439588546753, "2731": 0.4788752794265747, "2740": 0.6543170213699341, "2747": 0.07341018319129944, "2750": 0.010684899985790253, "2765": 0.3897167444229126, "2777": 0.2447827309370041, "2783": 0.6118015646934509, "2817": 0.43244171142578125, "2828": 0.5238267183303833, "2836": 0.03831886500120163, "2847": 0.371698260307312, "2866": 0.8161250352859497, "2881": 0.18978065252304077, "2885": 0.16690383851528168, "2890": 0.35060185194015503, "2894": 0.10906458646059036, "2902": 0.31132611632347107, "2903": 0.5098485946655273, "2913": 0.2089812457561493, "2933": 0.10203468054533005, "2951": 0.7528522610664368, "2966": 0.4132472574710846, "2967": 0.3750596046447754, "2968": 0.7445381283760071, "2969": 0.9217445850372314, "2970": 0.11604541540145874, "2983": 0.6327666640281677, "3078": 1.068206787109375, "3091": 0.15023678541183472, "3112": 0.38441169261932373, "3144": 0.19782574474811554, "3160": 0.4330752193927765, "3167": 0.08154398202896118, "3195": 0.083342544734478, "3208": 0.14686977863311768, "3209": 0.176772341132164, "3218": 0.6960725784301758, "3231": 0.13925230503082275, "3251": 0.3949938118457794, "3252": 0.09495500475168228, "3266": 0.25239890813827515, "3268": 0.22782009840011597, "3278": 0.8567397594451904, "3289": 0.036437395960092545, "3319": 0.12728634476661682, "3345": 0.12038381397724152, "3373": 0.12038381397724152, "3416": 0.12986256182193756, "3438": 0.8004589080810547, "3446": 0.22626367211341858, "3450": 0.15023678541183472, "3454": 0.2493593990802765, "3463": 0.659380316734314, "3466": 0.15777134895324707, "3491": 0.036437395960092545, "3523": 0.1229778528213501, "3550": 0.14433705806732178, "3556": 0.6415454745292664, "3558": 0.5860490798950195, "3570": 0.637939989566803, "3577": 0.016465263441205025, "3582": 0.8567397594451904, "3593": 0.5267143249511719, "3635": 0.7210738658905029, "3674": 0.1930064558982849, "3676": 1.1160377264022827, "3725": 0.3127557039260864, "3737": 0.8885661959648132, "3778": 0.7105726003646851, "3798": 0.6911921501159668, "3807": 0.011650617234408855, "3867": 0.09406650811433792, "3885": 0.08603433519601822, "3895": 0.16359257698059082, "3896": 0.20818853378295898, "3905": 0.8748174905776978, "3949": 0.12728634476661682, "3963": 0.4818955361843109, "3979": 1.1109062433242798, "3980": 0.05139094591140747, "3989": 0.29400965571403503, "4023": 0.48068851232528687, "4045": 0.06429435312747955, "4076": 0.0354953333735466, "4083": 0.2184450328350067, "4094": 0.18248429894447327, "4102": 0.6674286723136902, "4106": 0.2749055027961731, "4135": 0.4891071021556854, "4146": 0.1734936386346817, "4236": 0.7115318179130554, "4237": 0.06246116757392883, "4252": 0.18329764902591705, "4254": 0.6471850275993347, "4279": 0.27342069149017334, "4292": 0.6369074583053589, "4295": 0.3824150264263153, "4319": 0.52266925573349, "4397": 0.7258110046386719, "4426": 0.02412080205976963, "4456": 0.02887592278420925, "4489": 0.5033760666847229, "4547": 0.6197150945663452, "4573": 0.5701626539230347, "4577": 0.14433705806732178, "4621": 0.2622140049934387, "4695": 0.034552380442619324, "4730": 0.14179791510105133, "4738": 0.637939989566803, "4746": 0.7239188551902771, "4752": 0.020300358533859253, "4758": 0.8973627090454102, "4800": 0.75193190574646, "4812": 0.0354953333735466, "4868": 0.1064341589808464, "5002": 0.2026219218969345, "5022": 0.469759464263916, "5067": 0.24554696679115295, "5068": 0.5209306478500366, "5082": 0.12814582884311676, "5084": 0.5723689198493958, "5092": 0.129004567861557, "5156": 0.46608972549438477, "5175": 0.053244512528181076, "5177": 0.04767346754670143, "5198": 0.016465263441205025, "5224": 0.06429435312747955, "5292": 0.5290185213088989, "5301": 0.401551216840744, "5335": 0.4537591338157654, "5345": 0.5822374224662781, "5359": 0.5640701055526733, "5423": 0.8298473954200745, "5427": 0.012615402229130268, "5468": 0.7276995778083801, "5486": 0.0029254043474793434, "5531": 0.35950297117233276, "5567": 0.10203468054533005, "5604": 0.13157635927200317, "5610": 0.32199856638908386, "5617": 0.3353555500507355, "5679": 0.013579257763922215, "5699": 0.45623743534088135, "5717": 0.1619328260421753, "5719": 0.13670019805431366, "5739": 0.14095009863376617, "5761": 0.6862877607345581, "5770": 0.6931471824645996, "5776": 0.4512746334075928, "5790": 0.16524957120418549, "5842": 0.15526613593101501, "5850": 0.4349733293056488, "5859": 0.2105647772550583, "5966": 0.37304413318634033, "6001": 0.036437395960092545, "6022": 0.4500300884246826, "6025": 0.02316705882549286, "6032": 0.03266380727291107, "6075": 0.11865071207284927, "6078": 0.7038320899009705, "6133": 0.16690383851528168, "6169": 0.12814582884311676, "6179": 0.0770333781838417, "6185": 0.175953671336174, "6245": 1.1287524700164795, "6279": 0.1332872211933136, "6388": 0.29328158497810364, "6421": 0.49923527240753174, "6427": 0.3191637098789215, "6445": 0.5127768516540527, "6480": 0.5180262327194214, "6521": 0.06154331564903259, "6522": 0.13071982562541962, "6564": 0.04674193635582924, "6577": 0.02316705882549286, "6600": 0.13243216276168823, "6605": 0.3416208028793335, "6612": 0.3877306580543518, "6633": 0.28670501708984375, "6640": 0.12642613053321838, "6648": 0.7038320899009705, "6666": 0.791648268699646, "6699": 0.4248080551624298, "6721": 0.7898768186569214, "6747": 0.32553088665008545, "6772": 0.8989537954330444, "6818": 0.7528522610664368, "6832": 0.7969439625740051, "6897": 0.21530038118362427, "6911": 0.053244512528181076, "6937": 0.08782484382390976, "6939": 0.20818853378295898, "6959": 0.27786844968795776, "7012": 1.0748957395553589, "7017": 0.36358460783958435, "7023": 1.0144377946853638, "7065": 0.00875066313892603, "7091": 0.7258110046386719, "7099": 0.06520967930555344, "7164": 0.009718249551951885, "7242": 0.24631060659885406, "7355": 0.5707147121429443, "7375": 0.07612881064414978, "7461": 0.09406650811433792, "7551": 0.4113073945045471, "7559": 0.036437395960092545, "7594": 0.32270604372024536, "7603": 0.32270604372024536, "7620": 0.669430673122406, "7644": 0.6006163358688354, "7645": 0.07431721687316895, "7667": 0.20739519596099854, "7691": 0.23864774405956268, "7711": 0.1358480453491211, "7778": 0.22079704701900482, "7784": 0.5540198087692261, "7792": 0.19541899859905243, "7831": 0.6430866718292236, "7843": 0.11430477350950241, "7863": 1.0409941673278809, "7870": 0.22079704701900482, "7885": 0.15693697333335876, "7965": 0.08961215615272522, "8089": 0.15526613593101501, "8116": 0.15275461971759796, "8137": 0.12384103983640671, "8192": 0.045809537172317505, "8317": 0.20818853378295898, "8377": 0.5261374711990356, "8390": 0.09406650811433792, "8428": 0.848413348197937, "8442": 0.053244512528181076, "8497": 0.6218147873878479, "8586": 0.08782484382390976, "8599": 0.30989447236061096, "8649": 0.4145384132862091, "8760": 0.960606575012207, "8778": 0.026025565341114998, "8781": 0.11778303235769272, "8819": 0.8813109993934631, "8830": 0.8674615025520325, "8853": 0.05786345899105072, "8882": 0.14686977863311768, "8929": 0.09317722171545029, "8980": 0.03831886500120163, "9029": 0.8941729068756104, "9084": 0.319873183965683, "9098": 0.07884006202220917, "9147": 0.04487626627087593, "9229": 0.12986256182193756, "9312": 0.04860413447022438, "9324": 1.2318994998931885, "9349": 0.3381449282169342, "9355": 0.1873544454574585, "9358": 0.10906458646059036, "9367": 0.603290855884552, "9398": 0.0842406153678894, "9422": 0.6096806526184082, "9468": 0.013579257763922215, "9556": 0.36358460783958435, "9560": 0.9929623603820801, "9580": 0.8682814836502075, "9657": 0.07068414986133575, "9690": 0.03831886500120163, "9756": 0.11951763927936554, "9818": 0.20580662786960602, "9821": 0.18978065252304077, "9871": 0.5506471395492554, "9885": 0.16276304423809052, "9895": 0.1619328260421753, "9967": 0.083342544734478, "10089": 0.38174858689308167, "10199": 0.11691460013389587, "10426": 0.5865923762321472, "10548": 0.31845372915267944, "10640": 0.06886265426874161, "10652": 0.2539152204990387, "10719": 0.18492233753204346, "10744": 0.15275461971759796, "10857": 0.05046287178993225, "10903": 0.3177432417869568, "11100": 0.7701805830001831, "11179": 0.3883931338787079, "11213": 0.006812678650021553, "11234": 0.8731874823570251, "11326": 0.06612417846918106, "11395": 0.10467668622732162, "11441": 0.757441520690918, "11463": 0.7295845746994019, "11490": 0.13157635927200317, "11616": 0.5712664127349854, "11709": 0.055094651877880096, "11890": 0.8195732831954956, "12353": 0.371698260307312, "12435": 0.2026219218969345, "12503": 0.08961215615272522, "12504": 0.2852376699447632, "12596": 0.13755162060260773, "12637": 0.2741633653640747, "12654": 0.22859740257263184, "12697": 0.2711893916130066, "12771": 0.10906458646059036, "12826": 0.3949938118457794, "12906": 0.8973627090454102, "12921": 0.5573811531066895, "13013": 0.8281423449516296, "13105": 1.1205062866210938, "13180": 0.5478278398513794, "13356": 0.09672962874174118, "13483": 0.9310253858566284, "13494": 0.026976587250828743, "13506": 0.1477125883102417, "13599": 0.49982786178588867, "13859": 0.17020416259765625, "13866": 0.012615402229130268, "14025": 0.567397952079773, "14142": 0.1619328260421753, "14155": 0.2247048318386078, "14171": 0.35334911942481995, "14246": 0.029824240133166313, "14280": 0.16524957120418549, "14336": 0.9131608605384827, "14358": 0.2881702482700348, "14667": 0.45499902963638306, "14670": 0.19220098853111267, "14671": 1.3449229001998901, "14702": 0.06429435312747955, "14777": 0.4914994537830353, "14868": 0.7067264318466187, "14876": 0.0029254043474793434, "15000": 0.04207121208310127, "15001": 0.14179791510105133, "15189": 0.35403475165367126, "15258": 0.026025565341114998, "15306": 0.7163142561912537, "15330": 0.1718502640724182, "15354": 0.38308101892471313, "15509": 0.48068851232528687, "15584": 0.22782009840011597, "15643": 0.07159364968538284, "15732": 0.010684899985790253, "15770": 0.6709295511245728, "15877": 0.23015019297599792, "15909": 0.6613984704017639, "16012": 0.7314660549163818, "16048": 0.22937409579753876, "16134": 0.1946154683828354, "16302": 0.3588210940361023, "16406": 0.12986256182193756, "16519": 0.32199856638908386, "16576": 0.48068851232528687, "16731": 0.3743882179260254, "16762": 0.1477125883102417, "16813": 0.19782574474811554, "16866": 0.037378571927547455, "16957": 0.10993985831737518, "16965": 0.0770333781838417, "17042": 0.25239890813827515, "17237": 0.5151132941246033, "17350": 0.11430477350950241, "17464": 0.24554696679115295, "17503": 0.011650617234408855, "17531": 0.40546512603759766, "17568": 0.17840765416622162, "17577": 0.18411032855510712, "17592": 0.13499516248703003, "17785": 0.045809537172317505, "17850": 0.1212492436170578, "18094": 0.09584271162748337, "18100": 0.23092569410800934, "18154": 0.3723714053630829, "18403": 0.01934296265244484, "18410": 0.4412745535373688, "18423": 0.5701626539230347, "18512": 0.32058215141296387, "18539": 0.2689530849456787, "18687": 0.304147332906723, "18700": 0.034552380442619324, "18960": 0.014542185701429844, "19037": 0.4855078160762787, "19064": 0.1994270235300064, "19156": 0.29036402702331543, "19158": 0.4837033152580261, "19209": 0.14349138736724854, "19319": 0.18573370575904846, "19332": 0.0752234235405922, "19388": 0.6684301495552063, "19389": 0.1677299439907074, "19541": 0.18329764902591705, "19727": 0.0317181795835495, "19736": 0.3903779089450836, "19843": 0.5341835021972656, "20063": 0.02412080205976963, "20110": 0.41840189695358276, "20155": 0.012615402229130268, "20162": 0.08154398202896118, "20166": 0.007782140281051397, "20272": 0.14686977863311768, "20310": 0.007782140281051397, "20353": 0.29400965571403503, "20482": 0.04207121208310127, "20576": 0.1970241367816925, "20588": 0.2470736801624298, "20589": 0.7755908370018005, "20775": 0.0058422754518687725, "20900": 0.28890204429626465, "20906": 1.134421706199646, "20915": 1.2244645357131958, "21150": 0.45623743534088135, "21891": 0.21687394380569458, "21961": 0.25694093108177185, "22083": 0.2531573474407196, "22110": 0.083342544734478, "22597": 0.5330380201339722, "22663": 0.3269403576850891, "22851": 0.06429435312747955, "22932": 0.3963087201118469, "22939": 0.32199856638908386, "22963": 0.3339579105377197, "23041": 0.0029254043474793434, "23260": 0.08871890604496002, "23284": 0.022212404757738113, "23561": 0.0842406153678894, "23746": 0.026025565341114998, "24010": 0.06612417846918106, "24081": 0.34508460760116577, "24096": 0.574020504951477, "24552": 0.2852376699447632, "24580": 0.15860503911972046, "24757": 0.2990913391113281, "24840": 0.012615402229130268, "25015": 0.13499516248703003, "25088": 0.21293537318706512, "25221": 0.791648268699646, "25719": 0.4770587682723999, "25775": 0.12384103983640671, "26134": 0.272677481174469, "26163": 0.7592713832855225, "26236": 0.304147332906723, "26319": 0.08782484382390976, "26452": 0.22392450273036957, "26462": 0.5495203733444214, "26745": 0.3012613356113434, "26758": 0.07250232994556427, "26906": 0.02412080205976963, "27354": 0.15777134895324707, "27484": 0.36290550231933594, "27615": 0.1602703034877777, "27794": 0.2247048318386078, "27833": 0.19782574474811554, "28093": 0.03831886500120163, "28139": 0.0009760859538801014, "28225": 0.006812678650021553, "28297": 0.3346569836139679, "28329": 0.11778303235769272, "28389": 0.07884006202220917, "29048": 0.31845372915267944, "29486": 0.23247487843036652} | 12584053 | OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years. DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level. SETTING 207 general practices in 13 primary care sites in the United Kingdom. PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up. Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants. INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care. MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels. The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years. RESULTS HbA(1c) levels at three years had decreased in both groups. After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17). The groups did not differ for the other biomedical and lifestyle outcomes and drug use. The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01). Depression scores and quality of life did not differ at three years. CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs. TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016. | Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care |
{"1011": 0.4879087805747986, "1015": 0.6911921501159668, "1017": 0.11430477350950241, "1020": 0.030771657824516296, "1044": 0.5936289429664612, "1048": 0.30558720231056213, "1050": 0.08154398202896118, "1996": 0.0038986403960734606, "1997": 0.08064348995685577, "1999": 0.09317722171545029, "2002": 0.11865071207284927, "2005": 0.15442965924739838, "2006": 0.05786345899105072, "2008": 0.09850110858678818, "2010": 1.0868242979049683, "2011": 0.43244171142578125, "2012": 0.15693697333335876, "2028": 0.319873183965683, "2029": 0.35813871026039124, "2046": 0.3304552733898163, "2047": 0.24248650670051575, "2049": 0.23092569410800934, "2050": 0.004870930220931768, "2076": 0.2954642176628113, "2079": 0.1485546976327896, "2102": 0.6654226183891296, "2135": 0.06795065850019455, "2166": 0.35128939151763916, "2184": 0.35677260160446167, "2243": 0.8366385698318481, "2278": 0.0058422754518687725, "2416": 0.259204238653183, "2433": 0.5450005531311035, "2487": 0.6980181336402893, "2509": 0.6522845029830933, "2512": 0.3381449282169342, "2515": 0.19622190296649933, "2535": 0.37371641397476196, "2537": 0.06703783571720123, "2549": 0.5168620347976685, "2552": 0.3325583338737488, "2575": 0.8366385698318481, "2590": 0.026025565341114998, "2669": 0.06429435312747955, "2719": 0.2983669638633728, "2765": 0.3485364317893982, "2832": 0.4909018874168396, "2895": 0.22157983481884003, "2920": 0.41195443272590637, "3031": 0.637939989566803, "3170": 0.0606246218085289, "3215": 0.35128939151763916, "3252": 0.5860490798950195, "3320": 1.437685251235962, "3370": 0.15693697333335876, "3372": 0.2394166737794876, "3436": 0.37907835841178894, "3463": 0.42096930742263794, "3491": 0.043007105588912964, "3526": 0.6160298585891724, "3596": 0.35334911942481995, "3625": 0.25239890813827515, "3670": 0.1873544454574585, "3723": 0.7018978595733643, "3754": 0.4818955361843109, "3800": 0.1693800985813141, "3853": 0.6613984704017639, "3930": 0.06977381557226181, "3936": 0.22392450273036957, "4013": 0.6441128253936768, "4072": 0.08961215615272522, "4106": 0.36086538434028625, "4114": 0.05139094591140747, "4157": 0.8957691192626953, "4160": 0.014542185701429844, "4168": 0.5033760666847229, "4187": 0.5696102976799011, "4194": 0.10731173306703568, "4195": 0.4855078160762787, "4242": 0.05046287178993225, "4395": 0.030771657824516296, "4397": 0.8004589080810547, "4442": 0.5893046259880066, "4490": 0.47463157773017883, "4506": 0.011650617234408855, "4517": 0.030771657824516296, "4758": 0.06795065850019455, "4809": 0.020300358533859253, "4842": 0.4537591338157654, "4957": 0.03360854089260101, "4962": 0.7610978484153748, "4972": 0.5562619566917419, "5072": 0.2719337046146393, "5090": 0.5685047507286072, "5100": 0.6394867897033691, "5158": 0.08513788133859634, "5179": 0.7863243818283081, "5214": 0.129004567861557, "5224": 0.13243216276168823, "5250": 0.2696990668773651, "5258": 0.04860413447022438, "5387": 1.0492360591888428, "5393": 0.2837681770324707, "5441": 0.4196864068508148, "5449": 0.6502478122711182, "5450": 0.1808556467294693, "5524": 0.8500841856002808, "5536": 0.9194108247756958, "5589": 0.5947071313858032, "5596": 0.7881022095680237, "5642": 0.11778303235769272, "5643": 0.4788752794265747, "5705": 0.25467249751091003, "5716": 0.3416208028793335, "5769": 0.36086538434028625, "5876": 0.757441520690918, "6032": 0.6517757177352905, "6064": 1.245482087135315, "6194": 0.22859740257263184, "6305": 0.9470623731613159, "6370": 0.10026945173740387, "6377": 0.4145384132862091, "6540": 0.5827828645706177, "6577": 0.11256109178066254, "6827": 0.025073638185858727, "7011": 0.21687394380569458, "7065": 0.0038986403960734606, "7127": 0.306306391954422, "7148": 0.026025565341114998, "7274": 0.7995813488960266, "7337": 0.804835319519043, "7342": 0.10731173306703568, "7366": 0.25995752215385437, "7403": 0.77198725938797, "7453": 0.08513788133859634, "7487": 0.5398913025856018, "7590": 0.10555581003427505, "7629": 0.014542185701429844, "7645": 0.08244366943836212, "7657": 0.32129061222076416, "7668": 0.5421652793884277, "7711": 0.3883931338787079, "7772": 0.7009293437004089, "7783": 0.02887592278420925, "7816": 0.39367714524269104, "7834": 0.3784096837043762, "7900": 0.3923587501049042, "8019": 0.016465263441205025, "8031": 0.817850649356842, "8156": 0.319873183965683, "8171": 0.24631060659885406, "8332": 0.3106105625629425, "8346": 0.4041621685028076, "8360": 0.6684301495552063, "8382": 0.5466978549957275, "8498": 0.32270604372024536, "8586": 0.19381128251552582, "8790": 0.052318159490823746, "8991": 0.32199856638908386, "9007": 0.7809720039367676, "9078": 1.039613962173462, "9165": 0.5968599319458008, "9211": 0.8682814836502075, "9240": 0.791648268699646, "9250": 0.2478361576795578, "9319": 0.3949938118457794, "9412": 0.36697331070899963, "9572": 0.2576959431171417, "9597": 0.025073638185858727, "9677": 0.014542185701429844, "9897": 0.176772341132164, "10077": 0.06886265426874161, "10232": 0.04953393340110779, "10266": 0.10203468054533005, "10288": 0.01934296265244484, "10381": 0.8813109993934631, "10572": 0.10467668622732162, "10595": 0.6327666640281677, "10737": 0.347847044467926, "10738": 0.11691460013389587, "10752": 0.7665573358535767, "10790": 1.1456648111343384, "10949": 0.2990913391113281, "11022": 0.23633737862110138, "11115": 0.7546905279159546, "11211": 1.1153976917266846, "11539": 0.1221139207482338, "11598": 0.6553317308425903, "11657": 0.41195443272590637, "11966": 0.1693800985813141, "12222": 0.4914994537830353, "12374": 0.2763880789279938, "12484": 0.12642613053321838, "12562": 0.014542185701429844, "12649": 0.1332872211933136, "12732": 0.8374842405319214, "12816": 0.058784693479537964, "12839": 0.5662899017333984, "12987": 0.42926809191703796, "13096": 0.056018441915512085, "13265": 0.3601844012737274, "13458": 0.861702561378479, "13490": 1.0030416250228882, "13502": 0.3339579105377197, "13776": 0.6165571808815002, "13806": 0.15526613593101501, "13922": 0.3304552733898163, "14045": 0.16276304423809052, "14080": 0.02792670577764511, "14140": 0.3723714053630829, "14187": 0.33953672647476196, "14193": 0.6543170213699341, "14228": 0.020300358533859253, "14321": 0.8117979168891907, "14471": 0.3526630103588104, "14526": 0.11691460013389587, "14627": 0.12986256182193756, "14751": 0.052318159490823746, "14774": 0.28743788599967957, "14800": 0.1485546976327896, "15059": 1.059443712234497, "15172": 0.5893046259880066, "15176": 0.6260011196136475, "15509": 0.8933739066123962, "15543": 0.3034266233444214, "15775": 0.6639154553413391, "16086": 0.11343330889940262, "16221": 0.175953671336174, "16285": 0.5057345628738403, "16371": 0.9440274834632874, "16463": 0.07612881064414978, "16706": 0.5336109399795532, "16730": 0.7969439625740051, "16731": 0.03925827145576477, "16910": 0.6902132034301758, "16935": 0.28082266449928284, "17009": 0.24325250089168549, "17257": 0.37035053968429565, "17344": 0.03925827145576477, "17379": 0.10291612148284912, "17409": 0.04113444685935974, "17703": 0.4794800877571106, "17720": 0.8109301924705505, "17782": 0.2105647772550583, "17908": 0.15359249711036682, "18231": 0.27786844968795776, "18426": 0.9583619832992554, "18499": 0.2852376699447632, "18514": 0.26820653676986694, "18549": 0.3443928062915802, "18856": 0.24248650670051575, "19137": 1.0927356481552124, "19274": 0.17431432008743286, "19387": 0.9333322048187256, "19601": 0.23402166366577148, "19653": 0.015504186972975731, "19661": 0.16524957120418549, "19780": 0.8013357520103455, "19806": 1.1128336191177368, "19817": 0.055094651877880096, "19872": 0.8756314516067505, "20232": 0.2954642176628113, "20250": 0.05046287178993225, "20299": 0.3339579105377197, "20363": 1.2488490343093872, "20544": 0.022212404757738113, "20817": 0.4926934838294983, "21053": 0.07159364968538284, "21114": 0.23247487843036652, "21312": 0.06977381557226181, "21365": 1.2499688863754272, "21557": 0.16607704758644104, "21575": 0.25995752215385437, "21618": 0.20739519596099854, "21647": 1.315486192703247, "21707": 0.13243216276168823, "21716": 1.061472773551941, "21821": 0.9123768210411072, "21903": 0.7500885725021362, "22090": 0.06612417846918106, "22248": 0.07068414986133575, "22415": 0.015504186972975731, "22644": 0.6538092494010925, "22869": 0.23710809648036957, "23572": 0.8332487344741821, "23737": 0.15023678541183472, "23767": 0.43244171142578125, "23931": 0.15526613593101501, "24054": 0.2089812457561493, "24203": 0.6773988008499146, "24312": 0.16276304423809052, "24473": 0.1994270235300064, "24689": 1.5728387832641602, "24731": 0.11691460013389587, "25003": 0.0752234235405922, "26244": 0.06429435312747955, "26285": 0.14602625370025635, "26402": 0.15275461971759796, "26462": 0.175953671336174, "26475": 0.23556606471538544, "26483": 0.06337817758321762, "26512": 0.056018441915512085, "26520": 0.31845372915267944, "26601": 0.10291612148284912, "26757": 1.0628231763839722, "26773": 0.7987030148506165, "26786": 0.07431721687316895, "26874": 0.33325836062431335, "26906": 0.15526613593101501, "26925": 0.3850763738155365, "26976": 0.9287132620811462, "27598": 0.0009760859538801014, "27642": 0.4879087805747986, "27777": 0.040196798741817474, "27790": 0.05139094591140747, "27854": 0.2018241584300995, "28024": 0.77198725938797, "28031": 0.3269403576850891, "28041": 0.22001366317272186, "28125": 0.49686139822006226, "28964": 0.19862671196460724} | 12588500 | Chromatin assembly factor 1 (CAF-1) and Rtt106 participate in the deposition of newly synthesized histones onto replicating DNA to form nucleosomes. This process is critical for the maintenance of genome stability and inheritance of functionally specialized chromatin structures in proliferating cells. However, the molecular functions of the acetylation of newly synthesized histones in this DNA replication-coupled nucleosome assembly pathway remain enigmatic. Here we show that histone H3 acetylated at lysine 56 (H3K56Ac) is incorporated onto replicating DNA and, by increasing the binding affinity of CAF-1 and Rtt106 for histone H3, H3K56Ac enhances the ability of these histone chaperones to assemble DNA into nucleosomes. Genetic analysis indicates that H3K56Ac acts in a nonredundant manner with the acetylation of the N-terminal residues of H3 and H4 in nucleosome assembly. These results reveal a mechanism by which H3K56Ac regulates replication-coupled nucleosome assembly mediated by CAF-1 and Rtt106. | Acetylation of Histone H3 Lysine 56 Regulates Replication-Coupled Nucleosome Assembly |
{"1011": 0.3877306580543518, "1041": 0.5903874635696411, "1048": 0.021256839856505394, "1051": 0.045809537172317505, "1055": 0.7934166193008423, "1056": 0.22782009840011597, "1999": 0.14264501631259918, "2003": 0.2689530849456787, "2004": 0.13670019805431366, "2011": 0.34922540187835693, "2015": 1.2421036958694458, "2029": 0.06429435312747955, "2064": 0.15943801403045654, "2079": 0.176772341132164, "2140": 0.3141832649707794, "2152": 0.23324857652187347, "2174": 0.23402166366577148, "2184": 0.09672962874174118, "2213": 0.3374483287334442, "2229": 0.02412080205976963, "2291": 0.151916041970253, "2339": 0.14686977863311768, "2348": 0.19622190296649933, "2358": 0.3077431619167328, "2416": 0.04860413447022438, "2475": 0.27044451236724854, "2482": 0.6160298585891724, "2487": 0.07884006202220917, "2489": 0.40351006388664246, "2504": 0.1384023278951645, "2509": 0.29036402702331543, "2515": 0.5232481360435486, "2519": 0.6608943343162537, "2521": 1.0973093509674072, "2529": 0.24401791393756866, "2531": 0.6155022978782654, "2535": 0.011650617234408855, "2552": 0.4709797203540802, "2575": 0.7389566898345947, "2582": 0.12038381397724152, "2594": 0.3339579105377197, "2638": 0.0752234235405922, "2750": 0.2881702482700348, "2753": 0.6043586730957031, "2777": 0.2969166338443756, "2794": 0.2089812457561493, "2822": 0.7096124291419983, "2828": 0.00875066313892603, "2844": 0.006812678650021553, "2859": 0.44753631949424744, "2863": 0.3777405619621277, "2871": 0.09228714555501938, "2895": 0.42225050926208496, "2971": 0.38905516266822815, "2981": 0.32199856638908386, "3001": 0.26446542143821716, "3027": 1.5075435638427734, "3064": 0.4531385898590088, "3117": 0.7276995778083801, "3141": 0.14518201351165771, "3161": 0.026976587250828743, "3210": 0.04767346754670143, "3223": 0.26146242022514343, "3226": 0.3949938118457794, "3252": 0.14602625370025635, "3283": 0.012615402229130268, "3284": 0.0009760859538801014, "3329": 0.5551415085792542, "3366": 0.3519764244556427, "3367": 0.04394211992621422, "3370": 0.6808650493621826, "3406": 0.6734226942062378, "3424": 0.15023678541183472, "3466": 0.45870962738990784, "3481": 0.3923587501049042, "3497": 0.18248429894447327, "3501": 0.6027565002441406, "3508": 0.010684899985790253, "3526": 0.736154317855835, "3528": 0.18167030811309814, "3560": 0.04487626627087593, "3619": 0.5021947622299194, "3653": 0.7009293437004089, "3686": 0.4879087805747986, "3723": 0.48068851232528687, "3768": 0.5816917419433594, "3772": 0.31204116344451904, "3796": 0.6389714479446411, "3798": 0.30989447236061096, "3853": 0.10993985831737518, "3896": 0.3485364317893982, "3930": 0.7473171949386597, "4005": 0.1710275560617447, "4084": 0.05694137513637543, "4286": 0.10291612148284912, "4297": 0.04487626627087593, "4319": 0.7210738658905029, "4359": 0.21135559678077698, "4406": 0.06520967930555344, "4442": 0.8091925978660583, "4456": 0.18978065252304077, "4490": 0.5393219590187073, "4539": 0.1946154683828354, "4621": 0.04113444685935974, "4654": 0.1873544454574585, "4659": 0.6265231370925903, "4675": 0.036437395960092545, "4757": 0.6075552701950073, "4863": 0.06520967930555344, "4890": 0.6892333030700684, "4903": 0.33675122261047363, "4962": 0.28963330388069153, "4982": 0.16442140936851501, "5072": 0.3388410806655884, "5144": 0.13157635927200317, "5159": 0.2478361576795578, "5250": 0.7417513132095337, "5267": 0.9769153594970703, "5292": 0.2317005842924118, "5360": 0.4462870955467224, "5410": 0.8264343738555908, "5449": 0.1994270235300064, "5450": 0.05139094591140747, "5536": 0.9052929878234863, "5547": 0.28670501708984375, "5566": 0.0606246218085289, "5596": 0.46117570996284485, "5648": 0.9123768210411072, "5850": 0.6980181336402893, "5991": 0.40285754203796387, "6064": 0.472198486328125, "6074": 0.17759032547473907, "6238": 0.7172679901123047, "6310": 0.06429435312747955, "6364": 0.29255300760269165, "6370": 0.07612881064414978, "6459": 0.07431721687316895, "6494": 0.5483922958374023, "6600": 0.7881022095680237, "6693": 0.49982786178588867, "6761": 0.956112265586853, "6897": 0.056018441915512085, "6914": 0.6327666640281677, "6975": 0.9650808572769165, "7020": 0.3464667797088623, "7065": 0.1485546976327896, "7148": 1.0601204633712769, "7328": 0.011650617234408855, "7337": 0.25845035910606384, "7342": 0.2711893916130066, "7366": 0.23556606471538544, "7461": 0.6022219061851501, "7473": 0.3325583338737488, "7512": 0.574020504951477, "7704": 0.44691193103790283, "7790": 0.8731874823570251, "7889": 0.0174254160374403, "7901": 0.7737906575202942, "7977": 0.6312094330787659, "8000": 0.2160874605178833, "8031": 0.7239188551902771, "8153": 0.3339579105377197, "8171": 0.6911921501159668, "8290": 0.045809537172317505, "8335": 0.09761575609445572, "8360": 0.21293537318706512, "8516": 0.7537717819213867, "8520": 0.6502478122711182, "8534": 0.06886265426874161, "8578": 0.1994270235300064, "8583": 0.13670019805431366, "8590": 0.7987030148506165, "8602": 0.966567873954773, "8651": 0.7426811456680298, "8715": 0.15023678541183472, "8736": 0.18004031479358673, "8758": 0.8829278349876404, "8820": 0.8925741910934448, "9007": 0.9747070074081421, "9048": 0.7925328612327576, "9078": 0.6420594453811646, "9096": 0.034552380442619324, "9099": 1.20884370803833, "9152": 0.3177432417869568, "9174": 0.4196864068508148, "9308": 0.15943801403045654, "9350": 0.9447870850563049, "9413": 0.417115718126297, "9416": 0.007782140281051397, "9690": 0.4654768109321594, "9998": 0.19381128251552582, "10109": 0.9100211262702942, "10322": 0.619189441204071, "10415": 0.5696102976799011, "10572": 0.8600510358810425, "10610": 0.040196798741817474, "10654": 0.6563454270362854, "10708": 0.15693697333335876, "10755": 0.5215105414390564, "10804": 0.41065993905067444, "10851": 0.5517725944519043, "10882": 0.4831010699272156, "10938": 0.5404602885246277, "11022": 0.5381823778152466, "11099": 0.5718178153038025, "11158": 0.3850763738155365, "11251": 0.5618454217910767, "11382": 0.3615458607673645, "11432": 0.7791815400123596, "11463": 0.6583697199821472, "11674": 0.5244048833847046, "11704": 0.5116065740585327, "11835": 0.11517547070980072, "11841": 0.8366385698318481, "12328": 0.36426326632499695, "12377": 0.6950984001159668, "12521": 0.3588210940361023, "12530": 0.151916041970253, "12562": 0.1946154683828354, "12618": 0.7872136831283569, "12702": 0.9531047344207764, "12737": 0.6970458030700684, "12765": 0.010684899985790253, "12837": 0.4145384132862091, "12972": 0.9994535446166992, "12987": 0.304147332906723, "13004": 0.1485546976327896, "13070": 0.2990913391113281, "13096": 0.1685553640127182, "13228": 0.06246116757392883, "13306": 0.016465263441205025, "13416": 0.24631060659885406, "13490": 0.659380316734314, "13531": 0.24171993136405945, "13776": 0.8152611255645752, "13791": 0.083342544734478, "13806": 0.2539152204990387, "13819": 0.791648268699646, "13859": 0.1064341589808464, "13922": 0.26446542143821716, "13995": 0.2470736801624298, "14031": 0.16442140936851501, "14061": 0.5540198087692261, "14080": 0.04767346754670143, "14087": 0.22392450273036957, "14095": 0.28082266449928284, "14181": 0.669430673122406, "14187": 0.24018502235412598, "14667": 0.2918238639831543, "14719": 0.01934296265244484, "14956": 0.12728634476661682, "14971": 0.36697331070899963, "15115": 0.9900637865066528, "15222": 0.8699195384979248, "15316": 0.21372433006763458, "15460": 0.0842406153678894, "15472": 0.5290185213088989, "15527": 0.14602625370025635, "15608": 0.2852376699447632, "15663": 0.2800849378108978, "15863": 0.31845372915267944, "16007": 0.012615402229130268, "16081": 0.06886265426874161, "16150": 0.2749055027961731, "16285": 0.791648268699646, "16305": 0.6744182109832764, "16389": 0.11256109178066254, "16505": 0.29036402702331543, "16627": 0.09761575609445572, "16771": 0.04207121208310127, "16824": 0.09317722171545029, "16834": 0.8525851964950562, "16942": 0.5551415085792542, "17379": 0.3601844012737274, "17663": 0.05970508232712746, "17666": 0.12470348179340363, "17703": 0.3526630103588104, "17727": 0.022212404757738113, "17903": 0.3995884954929352, "18044": 0.014542185701429844, "18178": 0.0842406153678894, "18260": 0.2516399025917053, "18639": 0.3141832649707794, "18714": 0.2034190446138382, "18908": 0.10993985831737518, "19425": 0.14686977863311768, "19476": 0.7201237678527832, "19653": 0.46363574266433716, "19817": 0.23710809648036957, "19872": 0.021256839856505394, "20194": 0.083342544734478, "20232": 0.02316705882549286, "20250": 0.20977331697940826, "20303": 0.1229778528213501, "20492": 0.7881022095680237, "20710": 1.0030416250228882, "20752": 0.0797421783208847, "20770": 0.011650617234408855, "20817": 0.3743882179260254, "20939": 0.1751343309879303, "20992": 0.07250232994556427, "21150": 0.04860413447022438, "21230": 0.015504186972975731, "21639": 0.5712664127349854, "21743": 0.22782009840011597, "21800": 0.03360854089260101, "21865": 0.5427330136299133, "21903": 0.42225050926208496, "22119": 0.29036402702331543, "22154": 0.08603433519601822, "22214": 0.058784693479537964, "22248": 0.034552380442619324, "22330": 0.6699305176734924, "22423": 0.40089741349220276, "22618": 0.10203468054533005, "22694": 0.0770333781838417, "22930": 0.07884006202220917, "22931": 0.21765978634357452, "23021": 0.11343330889940262, "23096": 0.020300358533859253, "23150": 0.02412080205976963, "23163": 0.3995884954929352, "23217": 0.009718249551951885, "23310": 0.08603433519601822, "23586": 0.8877626657485962, "23725": 0.6916812658309937, "23737": 0.05786345899105072, "23797": 0.06520967930555344, "23924": 0.6312094330787659, "23943": 0.8039615154266357, "24004": 0.8272887468338013, "24012": 0.29328158497810364, "24054": 1.2566616535186768, "24171": 0.5662899017333984, "24269": 0.35950297117233276, "24278": 0.25467249751091003, "24324": 0.48068851232528687, "24479": 0.15023678541183472, "24972": 0.48068851232528687, "25003": 1.180456280708313, "25117": 0.18248429894447327, "25456": 1.024303913116455, "25714": 0.8550800085067749, "25937": 0.0019512200960889459, "26206": 0.14433705806732178, "26244": 0.026025565341114998, "26402": 1.2392796277999878, "26702": 0.19220098853111267, "26754": 0.09850110858678818, "27144": 0.2145126610994339, "27268": 0.6709295511245728, "27709": 0.7934166193008423, "27781": 0.12986256182193756, "27854": 0.04207121208310127, "28156": 0.10555581003427505, "28517": 0.0038986403960734606, "28522": 0.7647408246994019, "28691": 0.17922431230545044, "28873": 0.7683706283569336, "28976": 0.23787821829319, "29090": 0.15023678541183472, "29290": 0.14095009863376617, "29491": 0.6862877607345581} | 12622860 | S-trans,trans-Farnesylthiosalicylic acid (FTS) is a novel farnesylated rigid carboxylic acid derivative. In cell-free systems, it acts as a potent competitive inhibitor (Ki = 2.6 microM) of the enzyme prenylated protein methyltransferase (PPMTase), which methylates the carboxyl-terminal S-prenylcysteine in a large number of prenylated proteins including Ras. In such systems, FTS inhibits Ras methylation but not Ras farnesylation. Inhibition of the PPMTase by FTS in homogenates or membranes of a variety of tissues and cell lines is inferred from a block in the methylation of exogenously added substrates such as N-acetyl-S-trans,trans-farnesyl-L-cysteine and of endogenous substrates including small GTP-binding proteins. FTS can also inhibit methylation of these proteins in intact cells (e.g. in Rat-1 fibroblasts, Ras-transformed Rat-1, and B16 melanoma cells). Unlike in cell-free systems, however, relatively high concentrations of FTS (50-100 microM) are required for partial blocking (10-40%) of protein methylation in the intact cells. Thus, FTS is a weak inhibitor of methylation in intact cells. Because methylation is the last step in the processing of Ras and related proteins, FTS is not likely to affect steps that precede it, e.g. protein prenylation. This may explain why the growth and gross morphology of a variety of cultured cell types (including Chinese hamster ovary, NIH3T3, Rat1, B16 melanoma, and PC12) is not affected by up to 25 microM FTS and is consistent with the observed lack of FTS-induced cytotoxicity. Nevertheless, FTS reduces the levels of Ras in cell membranes and can inhibit Ras-dependent cell growth in vitro, independently of methylation. It inhibits the growth of human Ha-ras-transformed cells (EJ cells) and reverses their transformed morphology in a dose-dependent manner (0.1-10 microM). The drug does not interfere with the growth of cells transformed by v-Raf or T-antigen but inhibits the growth of ErbB2-transformed cells and blocks the mitogenic effects of epidermal and basic fibroblast growth factors, thus implying its selectivity toward Ras growth signaling, possibly via modulation of Ras-Raf communication. Taken together, the results raise the possibility that FTS may specifically interfere with the interaction of Ras with a farnesylcysteine recognition domain in the cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS) | Selective inhibition of Ras-dependent cell growth by farnesylthiosalisylic acid. |
{"1009": 0.2881702482700348, "1011": 0.10731173306703568, "1016": 0.22782009840011597, "1039": 0.5376120805740356, "1044": 0.07612881064414978, "1049": 0.29619070887565613, "1055": 0.3409265875816345, "1058": 0.12470348179340363, "1060": 0.20102575421333313, "1996": 0.045809537172317505, "1999": 0.1946154683828354, "2005": 0.2516399025917053, "2008": 0.0317181795835495, "2011": 0.08871890604496002, "2015": 0.7105726003646851, "2029": 0.40806588530540466, "2053": 1.1166772842407227, "2062": 0.20660123229026794, "2076": 0.06154331564903259, "2084": 0.4974553883075714, "2087": 0.09406650811433792, "2094": 0.2231435477733612, "2119": 0.16607704758644104, "2152": 0.052318159490823746, "2179": 0.21530038118362427, "2203": 0.5127768516540527, "2290": 0.4431571960449219, "2349": 0.10555581003427505, "2350": 0.5370414853096008, "2365": 0.4980490207672119, "2377": 0.0174254160374403, "2389": 0.2983669638633728, "2427": 0.5773153901100159, "2475": 1.1051015853881836, "2487": 0.30917787551879883, "2504": 0.22157983481884003, "2512": 0.07431721687316895, "2515": 0.16524957120418549, "2529": 0.6400018334388733, "2535": 0.7491656541824341, "2537": 0.7067264318466187, "2550": 0.5104349255561829, "2556": 0.04953393340110779, "2590": 0.09761575609445572, "2595": 1.216395378112793, "2618": 0.4537591338157654, "2683": 0.684319257736206, "2692": 0.10906458646059036, "2734": 0.04860413447022438, "2748": 0.13071982562541962, "2892": 0.8925741910934448, "2895": 0.08871890604496002, "2920": 0.2447827309370041, "2944": 0.5174443125724792, "3020": 0.5393219590187073, "3161": 0.6512666940689087, "3223": 0.4196864068508148, "3248": 0.2145126610994339, "3273": 0.09050461649894714, "3284": 0.2852376699447632, "3351": 0.025073638185858727, "3366": 0.9052929878234863, "3378": 0.11517547070980072, "3433": 0.27342069149017334, "3445": 0.40546512603759766, "3450": 0.5415972471237183, "3466": 0.0752234235405922, "3491": 0.25995752215385437, "3517": 0.5220900774002075, "3526": 0.7746911644935608, "3560": 0.3622259199619293, "3591": 0.5232481360435486, "3595": 0.06886265426874161, "3618": 0.22782009840011597, "3623": 0.29036402702331543, "3625": 0.25239890813827515, "3630": 0.2394166737794876, "3662": 0.07159364968538284, "3670": 0.8109301924705505, "3728": 0.1685553640127182, "3739": 0.3588210940361023, "3755": 0.129004567861557, "3798": 0.43875885009765625, "3853": 0.2881702482700348, "3893": 0.0029254043474793434, "3904": 0.15359249711036682, "3965": 0.34508460760116577, "4023": 0.9531047344207764, "4072": 0.16110190749168396, "4106": 0.10731173306703568, "4187": 0.6578640341758728, "4195": 0.0009760859538801014, "4275": 0.23556606471538544, "4286": 0.5267143249511719, "4295": 0.3485364317893982, "4395": 0.6170841455459595, "4442": 0.9302552938461304, "4456": 0.4431571960449219, "4489": 0.08154398202896118, "4496": 0.5209306478500366, "4539": 0.08871890604496002, "4570": 0.04113444685935974, "4588": 0.056018441915512085, "4625": 0.3012613356113434, "4652": 0.5990082025527954, "4654": 0.020300358533859253, "4668": 0.04113444685935974, "4758": 0.2184450328350067, "4812": 0.1685553640127182, "4962": 0.2741633653640747, "4972": 0.10993985831737518, "5022": 0.4093637466430664, "5072": 0.2231435477733612, "5153": 0.3485364317893982, "5155": 0.10906458646059036, "5173": 0.4926934838294983, "5228": 0.3519764244556427, "5250": 0.31204116344451904, "5326": 0.2969166338443756, "5387": 0.1221139207482338, "5402": 0.025073638185858727, "5531": 0.4891071021556854, "5589": 0.38174858689308167, "5648": 0.8813109993934631, "5666": 0.9021284580230713, "5688": 0.18978065252304077, "5776": 0.33953672647476196, "5887": 1.1870332956314087, "5942": 0.05139094591140747, "6020": 0.06795065850019455, "6064": 0.1477125883102417, "6296": 0.0842406153678894, "6370": 0.053244512528181076, "6428": 0.02887592278420925, "6438": 0.48068851232528687, "6583": 0.04207121208310127, "6612": 0.018384648486971855, "6693": 0.07068414986133575, "6705": 0.8357921838760376, "6827": 0.15526613593101501, "6887": 0.8649974465370178, "6955": 0.07159364968538284, "7137": 0.306306391954422, "7337": 0.18654440343379974, "7366": 0.27786844968795776, "7457": 0.3409265875816345, "7461": 0.17431432008743286, "7645": 0.3560888469219208, "7646": 0.06886265426874161, "7694": 0.49626702070236206, "7711": 0.2881702482700348, "7722": 0.966567873954773, "7730": 0.08513788133859634, "7810": 0.0770333781838417, "7816": 0.6629094481468201, "7821": 0.4770587682723999, "7870": 0.23092569410800934, "7939": 0.9115922451019287, "7965": 0.18329764902591705, "8000": 1.1076855659484863, "8114": 0.7583568692207336, "8122": 0.5696102976799011, "8153": 0.22001366317272186, "8171": 0.20977331697940826, "8290": 0.0606246218085289, "8312": 0.7782850861549377, "8319": 0.1384023278951645, "8449": 0.7398891448974609, "8458": 1.0655186176300049, "8524": 1.0464962720870972, "8528": 0.07431721687316895, "8556": 0.20660123229026794, "8670": 0.6301699280738831, "8729": 0.5596157908439636, "8733": 0.04767346754670143, "8757": 0.6654226183891296, "8776": 0.0174254160374403, "8878": 0.27564704418182373, "9007": 0.9005423784255981, "9031": 1.0560526847839355, "9096": 0.03925827145576477, "9305": 0.6773988008499146, "9350": 0.25088030099868774, "9412": 0.0009760859538801014, "9597": 0.07068414986133575, "9885": 0.4067663550376892, "9962": 0.0174254160374403, "10232": 0.052318159490823746, "10266": 0.012615402229130268, "10327": 0.5301685929298401, "10509": 0.17431432008743286, "10548": 0.5882205963134766, "10723": 0.32058215141296387, "10737": 0.09850110858678818, "10738": 0.2622140049934387, "10744": 0.3084607720375061, "10841": 0.3923587501049042, "10847": 0.3388410806655884, "10886": 0.2184450328350067, "10893": 0.045809537172317505, "11022": 0.9263957738876343, "11311": 0.8408597707748413, "11423": 0.23324857652187347, "11432": 0.19622190296649933, "11538": 0.04674193635582924, "11598": 0.09584271162748337, "11636": 0.5767669677734375, "11643": 0.06154331564903259, "11787": 0.32129061222076416, "11888": 0.5244048833847046, "12115": 0.05694137513637543, "12222": 0.5562619566917419, "12328": 1.0444365739822388, "12436": 0.574020504951477, "12562": 0.08603433519601822, "12604": 0.6275664567947388, "12649": 1.068206787109375, "12702": 0.08782484382390976, "12732": 0.06886265426874161, "12737": 0.34508460760116577, "12987": 0.12556517124176025, "13024": 0.5433003902435303, "13345": 0.15693697333335876, "13445": 0.37974658608436584, "13626": 0.757441520690918, "13656": 0.7610978484153748, "13791": 0.20022670924663544, "13833": 0.08961215615272522, "13922": 0.36086538434028625, "14045": 0.8161250352859497, "14061": 0.1751343309879303, "14067": 0.18167030811309814, "14193": 0.09850110858678818, "14228": 0.1718502640724182, "14246": 0.6892333030700684, "14357": 0.35745587944984436, "14384": 0.4770587682723999, "14828": 0.058784693479537964, "15009": 0.6022219061851501, "15176": 0.45994341373443604, "15306": 0.030771657824516296, "15403": 0.9710156321525574, "15527": 0.23864774405956268, "15663": 0.030771657824516296, "15680": 0.8658194541931152, "15772": 0.030771657824516296, "16263": 0.6950984001159668, "16285": 0.7295845746994019, "16305": 0.1011524572968483, "16335": 0.11081436276435852, "16371": 0.13071982562541962, "16389": 0.15943801403045654, "16519": 0.16524957120418549, "16578": 0.14518201351165771, "16706": 0.5838727951049805, "16771": 0.09761575609445572, "16839": 0.37102460861206055, "17250": 0.17020416259765625, "17257": 0.5398913025856018, "17341": 0.14518201351165771, "17379": 0.2837681770324707, "17404": 0.1510767638683319, "17441": 0.04860413447022438, "17698": 0.014542185701429844, "17843": 0.7601850032806396, "17908": 0.14349138736724854, "17913": 0.41195443272590637, "17926": 0.10818854719400406, "18037": 0.004870930220931768, "18089": 0.04674193635582924, "18216": 0.26146242022514343, "18228": 0.43938836455345154, "18234": 0.7258110046386719, "18260": 0.5151132941246033, "18291": 0.6882523894309998, "18684": 0.20421554148197174, "18714": 0.4126010537147522, "18715": 0.09761575609445572, "18757": 0.4914994537830353, "18845": 0.6233867406845093, "18847": 0.3241194784641266, "18900": 0.7737906575202942, "19293": 0.1970241367816925, "19332": 0.3141832649707794, "19478": 0.9052929878234863, "19500": 0.014542185701429844, "19577": 0.5662899017333984, "19612": 0.23402166366577148, "19653": 0.3106105625629425, "19872": 0.18816383183002472, "20303": 0.2478361576795578, "20360": 0.0797421783208847, "20544": 0.24401791393756866, "20752": 0.2561853528022766, "20843": 0.6867793202400208, "20958": 0.1384023278951645, "20996": 1.0802149772644043, "21150": 0.02412080205976963, "21162": 0.8195732831954956, "21252": 0.18492233753204346, "21357": 0.28082266449928284, "21434": 0.5562619566917419, "21471": 0.07884006202220917, "21486": 0.10203468054533005, "21575": 0.2990913391113281, "21618": 0.26296505331993103, "21685": 0.1229778528213501, "21890": 0.6872705817222595, "21903": 0.32129061222076416, "22330": 0.08692999184131622, "22643": 1.0257055759429932, "22916": 0.04487626627087593, "22931": 0.4926934838294983, "23041": 0.5756692886352539, "23060": 1.0506030321121216, "23233": 1.4358283281326294, "23586": 0.42544642090797424, "23618": 0.030771657824516296, "23692": 1.3635773658752441, "23797": 0.1221139207482338, "23807": 0.0174254160374403, "23900": 0.01934296265244484, "23943": 0.04953393340110779, "24054": 0.9139442443847656, "24171": 0.7638313174247742, "24260": 0.2976420819759369, "24491": 0.03360854089260101, "25002": 0.11256109178066254, "25172": 0.472198486328125, "25426": 0.678390383720398, "25456": 0.7067264318466187, "25605": 1.1481462717056274, "25644": 0.06154331564903259, "25714": 0.10818854719400406, "26218": 0.009718249551951885, "26282": 0.0752234235405922, "26402": 0.520350456237793, "26520": 0.2160874605178833, "26524": 0.18978065252304077, "26632": 0.6244332790374756, "26773": 0.5370414853096008, "26807": 0.040196798741817474, "26835": 0.45870962738990784, "26874": 0.2561853528022766, "27321": 0.8534175157546997, "27642": 0.7370892763137817, "27781": 0.38574060797691345, "28156": 0.32553088665008545, "28309": 0.05694137513637543, "28479": 0.16359257698059082, "28691": 0.07612881064414978, "28775": 0.6793810129165649, "28788": 0.22626367211341858, "28835": 0.4450363218784332, "28873": 1.0894558429718018, "28896": 0.05970508232712746} | 12631182 | The phagocyte NADPH oxidase (NOX2) is critical for the bactericidal activity of phagocytic cells and plays a major role in innate immunity. We showed recently that NOX2 activity in mouse dendritic cells (DCs) prevents acidification of phagosomes, promoting antigen cross-presentation. In order to investigate the role of NOX2 in the regulation of the phagosomal pH in human DCs, we analyzed the production of reactive oxygen species (ROS) and the phagosomal/endosomal pH in monocyte-derived DCs and macrophages (M(diameter)s) from healthy donors or patients with chronic granulomatous disease (CGD). As expected, we found that human M(diameter)s acidify their phagosomes more efficiently than human DCs. Accordingly, the expression of the vacuolar proton ATPase (V-H(+)-ATPase) was higher in M(diameter)s than in DCs. Phagosomal ROS production, however, was also higher in M(diameter)s than in DCs, due to higher levels of gp91phox expression and recruitment to phagosomes. In contrast, in the absence of active NOX2, the phagosomal and endosomal pH decreased. Both in the presence of a NOX2 inhibitor and in DCs derived from patients with CGD, the cross-presentation of 2 model tumor antigens was impaired. We conclude that NOX2 activity participates in the regulation of the phagosomal and endosomal pH in human DCs, and is required for efficient antigen cross-presentation. | NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells. |
{"1011": 0.3662964701652527, "1021": 0.3916989266872406, "1039": 0.3443928062915802, "2000": 0.025073638185858727, "2004": 0.004870930220931768, "2005": 0.28963330388069153, "2023": 0.1332872211933136, "2043": 0.14095009863376617, "2044": 0.083342544734478, "2047": 0.23092569410800934, "2076": 0.07068414986133575, "2078": 0.5162794589996338, "2079": 0.2089812457561493, "2089": 0.03831886500120163, "2090": 0.1751343309879303, "2094": 0.35128939151763916, "2109": 0.13157635927200317, "2135": 0.1602703034877777, "2138": 0.2447827309370041, "2187": 0.29328158497810364, "2193": 0.09228714555501938, "2207": 0.08782484382390976, "2235": 0.6202403903007507, "2239": 0.09406650811433792, "2271": 0.11951763927936554, "2309": 0.5500838756561279, "2339": 0.45994341373443604, "2348": 0.0606246218085289, "2349": 0.05139094591140747, "2378": 0.1913948506116867, "2401": 0.5968599319458008, "2418": 0.8534175157546997, "2458": 0.011650617234408855, "2459": 0.040196798741817474, "2486": 0.9092346429824829, "2515": 0.4145384132862091, "2535": 0.02412080205976963, "2537": 0.5168620347976685, "2550": 0.036437395960092545, "2552": 0.7352184057235718, "2581": 1.1994705200195312, "2629": 0.037378571927547455, "2698": 0.08244366943836212, "2713": 0.25694093108177185, "2749": 0.6249561905860901, "2764": 0.5415972471237183, "2765": 0.5640701055526733, "2844": 0.4574742913246155, "2855": 0.0058422754518687725, "2895": 0.129004567861557, "2944": 0.6296497583389282, "2962": 0.1401015669107437, "2966": 0.040196798741817474, "3024": 0.040196798741817474, "3073": 0.14095009863376617, "3132": 0.960606575012207, "3161": 0.10993985831737518, "3177": 0.03925827145576477, "3202": 0.49982786178588867, "3276": 0.567397952079773, "3283": 0.11517547070980072, "3375": 1.0116009712219238, "3426": 0.1693800985813141, "3433": 0.8247235417366028, "3435": 0.8255793452262878, "3445": 0.45623743534088135, "3446": 0.6075552701950073, "3447": 0.5104349255561829, "3450": 0.3248254358768463, "3463": 0.6456501483917236, "3466": 0.272677481174469, "3486": 0.3241194784641266, "3490": 0.06886265426874161, "3491": 0.33605360984802246, "3550": 0.3683255612850189, "3558": 0.7408206462860107, "3623": 0.7491656541824341, "3640": 0.1693800985813141, "3642": 0.41001203656196594, "3669": 0.5618454217910767, "3853": 0.637939989566803, "3896": 0.3297532796859741, "3905": 0.6911921501159668, "3921": 0.6451379656791687, "3940": 0.6202403903007507, "3949": 0.23710809648036957, "3965": 0.06154331564903259, "3989": 0.854249119758606, "3997": 0.906871497631073, "4023": 0.672426164150238, "4030": 0.3241194784641266, "4115": 0.2018241584300995, "4167": 0.04674193635582924, "4263": 0.8298473954200745, "4275": 0.3870677351951599, "4295": 0.8247235417366028, "4304": 0.7352184057235718, "4359": 0.3870677351951599, "4490": 0.1970241367816925, "4503": 0.25088030099868774, "4504": 0.1970241367816925, "4525": 0.24325250089168549, "4539": 0.0038986403960734606, "4555": 0.3656192123889923, "4588": 0.17922431230545044, "4632": 0.08961215615272522, "4647": 0.0354953333735466, "4668": 0.18816383183002472, "4728": 0.1889725625514984, "4852": 0.34023189544677734, "4942": 0.06429435312747955, "4972": 0.22782009840011597, "4975": 0.10379679501056671, "5013": 0.0606246218085289, "5072": 0.01934296265244484, "5084": 0.15693697333335876, "5098": 0.8861536383628845, "5110": 0.4203280806541443, "5114": 0.25694093108177185, "5301": 0.4891071021556854, "5320": 0.25995752215385437, "5333": 0.3027053773403168, "5335": 0.7009293437004089, "5387": 0.022212404757738113, "5393": 0.016465263441205025, "5410": 0.8450632095336914, "5422": 0.052318159490823746, "5429": 0.13157635927200317, "5449": 0.018384648486971855, "5468": 0.07341018319129944, "5514": 0.2231435477733612, "5546": 0.37304413318634033, "5547": 0.15610189735889435, "5643": 0.31204116344451904, "5670": 0.27934664487838745, "5787": 0.10467668622732162, "5838": 0.0029254043474793434, "5850": 0.06612417846918106, "5901": 0.13755162060260773, "5915": 0.44691193103790283, "6026": 0.3750596046447754, "6075": 0.6872705817222595, "6091": 0.3519764244556427, "6165": 0.15275461971759796, "6218": 0.9271688461303711, "6234": 0.2881702482700348, "6428": 0.3027053773403168, "6434": 0.021256839856505394, "6537": 0.1229778528213501, "6591": 0.5963221788406372, "6648": 0.5162794589996338, "6650": 1.0546929836273193, "6666": 0.18573370575904846, "6726": 0.7258110046386719, "6740": 1.202995777130127, "6789": 0.006812678650021553, "6869": 0.34715715050697327, "6912": 0.29981520771980286, "7068": 0.08064348995685577, "7189": 0.09495500475168228, "7242": 0.6813592314720154, "7274": 0.04674193635582924, "7312": 0.6011518239974976, "7337": 0.26820653676986694, "7361": 0.8682814836502075, "7438": 0.05046287178993225, "7457": 0.6405166387557983, "7461": 0.05046287178993225, "7591": 0.06612417846918106, "7606": 1.1141164302825928, "7620": 0.4196864068508148, "7645": 0.25694093108177185, "7652": 0.469759464263916, "7689": 0.6011518239974976, "7775": 0.05139094591140747, "7870": 0.6054253578186035, "7915": 0.3019835948944092, "7953": 1.0855059623718262, "8031": 0.8780695199966431, "8107": 0.5174443125724792, "8114": 0.5651806592941284, "8122": 0.7239188551902771, "8161": 0.15442965924739838, "8290": 0.18411032855510712, "8346": 0.14349138736724854, "8360": 0.2026219218969345, "8377": 0.2976420819759369, "8382": 0.21530038118362427, "8564": 0.5483922958374023, "8715": 0.20818853378295898, "8761": 0.1913948506116867, "8878": 0.7546905279159546, "9007": 0.2674594223499298, "9031": 0.0009760859538801014, "9113": 0.9186317324638367, "9211": 0.07250232994556427, "9229": 0.37371641397476196, "9276": 0.23556606471538544, "9331": 0.619189441204071, "9412": 0.27044451236724854, "9495": 0.0797421783208847, "9509": 0.304147332906723, "9560": 0.09761575609445572, "9672": 0.14264501631259918, "9742": 0.29981520771980286, "9771": 0.09938567131757736, "9885": 0.1510767638683319, "9998": 0.3262358605861664, "10057": 0.39893341064453125, "10222": 1.1610734462738037, "10250": 0.026976587250828743, "10473": 0.037378571927547455, "10479": 0.14602625370025635, "10509": 0.13755162060260773, "10548": 0.22079704701900482, "10556": 0.04207121208310127, "10572": 0.03831886500120163, "10616": 0.3304552733898163, "10627": 0.6358738541603088, "10698": 1.179255723953247, "10737": 0.5584990978240967, "10803": 0.36290550231933594, "10840": 0.13670019805431366, "10960": 0.34922540187835693, "10976": 0.7473171949386597, "11211": 0.0913962796330452, "11251": 1.0999135971069336, "11265": 0.6734226942062378, "11444": 0.8366385698318481, "11598": 0.2689530849456787, "11643": 0.3519764244556427, "11835": 0.0009760859538801014, "11855": 0.1332872211933136, "11860": 0.3262358605861664, "11917": 0.10379679501056671, "11923": 0.129004567861557, "11937": 0.2409527748823166, "12014": 0.39893341064453125, "12031": 0.6254787445068359, "12154": 0.1889725625514984, "12247": 0.20660123229026794, "12363": 0.2976420819759369, "12411": 0.7096124291419983, "12448": 0.083342544734478, "12546": 0.4531385898590088, "12919": 0.41065993905067444, "12992": 0.05694137513637543, "13004": 0.46117570996284485, "13012": 0.11256109178066254, "13105": 0.13499516248703003, "13139": 0.27712854743003845, "13221": 0.0317181795835495, "13228": 0.7951818704605103, "13330": 0.011650617234408855, "13331": 0.14939609169960022, "13341": 0.49864232540130615, "13416": 0.083342544734478, "13472": 0.7210738658905029, "13526": 0.025073638185858727, "13791": 1.1437997817993164, "13853": 1.3112845420837402, "13922": 0.736154317855835, "13940": 0.45623743534088135, "13949": 0.1358480453491211, "14083": 0.8957691192626953, "14116": 0.6400018334388733, "14120": 0.4624064862728119, "14142": 0.1970241367816925, "14187": 0.2976420819759369, "14280": 0.08871890604496002, "14613": 0.12728634476661682, "14667": 0.32764431834220886, "14679": 0.23479416966438293, "14856": 0.07884006202220917, "14863": 0.07341018319129944, "14879": 0.2089812457561493, "15067": 0.13670019805431366, "15295": 0.18573370575904846, "15420": 0.603290855884552, "15431": 1.1205062866210938, "15476": 0.14602625370025635, "15660": 0.09228714555501938, "15698": 0.46363574266433716, "15756": 0.8583967685699463, "15863": 0.37907835841178894, "15911": 0.684319257736206, "16003": 0.3339579105377197, "16026": 0.022212404757738113, "16342": 0.20022670924663544, "16412": 0.16359257698059082, "16492": 0.03831886500120163, "16576": 0.2447827309370041, "16585": 0.21765978634357452, "16662": 0.2719337046146393, "16840": 0.03831886500120163, "16952": 0.3615458607673645, "16991": 0.18329764902591705, "17261": 0.7818660736083984, "17379": 0.2026219218969345, "17441": 0.6613984704017639, "17473": 0.12986256182193756, "17629": 0.07612881064414978, "17788": 0.1751343309879303, "17914": 0.06246116757392883, "18044": 0.21922965347766876, "18068": 0.05786345899105072, "18234": 0.07612881064414978, "18595": 0.05970508232712746, "18622": 0.09938567131757736, "18714": 0.35128939151763916, "18891": 1.0546929836273193, "19220": 0.32199856638908386, "19362": 0.12384103983640671, "19389": 0.034552380442619324, "19481": 1.3393092155456543, "19653": 0.06337817758321762, "19780": 0.08871890604496002, "19788": 0.11081436276435852, "19817": 1.001607894897461, "19818": 0.1602703034877777, "19841": 0.28890204429626465, "19962": 0.6892333030700684, "20049": 0.021256839856505394, "20194": 0.06154331564903259, "20350": 0.22704219818115234, "20407": 0.8649974465370178, "20415": 1.1671710014343262, "20419": 0.4709797203540802, "20544": 0.7881022095680237, "20752": 0.16110190749168396, "20766": 0.016465263441205025, "20817": 0.40806588530540466, "20828": 0.35403475165367126, "20858": 0.9621002674102783, "20962": 0.05046287178993225, "20992": 0.025073638185858727, "21017": 0.20421554148197174, "21057": 0.016465263441205025, "21117": 0.21135559678077698, "21150": 0.0797421783208847, "21466": 0.1994270235300064, "21497": 0.2105647772550583, "21596": 0.732405424118042, "21619": 0.03266380727291107, "21656": 0.5833279490470886, "21670": 0.08871890604496002, "21775": 0.27934664487838745, "21903": 0.5139457583427429, "21967": 0.259204238653183, "22022": 0.21765978634357452, "22031": 0.19782574474811554, "22239": 0.36697331070899963, "22318": 0.04860413447022438, "22348": 0.03266380727291107, "22394": 0.16690383851528168, "22415": 0.0009760859538801014, "22686": 0.0842406153678894, "22718": 0.5415972471237183, "22778": 0.2447827309370041, "22907": 0.2018241584300995, "22930": 0.31560876965522766, "23021": 0.39367714524269104, "23130": 0.36290550231933594, "23212": 0.1946154683828354, "23216": 0.524982750415802, "23352": 0.2470736801624298, "23468": 0.0029254043474793434, "23616": 1.3367470502853394, "23713": 0.9217445850372314, "23715": 0.018384648486971855, "23943": 0.0058422754518687725, "24054": 0.39893341064453125, "24434": 0.09406650811433792, "24665": 0.8450632095336914, "24758": 0.25694093108177185, "24840": 0.5215105414390564, "25006": 0.2622140049934387, "25117": 0.02412080205976963, "25194": 0.5506471395492554, "25284": 0.06246116757392883, "25580": 0.00875066313892603, "25761": 0.27712854743003845, "26179": 0.9287132620811462, "26187": 0.2247048318386078, "26243": 0.24171993136405945, "26287": 0.40806588530540466, "26651": 0.2447827309370041, "26986": 0.2447827309370041, "27142": 0.04394211992621422, "27169": 0.6813592314720154, "27295": 0.5086748600006104, "27296": 0.20818853378295898, "27570": 0.0038986403960734606, "27641": 0.0606246218085289, "27651": 0.10818854719400406, "28032": 0.8298473954200745, "28965": 0.02316705882549286, "29160": 0.5174443125724792, "29401": 0.11604541540145874} | 12631697 | Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission. We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease. Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates. Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised. | Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases |
{"1017": 0.0058422754518687725, "1018": 0.14518201351165771, "1999": 0.9842413663864136, "2003": 0.32270604372024536, "2011": 0.015504186972975731, "2024": 0.4450363218784332, "2029": 0.06520967930555344, "2044": 0.04487626627087593, "2072": 0.14349138736724854, "2075": 0.31132611632347107, "2076": 0.42225050926208496, "2079": 0.02887592278420925, "2109": 0.2105647772550583, "2139": 0.48430517315864563, "2176": 0.5472630262374878, "2179": 0.2184450328350067, "2203": 0.07431721687316895, "2207": 0.18004031479358673, "2224": 0.03266380727291107, "2361": 0.2822965085506439, "2378": 0.7105726003646851, "2401": 0.9680526852607727, "2475": 0.38041436672210693, "2482": 0.5718178153038025, "2490": 0.319873183965683, "2509": 0.0058422754518687725, "2515": 0.026976587250828743, "2522": 0.6729245185852051, "2535": 0.14602625370025635, "2552": 1.0116009712219238, "2594": 0.0842406153678894, "2713": 0.2622140049934387, "2719": 0.22157983481884003, "2754": 0.6950984001159668, "2819": 0.36426326632499695, "2832": 0.3757305145263672, "2850": 0.04767346754670143, "2863": 0.6207655072212219, "2891": 0.637939989566803, "2920": 0.015504186972975731, "2953": 0.23479416966438293, "3040": 0.7665573358535767, "3117": 0.4950772523880005, "3161": 0.40220460295677185, "3223": 0.11168810725212097, "3252": 0.12556517124176025, "3320": 1.1070401668548584, "3370": 0.19220098853111267, "3375": 0.47827014327049255, "3443": 0.12642613053321838, "3450": 0.36697331070899963, "3466": 0.06520967930555344, "3495": 0.02887592278420925, "3526": 0.7755908370018005, "3527": 1.067535400390625, "3540": 0.06795065850019455, "3550": 0.3656192123889923, "3567": 1.0158531665802002, "3670": 0.129004567861557, "3676": 0.07068414986133575, "3726": 0.17431432008743286, "3774": 0.31204116344451904, "3796": 0.7076893448829651, "3853": 0.18248429894447327, "3930": 0.16690383851528168, "3989": 0.8109301924705505, "3995": 0.09317722171545029, "4013": 0.5718178153038025, "4023": 0.7124901413917542, "4115": 0.8534175157546997, "4135": 0.0038986403960734606, "4195": 0.757441520690918, "4403": 0.3784096837043762, "4442": 0.8805016279220581, "4453": 0.05046287178993225, "4456": 0.7683706283569336, "4490": 0.3777405619621277, "4515": 0.37304413318634033, "4697": 0.2026219218969345, "4758": 0.04767346754670143, "4962": 0.0797421783208847, "5007": 0.9546096324920654, "5084": 0.01934296265244484, "5158": 0.00875066313892603, "5250": 0.03925827145576477, "5398": 0.2741633653640747, "5400": 0.05970508232712746, "5449": 0.1889725625514984, "5711": 0.8374842405319214, "5716": 0.0770333781838417, "5737": 0.15442965924739838, "5972": 0.18573370575904846, "5991": 0.7629209756851196, "6026": 0.49626702070236206, "6137": 0.1718502640724182, "6194": 0.41389304399490356, "6215": 0.1064341589808464, "6228": 0.02316705882549286, "6299": 0.8383291959762573, "6525": 0.026025565341114998, "6540": 0.40806588530540466, "6559": 0.034552380442619324, "6593": 0.7987030148506165, "6632": 0.02412080205976963, "6648": 0.3353555500507355, "6679": 0.09317722171545029, "6753": 0.04487626627087593, "6761": 0.5209306478500366, "6767": 0.034552380442619324, "6774": 0.05139094591140747, "6844": 0.05694137513637543, "6887": 0.5562619566917419, "6894": 0.058784693479537964, "6895": 0.012615402229130268, "6942": 0.9432673454284668, "7076": 0.2105647772550583, "7085": 0.06429435312747955, "7174": 0.0770333781838417, "7237": 0.04674193635582924, "7337": 0.9348671436309814, "7356": 0.06886265426874161, "7361": 0.14939609169960022, "7366": 0.3106105625629425, "7367": 0.8408597707748413, "7393": 0.020300358533859253, "7446": 0.12556517124176025, "7711": 0.2667117714881897, "7712": 0.175953671336174, "7716": 0.2531573474407196, "7790": 0.9225212931632996, "7816": 0.49626702070236206, "7911": 0.32553088665008545, "7951": 0.3070250153541565, "8031": 0.19622190296649933, "8153": 0.34508460760116577, "8185": 1.138809084892273, "8458": 0.5865923762321472, "8534": 0.10467668622732162, "8651": 0.15275461971759796, "8676": 0.4487839937210083, "8873": 0.9440274834632874, "8878": 0.20580662786960602, "9005": 0.05417001247406006, "9007": 0.52266925573349, "9031": 0.056018441915512085, "9142": 0.1808556467294693, "9211": 0.35950297117233276, "9240": 0.31845372915267944, "9314": 0.05970508232712746, "9335": 0.01934296265244484, "9336": 0.013579257763922215, "9513": 0.015504186972975731, "9556": 0.48970574140548706, "9572": 0.08513788133859634, "9574": 0.20022670924663544, "9597": 0.053244512528181076, "9626": 0.08154398202896118, "9677": 0.12986256182193756, "9846": 0.05046287178993225, "9890": 0.3134697377681732, "9956": 0.03266380727291107, "9997": 0.19220098853111267, "10010": 0.058784693479537964, "10057": 0.3870677351951599, "10085": 0.2800849378108978, "10175": 0.24325250089168549, "10253": 0.8649974465370178, "10278": 0.6415454745292664, "10440": 0.13925230503082275, "10595": 0.9209672808647156, "10610": 0.0770333781838417, "10738": 0.2852376699447632, "10752": 0.1011524572968483, "10755": 0.33675122261047363, "10804": 0.9485763907432556, "10851": 0.23556606471538544, "10882": 0.025073638185858727, "10985": 0.06154331564903259, "11122": 0.1510767638683319, "11187": 0.11517547070980072, "11254": 0.0317181795835495, "11393": 1.0137293338775635, "11411": 0.00875066313892603, "11607": 0.07431721687316895, "11733": 0.17267228662967682, "11748": 0.1401015669107437, "11991": 0.36967599391937256, "12044": 0.5640701055526733, "12098": 0.8500841856002808, "12222": 0.5909284353256226, "12228": 0.13499516248703003, "12269": 0.5151132941246033, "12335": 0.27564704418182373, "12436": 0.27564704418182373, "12462": 0.25845035910606384, "12554": 0.25694093108177185, "12798": 0.22859740257263184, "12952": 0.151916041970253, "13197": 0.1011524572968483, "13320": 1.2267581224441528, "13438": 0.03925827145576477, "13469": 0.14433705806732178, "13490": 0.7755908370018005, "13523": 1.004473328590393, "13656": 0.4556184411048889, "13776": 0.5893046259880066, "13791": 0.22157983481884003, "13820": 0.23556606471538544, "13833": 0.2493593990802765, "13936": 0.26446542143821716, "14028": 0.34370049834251404, "14031": 0.011650617234408855, "14080": 0.2539152204990387, "14173": 0.2223619967699051, "14187": 0.1677299439907074, "14499": 0.9037119746208191, "14709": 0.1485546976327896, "14774": 0.03360854089260101, "14905": 0.129004567861557, "14907": 0.1064341589808464, "14988": 0.9363996982574463, "15006": 0.0029254043474793434, "15176": 0.7182208299636841, "15420": 0.1905880719423294, "15482": 0.18978065252304077, "15534": 0.23092569410800934, "15671": 0.15693697333335876, "15799": 0.1889725625514984, "15924": 0.9944084882736206, "15929": 0.03925827145576477, "15962": 0.036437395960092545, "16285": 0.23710809648036957, "16307": 1.0920805931091309, "16340": 0.24401791393756866, "16344": 0.9485763907432556, "16429": 0.2493593990802765, "16627": 1.0920805931091309, "16677": 0.7800771594047546, "16771": 0.1358480453491211, "16882": 0.10026945173740387, "16924": 0.009718249551951885, "17079": 0.9591107368469238, "17250": 0.1332872211933136, "17258": 0.18492233753204346, "17342": 0.1693800985813141, "17379": 0.12728634476661682, "17441": 0.07884006202220917, "17491": 0.6512666940689087, "17503": 1.0735615491867065, "17629": 0.25239890813827515, "17720": 0.4709797203540802, "17782": 1.12938392162323, "17926": 0.01934296265244484, "18089": 0.2231435477733612, "18153": 0.18816383183002472, "18622": 0.6833335757255554, "18714": 0.053244512528181076, "18757": 0.016465263441205025, "18804": 0.8433839678764343, "18924": 0.8813109993934631, "18938": 0.004870930220931768, "19001": 0.12642613053321838, "19146": 0.04113444685935974, "19570": 0.0797421783208847, "19653": 0.10555581003427505, "19731": 0.36426326632499695, "19825": 0.440646231174469, "19830": 0.012615402229130268, "19872": 0.19862671196460724, "20350": 0.04487626627087593, "20544": 0.043007105588912964, "20620": 0.0752234235405922, "20817": 0.42608439922332764, "20875": 0.13499516248703003, "20881": 0.20977331697940826, "20961": 0.0009760859538801014, "21081": 1.020087480545044, "21335": 0.3163207769393921, "21365": 0.6950984001159668, "21434": 0.3005385100841522, "21471": 0.23247487843036652, "21520": 0.4512746334075928, "21575": 0.524982750415802, "21618": 0.4311734735965729, "21700": 0.11604541540145874, "21758": 0.11778303235769272, "21903": 0.24171993136405945, "21963": 0.04767346754670143, "22016": 0.7737906575202942, "22242": 0.055094651877880096, "22244": 0.3084607720375061, "22248": 0.16276304423809052, "22281": 0.4132472574710846, "22318": 0.12556517124176025, "22412": 0.010684899985790253, "22869": 0.13670019805431366, "22923": 0.10467668622732162, "22925": 1.1160377264022827, "23221": 0.10203468054533005, "23265": 0.007782140281051397, "23267": 0.09406650811433792, "23309": 0.0058422754518687725, "23316": 0.2822965085506439, "23586": 0.684319257736206, "23758": 0.0009760859538801014, "23943": 0.10467668622732162, "24054": 0.4624064862728119, "24137": 0.05786345899105072, "24170": 0.6897233724594116, "24203": 0.06520967930555344, "24330": 0.007782140281051397, "24412": 0.49982786178588867, "24587": 0.037378571927547455, "24848": 0.2493593990802765, "24972": 0.6931471824645996, "25007": 1.158010721206665, "25292": 0.2539152204990387, "25409": 0.1510767638683319, "25456": 0.20739519596099854, "25644": 0.23092569410800934, "25761": 0.04674193635582924, "25896": 0.036437395960092545, "26061": 0.0058422754518687725, "26118": 0.14349138736724854, "26131": 0.43244171142578125, "26394": 0.3070250153541565, "26402": 0.5074998140335083, "26461": 0.021256839856505394, "26723": 0.23864774405956268, "26773": 0.6989894509315491, "26786": 0.045809537172317505, "27216": 0.7220231294631958, "27633": 1.5014698505401611, "27697": 0.8877626657485962, "27790": 0.8748174905776978, "27854": 0.09584271162748337, "28041": 0.13755162060260773, "28086": 0.029824240133166313, "28507": 0.1011524572968483, "28691": 0.3949938118457794, "28715": 1.0748957395553589, "28742": 0.04207121208310127, "28751": 0.0317181795835495, "29111": 0.18816383183002472} | 12640810 | Invadopodia are matrix-degrading membrane protrusions in invasive carcinoma cells. The mechanisms regulating invadopodium assembly and maturation are not understood. We have dissected the stages of invadopodium assembly and maturation and show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, cortactin phosphorylation was found to regulate cofilin and Arp2/3 complex-dependent actin polymerization. Cortactin directly binds cofilin and inhibits its severing activity. Cortactin phosphorylation is required to release this inhibition so cofilin can sever actin filaments to create barbed ends at invadopodia to support Arp2/3-dependent actin polymerization. After barbed end formation, cortactin is dephosphorylated, which blocks cofilin severing activity thereby stabilizing invadopodia. These findings identify novel mechanisms for actin polymerization in the invadopodia of metastatic carcinoma cells and define four distinct stages of invadopodium assembly and maturation consisting of invadopodium precursor formation, actin polymerization, stabilization, and matrix degradation. | Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation |
{"1039": 0.7380234599113464, "2004": 0.10291612148284912, "2005": 0.25995752215385437, "2011": 0.255429208278656, "2025": 0.3554046154022217, "2029": 0.06703783571720123, "2060": 0.20739519596099854, "2079": 0.28890204429626465, "2091": 0.18329764902591705, "2102": 0.8450632095336914, "2109": 0.13925230503082275, "2147": 0.0019512200960889459, "2278": 0.18816383183002472, "2331": 0.848413348197937, "2378": 0.7105726003646851, "2515": 0.401551216840744, "2527": 0.11343330889940262, "2535": 0.02412080205976963, "2594": 0.38574060797691345, "2730": 0.1970241367816925, "2757": 0.26446542143821716, "2825": 0.3409265875816345, "2838": 0.2837681770324707, "2891": 0.4914994537830353, "2895": 0.2659635543823242, "2951": 0.026976587250828743, "2953": 0.6502478122711182, "3012": 0.016465263441205025, "3102": 0.5069117546081543, "3123": 0.1685553640127182, "3145": 0.36426326632499695, "3161": 0.1229778528213501, "3170": 0.4286321699619293, "3207": 0.4914994537830353, "3215": 0.3757305145263672, "3280": 0.4770587682723999, "3302": 0.6086184978485107, "3303": 0.02316705882549286, "3372": 0.21765978634357452, "3375": 0.5734702348709106, "3391": 0.18816383183002472, "3406": 0.5347557663917542, "3424": 0.77198725938797, "3426": 0.15526613593101501, "3433": 0.9029204845428467, "3435": 0.14518201351165771, "3444": 0.3084607720375061, "3447": 0.304147332906723, "3466": 0.6022219061851501, "3491": 0.1685553640127182, "3526": 0.9178520441055298, "3597": 0.1994270235300064, "3653": 0.42416930198669434, "3686": 0.15610189735889435, "3796": 0.3127557039260864, "3802": 0.7592713832855225, "3896": 0.6415454745292664, "3928": 0.018384648486971855, "3949": 0.6233867406845093, "3972": 0.9108069539070129, "4005": 0.6533012986183167, "4053": 0.44753631949424744, "4090": 0.18004031479358673, "4135": 0.48850810527801514, "4176": 0.013579257763922215, "4200": 0.07341018319129944, "4288": 0.4709797203540802, "4319": 0.37974658608436584, "4340": 0.13243216276168823, "4442": 0.953857421875, "4453": 0.15777134895324707, "4456": 0.9340999722480774, "4506": 0.10203468054533005, "4539": 0.20421554148197174, "4588": 0.4196864068508148, "4621": 0.804835319519043, "4668": 0.2954642176628113, "4758": 0.0752234235405922, "5072": 0.006812678650021553, "5250": 0.5957841277122498, "5591": 0.23556606471538544, "5656": 0.669430673122406, "5666": 0.755608320236206, "5668": 0.3547199070453644, "5845": 0.6296497583389282, "5850": 0.6054253578186035, "5854": 0.3443928062915802, "5901": 0.21372433006763458, "5915": 0.6619023680686951, "5991": 0.12986256182193756, "5996": 0.26296505331993103, "6033": 0.11430477350950241, "6064": 0.9783848524093628, "6074": 0.7809720039367676, "6359": 0.15442965924739838, "6464": 0.18329764902591705, "6573": 0.4770587682723999, "6666": 0.0354953333735466, "6709": 0.04113444685935974, "6869": 0.47402387857437134, "6887": 0.5506471395492554, "7028": 0.21214580535888672, "7076": 0.5404602885246277, "7096": 0.0174254160374403, "7213": 0.07341018319129944, "7242": 0.4374985992908478, "7324": 0.8592242002487183, "7337": 0.3325583338737488, "7361": 0.6048921346664429, "7403": 0.20580662786960602, "7438": 0.5898461937904358, "7461": 0.28670501708984375, "7629": 0.1873544454574585, "7645": 0.25088030099868774, "7691": 0.15610189735889435, "7698": 0.48670899868011475, "7889": 0.03831886500120163, "7939": 0.7163142561912537, "8000": 0.4764525294303894, "8126": 0.18329764902591705, "8153": 0.08064348995685577, "8171": 0.45499902963638306, "8563": 0.1212492436170578, "8564": 0.3485364317893982, "8878": 0.20818853378295898, "8961": 0.3897167444229126, "8980": 0.012615402229130268, "9007": 0.09406650811433792, "9031": 0.12556517124176025, "9099": 0.8845420479774475, "9239": 0.4462870955467224, "9252": 0.029824240133166313, "9253": 0.17759032547473907, "9331": 0.7352184057235718, "9336": 0.8941729068756104, "9350": 0.08871890604496002, "9412": 0.6769026517868042, "9416": 0.05046287178993225, "9495": 0.24018502235412598, "9597": 0.3388410806655884, "9846": 0.27934664487838745, "9942": 0.5651806592941284, "9972": 0.36086538434028625, "10047": 0.5707147121429443, "10210": 1.020087480545044, "10225": 0.13243216276168823, "10250": 0.7239188551902771, "10509": 0.29255300760269165, "10572": 1.0271050930023193, "10586": 0.10379679501056671, "10591": 0.401551216840744, "10719": 1.0285027027130127, "10851": 0.35060185194015503, "10960": 0.6286086440086365, "11311": 0.9710156321525574, "11369": 0.38905516266822815, "11432": 0.2018241584300995, "11598": 0.4879087805747986, "11667": 0.7978238463401794, "11674": 0.1718502640724182, "11704": 0.056018441915512085, "11721": 0.7683706283569336, "11937": 0.09761575609445572, "12005": 0.8796916007995605, "12318": 0.16110190749168396, "12328": 0.7701805830001831, "12353": 0.5601736903190613, "12515": 0.14349138736724854, "12562": 0.18411032855510712, "12637": 0.07612881064414978, "12765": 0.23556606471538544, "12798": 0.0009760859538801014, "12921": 0.32553088665008545, "13070": 0.04767346754670143, "13153": 0.02316705882549286, "13330": 0.24018502235412598, "13341": 0.10026945173740387, "13441": 0.33115679025650024, "13465": 0.8829278349876404, "13492": 1.223315715789795, "13531": 0.0038986403960734606, "13626": 0.6729245185852051, "13656": 1.0250049829483032, "13675": 1.3123366832733154, "13712": 0.5909284353256226, "13791": 0.02887592278420925, "14120": 0.3177432417869568, "14141": 1.0815403461456299, "14405": 1.105748176574707, "14613": 0.14433705806732178, "14667": 0.38174858689308167, "14956": 0.056018441915512085, "15011": 0.7105726003646851, "15059": 0.04113444685935974, "15403": 0.574020504951477, "15459": 0.890972912311554, "15615": 0.1873544454574585, "15663": 0.23092569410800934, "15823": 0.8109301924705505, "15859": 0.018384648486971855, "15946": 0.43244171142578125, "16007": 0.08154398202896118, "16081": 0.5186077356338501, "16111": 0.4980490207672119, "16280": 0.13499516248703003, "16307": 0.0317181795835495, "16341": 0.4196864068508148, "16463": 0.13157635927200317, "16505": 0.46117570996284485, "16670": 0.20421554148197174, "16834": 0.06337817758321762, "16940": 0.7546905279159546, "17119": 0.7105726003646851, "17261": 0.05970508232712746, "17379": 0.32553088665008545, "17404": 0.3241194784641266, "17631": 0.2561853528022766, "17820": 0.2089812457561493, "17847": 0.8425432443618774, "18178": 1.162295937538147, "18260": 1.0403043031692505, "18291": 0.5278670787811279, "18639": 0.960606575012207, "18647": 0.13243216276168823, "18715": 0.2034190446138382, "18804": 0.13670019805431366, "18941": 0.11081436276435852, "19563": 0.2652147710323334, "19653": 1.060796856880188, "19824": 0.3777405619621277, "19872": 0.06977381557226181, "20017": 0.1332872211933136, "20049": 0.9886114001274109, "20233": 0.022212404757738113, "20360": 0.33115679025650024, "20464": 1.1512393951416016, "20544": 0.029824240133166313, "20694": 0.08782484382390976, "20842": 0.022212404757738113, "20858": 0.0009760859538801014, "20900": 0.06246116757392883, "20936": 0.11865071207284927, "20958": 0.036437395960092545, "20992": 0.34508460760116577, "21081": 0.39762192964553833, "21114": 0.9635916948318481, "21150": 0.49686139822006226, "21202": 0.2231435477733612, "21252": 0.1485546976327896, "21391": 0.08603433519601822, "21434": 0.8740028142929077, "21486": 0.29619070887565613, "21823": 0.2447827309370041, "21890": 0.5838727951049805, "21903": 0.3547199070453644, "22022": 1.176850438117981, "22025": 0.15023678541183472, "22394": 0.23247487843036652, "22407": 0.0019512200960889459, "22415": 0.0842406153678894, "22444": 0.13243216276168823, "22931": 0.19381128251552582, "22932": 0.056018441915512085, "23041": 0.8509185314178467, "23150": 1.1469062566757202, "23216": 0.34508460760116577, "23217": 0.08513788133859634, "23586": 0.7638313174247742, "23692": 0.890972912311554, "23924": 0.2983669638633728, "24054": 0.8633513450622559, "24269": 1.0775588750839233, "24278": 1.1005635261535645, "24479": 0.66441810131073, "24759": 0.05786345899105072, "24848": 0.1212492436170578, "25194": 0.07250232994556427, "25409": 0.31560876965522766, "25456": 0.7845434546470642, "25468": 0.1718502640724182, "25714": 0.6538092494010925, "25778": 0.29981520771980286, "25950": 0.8500841856002808, "26243": 0.8187123537063599, "26378": 0.0606246218085289, "26402": 0.669430673122406, "26591": 0.39762192964553833, "26633": 0.14518201351165771, "26642": 0.3106105625629425, "26651": 0.2223619967699051, "26835": 0.20580662786960602, "27009": 0.23864774405956268, "27144": 1.2261852025985718, "27321": 0.06703783571720123, "28024": 0.4318077862262726, "28518": 0.0009760859538801014, "28667": 0.5789587497711182, "28696": 0.06886265426874161, "28835": 0.2018241584300995, "28873": 0.06703783571720123, "28896": 0.1064341589808464, "29090": 0.036437395960092545, "29290": 0.5461324453353882, "29458": 0.04674193635582924} | 12641252 | Anthracyclin-treated tumor cells are particularly effective in eliciting an anticancer immune response, whereas other DNA-damaging agents such as etoposide and mitomycin C do not induce immunogenic cell death. Here we show that anthracyclins induce the rapid, preapoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knockdown of CRT suppressed the phagocytosis of anthracyclin-treated tumor cells by dendritic cells and abolished their immunogenicity in mice. The anthracyclin-induced CRT translocation was mimicked by inhibition of the protein phosphatase 1/GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase 1/GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anticancer immune responses and delineate a possible strategy for immunogenic chemotherapy. | Calreticulin exposure dictates the immunogenicity of cancer cell death |
{"1001": 0.4494072198867798, "1011": 0.2184450328350067, "1016": 0.1358480453491211, "1017": 0.46424978971481323, "1019": 0.22859740257263184, "1022": 0.05694137513637543, "1051": 0.5347557663917542, "1055": 0.7201237678527832, "1057": 0.9621002674102783, "1060": 0.6348392367362976, "1997": 0.01934296265244484, "1999": 0.09317722171545029, "2008": 0.00875066313892603, "2012": 0.49626702070236206, "2015": 0.46363574266433716, "2028": 0.22001366317272186, "2029": 0.306306391954422, "2031": 0.3070250153541565, "2034": 0.4450363218784332, "2038": 0.15860503911972046, "2046": 0.347847044467926, "2048": 0.5415972471237183, "2064": 0.3163207769393921, "2073": 0.08513788133859634, "2076": 0.020300358533859253, "2077": 0.18654440343379974, "2091": 0.009718249551951885, "2093": 0.46608972549438477, "2116": 0.18329764902591705, "2117": 0.7755908370018005, "2118": 0.036437395960092545, "2179": 0.2447827309370041, "2193": 0.18167030811309814, "2203": 0.6054253578186035, "2274": 0.18492233753204346, "2309": 0.7782850861549377, "2322": 0.6043586730957031, "2353": 0.8281423449516296, "2362": 0.02887592278420925, "2377": 0.0058422754518687725, "2391": 0.03925827145576477, "2509": 0.9005423784255981, "2515": 0.04953393340110779, "2522": 0.04487626627087593, "2532": 0.9568626880645752, "2535": 0.40871503949165344, "2538": 0.1905880719423294, "2556": 0.07159364968538284, "2609": 0.8796916007995605, "2695": 0.42608439922332764, "2765": 0.0029254043474793434, "2809": 0.02412080205976963, "2825": 0.02316705882549286, "2832": 0.5914691090583801, "2915": 0.06612417846918106, "2920": 0.3027053773403168, "3013": 0.129004567861557, "3107": 0.07431721687316895, "3174": 0.39367714524269104, "3248": 0.2160874605178833, "3252": 0.3283478021621704, "3303": 0.33325836062431335, "3338": 0.304147332906723, "3351": 0.2622140049934387, "3367": 0.27786844968795776, "3370": 0.6102113127708435, "3416": 0.3283478021621704, "3426": 0.3325583338737488, "3445": 0.22782009840011597, "3466": 0.7028654217720032, "3491": 0.0354953333735466, "3526": 0.4891071021556854, "3560": 0.22157983481884003, "3590": 0.659380316734314, "3603": 0.1229778528213501, "3623": 0.34922540187835693, "3625": 0.08782484382390976, "3653": 0.7746911644935608, "3674": 0.12642613053321838, "3688": 0.3170322775840759, "3796": 0.11256109178066254, "3807": 0.00875066313892603, "3822": 0.1905880719423294, "3896": 0.5278670787811279, "3905": 0.15023678541183472, "3949": 0.5849615335464478, "3983": 0.3019835948944092, "4029": 0.940220832824707, "4031": 0.22001366317272186, "4045": 0.055094651877880096, "4053": 0.03925827145576477, "4090": 0.13925230503082275, "4130": 0.3519764244556427, "4176": 0.01934296265244484, "4195": 0.1734936386346817, "4254": 0.14264501631259918, "4266": 0.32270604372024536, "4359": 0.22937409579753876, "4395": 0.30558720231056213, "4442": 0.4286321699619293, "4444": 0.23402166366577148, "4466": 0.037378571927547455, "4487": 0.5860490798950195, "4517": 0.09495500475168228, "4573": 0.8517522215843201, "4668": 0.11865071207284927, "4786": 0.037378571927547455, "4957": 0.49864232540130615, "4962": 0.6296497583389282, "5158": 0.056018441915512085, "5159": 0.347847044467926, "5250": 0.09850110858678818, "5258": 0.11691460013389587, "5320": 0.4425300657749176, "5360": 0.6649205088615417, "5449": 0.5174443125724792, "5537": 0.6603899002075195, "5547": 0.06520967930555344, "5566": 0.06337817758321762, "5591": 0.25239890813827515, "5799": 0.27712854743003845, "5845": 0.23402166366577148, "5867": 0.004870930220931768, "5991": 0.0770333781838417, "6064": 1.0560526847839355, "6149": 0.6080870032310486, "6192": 0.6064908504486084, "6194": 0.11430477350950241, "6314": 0.20739519596099854, "6364": 0.9162907600402832, "6420": 0.0797421783208847, "6578": 0.04394211992621422, "6970": 0.036437395960092545, "6971": 0.6502478122711182, "6999": 0.7907629609107971, "7077": 0.19862671196460724, "7153": 0.13243216276168823, "7242": 0.011650617234408855, "7312": 0.5455666780471802, "7337": 0.3810817003250122, "7366": 0.4093637466430664, "7372": 0.3615458607673645, "7403": 0.4624064862728119, "7405": 0.2659635543823242, "7438": 0.1970241367816925, "7457": 0.3297532796859741, "7461": 0.5762182474136353, "7551": 0.15442965924739838, "7606": 0.05046287178993225, "7645": 0.3588210940361023, "7783": 0.8567397594451904, "7807": 0.14349138736724854, "7816": 0.3910386264324188, "7885": 0.15943801403045654, "7888": 0.08244366943836212, "7910": 0.020300358533859253, "7939": 0.021256839856505394, "8000": 0.39762192964553833, "8119": 0.14349138736724854, "8189": 0.0354953333735466, "8290": 0.1718502640724182, "8524": 0.12728634476661682, "8776": 0.22157983481884003, "8898": 0.19220098853111267, "8920": 0.32058215141296387, "9007": 0.5197699069976807, "9048": 0.8400169610977173, "9096": 0.33675122261047363, "9165": 0.2689530849456787, "9190": 0.27342069149017334, "9597": 0.04487626627087593, "9869": 0.66441810131073, "9885": 0.030771657824516296, "10054": 0.2231435477733612, "10071": 0.5584990978240967, "10085": 0.7295845746994019, "10266": 0.18816383183002472, "10467": 0.36086538434028625, "10514": 0.04207121208310127, "10572": 0.16524957120418549, "10671": 0.9225212931632996, "10708": 0.23324857652187347, "10719": 0.025073638185858727, "10729": 0.890972912311554, "10738": 0.15023678541183472, "10744": 0.17431432008743286, "10777": 0.2881702482700348, "10847": 0.08782484382390976, "10879": 0.004870930220931768, "10924": 0.22548456490039825, "11022": 0.036437395960092545, "11099": 0.029824240133166313, "11178": 0.04674193635582924, "11231": 0.7809720039367676, "11307": 0.022212404757738113, "11369": 0.025073638185858727, "11383": 0.07612881064414978, "11387": 0.11430477350950241, "11477": 0.2918238639831543, "11628": 0.09672962874174118, "11649": 0.46363574266433716, "11767": 0.010684899985790253, "11835": 0.1946154683828354, "12014": 0.12642613053321838, "12207": 1.319148302078247, "12263": 0.4311734735965729, "12328": 0.24859806895256042, "12359": 0.09584271162748337, "12473": 0.1946154683828354, "12491": 0.53589928150177, "12510": 0.006812678650021553, "12554": 0.012615402229130268, "12644": 0.04860413447022438, "12667": 0.09850110858678818, "12702": 0.0354953333735466, "12732": 1.117316484451294, "12745": 0.603290855884552, "12789": 0.4330752193927765, "12837": 0.1930064558982849, "12884": 0.2837681770324707, "12889": 0.11865071207284927, "12987": 0.9302552938461304, "13007": 0.20022670924663544, "13151": 0.1685553640127182, "13231": 0.083342544734478, "13248": 0.11778303235769272, "13341": 0.75193190574646, "13371": 0.2837681770324707, "13441": 0.4311734735965729, "13458": 0.3106105625629425, "13490": 0.009718249551951885, "13496": 0.1229778528213501, "13502": 0.5156965255737305, "13531": 0.3963087201118469, "13711": 0.6223390698432922, "13791": 0.0058422754518687725, "13909": 0.083342544734478, "13922": 0.07341018319129944, "13995": 0.5914691090583801, "14031": 0.9944084882736206, "14080": 0.14433705806732178, "14193": 0.6882523894309998, "14247": 0.16690383851528168, "14321": 0.1602703034877777, "14494": 0.2837681770324707, "14627": 0.23710809648036957, "14828": 0.2247048318386078, "14876": 0.10906458646059036, "15049": 0.23710809648036957, "15053": 0.2837681770324707, "15115": 0.34023189544677734, "15316": 0.05417001247406006, "15439": 0.9115922451019287, "15527": 0.25467249751091003, "15543": 0.0770333781838417, "15599": 0.15442965924739838, "15778": 0.16607704758644104, "15923": 0.08064348995685577, "16118": 1.197703242301941, "16221": 0.5707147121429443, "16275": 0.822151780128479, "16285": 0.25845035910606384, "16305": 1.0193830728530884, "16515": 1.020087480545044, "16627": 0.053244512528181076, "16690": 0.09761575609445572, "16706": 0.1710275560617447, "16771": 0.12470348179340363, "16882": 0.058784693479537964, "16910": 0.9621002674102783, "16915": 0.49864232540130615, "17070": 0.1619328260421753, "17212": 0.12642613053321838, "17250": 0.7482418417930603, "17582": 1.0702182054519653, "17702": 0.1994270235300064, "17938": 0.23402166366577148, "18136": 0.11778303235769272, "18279": 0.010684899985790253, "18419": 0.08603433519601822, "18714": 0.08692999184131622, "18819": 0.33953672647476196, "18931": 0.12470348179340363, "18938": 0.06429435312747955, "18946": 0.5127768516540527, "18969": 0.417115718126297, "19209": 0.1212492436170578, "19274": 0.14264501631259918, "19326": 0.004870930220931768, "19330": 0.5404602885246277, "19395": 0.23864774405956268, "19539": 0.20501139760017395, "19563": 0.04767346754670143, "19653": 0.22626367211341858, "19699": 0.10203468054533005, "19737": 0.8893690705299377, "19825": 0.053244512528181076, "20203": 0.04953393340110779, "20275": 0.7370892763137817, "20320": 0.020300358533859253, "20325": 0.176772341132164, "20363": 0.01934296265244484, "20461": 0.9147270321846008, "20567": 0.0317181795835495, "20614": 0.42735910415649414, "20766": 0.10993985831737518, "20870": 0.12384103983640671, "20904": 0.2018241584300995, "20909": 0.0029254043474793434, "21053": 0.9739698171615601, "21112": 0.07341018319129944, "21218": 0.0019512200960889459, "21262": 0.23787821829319, "21344": 1.695472240447998, "21376": 0.029824240133166313, "21486": 0.0770333781838417, "21557": 0.11081436276435852, "21647": 0.35060185194015503, "21903": 0.20739519596099854, "22026": 0.029824240133166313, "22244": 0.0606246218085289, "22694": 0.0009760859538801014, "22869": 0.08871890604496002, "22995": 0.0842406153678894, "23068": 0.0058422754518687725, "23093": 0.35060185194015503, "23150": 0.40546512603759766, "23217": 1.0933903455734253, "23233": 0.055094651877880096, "23343": 0.29400965571403503, "23535": 0.1011524572968483, "23572": 0.009718249551951885, "23584": 0.03266380727291107, "23586": 0.11081436276435852, "23725": 0.8272887468338013, "23737": 0.20818853378295898, "23758": 1.0855059623718262, "23767": 0.7951818704605103, "23797": 0.04953393340110779, "23833": 0.06977381557226181, "23892": 0.0354953333735466, "23924": 0.8649974465370178, "23959": 0.1718502640724182, "24137": 0.41840189695358276, "24191": 0.16524957120418549, "24198": 0.39893341064453125, "24269": 0.672426164150238, "24278": 0.4568560719490051, "24312": 0.06337817758321762, "24471": 0.0019512200960889459, "24535": 0.3388410806655884, "24558": 0.12556517124176025, "24873": 0.6999598741531372, "24879": 0.022212404757738113, "25002": 0.4286321699619293, "25006": 0.2652147710323334, "25269": 1.2012346982955933, "25413": 0.12384103983640671, "25423": 0.13414156436920166, "25456": 0.04767346754670143, "25572": 0.9232974052429199, "25597": 0.29255300760269165, "25714": 0.26146242022514343, "25761": 0.03360854089260101, "25876": 0.06703783571720123, "26014": 0.11604541540145874, "26083": 0.21530038118362427, "26244": 0.14518201351165771, "26313": 0.24325250089168549, "26376": 0.6212902665138245, "26394": 0.255429208278656, "26402": 0.2976420819759369, "26563": 0.08603433519601822, "26601": 1.0464962720870972, "27074": 0.8699195384979248, "27642": 0.12814582884311676, "28086": 0.3248254358768463, "28424": 0.09761575609445572, "28691": 1.5075435638427734, "28788": 0.3248254358768463, "28848": 0.1930064558982849, "28992": 0.034552380442619324} | 12642224 | DNA oligonucleotide complementary to sequences in the 5' third of U3 snRNA were injected into Xenopus oocyte nuclei to disrupt endogenous U3 snRNA. The effect of this treatment on rRNA processing was examined. We found that some toads have a single rRNA processing pathway, whereas in other toads, two rRNA processing pathways can coexist in a single oocyte. U3 snRNA disruption in toads with the single rRNA processing pathway caused a reduction in 20S and '32S' pre-rRNA. In addition, in toads with two rRNA processing pathways, an increase in '36S' pre-rRNA of the second pathway is observed. This is the first in vivo demonstration that U3 snRNA plays a role in rRNA processing. Cleavage site #3 is at the boundary of ITS 1 and 5.8S and links all of the affected rRNA intermediates: 20S and '32S' are the products of site #3 cleavage in the first pathway and '36S' is the substrate for cleavage at site #3 in the second pathway. We postulate that U3 snRNP folds pre-rRNA into a conformation dictating correct cleavage at processing site #3. | In vivo disruption of Xenopus U3 snRNA affects ribosomal RNA processing. |
{"1016": 0.11865071207284927, "1039": 0.07068414986133575, "1044": 0.7592713832855225, "1053": 0.15359249711036682, "1157": 0.21530038118362427, "2001": 0.0317181795835495, "2005": 0.11691460013389587, "2010": 0.8459017872810364, "2011": 0.16359257698059082, "2029": 0.043007105588912964, "2057": 0.09317722171545029, "2060": 0.015504186972975731, "2062": 0.045809537172317505, "2076": 0.02316705882549286, "2079": 0.2145126610994339, "2084": 0.0029254043474793434, "2091": 0.8247235417366028, "2102": 0.9958525896072388, "2106": 0.07159364968538284, "2109": 0.3283478021621704, "2152": 0.034552380442619324, "2179": 0.05139094591140747, "2182": 0.4132472574710846, "2195": 0.026025565341114998, "2220": 0.3777405619621277, "2232": 0.5220900774002075, "2339": 0.38374659419059753, "2419": 0.24859806895256042, "2465": 0.010684899985790253, "2470": 0.08782484382390976, "2475": 0.8152611255645752, "2504": 0.21687394380569458, "2515": 0.18654440343379974, "2532": 0.966567873954773, "2535": 0.8039615154266357, "2582": 0.2637155055999756, "2590": 0.2501201331615448, "2592": 0.10203468054533005, "2595": 0.4487839937210083, "2599": 0.18654440343379974, "2650": 0.006812678650021553, "2669": 0.05046287178993225, "2804": 0.30558720231056213, "2832": 0.29473719000816345, "2864": 0.24171993136405945, "2890": 0.21293537318706512, "2891": 0.6892333030700684, "2897": 0.5255602598190308, "2898": 0.8666408061981201, "2909": 1.2671676874160767, "2919": 0.018384648486971855, "2920": 0.8715548515319824, "2928": 0.6048921346664429, "2951": 0.5963221788406372, "3041": 0.16524957120418549, "3089": 0.09317722171545029, "3130": 0.12384103983640671, "3141": 0.17020416259765625, "3176": 0.8658194541931152, "3215": 0.5186077356338501, "3231": 0.5596157908439636, "3252": 0.2105647772550583, "3303": 0.1913948506116867, "3370": 0.6118015646934509, "3375": 0.5063233375549316, "3378": 0.11517547070980072, "3426": 0.12038381397724152, "3433": 1.0519683361053467, "3445": 0.49626702070236206, "3466": 0.11604541540145874, "3469": 0.004870930220931768, "3491": 0.07341018319129944, "3526": 0.0174254160374403, "3603": 0.29981520771980286, "3618": 0.1229778528213501, "3623": 0.12814582884311676, "3625": 0.3353555500507355, "3714": 0.1685553640127182, "3798": 0.46608972549438477, "3800": 0.2667117714881897, "3853": 0.35950297117233276, "3898": 1.072225570678711, "3908": 0.16359257698059082, "3936": 0.4248080551624298, "4047": 0.1873544454574585, "4053": 1.1994705200195312, "4072": 0.3683255612850189, "4091": 0.8408597707748413, "4098": 0.011650617234408855, "4106": 0.27044451236724854, "4125": 0.016465263441205025, "4130": 0.11951763927936554, "4146": 0.026025565341114998, "4160": 0.11256109178066254, "4167": 0.056018441915512085, "4187": 0.10026945173740387, "4198": 0.09850110858678818, "4235": 0.12556517124176025, "4254": 0.02316705882549286, "4295": 0.5990082025527954, "4395": 0.6425731778144836, "4417": 0.23864774405956268, "4453": 0.6921701431274414, "4456": 0.9209672808647156, "4469": 0.2317005842924118, "4531": 0.012615402229130268, "4539": 0.09584271162748337, "4544": 0.21530038118362427, "4603": 0.2561853528022766, "4642": 1.180456280708313, "4652": 0.3588210940361023, "4668": 0.5021947622299194, "4710": 0.4794800877571106, "4742": 0.4673144817352295, "4846": 0.36086538434028625, "4895": 0.3339579105377197, "4957": 0.32905077934265137, "4962": 1.1375575065612793, "4972": 0.23864774405956268, "5032": 0.8583967685699463, "5090": 0.14602625370025635, "5197": 0.1401015669107437, "5224": 0.2719337046146393, "5250": 0.6338034868240356, "5292": 0.1685553640127182, "5320": 0.29981520771980286, "5360": 0.09495500475168228, "5387": 0.24171993136405945, "5393": 0.37371641397476196, "5441": 0.5045560002326965, "5456": 0.22626367211341858, "5524": 0.9591107368469238, "5531": 0.0038986403960734606, "5537": 0.036437395960092545, "5589": 0.19782574474811554, "5591": 1.0271050930023193, "5604": 0.47463157773017883, "5606": 0.04860413447022438, "5646": 0.052318159490823746, "5678": 0.19220098853111267, "5680": 0.2223619967699051, "5700": 0.06246116757392883, "5761": 0.0770333781838417, "5769": 0.4673144817352295, "5799": 0.6128603219985962, "5838": 0.47158926725387573, "5852": 0.10993985831737518, "5876": 0.29255300760269165, "5994": 0.0606246218085289, "5997": 0.29036402702331543, "6017": 0.38441169261932373, "6028": 0.06795065850019455, "6032": 0.6754127144813538, "6033": 0.2247048318386078, "6064": 1.2753846645355225, "6125": 0.3381449282169342, "6150": 0.010684899985790253, "6194": 0.2954642176628113, "6215": 0.5324648022651672, "6364": 0.47463157773017883, "6418": 0.04113444685935974, "6529": 0.17431432008743286, "6540": 1.04512357711792, "6560": 0.7683706283569336, "6624": 0.35334911942481995, "6678": 0.28155985474586487, "6709": 0.512191891670227, "6827": 0.5444341897964478, "6869": 0.8740028142929077, "6887": 0.5640701055526733, "6897": 0.7537717819213867, "6923": 0.6270449161529541, "6971": 0.37304413318634033, "7127": 0.18492233753204346, "7192": 0.3269403576850891, "7233": 0.2652147710323334, "7264": 0.07431721687316895, "7297": 0.11778303235769272, "7336": 0.2990913391113281, "7337": 0.09584271162748337, "7366": 0.630689799785614, "7386": 0.41840189695358276, "7403": 1.0087559223175049, "7457": 0.10291612148284912, "7461": 0.21214580535888672, "7487": 0.31845372915267944, "7523": 0.01934296265244484, "7532": 0.045809537172317505, "7591": 0.04207121208310127, "7594": 0.05694137513637543, "7632": 0.11604541540145874, "7645": 0.5104349255561829, "7657": 0.2741633653640747, "7691": 0.27786844968795776, "7711": 0.016465263441205025, "7755": 0.417115718126297, "7784": 0.0009760859538801014, "7809": 0.009718249551951885, "7810": 0.7210738658905029, "7816": 0.0038986403960734606, "7870": 0.6064908504486084, "7885": 0.04113444685935974, "7969": 0.57457035779953, "8080": 0.678885817527771, "8171": 0.6583697199821472, "8211": 0.1619328260421753, "8247": 0.009718249551951885, "8250": 0.21372433006763458, "8319": 0.7951818704605103, "8332": 0.1384023278951645, "8347": 1.06619131565094, "8349": 0.5833279490470886, "8360": 0.10906458646059036, "8458": 0.4330752193927765, "8498": 0.48670899868011475, "8528": 1.4515039920806885, "8553": 0.18573370575904846, "8715": 0.8255793452262878, "8729": 0.17267228662967682, "8761": 0.6573580503463745, "8790": 0.09495500475168228, "8822": 0.8740028142929077, "8980": 0.06337817758321762, "8991": 0.8805016279220581, "9007": 0.26146242022514343, "9031": 0.5562619566917419, "9084": 0.1751343309879303, "9113": 0.05786345899105072, "9120": 0.1946154683828354, "9125": 0.43623676896095276, "9165": 1.2318994998931885, "9211": 1.3862943649291992, "9239": 0.5805994272232056, "9319": 0.4093637466430664, "9358": 0.21372433006763458, "9416": 0.0317181795835495, "9447": 0.06703783571720123, "9597": 0.24171993136405945, "9651": 0.22782009840011597, "9740": 0.09672962874174118, "9846": 0.259204238653183, "9867": 0.17431432008743286, "9896": 0.0019512200960889459, "10060": 0.2990913391113281, "10109": 0.22782009840011597, "10176": 0.30486753582954407, "10253": 0.8845420479774475, "10266": 0.07068414986133575, "10288": 0.33325836062431335, "10315": 0.04860413447022438, "10509": 0.36697331070899963, "10539": 0.16607704758644104, "10580": 0.39893341064453125, "10708": 0.3877306580543518, "10723": 0.28743788599967957, "10738": 0.09050461649894714, "10744": 0.14686977863311768, "10788": 0.09317722171545029, "10840": 0.5151132941246033, "10847": 0.055094651877880096, "10960": 0.4794800877571106, "10976": 0.16359257698059082, "11109": 0.3084607720375061, "11115": 0.6471850275993347, "11129": 0.28670501708984375, "11156": 0.3485364317893982, "11265": 0.0019512200960889459, "11326": 0.966567873954773, "11394": 0.2719337046146393, "11487": 0.3339579105377197, "11649": 0.2034190446138382, "11787": 0.040196798741817474, "11868": 0.983511209487915, "12115": 0.18004031479358673, "12117": 0.7701805830001831, "12151": 0.2696990668773651, "12222": 0.20022670924663544, "12238": 0.6112717390060425, "12284": 0.12814582884311676, "12315": 0.5914691090583801, "12394": 0.7286425232887268, "12407": 0.1677299439907074, "12482": 0.24018502235412598, "12491": 0.052318159490823746, "12550": 0.14349138736724854, "12562": 0.347847044467926, "12603": 0.08961215615272522, "12732": 0.841701865196228, "12987": 0.9287132620811462, "13070": 0.3034266233444214, "13072": 0.18248429894447327, "13091": 1.020087480545044, "13134": 0.030771657824516296, "13248": 0.06703783571720123, "13331": 0.32199856638908386, "13458": 1.1971133947372437, "13490": 0.8517522215843201, "13594": 0.32129061222076416, "13656": 0.19381128251552582, "13671": 0.1064341589808464, "13722": 0.1619328260421753, "13776": 0.13157635927200317, "13791": 0.11778303235769272, "13938": 0.2837681770324707, "13995": 0.08603433519601822, "14048": 0.44691193103790283, "14080": 0.09317722171545029, "14120": 0.7610978484153748, "14193": 0.3141832649707794, "14313": 0.16359257698059082, "14442": 0.04860413447022438, "14471": 0.6719275116920471, "14480": 0.6999598741531372, "14486": 0.10993985831737518, "14494": 0.26296505331993103, "14800": 0.14179791510105133, "14828": 0.956112265586853, "14847": 0.2983669638633728, "14863": 0.46914875507354736, "15011": 0.6808650493621826, "15059": 0.009718249551951885, "15113": 0.35334911942481995, "15115": 0.013579257763922215, "15169": 0.14433705806732178, "15224": 0.5640701055526733, "15258": 0.35334911942481995, "15410": 0.45994341373443604, "15420": 0.7086513638496399, "15527": 0.11951763927936554, "15543": 0.12384103983640671, "15615": 0.25995752215385437, "15770": 0.3012613356113434, "15873": 0.1485546976327896, "16007": 0.12038381397724152, "16012": 0.5860490798950195, "16081": 0.12470348179340363, "16186": 0.02792670577764511, "16221": 0.5045560002326965, "16263": 0.18329764902591705, "16281": 0.0752234235405922, "16285": 0.11343330889940262, "16307": 0.0606246218085289, "16412": 0.6363908052444458, "16599": 0.01934296265244484, "16605": 0.013579257763922215, "16627": 0.37640097737312317, "16691": 0.22704219818115234, "16706": 0.40546512603759766, "16731": 0.08064348995685577, "16771": 0.016465263441205025, "16840": 0.036437395960092545, "16910": 0.890972912311554, "16924": 0.3588210940361023, "16991": 0.2478361576795578, "17079": 0.43053874373435974, "17245": 0.04674193635582924, "17431": 0.0317181795835495, "17631": 0.29400965571403503, "17698": 0.13925230503082275, "17785": 0.7067264318466187, "18089": 0.06337817758321762, "18130": 0.33605360984802246, "18182": 0.4909018874168396, "18419": 0.02316705882549286, "18536": 0.06246116757392883, "18549": 0.8349450826644897, "18714": 0.07068414986133575, "18920": 0.09850110858678818, "19293": 0.08513788133859634, "19319": 0.09672962874174118, "19345": 0.2837681770324707, "19470": 0.0354953333735466, "19601": 0.21687394380569458, "19824": 0.15693697333335876, "19872": 0.8433839678764343, "19995": 0.21765978634357452, "20063": 0.12986256182193756, "20275": 0.037378571927547455, "20303": 0.12642613053321838, "20353": 0.3601844012737274, "20467": 0.3084607720375061, "20621": 0.04674193635582924, "20735": 0.040196798741817474, "20906": 0.16110190749168396, "21081": 0.07612881064414978, "21312": 0.026025565341114998, "21434": 0.14179791510105133, "21903": 0.2478361576795578, "21919": 0.5723689198493958, "21961": 0.09228714555501938, "22026": 0.37640097737312317, "22156": 0.04487626627087593, "22248": 0.06337817758321762, "22422": 0.0842406153678894, "22517": 0.24554696679115295, "22796": 0.0038986403960734606, "22916": 0.2954642176628113, "23079": 0.03925827145576477, "23130": 0.7229714393615723, "23217": 0.22001366317272186, "23316": 0.2223619967699051, "23355": 0.045809537172317505, "23900": 0.0770333781838417, "23934": 0.06795065850019455, "24054": 0.02887592278420925, "24170": 0.22626367211341858, "24310": 0.9546096324920654, "24410": 0.33953672647476196, "24501": 0.3027053773403168, "24558": 0.43244171142578125, "24848": 1.0688776969909668, "24868": 0.22626367211341858, "25077": 0.0797421783208847, "25141": 0.006812678650021553, "25172": 0.053244512528181076, "25206": 0.0174254160374403, "25409": 0.5290185213088989, "25437": 0.1751343309879303, "25524": 0.5027855634689331, "25596": 0.06612417846918106, "25869": 0.6714286804199219, "26118": 0.0752234235405922, "26236": 0.22001366317272186, "26266": 0.8534175157546997, "26520": 0.1710275560617447, "26651": 0.32553088665008545, "26702": 0.2539152204990387, "27325": 0.18411032855510712, "27487": 0.4311734735965729, "27697": 1.1487655639648438, "27755": 0.15526613593101501, "27790": 1.1894142627716064, "28297": 0.08154398202896118, "28327": 0.8989537954330444, "28498": 0.22079704701900482, "28715": 1.3238370418548584, "28805": 0.06612417846918106, "28848": 0.6482070088386536, "29172": 0.1889725625514984, "29206": 0.35060185194015503} | 12643937 | Signaling pathways that respond to DNA damage are essential for the maintenance of genome stability and are linked to many diseases, including cancer. Here, a genome-wide siRNA screen was employed to identify additional genes involved in genome stabilization by monitoring phosphorylation of the histone variant H2AX, an early mark of DNA damage. We identified hundreds of genes whose downregulation led to elevated levels of H2AX phosphorylation (gammaH2AX) and revealed links to cellular complexes and to genes with unclassified functions. We demonstrate a widespread role for mRNA-processing factors in preventing DNA damage, which in some cases is caused by aberrant RNA-DNA structures. Furthermore, we connect increased gammaH2AX levels to the neurological disorder Charcot-Marie-Tooth (CMT) syndrome, and we find a role for several CMT proteins in the DNA-damage response. These data indicate that preservation of genome stability is mediated by a larger network of biological processes than previously appreciated. | A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. |
{"1011": 0.17759032547473907, "1017": 0.1734936386346817, "1020": 0.757441520690918, "1038": 0.09317722171545029, "1042": 0.8450632095336914, "1045": 0.28155985474586487, "1156": 0.5398913025856018, "1999": 0.004870930220931768, "2007": 0.10993985831737518, "2011": 0.3325583338737488, "2029": 0.28890204429626465, "2076": 0.04767346754670143, "2078": 0.037378571927547455, "2079": 0.04767346754670143, "2179": 0.052318159490823746, "2243": 0.6684301495552063, "2278": 0.7995813488960266, "2378": 0.38374659419059753, "2416": 0.7791815400123596, "2470": 0.15023678541183472, "2482": 0.2247048318386078, "2497": 0.052318159490823746, "2515": 0.28597161173820496, "2535": 0.20102575421333313, "2556": 0.034552380442619324, "2575": 1.2883929014205933, "2677": 1.0326838493347168, "2817": 0.36426326632499695, "2863": 0.6931471824645996, "2865": 0.04767346754670143, "2913": 0.34300774335861206, "2920": 0.18978065252304077, "2947": 0.3163207769393921, "3161": 0.27044451236724854, "3232": 0.6405166387557983, "3273": 0.12986256182193756, "3375": 0.7342816591262817, "3378": 0.4067663550376892, "3384": 0.6446255445480347, "3433": 0.1212492436170578, "3466": 0.1930064558982849, "3491": 0.3170322775840759, "3526": 0.755608320236206, "3603": 0.04113444685935974, "3623": 0.0770333781838417, "3670": 0.6573580503463745, "3755": 0.7710843086242676, "3800": 0.6254787445068359, "3853": 0.45251765847206116, "3930": 0.3170322775840759, "3935": 0.0019512200960889459, "3940": 0.11778303235769272, "4072": 0.45499902963638306, "4091": 0.48008447885513306, "4115": 0.05970508232712746, "4130": 0.04953393340110779, "4135": 0.272677481174469, "4340": 0.09228714555501938, "4369": 0.45499902963638306, "4416": 0.2954642176628113, "4442": 0.7389566898345947, "4456": 1.1738357543945312, "4539": 0.09228714555501938, "4607": 0.010684899985790253, "4649": 0.2674594223499298, "4671": 0.1510767638683319, "4712": 0.3084607720375061, "4742": 0.5336109399795532, "4812": 0.04860413447022438, "4921": 0.040196798741817474, "4935": 0.09761575609445572, "4949": 0.5914691090583801, "4962": 0.8272887468338013, "4972": 0.20421554148197174, "5048": 0.06520967930555344, "5082": 0.5903874635696411, "5228": 0.8143964409828186, "5250": 0.40806588530540466, "5326": 0.7182208299636841, "5387": 0.42353010177612305, "5393": 0.04674193635582924, "5423": 0.2478361576795578, "5490": 0.7592713832855225, "5646": 0.03360854089260101, "5682": 0.052318159490823746, "5705": 0.18978065252304077, "5769": 0.18978065252304077, "5799": 0.32553088665008545, "6038": 1.001607894897461, "6062": 0.4400174915790558, "6064": 0.11343330889940262, "6146": 0.04113444685935974, "6169": 0.15943801403045654, "6190": 0.42608439922332764, "6335": 0.026976587250828743, "6377": 0.22626367211341858, "6388": 0.6664261221885681, "6555": 0.2652147710323334, "6622": 0.06429435312747955, "6657": 1.0992631912231445, "6692": 0.5941681861877441, "6761": 0.4286321699619293, "6970": 0.06795065850019455, "7065": 0.06429435312747955, "7148": 1.1965231895446777, "7337": 0.9394577741622925, "7403": 0.3676496744155884, "7457": 0.004870930220931768, "7461": 0.07884006202220917, "7551": 0.19782574474811554, "7645": 0.23864774405956268, "7689": 0.0009760859538801014, "7694": 0.5255602598190308, "7711": 0.06337817758321762, "7755": 0.31132611632347107, "7816": 0.0842406153678894, "7863": 0.0019512200960889459, "7885": 0.3683255612850189, "8018": 0.6684301495552063, "8040": 1.1683861017227173, "8067": 0.040196798741817474, "8153": 0.2674594223499298, "8171": 0.11865071207284927, "8185": 0.678390383720398, "8247": 1.3745063543319702, "8700": 1.3809088468551636, "8733": 0.436867892742157, "8878": 0.987156867980957, "9007": 0.5290185213088989, "9152": 0.27712854743003845, "9153": 0.5562619566917419, "9165": 0.6902132034301758, "9253": 0.5478278398513794, "9335": 0.2852376699447632, "9336": 0.24171993136405945, "9413": 0.6327666640281677, "9495": 0.04953393340110779, "9556": 0.3982778787612915, "9589": 0.7445381283760071, "9626": 0.1946154683828354, "9654": 0.24631060659885406, "10047": 0.3005385100841522, "10210": 0.2026219218969345, "10572": 0.2659635543823242, "10577": 0.015504186972975731, "10595": 0.7305257320404053, "10737": 0.4419025182723999, "10769": 0.021256839856505394, "10787": 0.175953671336174, "10847": 0.3141832649707794, "10882": 0.24554696679115295, "11022": 0.659380316734314, "11211": 0.5461324453353882, "11394": 0.75193190574646, "11598": 0.06429435312747955, "11835": 0.03360854089260101, "11868": 0.5197699069976807, "11952": 0.11343330889940262, "11970": 0.1693800985813141, "12115": 0.0058422754518687725, "12375": 0.18654440343379974, "12506": 0.24018502235412598, "12541": 0.05694137513637543, "12607": 0.022212404757738113, "12732": 0.848413348197937, "13024": 0.1677299439907074, "13330": 0.22626367211341858, "13656": 0.9732321500778198, "13791": 0.8813109993934631, "13833": 0.18004031479358673, "13910": 1.0073304176330566, "13922": 0.35128939151763916, "14021": 0.9021284580230713, "14026": 0.10379679501056671, "14067": 0.7370892763137817, "14193": 0.8649974465370178, "14828": 1.013020396232605, "14967": 1.0271050930023193, "15396": 0.0317181795835495, "15420": 0.417115718126297, "15543": 0.3012613356113434, "15680": 0.35950297117233276, "15918": 0.4487839937210083, "16007": 0.2674594223499298, "16026": 0.04674193635582924, "16031": 0.32058215141296387, "16086": 0.24554696679115295, "16221": 0.19541899859905243, "16285": 0.31132611632347107, "16463": 0.07250232994556427, "16677": 0.08603433519601822, "16902": 0.46486347913742065, "16910": 0.6430866718292236, "17379": 0.16607704758644104, "17441": 0.5209306478500366, "17503": 0.9827804565429688, "17820": 0.052318159490823746, "18178": 0.12556517124176025, "18260": 0.2447827309370041, "18468": 0.043007105588912964, "18714": 0.574020504951477, "18804": 0.7220231294631958, "19653": 0.45870962738990784, "19780": 0.5021947622299194, "19824": 0.022212404757738113, "19872": 0.23092569410800934, "20014": 1.1363043785095215, "20069": 0.13670019805431366, "20250": 0.9178520441055298, "20360": 0.21922965347766876, "20544": 0.8625272512435913, "20752": 0.4286321699619293, "20868": 0.2478361576795578, "20875": 0.10379679501056671, "21081": 1.0172666311264038, "21307": 0.15777134895324707, "21337": 0.9084475636482239, "21418": 0.04487626627087593, "21434": 0.8074519634246826, "21466": 0.09495500475168228, "21471": 1.018678069114685, "21572": 0.31132611632347107, "21579": 0.12642613053321838, "21618": 0.07250232994556427, "21903": 1.0229004621505737, "21919": 0.6016870141029358, "22123": 0.09672962874174118, "22471": 0.7583568692207336, "22520": 0.11517547070980072, "22901": 0.2667117714881897, "23216": 0.38308101892471313, "23282": 0.004870930220931768, "23586": 0.10906458646059036, "23737": 0.05694137513637543, "23900": 0.8583967685699463, "24054": 0.3141832649707794, "24269": 1.0423725843429565, "24435": 0.1477125883102417, "24587": 0.3777405619621277, "25194": 0.3170322775840759, "25409": 0.8057082891464233, "25714": 0.4831010699272156, "26244": 0.02412080205976963, "26308": 0.5573811531066895, "26402": 0.25845035910606384, "26512": 0.15275461971759796, "26520": 0.05046287178993225, "26556": 0.08603433519601822, "26721": 0.16524957120418549, "26773": 0.09672962874174118, "27144": 0.006812678650021553, "27295": 0.03266380727291107, "27427": 0.21922965347766876, "27673": 0.25995752215385437, "27711": 1.0848461389541626, "27777": 0.1384023278951645, "27854": 0.29328158497810364, "27881": 0.0038986403960734606, "29107": 0.10379679501056671, "29464": 0.036437395960092545, "29484": 0.26296505331993103, "29720": 0.20818853378295898} | 12650610 | We have previously shown that the integrin beta6 is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple beta6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin beta6 signaling activates Fyn and thus promotes oral cancer progression. | Alphavbeta6-Fyn signaling promotes oral cancer progression. |
{"100": 0.11081436276435852, "1011": 0.24401791393756866, "1017": 0.08064348995685577, "1996": 0.04487626627087593, "2003": 0.25694093108177185, "2004": 0.007782140281051397, "2008": 0.26146242022514343, "2011": 0.11691460013389587, "2015": 0.41840189695358276, "2024": 0.472198486328125, "2029": 0.23015019297599792, "2050": 0.04767346754670143, "2054": 0.0770333781838417, "2064": 0.21293537318706512, "2078": 0.6207655072212219, "2079": 0.25088030099868774, "2090": 0.05139094591140747, "2091": 0.0770333781838417, "2099": 0.5517725944519043, "2109": 0.053244512528181076, "2139": 0.010684899985790253, "2182": 0.08782484382390976, "2239": 0.2659635543823242, "2389": 0.1889725625514984, "2487": 0.3956514894962311, "2491": 0.12470348179340363, "2512": 1.0641717910766602, "2515": 0.23787821829319, "2529": 0.40089741349220276, "2532": 1.3300546407699585, "2535": 0.29328158497810364, "2581": 0.0913962796330452, "2696": 0.1734936386346817, "2765": 0.03925827145576477, "2818": 0.4728073179721832, "2856": 0.6048921346664429, "2890": 0.2969166338443756, "2920": 0.0606246218085289, "2981": 0.10731173306703568, "3075": 0.07250232994556427, "3117": 0.3019835948944092, "3141": 0.36358460783958435, "3227": 0.10026945173740387, "3252": 0.09406650811433792, "3283": 0.7124901413917542, "3350": 0.40481385588645935, "3366": 0.6882523894309998, "3370": 0.29473719000816345, "3378": 0.21214580535888672, "3385": 0.10026945173740387, "3424": 1.0382318496704102, "3463": 0.01934296265244484, "3466": 0.1229778528213501, "3491": 0.07068414986133575, "3526": 0.4158279001712799, "3563": 0.026976587250828743, "3619": 0.06703783571720123, "3622": 0.053244512528181076, "3625": 0.04674193635582924, "3642": 0.3070250153541565, "3654": 0.29981520771980286, "3670": 0.9724938273429871, "3729": 0.861702561378479, "3798": 0.06612417846918106, "3800": 0.006812678650021553, "3853": 0.23479416966438293, "3893": 0.5723689198493958, "3952": 0.07884006202220917, "3989": 0.3005385100841522, "4050": 0.40741631388664246, "4078": 0.7370892763137817, "4167": 0.1011524572968483, "4195": 0.1685553640127182, "4286": 0.37102460861206055, "4442": 0.38574060797691345, "4496": 0.052318159490823746, "4525": 0.07793712615966797, "4539": 0.9100211262702942, "4671": 0.14349138736724854, "4758": 0.20580662786960602, "4895": 0.20580662786960602, "4919": 0.25088030099868774, "4962": 1.0179725885391235, "4971": 0.21214580535888672, "5017": 0.2749055027961731, "5054": 1.248288631439209, "5171": 0.10203468054533005, "5228": 0.2516399025917053, "5250": 0.5685047507286072, "5391": 0.1930064558982849, "5449": 0.890972912311554, "5537": 0.12470348179340363, "5799": 0.05139094591140747, "5802": 0.015504186972975731, "6064": 0.5751199722290039, "6163": 0.956112265586853, "6210": 0.026976587250828743, "6914": 0.22859740257263184, "7077": 0.2622140049934387, "7163": 0.1734936386346817, "7229": 0.3070250153541565, "7337": 0.6950984001159668, "7366": 0.3615458607673645, "7403": 0.7096124291419983, "7591": 0.040196798741817474, "7645": 0.07431721687316895, "7711": 0.5209306478500366, "7723": 0.12038381397724152, "7790": 0.3269403576850891, "7816": 0.5882205963134766, "7856": 0.03266380727291107, "7883": 0.12728634476661682, "7889": 0.8143964409828186, "8031": 0.7220231294631958, "8171": 0.436867892742157, "8206": 0.8383291959762573, "8292": 0.4113073945045471, "8303": 0.2852376699447632, "8360": 0.6420594453811646, "8523": 0.7809720039367676, "8546": 0.05417001247406006, "8718": 0.04394211992621422, "8840": 0.040196798741817474, "8991": 0.11778303235769272, "9006": 0.34577593207359314, "9007": 0.45251765847206116, "9099": 0.2247048318386078, "9152": 0.05786345899105072, "9165": 0.8715548515319824, "9174": 0.1930064558982849, "9416": 0.7267557382583618, "9521": 0.08244366943836212, "9530": 0.1619328260421753, "9568": 0.1064341589808464, "9756": 0.00875066313892603, "9855": 0.45870962738990784, "9885": 0.29981520771980286, "10071": 0.08603433519601822, "10266": 0.040196798741817474, "10548": 0.1602703034877777, "10595": 0.4481603503227234, "10624": 0.19220098853111267, "10737": 0.3141832649707794, "10738": 0.9092346429824829, "11022": 0.007782140281051397, "11226": 0.015504186972975731, "11231": 0.055094651877880096, "11423": 0.5301685929298401, "11649": 1.3940764665603638, "11968": 0.03831886500120163, "11981": 0.3883931338787079, "12222": 0.77198725938797, "12359": 0.23247487843036652, "12702": 1.390192985534668, "12789": 1.629546880722046, "12987": 1.5297857522964478, "13348": 0.26820653676986694, "13451": 0.04113444685935974, "13458": 0.4818955361843109, "13712": 0.10379679501056671, "13791": 0.2018241584300995, "13833": 0.129004567861557, "13922": 0.35745587944984436, "14026": 0.08513788133859634, "14031": 0.018384648486971855, "14085": 0.04767346754670143, "14126": 0.7854343056678772, "14163": 0.13670019805431366, "14187": 0.966567873954773, "14192": 0.05046287178993225, "14193": 0.7086513638496399, "14262": 0.33953672647476196, "14399": 0.6970458030700684, "14454": 0.8893690705299377, "14471": 0.35334911942481995, "14704": 0.8699195384979248, "14719": 1.775349497795105, "14774": 0.19220098853111267, "15115": 0.1602703034877777, "15176": 0.9240728616714478, "15543": 0.304147332906723, "15663": 0.11604541540145874, "15723": 0.3554046154022217, "15920": 0.2561853528022766, "16007": 0.03925827145576477, "16044": 0.35677260160446167, "16069": 0.6075552701950073, "16081": 0.42608439922332764, "16119": 0.10818854719400406, "16221": 0.19381128251552582, "16275": 0.1734936386346817, "16285": 0.15610189735889435, "16341": 0.2741633653640747, "16416": 0.15023678541183472, "16554": 0.04674193635582924, "16627": 0.05046287178993225, "16706": 0.0009760859538801014, "16754": 0.6833335757255554, "16840": 0.10291612148284912, "16861": 0.857568621635437, "16902": 0.7086513638496399, "17181": 0.21530038118362427, "17235": 0.015504186972975731, "17327": 0.09228714555501938, "17379": 0.22001366317272186, "17452": 0.14264501631259918, "17830": 0.058784693479537964, "17913": 0.22937409579753876, "18062": 0.3949938118457794, "18330": 0.09495500475168228, "18357": 0.4450363218784332, "18447": 0.12038381397724152, "18639": 0.08603433519601822, "19137": 0.020300358533859253, "19563": 0.20580662786960602, "19653": 0.0770333781838417, "19833": 0.05786345899105072, "19872": 0.11951763927936554, "20363": 0.8306987881660461, "20503": 0.20739519596099854, "20817": 0.8433839678764343, "21031": 0.09938567131757736, "21183": 0.6916812658309937, "21442": 0.34922540187835693, "21575": 0.524982750415802, "21618": 0.48970574140548706, "21700": 1.1063944101333618, "21709": 0.09672962874174118, "21716": 0.7220231294631958, "21770": 0.7163142561912537, "22026": 0.0752234235405922, "22330": 0.5267143249511719, "22402": 0.27934664487838745, "22422": 1.1166772842407227, "22476": 0.19622190296649933, "22822": 0.036437395960092545, "22993": 0.20580662786960602, "23303": 0.6654226183891296, "23586": 0.2954642176628113, "23900": 0.5805994272232056, "23961": 0.7314660549163818, "24051": 0.841701865196228, "24054": 0.16690383851528168, "24328": 0.1734936386346817, "24494": 0.022212404757738113, "24558": 0.052318159490823746, "24848": 0.672426164150238, "25175": 0.42608439922332764, "25206": 0.8289952278137207, "25451": 0.679875910282135, "25456": 0.18978065252304077, "25609": 0.04113444685935974, "25644": 0.25995752215385437, "25761": 0.08782484382390976, "26244": 0.0058422754518687725, "26358": 0.16607704758644104, "26402": 0.3883931338787079, "26512": 0.05694137513637543, "26514": 0.7665573358535767, "26534": 0.08782484382390976, "26601": 0.11343330889940262, "26773": 0.8917738795280457, "27777": 0.16110190749168396, "27854": 0.10026945173740387, "27965": 0.35677260160446167, "28691": 1.072225570678711, "28848": 1.04512357711792, "28991": 0.09584271162748337, "29032": 0.05786345899105072, "29533": 0.20580662786960602} | 12652963 | MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels. | miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. |
{"1009": 0.4337083101272583, "1011": 0.1011524572968483, "1014": 0.29400965571403503, "1017": 0.34370049834251404, "1019": 0.03925827145576477, "1020": 0.10026945173740387, "1021": 0.0038986403960734606, "1022": 0.1913948506116867, "1023": 0.11778303235769272, "1026": 0.015504186972975731, "1048": 0.05046287178993225, "1050": 0.6425731778144836, "1052": 0.2954642176628113, "1056": 0.1930064558982849, "1164": 0.15610189735889435, "2002": 0.34023189544677734, "2004": 0.0606246218085289, "2011": 0.10731173306703568, "2013": 0.2493593990802765, "2015": 0.6441128253936768, "2026": 0.6659244894981384, "2029": 0.07341018319129944, "2033": 0.45932671427726746, "2038": 0.1011524572968483, "2042": 0.09850110858678818, "2050": 0.8004589080810547, "2057": 0.19381128251552582, "2058": 0.11081436276435852, "2064": 0.22859740257263184, "2066": 0.0019512200960889459, "2079": 0.026976587250828743, "2083": 0.0770333781838417, "2089": 0.18978065252304077, "2090": 0.23092569410800934, "2106": 0.010684899985790253, "2135": 0.2478361576795578, "2179": 0.29981520771980286, "2339": 0.04953393340110779, "2378": 0.3423145115375519, "2458": 0.38441169261932373, "2470": 0.04953393340110779, "2487": 0.07159364968538284, "2489": 0.30989447236061096, "2497": 0.40806588530540466, "2509": 0.9710156321525574, "2515": 0.25845035910606384, "2535": 0.6011518239974976, "2546": 0.4709797203540802, "2550": 0.043007105588912964, "2594": 0.45251765847206116, "2618": 0.4673144817352295, "2620": 0.9680526852607727, "2649": 0.015504186972975731, "2659": 0.037378571927547455, "2676": 0.5778634548187256, "2696": 0.8500841856002808, "2817": 0.25239890813827515, "2864": 0.1602703034877777, "2865": 0.7239188551902771, "2884": 0.09495500475168228, "2913": 0.1905880719423294, "2920": 0.1602703034877777, "2944": 0.3339579105377197, "2947": 0.021256839856505394, "2951": 0.35813871026039124, "2988": 0.02792670577764511, "2992": 0.5069117546081543, "3022": 0.28963330388069153, "3120": 0.1229778528213501, "3128": 0.4093637466430664, "3141": 0.11517547070980072, "3170": 0.24018502235412598, "3189": 0.1221139207482338, "3273": 0.4400174915790558, "3276": 0.03266380727291107, "3278": 0.015504186972975731, "3286": 0.5074998140335083, "3303": 0.045809537172317505, "3350": 0.5849615335464478, "3351": 0.08244366943836212, "3366": 0.17759032547473907, "3378": 0.7537717819213867, "3399": 0.12384103983640671, "3426": 0.17840765416622162, "3433": 0.7352184057235718, "3445": 0.5104349255561829, "3449": 0.49626702070236206, "3466": 0.2531573474407196, "3491": 0.2247048318386078, "3522": 0.32058215141296387, "3526": 0.29036402702331543, "3603": 0.007782140281051397, "3623": 0.42990362644195557, "3625": 0.7182208299636841, "3635": 0.28963330388069153, "3662": 0.083342544734478, "3670": 0.8780695199966431, "3677": 1.013020396232605, "3688": 0.3870677351951599, "3694": 0.5069117546081543, "3728": 0.21922965347766876, "3739": 0.4196864068508148, "3747": 0.04394211992621422, "3798": 0.31204116344451904, "3818": 0.6228629946708679, "3896": 0.3170322775840759, "3930": 0.05417001247406006, "3949": 0.1905880719423294, "3973": 0.029824240133166313, "4013": 0.6022219061851501, "4022": 0.6833335757255554, "4023": 0.15943801403045654, "4031": 0.2837681770324707, "4044": 0.7028654217720032, "4081": 0.4067663550376892, "4106": 0.39367714524269104, "4176": 0.11604541540145874, "4216": 0.2247048318386078, "4263": 0.5404602885246277, "4275": 0.23710809648036957, "4286": 0.08513788133859634, "4295": 0.5139457583427429, "4308": 0.25239890813827515, "4311": 0.27342069149017334, "4340": 0.5313173532485962, "4381": 0.021256839856505394, "4395": 0.4734157919883728, "4414": 0.19381128251552582, "4442": 0.5495203733444214, "4453": 0.38905516266822815, "4483": 0.841701865196228, "4503": 0.2089812457561493, "4654": 0.37907835841178894, "4668": 0.08064348995685577, "4671": 0.022212404757738113, "4742": 0.14264501631259918, "4747": 0.6327666640281677, "4758": 0.07068414986133575, "4783": 0.16276304423809052, "4785": 0.0058422754518687725, "4812": 0.03360854089260101, "4957": 0.5596157908439636, "4958": 0.5415972471237183, "4962": 0.47158926725387573, "4975": 0.20818853378295898, "5012": 1.1858406066894531, "5072": 0.22157983481884003, "5159": 0.3241194784641266, "5173": 0.9827804565429688, "5228": 0.45994341373443604, "5250": 0.6233867406845093, "5320": 0.20977331697940826, "5333": 0.3676496744155884, "5360": 0.3464667797088623, "5387": 0.7163142561912537, "5393": 0.176772341132164, "5423": 0.8143964409828186, "5443": 0.0354953333735466, "5666": 0.5398913025856018, "5668": 0.36426326632499695, "5709": 0.3283478021621704, "5769": 0.42608439922332764, "5799": 0.5180262327194214, "5876": 0.8289952278137207, "5890": 0.055094651877880096, "5967": 0.22001366317272186, "6022": 0.7629209756851196, "6064": 0.1619328260421753, "6074": 0.056018441915512085, "6083": 0.5568217039108276, "6184": 0.6107416749000549, "6274": 0.09406650811433792, "6284": 0.8091925978660583, "6305": 0.3877306580543518, "6310": 1.076228141784668, "6378": 0.036437395960092545, "6388": 0.28670501708984375, "6459": 0.15442965924739838, "6529": 0.020300358533859253, "6551": 0.15777134895324707, "6553": 0.6553317308425903, "6576": 0.11430477350950241, "6591": 0.8442239761352539, "6592": 0.6862877607345581, "6638": 0.7229714393615723, "6777": 0.0354953333735466, "6812": 0.37035053968429565, "6822": 0.42096930742263794, "6864": 0.8492490649223328, "6869": 0.2674594223499298, "6873": 0.0019512200960889459, "6897": 0.4145384132862091, "6948": 1.1487655639648438, "6971": 0.10026945173740387, "6999": 0.6275664567947388, "7108": 0.0317181795835495, "7127": 0.1011524572968483, "7274": 0.7153595685958862, "7337": 0.20818853378295898, "7356": 0.06337817758321762, "7361": 0.6773988008499146, "7366": 0.3916989266872406, "7403": 0.7239188551902771, "7438": 0.055094651877880096, "7457": 0.3615458607673645, "7461": 0.46055975556373596, "7507": 0.7086513638496399, "7511": 0.6410312056541443, "7531": 0.46302130818367004, "7551": 0.3601844012737274, "7645": 0.3170322775840759, "7704": 0.1011524572968483, "7711": 0.14518201351165771, "7755": 0.08961215615272522, "7790": 0.7086513638496399, "7816": 0.5607312321662903, "7842": 1.1906025409698486, "7870": 0.5347557663917542, "7885": 0.5370414853096008, "8000": 0.9907892942428589, "8092": 0.20818853378295898, "8123": 0.7737906575202942, "8153": 0.8366385698318481, "8171": 0.6838265657424927, "8197": 0.045809537172317505, "8290": 0.6588751673698425, "8319": 0.1905880719423294, "8327": 0.3177432417869568, "8382": 0.6649205088615417, "8449": 0.7800771594047546, "8469": 0.30558720231056213, "8524": 0.10203468054533005, "8556": 0.18654440343379974, "8578": 0.012615402229130268, "8776": 0.07612881064414978, "8939": 0.8764448165893555, "9002": 0.16607704758644104, "9007": 0.4196864068508148, "9104": 0.3464667797088623, "9165": 0.4400174915790558, "9280": 0.4337083101272583, "9350": 0.3676496744155884, "9412": 0.40806588530540466, "9420": 0.020300358533859253, "9495": 0.15442965924739838, "9507": 0.42225050926208496, "9532": 0.0058422754518687725, "9535": 1.4339678287506104, "9556": 0.15777134895324707, "9565": 0.674915611743927, "9597": 0.10818854719400406, "9757": 0.11778303235769272, "9839": 0.14264501631259918, "9936": 0.025073638185858727, "10058": 0.22392450273036957, "10088": 0.4113073945045471, "10230": 0.10818854719400406, "10253": 0.6853039860725403, "10258": 0.659380316734314, "10266": 0.8699195384979248, "10327": 1.0920805931091309, "10509": 0.13755162060260773, "10572": 0.7047978043556213, "10671": 0.9886114001274109, "10732": 0.48850810527801514, "10737": 0.23015019297599792, "10738": 0.14686977863311768, "10744": 0.6118015646934509, "10769": 0.5370414853096008, "10847": 0.2659635543823242, "10857": 0.2145126610994339, "10867": 0.7370892763137817, "10956": 0.022212404757738113, "10960": 0.3485364317893982, "11179": 0.7454653382301331, "11311": 0.11517547070980072, "11383": 0.0174254160374403, "11423": 0.38441169261932373, "11432": 0.5290185213088989, "11598": 0.036437395960092545, "11643": 0.05786345899105072, "11709": 0.08782484382390976, "11767": 0.34300774335861206, "11835": 0.4537591338157654, "11888": 0.6312094330787659, "11993": 0.6291293501853943, "12044": 0.022212404757738113, "12115": 0.5272908806800842, "12222": 0.6543170213699341, "12231": 0.18816383183002472, "12328": 1.2290464639663696, "12381": 0.14095009863376617, "12473": 0.04394211992621422, "12530": 0.02316705882549286, "12562": 0.255429208278656, "12681": 0.7398891448974609, "12702": 1.1413075923919678, "12719": 0.25239890813827515, "12745": 0.42990362644195557, "12987": 0.11691460013389587, "13070": 1.0257055759429932, "13181": 0.1734936386346817, "13275": 0.1602703034877777, "13330": 0.20739519596099854, "13331": 0.8796916007995605, "13434": 0.04860413447022438, "13441": 0.1808556467294693, "13458": 0.1913948506116867, "13531": 0.347847044467926, "13685": 0.38905516266822815, "13791": 0.11517547070980072, "13833": 0.6202403903007507, "13922": 0.10818854719400406, "13938": 0.19220098853111267, "14031": 0.1734936386346817, "14074": 0.09672962874174118, "14080": 0.7239188551902771, "14095": 0.5220900774002075, "14120": 0.21687394380569458, "14193": 0.08692999184131622, "14447": 0.056018441915512085, "14471": 0.3864043951034546, "14494": 0.14686977863311768, "14613": 0.015504186972975731, "14639": 0.15526613593101501, "14670": 0.0317181795835495, "14671": 0.4412745535373688, "14708": 0.11430477350950241, "14719": 0.20102575421333313, "14828": 0.7096124291419983, "14856": 1.0172666311264038, "15007": 0.021256839856505394, "15176": 0.37907835841178894, "15403": 0.4709797203540802, "15439": 0.46363574266433716, "15527": 0.07068414986133575, "15578": 0.9739698171615601, "15596": 0.0797421783208847, "15637": 0.7951818704605103, "15923": 0.3499138653278351, "15946": 0.7333439588546753, "16000": 1.2324692010879517, "16012": 0.7881022095680237, "16216": 0.6773988008499146, "16221": 0.26146242022514343, "16285": 0.36900100111961365, "16387": 0.6598852276802063, "16463": 0.23015019297599792, "16478": 0.05970508232712746, "16505": 0.28890204429626465, "16599": 0.3547199070453644, "16605": 0.2674594223499298, "16844": 1.156782865524292, "16927": 0.10906458646059036, "17146": 0.18492233753204346, "17338": 0.06703783571720123, "17341": 0.7276995778083801, "17820": 0.953857421875, "17886": 0.5920094847679138, "17890": 0.6603899002075195, "17908": 0.0174254160374403, "17914": 0.06795065850019455, "18002": 0.09495500475168228, "18089": 0.9162907600402832, "18178": 0.4374985992908478, "18453": 0.7737906575202942, "18547": 0.304147332906723, "18647": 0.0174254160374403, "18714": 0.06703783571720123, "18715": 1.0298984050750732, "18804": 0.10467668622732162, "18847": 0.28670501708984375, "18900": 0.6877616047859192, "18938": 0.5640701055526733, "19126": 0.9394577741622925, "19293": 0.04394211992621422, "19335": 0.9240728616714478, "19345": 0.8845420479774475, "19515": 0.03360854089260101, "19653": 0.6553317308425903, "19872": 0.2089812457561493, "20014": 1.0519683361053467, "20187": 1.102510929107666, "20194": 0.7144040465354919, "20353": 0.40481385588645935, "20467": 0.083342544734478, "20688": 0.9849710464477539, "20752": 0.06703783571720123, "20806": 0.3381449282169342, "20868": 0.11604541540145874, "20915": 0.39893341064453125, "20974": 0.8022117614746094, "21025": 0.009718249551951885, "21102": 0.5450005531311035, "21162": 0.6022219061851501, "21307": 0.02316705882549286, "21335": 0.08961215615272522, "21453": 1.0144377946853638, "21575": 0.17267228662967682, "21618": 0.14939609169960022, "21685": 0.6275664567947388, "21700": 0.02412080205976963, "21733": 0.9333322048187256, "21759": 0.3005385100841522, "21781": 0.0770333781838417, "21890": 0.6729245185852051, "21903": 0.2478361576795578, "21919": 0.3810817003250122, "21935": 0.05694137513637543, "21996": 0.040196798741817474, "22330": 0.6389714479446411, "22466": 0.08064348995685577, "22597": 1.2123361825942993, "23306": 0.15860503911972046, "23691": 0.1229778528213501, "23737": 0.14686977863311768, "23900": 0.2447827309370041, "23924": 0.21922965347766876, "23943": 0.13157635927200317, "23971": 0.0842406153678894, "24024": 0.27786844968795776, "24054": 0.16607704758644104, "24269": 0.1808556467294693, "24278": 0.3084607720375061, "24552": 1.3149620294570923, "24587": 0.6773988008499146, "24848": 0.09672962874174118, "24952": 0.8143964409828186, "25262": 0.3084607720375061, "25476": 0.34023189544677734, "25604": 0.9194108247756958, "25605": 0.07612881064414978, "25714": 0.7987030148506165, "26282": 1.1363043785095215, "26396": 0.24018502235412598, "26402": 0.05786345899105072, "26435": 0.09406650811433792, "26524": 0.5495203733444214, "26591": 0.6260011196136475, "26616": 0.5381823778152466, "26632": 0.757441520690918, "26651": 0.1332872211933136, "26773": 0.4764525294303894, "26835": 0.46486347913742065, "27099": 0.10818854719400406, "27133": 0.9958525896072388, "27287": 0.011650617234408855, "27321": 0.29328158497810364, "27441": 0.06703783571720123, "27710": 0.9371650815010071, "27895": 0.21135559678077698, "27920": 0.5209306478500366, "28156": 0.5596157908439636, "28483": 0.7408206462860107, "28696": 0.08871890604496002, "28804": 0.0354953333735466, "29170": 0.006812678650021553, "29290": 0.28743788599967957, "29295": 0.02887592278420925} | 12658073 | The gut microbiota has been proposed as an environmental factor that affects the development of metabolic and inflammatory diseases in mammals. Recent reports indicate that gut bacteria-derived lipopolysaccharide (LPS) can initiate obesity and insulin resistance in mice; however, the molecular interactions responsible for microbial regulation of host metabolism and mediators of inflammation have not been studied in detail. Hepatic serum amyloid A (SAA) proteins are markers and proposed mediators of inflammation that exhibit increased levels in serum of insulin-resistant mice. Adipose tissue-derived SAA3 displays monocyte chemotactic activity and may play a role in metabolic inflammation associated with obesity and insulin resistance. To investigate a potential mechanistic link between the intestinal microbiota and induction of proinflammatory host factors, we performed molecular analyses of germ-free, conventionally raised and genetically modified Myd88-/- mouse models. SAA3 expression was determined to be significantly augmented in adipose (9.9+/-1.9-fold; P<0.001) and colonic tissue (7.0+/-2.3-fold; P<0.05) by the presence of intestinal microbes. In the colon, we provided evidence that SAA3 is partially regulated through the Toll-like receptor (TLR)/MyD88/NF-kappaB signaling axis. We identified epithelial cells and macrophages as cellular sources of SAA3 in the colon and found that colonic epithelial expression of SAA3 may be part of an NF-kappaB-dependent response to LPS from gut bacteria. In vitro experiments showed that LPS treatments of both epithelial cells and macrophages induced SAA3 expression (27.1+/-2.5-fold vs. 1.6+/-0.1-fold, respectively). Our data suggest that LPS, and potentially other products of the indigenous gut microbiota, might elevate cytokine expression in tissues and thus exacerbate chronic low-grade inflammation observed in obesity. | Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota |
{"1015": 0.0354953333735466, "1016": 0.7755908370018005, "1038": 0.37035053968429565, "1043": 0.6348392367362976, "1044": 0.4248080551624298, "1056": 0.841701865196228, "2000": 0.06429435312747955, "2005": 0.23556606471538544, "2012": 0.16110190749168396, "2013": 0.2247048318386078, "2045": 0.004870930220931768, "2048": 0.3588210940361023, "2052": 0.17759032547473907, "2062": 0.18329764902591705, "2071": 0.1358480453491211, "2075": 0.53589928150177, "2079": 0.0009760859538801014, "2088": 0.1510767638683319, "2093": 0.45623743534088135, "2104": 0.2447827309370041, "2109": 0.06429435312747955, "2111": 0.35403475165367126, "2135": 0.7295845746994019, "2137": 0.680370569229126, "2179": 0.0354953333735466, "2201": 0.9598589539527893, "2213": 0.018384648486971855, "2220": 0.07793712615966797, "2278": 0.3084607720375061, "2290": 0.10818854719400406, "2304": 0.6674286723136902, "2313": 0.9500881433486938, "2339": 0.29400965571403503, "2378": 0.25239890813827515, "2401": 0.17431432008743286, "2408": 0.018384648486971855, "2426": 0.29400965571403503, "2462": 0.09406650811433792, "2470": 0.053244512528181076, "2475": 1.0101795196533203, "2487": 0.6634125709533691, "2488": 0.12986256182193756, "2491": 0.6207655072212219, "2535": 0.07612881064414978, "2571": 0.6471850275993347, "2589": 0.07159364968538284, "2637": 0.34715715050697327, "2668": 0.22937409579753876, "2679": 0.255429208278656, "2740": 0.6096806526184082, "2764": 0.0058422754518687725, "2765": 0.41840189695358276, "2777": 0.06703783571720123, "2794": 0.2561853528022766, "2804": 0.043007105588912964, "2825": 0.06337817758321762, "2828": 0.35128939151763916, "2830": 0.4879087805747986, "2863": 0.029824240133166313, "2864": 0.16442140936851501, "2890": 0.19381128251552582, "2966": 0.1889725625514984, "2988": 0.21214580535888672, "3041": 0.3949938118457794, "3060": 1.4496725797653198, "3064": 0.3070250153541565, "3073": 0.0038986403960734606, "3078": 0.6892333030700684, "3085": 0.6512666940689087, "3088": 1.2599912881851196, "3107": 0.08961215615272522, "3112": 0.04207121208310127, "3125": 0.08064348995685577, "3128": 0.06154331564903259, "3140": 0.08782484382390976, "3144": 0.16690383851528168, "3223": 0.26446542143821716, "3231": 0.7229714393615723, "3291": 0.27934664487838745, "3378": 0.08871890604496002, "3426": 0.04113444685935974, "3435": 0.554580807685852, "3452": 0.35334911942481995, "3463": 0.3127557039260864, "3466": 0.1229778528213501, "3471": 0.18816383183002472, "3526": 0.30486753582954407, "3532": 0.08154398202896118, "3540": 0.6619023680686951, "3603": 0.15943801403045654, "3633": 0.16690383851528168, "3676": 0.7201237678527832, "3768": 0.1011524572968483, "3795": 0.2184450328350067, "3800": 0.0019512200960889459, "3818": 0.20501139760017395, "3891": 0.19541899859905243, "3898": 0.4177590310573578, "3905": 0.9333322048187256, "3949": 0.0770333781838417, "4044": 0.45870962738990784, "4072": 0.12986256182193756, "4117": 0.2622140049934387, "4146": 0.0058422754518687725, "4219": 0.36290550231933594, "4244": 0.01934296265244484, "4295": 0.8340972661972046, "4328": 0.7925328612327576, "4348": 0.6471850275993347, "4359": 0.11343330889940262, "4442": 0.07431721687316895, "4453": 0.17267228662967682, "4483": 0.3615458607673645, "4504": 0.23247487843036652, "4525": 0.11430477350950241, "4621": 0.6260011196136475, "4632": 0.021256839856505394, "4652": 0.8550800085067749, "4719": 0.16359257698059082, "4725": 0.045809537172317505, "4758": 0.43875885009765625, "4761": 0.09672962874174118, "4839": 0.40806588530540466, "4841": 0.5010119676589966, "4866": 0.29109421372413635, "4919": 0.27786844968795776, "4962": 0.5651806592941284, "4969": 0.6573580503463745, "5092": 0.10555581003427505, "5133": 0.07612881064414978, "5152": 0.029824240133166313, "5201": 0.2607102394104004, "5244": 0.45994341373443604, "5257": 0.3956514894962311, "5305": 0.6374238729476929, "5320": 0.06429435312747955, "5360": 0.09672962874174118, "5387": 0.6921701431274414, "5393": 0.03266380727291107, "5427": 0.13157635927200317, "5456": 0.011650617234408855, "5478": 0.2800849378108978, "5542": 0.06977381557226181, "5547": 0.1751343309879303, "5587": 0.10467668622732162, "5604": 0.6054253578186035, "5636": 0.5701626539230347, "5656": 0.4248080551624298, "5699": 0.861702561378479, "5761": 0.04207121208310127, "5815": 0.29255300760269165, "5845": 0.05786345899105072, "5852": 0.6613984704017639, "5857": 0.03266380727291107, "5876": 0.6043586730957031, "5918": 0.026025565341114998, "5942": 0.26446542143821716, "6151": 0.7969439625740051, "6162": 0.2493593990802765, "6292": 0.1905880719423294, "6313": 0.05970508232712746, "6420": 0.015504186972975731, "6464": 0.3005385100841522, "6526": 0.3388410806655884, "6612": 0.2409527748823166, "6633": 0.055094651877880096, "6691": 0.24018502235412598, "6727": 0.5127768516540527, "6747": 0.5882205963134766, "6845": 0.05786345899105072, "6912": 0.40220460295677185, "6924": 0.1685553640127182, "6934": 1.2181298732757568, "7028": 0.02792670577764511, "7076": 0.0354953333735466, "7080": 0.8973627090454102, "7095": 0.11691460013389587, "7102": 0.1485546976327896, "7139": 1.0894558429718018, "7179": 0.04953393340110779, "7242": 0.10906458646059036, "7312": 0.42608439922332764, "7320": 0.4537591338157654, "7355": 0.06977381557226181, "7387": 0.2089812457561493, "7403": 0.6374238729476929, "7405": 0.6160298585891724, "7438": 0.05694137513637543, "7461": 0.05139094591140747, "7528": 0.05970508232712746, "7578": 0.4980490207672119, "7591": 0.8500841856002808, "7630": 0.25845035910606384, "7645": 0.08961215615272522, "7662": 0.025073638185858727, "7692": 0.3903779089450836, "7711": 0.4374985992908478, "7718": 0.2976420819759369, "7778": 0.22548456490039825, "7863": 0.12038381397724152, "7870": 0.7737906575202942, "7965": 0.05417001247406006, "8010": 0.1332872211933136, "8020": 0.4812922179698944, "8082": 0.12986256182193756, "8144": 0.24401791393756866, "8161": 0.030771657824516296, "8290": 0.7267557382583618, "8293": 0.4574742913246155, "8321": 0.6714286804199219, "8387": 0.34508460760116577, "8433": 0.8715548515319824, "8481": 0.12642613053321838, "8649": 0.347847044467926, "8729": 0.7191727757453918, "8738": 0.40285754203796387, "8778": 0.06246116757392883, "8830": 0.8100618124008179, "8832": 0.03925827145576477, "8906": 0.7528522610664368, "9002": 0.4574742913246155, "9030": 0.02887592278420925, "9156": 0.30486753582954407, "9165": 0.39696553349494934, "9287": 0.6989894509315491, "9323": 0.11604541540145874, "9429": 0.07612881064414978, "9525": 0.48430517315864563, "9556": 0.021256839856505394, "9560": 0.18004031479358673, "9580": 0.7683706283569336, "9614": 0.18816383183002472, "9701": 0.2659635543823242, "9737": 0.22157983481884003, "9740": 0.9805850982666016, "9756": 0.32341301441192627, "9820": 0.12642613053321838, "9867": 0.19622190296649933, "9871": 0.24554696679115295, "9895": 0.06154331564903259, "9942": 0.603290855884552, "9983": 0.3883931338787079, "10058": 0.03925827145576477, "10061": 0.7163142561912537, "10092": 0.3262358605861664, "10266": 0.9139442443847656, "10502": 0.10731173306703568, "10640": 0.4855078160762787, "10719": 0.3464667797088623, "10723": 0.3443928062915802, "10744": 0.0913962796330452, "10748": 0.02412080205976963, "10788": 0.7473171949386597, "10823": 0.49864232540130615, "10859": 1.0193830728530884, "10910": 0.06246116757392883, "10925": 0.1718502640724182, "11095": 0.37707099318504333, "11154": 0.2089812457561493, "11156": 0.5278670787811279, "11211": 0.018384648486971855, "11326": 0.9455460906028748, "11377": 0.4770587682723999, "11441": 0.6139179468154907, "11463": 0.5860490798950195, "11487": 0.47766464948654175, "11506": 0.11691460013389587, "11566": 0.6317287683486938, "11616": 0.8699195384979248, "11806": 0.8893690705299377, "11835": 0.5685047507286072, "11856": 0.2531573474407196, "11884": 0.28890204429626465, "11934": 0.11951763927936554, "12115": 0.8143964409828186, "12123": 0.7144040465354919, "12130": 0.4734157919883728, "12238": 0.5370414853096008, "12334": 0.06429435312747955, "12353": 0.5410289764404297, "12477": 0.036437395960092545, "12763": 0.6317287683486938, "12921": 0.8022117614746094, "12955": 0.3777405619621277, "13070": 0.022212404757738113, "13105": 0.18492233753204346, "13447": 0.004870930220931768, "13481": 0.04207121208310127, "13491": 0.13414156436920166, "13543": 0.058784693479537964, "13585": 0.007782140281051397, "13625": 0.1358480453491211, "13820": 0.19541899859905243, "13841": 0.34023189544677734, "14125": 0.1734936386346817, "14384": 0.23864774405956268, "14398": 0.029824240133166313, "14471": 0.2089812457561493, "14613": 0.026976587250828743, "14639": 0.7746911644935608, "14671": 1.335720419883728, "14676": 0.1332872211933136, "14800": 0.08244366943836212, "14841": 0.1358480453491211, "14864": 0.13499516248703003, "14930": 0.03360854089260101, "14971": 0.1946154683828354, "15000": 0.11081436276435852, "15101": 0.1229778528213501, "15157": 0.3325583338737488, "15189": 0.016465263441205025, "15463": 0.10555581003427505, "15502": 0.20022670924663544, "15877": 0.31845372915267944, "15909": 0.7683706283569336, "15982": 0.38441169261932373, "16028": 0.09228714555501938, "16169": 0.7408206462860107, "16263": 0.3526630103588104, "16311": 0.9987343549728394, "16387": 0.7009293437004089, "16396": 0.49626702070236206, "16452": 0.28890204429626465, "16474": 0.7380234599113464, "16514": 0.2470736801624298, "16605": 0.4132472574710846, "16670": 0.083342544734478, "16778": 0.04113444685935974, "16831": 0.026976587250828743, "16844": 0.08244366943836212, "16884": 0.3027053773403168, "16893": 0.04487626627087593, "17194": 0.13071982562541962, "17214": 0.01934296265244484, "17245": 0.22937409579753876, "17289": 0.08244366943836212, "17404": 0.13414156436920166, "17503": 0.2696990668773651, "17577": 0.9115922451019287, "17694": 0.5517725944519043, "17851": 0.29473719000816345, "18039": 0.10993985831737518, "18076": 1.022197961807251, "18137": 0.34023189544677734, "18231": 0.034552380442619324, "18239": 0.1751343309879303, "18240": 0.41840189695358276, "18275": 0.5045560002326965, "18410": 0.21687394380569458, "18423": 1.0123108625411987, "18428": 0.0606246218085289, "18595": 0.0770333781838417, "18609": 0.04767346754670143, "18793": 0.27342069149017334, "18855": 0.7500885725021362, "18888": 0.1718502640724182, "19132": 0.3547199070453644, "19335": 0.14179791510105133, "19388": 0.8957691192626953, "20272": 0.8608771562576294, "20647": 0.056018441915512085, "20694": 0.2018241584300995, "20915": 1.216973900794983, "20960": 0.025073638185858727, "21150": 0.3325583338737488, "21414": 0.17922431230545044, "21557": 0.3949938118457794, "21693": 0.11256109178066254, "21935": 0.15275461971759796, "22117": 1.4633277654647827, "22172": 0.07341018319129944, "22597": 0.7076893448829651, "22870": 1.1134753227233887, "22931": 0.04207121208310127, "22939": 0.5116065740585327, "23041": 0.029824240133166313, "23238": 0.7647408246994019, "23328": 0.06703783571720123, "23368": 0.3683255612850189, "23713": 0.272677481174469, "23746": 0.2969166338443756, "23760": 0.7057625651359558, "23867": 0.3034266233444214, "24333": 0.7201237678527832, "24505": 0.2918238639831543, "24529": 0.4926934838294983, "24552": 0.04674193635582924, "24759": 0.045809537172317505, "24766": 0.08244366943836212, "24854": 0.09050461649894714, "25006": 0.23556606471538544, "25027": 0.10731173306703568, "25032": 0.304147332906723, "25437": 0.5021947622299194, "25643": 1.2273306846618652, "25817": 0.151916041970253, "25971": 0.0752234235405922, "26022": 0.043007105588912964, "26319": 0.20977331697940826, "26419": 0.3443928062915802, "26629": 0.15860503911972046, "26651": 0.05786345899105072, "26728": 0.27786844968795776, "26745": 0.7889899015426636, "26835": 0.0058422754518687725, "26876": 0.02887592278420925, "26986": 0.848413348197937, "27423": 0.4909018874168396, "27438": 0.011650617234408855, "27514": 0.13243216276168823, "27615": 0.17922431230545044, "27695": 0.13499516248703003, "27833": 0.03831886500120163, "28093": 0.29981520771980286, "28321": 0.21372433006763458, "28428": 0.02412080205976963, "28600": 0.1913948506116867, "28749": 0.1221139207482338, "29098": 0.5174443125724792, "29361": 0.021256839856505394, "29365": 0.07250232994556427} | 12662435 | Abstract | Populations of African descent are at the forefront of the worldwide epidemic of type 2 diabetes mellitus (T2DM). The burden of T2DM is amplified by diagnosis after preventable complications of the disease have occurred. Earlier detection would result in a reduction in undiagnosed T2DM, more accurate statistics, more informed resource allocation and better health. An underappreciated factor contributing to undiagnosed T2DM in populations of African descent is that screening tests for hyperglycaemia, specifically, fasting plasma glucose and HbA1c, perform sub‐optimally in these populations. To offset this problem, combining tests or adding glycated albumin (a nonfasting marker of glycaemia), might be the way forward. However, differences in diet, exercise, BMI, environment, gene‐environment interactions and the prevalence of sickle cell trait mean that neither diagnostic tests nor interventions will be uniformly effective in individuals of African, Caribbean or African‐American descent. Among these three populations of African descent, intensive lifestyle interventions have been reported in only the African‐American population, in which they have been found to provide effective primary prevention of T2DM but not secondary prevention. Owing to a lack of health literacy and poor glycaemic control in Africa and the Caribbean, customized lifestyle interventions might achieve both secondary and primary prevention. Overall, diagnosis and prevention of T2DM requires innovative strategies that are sensitive to the diversity that exists within populations of African descent. | Reversing the tide — diagnosis and prevention of T2DM in populations of African descent |
{"1017": 0.05046287178993225, "1041": 0.18816383183002472, "1043": 0.25088030099868774, "2000": 0.05046287178993225, "2001": 0.01934296265244484, "2005": 0.3560888469219208, "2029": 0.025073638185858727, "2044": 0.3723714053630829, "2051": 0.2607102394104004, "2058": 0.0029254043474793434, "2067": 0.5871354341506958, "2072": 0.06886265426874161, "2075": 0.040196798741817474, "2086": 0.16524957120418549, "2092": 0.037378571927547455, "2093": 0.42353010177612305, "2098": 0.3409265875816345, "2106": 0.16359257698059082, "2109": 0.09672962874174118, "2116": 0.47584590315818787, "2125": 0.07884006202220917, "2129": 0.15526613593101501, "2132": 0.4728073179721832, "2146": 0.8109301924705505, "2147": 0.3127557039260864, "2169": 0.08603433519601822, "2172": 0.08961215615272522, "2177": 0.603290855884552, "2185": 0.12986256182193756, "2190": 0.28155985474586487, "2197": 0.07250232994556427, "2202": 0.18329764902591705, "2203": 0.05786345899105072, "2204": 0.04860413447022438, "2227": 0.1485546976327896, "2236": 0.5427330136299133, "2290": 0.956112265586853, "2322": 0.02792670577764511, "2335": 0.12728634476661682, "2363": 0.38041436672210693, "2393": 0.10467668622732162, "2411": 0.5450005531311035, "2416": 0.034552380442619324, "2445": 0.34370049834251404, "2470": 0.31132611632347107, "2471": 0.011650617234408855, "2483": 0.9546096324920654, "2488": 0.012615402229130268, "2491": 0.6064908504486084, "2497": 0.022212404757738113, "2499": 0.013579257763922215, "2551": 0.16690383851528168, "2565": 0.1384023278951645, "2566": 0.272677481174469, "2573": 0.05786345899105072, "2574": 0.14518201351165771, "2607": 0.3949938118457794, "2625": 0.14095009863376617, "2644": 0.2447827309370041, "2706": 0.574020504951477, "2731": 1.2313295602798462, "2733": 0.6902132034301758, "2764": 0.21530038118362427, "2817": 0.43875885009765625, "2836": 0.7592713832855225, "2847": 0.11081436276435852, "2855": 0.08782484382390976, "2864": 0.25694093108177185, "2886": 0.2689530849456787, "2913": 0.28743788599967957, "2920": 0.037378571927547455, "2936": 0.03831886500120163, "2949": 0.1212492436170578, "2967": 0.39367714524269104, "2980": 0.21214580535888672, "3096": 0.8074519634246826, "3112": 0.38041436672210693, "3134": 0.4196864068508148, "3141": 0.12384103983640671, "3143": 0.4337083101272583, "3144": 0.36967599391937256, "3147": 0.19220098853111267, "3174": 0.4556184411048889, "3204": 0.06977381557226181, "3218": 0.7800771594047546, "3227": 0.06520967930555344, "3231": 0.6543170213699341, "3255": 0.4286321699619293, "3273": 0.3297532796859741, "3276": 0.6348392367362976, "3294": 0.2918238639831543, "3325": 0.01934296265244484, "3345": 0.8666408061981201, "3431": 0.07612881064414978, "3435": 0.12384103983640671, "3450": 0.009718249551951885, "3454": 0.08961215615272522, "3463": 0.23324857652187347, "3466": 0.3241194784641266, "3550": 0.1930064558982849, "3623": 0.176772341132164, "3679": 0.04860413447022438, "3684": 0.8143964409828186, "3698": 0.018384648486971855, "3742": 0.8641747236251831, "3774": 0.0606246218085289, "3785": 0.4879087805747986, "3896": 0.2667117714881897, "3929": 0.17267228662967682, "3949": 0.4330752193927765, "3979": 0.47463157773017883, "3989": 0.6907027959823608, "4010": 0.4177590310573578, "4055": 0.24171993136405945, "4083": 0.07431721687316895, "4118": 0.05046287178993225, "4127": 0.016465263441205025, "4146": 0.2561853528022766, "4157": 0.10026945173740387, "4178": 0.09761575609445572, "4280": 0.015504186972975731, "4335": 0.18167030811309814, "4359": 0.255429208278656, "4374": 0.2160874605178833, "4488": 0.045809537172317505, "4491": 0.49626702070236206, "4499": 0.040196798741817474, "4553": 0.09938567131757736, "4621": 0.5466978549957275, "4650": 0.16690383851528168, "4658": 0.2026219218969345, "4685": 0.2881702482700348, "4719": 0.13755162060260773, "4725": 0.14686977863311768, "4738": 0.8366385698318481, "4758": 0.4318077862262726, "4812": 0.5162794589996338, "4860": 1.076228141784668, "4882": 0.5651806592941284, "5020": 0.16524957120418549, "5022": 0.6070231795310974, "5031": 0.10818854719400406, "5082": 0.4267219603061676, "5084": 0.5506471395492554, "5092": 0.10203468054533005, "5147": 0.18167030811309814, "5159": 0.23247487843036652, "5219": 0.8425432443618774, "5224": 0.14179791510105133, "5301": 0.7163142561912537, "5335": 0.7105726003646851, "5352": 0.18654440343379974, "5418": 0.0009760859538801014, "5441": 0.17020416259765625, "5461": 0.1710275560617447, "5475": 0.018384648486971855, "5514": 0.0009760859538801014, "5547": 0.4487839937210083, "5603": 0.10203468054533005, "5604": 0.5139457583427429, "5620": 0.3464667797088623, "5770": 0.09850110858678818, "5776": 0.46853771805763245, "5799": 0.20102575421333313, "5845": 0.021256839856505394, "5852": 0.49626702070236206, "5892": 0.5968599319458008, "5963": 1.0953518152236938, "6022": 0.1930064558982849, "6026": 0.2622140049934387, "6028": 0.14602625370025635, "6075": 0.14602625370025635, "6078": 0.5483922958374023, "6130": 0.05139094591140747, "6134": 0.18573370575904846, "6162": 0.04767346754670143, "6292": 0.00875066313892603, "6388": 0.17431432008743286, "6464": 0.0058422754518687725, "6521": 0.9929623603820801, "6550": 0.08513788133859634, "6612": 0.12814582884311676, "6625": 0.06795065850019455, "6648": 1.0257055759429932, "6666": 0.3963087201118469, "6762": 0.05786345899105072, "6818": 0.012615402229130268, "6897": 0.15860503911972046, "6911": 0.2478361576795578, "6912": 0.46117570996284485, "6939": 0.02792670577764511, "6980": 0.05970508232712746, "7012": 0.3910386264324188, "7060": 0.07159364968538284, "7126": 0.14518201351165771, "7189": 0.1619328260421753, "7233": 0.20421554148197174, "7242": 0.6348392367362976, "7312": 0.5324648022651672, "7438": 0.15526613593101501, "7551": 0.28963330388069153, "7620": 0.7389566898345947, "7645": 0.22937409579753876, "7685": 0.15860503911972046, "7709": 0.14264501631259918, "7711": 0.46117570996284485, "7715": 0.6327666640281677, "7718": 0.371698260307312, "7733": 0.11081436276435852, "7861": 1.117955207824707, "7879": 0.2852376699447632, "7885": 0.12814582884311676, "7959": 1.1134753227233887, "8015": 0.04394211992621422, "8030": 0.1751343309879303, "8031": 0.021256839856505394, "8114": 0.06520967930555344, "8161": 0.23787821829319, "8363": 0.4437839686870575, "8377": 0.7755908370018005, "8564": 0.06246116757392883, "8649": 0.0317181795835495, "8676": 0.567397952079773, "8737": 0.14602625370025635, "8778": 0.18492233753204346, "8853": 0.016465263441205025, "8915": 0.6548244953155518, "8961": 0.016465263441205025, "8980": 0.30917787551879883, "9032": 0.41840189695358276, "9051": 0.32553088665008545, "9113": 0.20022670924663544, "9229": 0.4286321699619293, "9312": 0.0354953333735466, "9349": 0.10379679501056671, "9355": 0.5232481360435486, "9367": 0.45251765847206116, "9436": 0.4337083101272583, "9462": 0.08064348995685577, "9483": 0.8534175157546997, "9526": 0.18816383183002472, "9560": 0.06612417846918106, "9573": 0.1889725625514984, "9614": 0.7389566898345947, "9685": 0.23710809648036957, "9751": 0.06246116757392883, "9756": 0.11865071207284927, "9829": 1.3377727270126343, "9879": 0.06612417846918106, "9885": 0.11604541540145874, "9999": 0.07341018319129944, "10003": 0.055094651877880096, "10089": 0.03925827145576477, "10354": 0.0019512200960889459, "10365": 0.678390383720398, "10440": 0.25694093108177185, "10808": 0.37304413318634033, "10847": 0.4437839686870575, "10867": 0.23402166366577148, "10924": 0.04767346754670143, "11005": 0.31132611632347107, "11007": 0.08871890604496002, "11027": 0.6000806093215942, "11110": 0.37907835841178894, "11201": 0.306306391954422, "11520": 0.2674594223499298, "11806": 0.23092569410800934, "12154": 0.07793712615966797, "12221": 0.48430517315864563, "12247": 0.13755162060260773, "12336": 0.09495500475168228, "12353": 0.4286321699619293, "12399": 0.016465263441205025, "12435": 0.09050461649894714, "12560": 0.16607704758644104, "12637": 0.13499516248703003, "12959": 0.3910386264324188, "13046": 0.20977331697940826, "13105": 0.08513788133859634, "13318": 0.06246116757392883, "13341": 0.007782140281051397, "13416": 0.3012613356113434, "13441": 0.22937409579753876, "13512": 0.06520967930555344, "13595": 0.15777134895324707, "13804": 0.24018502235412598, "14184": 0.02887592278420925, "14372": 0.46486347913742065, "14611": 0.176772341132164, "14617": 0.0029254043474793434, "14651": 0.02316705882549286, "14978": 1.4597045183181763, "15295": 0.10379679501056671, "15349": 0.37371641397476196, "15804": 0.23092569410800934, "15946": 0.34922540187835693, "16012": 1.195341944694519, "16175": 0.4794800877571106, "16670": 0.19622190296649933, "16684": 0.1212492436170578, "16754": 0.06886265426874161, "16817": 0.04860413447022438, "16902": 0.36697331070899963, "17225": 0.3963087201118469, "17336": 0.016465263441205025, "18279": 0.07341018319129944, "18940": 0.09672962874174118, "18960": 0.15860503911972046, "19117": 1.2353124618530273, "19124": 1.3377727270126343, "19613": 0.7647408246994019, "20353": 0.3339579105377197, "20858": 0.1994270235300064, "20900": 0.24325250089168549, "20906": 0.3241194784641266, "21150": 0.3381449282169342, "21391": 0.15526613593101501, "21992": 0.6466736793518066, "22318": 0.42735910415649414, "22415": 0.05139094591140747, "22442": 0.05046287178993225, "23296": 0.026976587250828743, "23367": 0.3547199070453644, "23370": 1.104454517364502, "23479": 0.38174858689308167, "23654": 0.42096930742263794, "23900": 0.15610189735889435, "24251": 0.08692999184131622, "24689": 0.17267228662967682, "24840": 0.41001203656196594, "25006": 0.3560888469219208, "25027": 0.026976587250828743, "25353": 0.1751343309879303, "25837": 0.02792670577764511, "25993": 0.12556517124176025, "26456": 1.261651873588562, "26758": 0.5773153901100159, "27090": 0.6107416749000549, "27918": 0.11778303235769272, "28215": 0.07159364968538284, "28428": 0.11343330889940262, "28696": 0.10731173306703568, "29023": 0.20739519596099854, "29031": 0.39367714524269104, "29212": 0.13414156436920166} | 12667988 | Twenty-seven migraine headache patients were divided into three equal groups which received thermal biofeedback, frontalis EMG biofeedback, or relaxation training. Training was given under "massed" practice conditions (nine sessions per week) and consisted of 18 training sessions and six test-generalisation sessions. While improvements in headaches were observed in all groups, the best improvements took place in the thermal biofeedback group, which had almost complete elimination of migraine attacks by the end of training, and maintained that performance as long as six months after training. Examination of the patterns of skin temperature and EMG changes in the three groups over the course of training also points to a relationship between skin temperature control and reduction in migraine headache symptomatology, and suggests that this relationship is worthy of further investigation. | Biofeedback and relaxation in the treatment of migraine headaches: comparative effectiveness and physiological correlates. |
{"1011": 0.5707147121429443, "1015": 0.1212492436170578, "1017": 0.07341018319129944, "1039": 0.8264343738555908, "1044": 0.401551216840744, "1045": 0.47158926725387573, "2000": 0.04207121208310127, "2002": 0.0797421783208847, "2003": 0.19220098853111267, "2005": 0.18411032855510712, "2007": 0.3134697377681732, "2011": 0.06429435312747955, "2029": 0.14349138736724854, "2034": 0.05417001247406006, "2048": 0.18167030811309814, "2058": 0.03925827145576477, "2063": 0.4462870955467224, "2075": 0.1685553640127182, "2078": 0.06154331564903259, "2083": 0.7276995778083801, "2093": 0.2719337046146393, "2109": 0.38441169261932373, "2152": 0.5255602598190308, "2170": 0.4041621685028076, "2182": 0.2409527748823166, "2224": 0.30989447236061096, "2240": 0.16442140936851501, "2241": 0.450652539730072, "2248": 0.05139094591140747, "2278": 0.6833335757255554, "2291": 0.036437395960092545, "2312": 0.1358480453491211, "2362": 0.018384648486971855, "2478": 0.06612417846918106, "2487": 0.03831886500120163, "2491": 0.14179791510105133, "2512": 0.2478361576795578, "2529": 0.42799583077430725, "2532": 1.1659544706344604, "2620": 0.20977331697940826, "2649": 0.2247048318386078, "2828": 0.37304413318634033, "2832": 0.40546512603759766, "2836": 0.0797421783208847, "2839": 0.029824240133166313, "2864": 0.09938567131757736, "2869": 0.14179791510105133, "2922": 0.08692999184131622, "2944": 0.009718249551951885, "2974": 0.7610978484153748, "2986": 0.6553317308425903, "3020": 0.10026945173740387, "3029": 0.9139442443847656, "3132": 0.562402069568634, "3177": 0.040196798741817474, "3210": 0.3485364317893982, "3232": 0.4487839937210083, "3252": 0.1212492436170578, "3284": 0.43875885009765625, "3305": 0.04674193635582924, "3330": 0.02792670577764511, "3351": 0.009718249551951885, "3366": 1.5023398399353027, "3370": 0.6000806093215942, "3375": 0.7408206462860107, "3401": 0.10291612148284912, "3405": 0.25239890813827515, "3447": 0.02792670577764511, "3463": 0.18654440343379974, "3512": 0.0317181795835495, "3526": 0.49982786178588867, "3563": 0.5301685929298401, "3565": 0.7728893756866455, "3594": 0.2493593990802765, "3597": 0.3995884954929352, "3670": 0.6197150945663452, "3698": 0.14349138736724854, "3795": 1.0073304176330566, "3800": 0.052318159490823746, "3811": 0.13071982562541962, "3853": 0.045809537172317505, "3921": 0.5860490798950195, "3935": 0.6070231795310974, "3936": 0.04113444685935974, "3940": 0.24325250089168549, "3967": 0.817850649356842, "3989": 0.3318578004837036, "4007": 0.2470736801624298, "4048": 0.2689530849456787, "4094": 0.6654226183891296, "4106": 0.3554046154022217, "4110": 0.5080875158309937, "4114": 0.6970458030700684, "4117": 0.2018241584300995, "4118": 0.9045027494430542, "4127": 0.3034266233444214, "4143": 0.030771657824516296, "4162": 0.3485364317893982, "4270": 0.007782140281051397, "4286": 0.3304552733898163, "4294": 0.684319257736206, "4411": 0.25088030099868774, "4442": 0.27342069149017334, "4539": 0.567951500415802, "4667": 0.49923527240753174, "4697": 0.36290550231933594, "4710": 0.31204116344451904, "4725": 0.8332487344741821, "4758": 0.48008447885513306, "4824": 0.3588210940361023, "4876": 0.09584271162748337, "4931": 0.07612881064414978, "4944": 0.06429435312747955, "4949": 0.6296497583389282, "4957": 0.28082266449928284, "4962": 0.7881022095680237, "4969": 0.11256109178066254, "5056": 0.10731173306703568, "5083": 0.29328158497810364, "5252": 0.04394211992621422, "5257": 0.11343330889940262, "5292": 0.4337083101272583, "5301": 0.5220900774002075, "5335": 0.32058215141296387, "5425": 1.278652548789978, "5449": 0.4400174915790558, "5461": 0.6410312056541443, "5502": 0.3547199070453644, "5514": 0.0038986403960734606, "5537": 0.20977331697940826, "5549": 0.09584271162748337, "5562": 0.3388410806655884, "5577": 0.1212492436170578, "5585": 0.5398913025856018, "5616": 0.1485546976327896, "5787": 0.11343330889940262, "5799": 0.30486753582954407, "5813": 0.9037119746208191, "5906": 0.175953671336174, "6022": 0.42735910415649414, "6026": 0.42990362644195557, "6028": 0.7105726003646851, "6062": 0.045809537172317505, "6064": 1.4918501377105713, "6162": 0.0317181795835495, "6169": 0.0913962796330452, "6194": 0.08154398202896118, "6235": 0.2711893916130066, "6315": 0.05970508232712746, "6364": 0.37907835841178894, "6522": 0.11343330889940262, "6537": 0.15610189735889435, "6549": 0.1229778528213501, "6551": 0.603290855884552, "6627": 0.09050461649894714, "6786": 0.6466736793518066, "6872": 0.016465263441205025, "6903": 0.22937409579753876, "6924": 0.4788752794265747, "6970": 0.5751199722290039, "6994": 0.09495500475168228, "7264": 0.319873183965683, "7337": 0.4132472574710846, "7341": 0.6043586730957031, "7359": 0.401551216840744, "7362": 0.04674193635582924, "7366": 0.2637155055999756, "7367": 0.28450319170951843, "7371": 0.5816917419433594, "7403": 0.6420594453811646, "7532": 0.007782140281051397, "7595": 0.08603433519601822, "7605": 1.1153976917266846, "7620": 0.0038986403960734606, "7632": 1.4189581871032715, "7689": 0.04767346754670143, "7709": 0.4158279001712799, "7711": 0.2089812457561493, "7721": 0.8264343738555908, "7741": 0.5871354341506958, "7775": 0.045809537172317505, "7889": 0.43938836455345154, "7910": 0.0606246218085289, "7915": 0.07884006202220917, "8043": 0.15023678541183472, "8107": 0.4437839686870575, "8114": 0.4487839937210083, "8122": 0.5483922958374023, "8171": 0.04207121208310127, "8278": 0.1946154683828354, "8303": 0.8885661959648132, "8346": 0.018384648486971855, "8377": 0.176772341132164, "8552": 0.04953393340110779, "8583": 0.5104349255561829, "8651": 0.01934296265244484, "8778": 0.15359249711036682, "8789": 0.822151780128479, "8853": 0.21372433006763458, "8893": 0.007782140281051397, "8991": 0.440646231174469, "9007": 0.8699195384979248, "9096": 0.24554696679115295, "9099": 0.02887592278420925, "9165": 0.8383291959762573, "9214": 0.004870930220931768, "9232": 0.20022670924663544, "9259": 0.08064348995685577, "9260": 0.2637155055999756, "9407": 0.056018441915512085, "9412": 0.5662899017333984, "9416": 0.7144040465354919, "9447": 0.06612417846918106, "9468": 0.2741633653640747, "9539": 0.23710809648036957, "9646": 0.1510767638683319, "9812": 0.19381128251552582, "9849": 0.3127557039260864, "9896": 0.45623743534088135, "10057": 0.04487626627087593, "10266": 0.32129061222076416, "10341": 0.47584590315818787, "10381": 0.6744182109832764, "10402": 1.1598494052886963, "10595": 0.4067663550376892, "10660": 0.04113444685935974, "10663": 0.259204238653183, "10708": 0.24018502235412598, "10787": 0.14095009863376617, "10863": 0.4734157919883728, "10939": 0.4158279001712799, "11022": 0.9131608605384827, "11160": 0.34023189544677734, "11163": 0.09761575609445572, "11211": 0.7656494975090027, "11383": 0.06795065850019455, "11409": 1.216395378112793, "11423": 0.083342544734478, "11566": 0.2576959431171417, "11598": 0.8666408061981201, "11619": 0.056018441915512085, "11636": 0.12642613053321838, "11643": 0.09584271162748337, "11649": 0.935633659362793, "11847": 1.0172666311264038, "12016": 0.0038986403960734606, "12099": 0.07250232994556427, "12126": 0.35745587944984436, "12185": 0.5370414853096008, "12188": 0.0029254043474793434, "12326": 0.20580662786960602, "12375": 1.072225570678711, "12546": 0.3870677351951599, "12562": 0.176772341132164, "12637": 0.1477125883102417, "12739": 0.1734936386346817, "12789": 0.1751343309879303, "12987": 0.9783848524093628, "13159": 0.0354953333735466, "13296": 0.674915611743927, "13369": 0.06703783571720123, "13458": 0.9769153594970703, "13538": 0.02412080205976963, "13589": 0.010684899985790253, "13594": 0.3416208028793335, "13722": 0.2969166338443756, "13729": 0.03925827145576477, "13792": 0.41001203656196594, "13995": 0.0317181795835495, "14126": 0.4537591338157654, "14134": 0.04953393340110779, "14193": 0.47463157773017883, "14388": 0.04207121208310127, "14471": 0.39762192964553833, "15113": 0.018384648486971855, "15420": 0.08782484382390976, "15472": 0.129004567861557, "15543": 0.8517522215843201, "15778": 0.6410312056541443, "16119": 0.1970241367816925, "16134": 0.6970458030700684, "16281": 0.3070250153541565, "16285": 0.9798521995544434, "16360": 0.47584590315818787, "16452": 0.6059582233428955, "16505": 0.42735910415649414, "16706": 1.1185935735702515, "16803": 0.20102575421333313, "16840": 0.9754437208175659, "16924": 0.06703783571720123, "17715": 0.6989894509315491, "17908": 0.12728634476661682, "17975": 0.33115679025650024, "18231": 0.37640097737312317, "18260": 0.11343330889940262, "18274": 0.8057082891464233, "18345": 0.0009760859538801014, "18780": 1.1406835317611694, "18853": 0.41195443272590637, "18856": 0.058784693479537964, "18953": 0.12470348179340363, "19012": 0.2160874605178833, "19345": 0.026025565341114998, "19566": 0.8534175157546997, "19780": 0.9980146884918213, "20226": 0.3034266233444214, "20240": 0.11430477350950241, "20363": 1.1198691129684448, "20600": 0.27786844968795776, "20939": 0.04207121208310127, "21150": 0.03360854089260101, "21647": 0.11517547070980072, "21688": 0.10291612148284912, "21716": 0.8788808584213257, "21852": 0.09050461649894714, "22013": 0.27786844968795776, "22026": 0.24325250089168549, "22415": 0.5186077356338501, "22471": 0.029824240133166313, "22718": 0.4145384132862091, "22731": 0.09495500475168228, "22778": 0.06520967930555344, "22863": 0.15526613593101501, "22933": 0.1221139207482338, "23191": 0.09406650811433792, "23274": 0.5347557663917542, "23701": 0.07068414986133575, "23758": 1.0567318201065063, "23767": 0.025073638185858727, "23797": 0.20977331697940826, "24370": 0.02887592278420925, "24490": 0.05970508232712746, "24558": 0.5596157908439636, "24821": 0.1905880719423294, "24840": 0.052318159490823746, "25002": 0.23247487843036652, "25169": 0.11604541540145874, "25524": 0.37907835841178894, "25932": 0.03831886500120163, "26236": 0.0797421783208847, "26242": 0.04674193635582924, "26512": 0.854249119758606, "26520": 0.08782484382390976, "26572": 0.49923527240753174, "26775": 0.7987030148506165, "26872": 0.7276995778083801, "26874": 0.9493325352668762, "27022": 0.16276304423809052, "27046": 0.15610189735889435, "27169": 0.16524957120418549, "27404": 0.10906458646059036, "27605": 0.040196798741817474, "27642": 0.7028654217720032, "28424": 1.17624831199646, "28472": 0.10203468054533005, "28835": 0.12814582884311676, "29304": 0.24171993136405945} | 12669325 | High-throughput methods based on chromosome conformation capture have greatly advanced our understanding of the three-dimensional (3D) organization of genomes but are limited in resolution by their reliance on restriction enzymes. Here we describe a method called DNase Hi-C for comprehensively mapping global chromatin contacts. DNase Hi-C uses DNase I for chromatin fragmentation, leading to greatly improved efficiency and resolution over that of Hi-C. Coupling this method with DNA-capture technology provides a high-throughput approach for targeted mapping of fine-scale chromatin architecture. We applied targeted DNase Hi-C to characterize the 3D organization of 998 large intergenic noncoding RNA (lincRNA) promoters in two human cell lines. Our results revealed that expression of lincRNAs is tightly controlled by complex mechanisms involving both super-enhancers and the Polycomb repressive complex. Our results provide the first glimpse of the cell type-specific 3D organization of lincRNA genes. | Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes |
{"1011": 0.10467668622732162, "1016": 0.20660123229026794, "1044": 0.4914994537830353, "1045": 0.8298473954200745, "1048": 0.6202403903007507, "1049": 0.33953672647476196, "1056": 0.5517725944519043, "2008": 0.025073638185858727, "2010": 0.7314660549163818, "2011": 0.3325583338737488, "2015": 0.04487626627087593, "2029": 0.23864774405956268, "2063": 1.1031591892242432, "2064": 0.2089812457561493, "2066": 0.4311734735965729, "2100": 0.1913948506116867, "2121": 0.3191637098789215, "2140": 0.319873183965683, "2155": 0.4926934838294983, "2229": 0.3423145115375519, "2271": 0.3554046154022217, "2331": 0.2247048318386078, "2350": 0.11691460013389587, "2370": 0.25239890813827515, "2393": 0.440646231174469, "2462": 0.24325250089168549, "2465": 0.3777405619621277, "2475": 0.3070250153541565, "2483": 0.38308101892471313, "2515": 0.14433705806732178, "2529": 0.306306391954422, "2535": 0.09050461649894714, "2537": 0.5174443125724792, "2545": 0.27934664487838745, "2550": 0.18329764902591705, "2556": 0.5712664127349854, "2575": 0.6389714479446411, "2599": 0.4617912769317627, "2668": 0.0606246218085289, "2721": 0.7701805830001831, "2828": 0.43875885009765625, "2852": 0.6207655072212219, "2877": 0.13157635927200317, "2886": 0.02316705882549286, "2891": 0.3416208028793335, "2920": 0.04207121208310127, "2945": 0.151916041970253, "2947": 0.09850110858678818, "2969": 1.237014651298523, "3161": 0.6212902665138245, "3189": 0.0174254160374403, "3209": 0.4500300884246826, "3303": 0.35745587944984436, "3351": 1.0144377946853638, "3375": 0.6813592314720154, "3378": 0.7067264318466187, "3393": 0.6410312056541443, "3406": 0.4203280806541443, "3426": 0.6497380137443542, "3433": 0.03925827145576477, "3445": 0.4145384132862091, "3450": 0.3248254358768463, "3466": 0.15359249711036682, "3526": 0.3519764244556427, "3563": 0.03925827145576477, "3623": 0.259204238653183, "3625": 0.05417001247406006, "3633": 0.18248429894447327, "3669": 0.6634125709533691, "3670": 0.10291612148284912, "3729": 0.5827828645706177, "3739": 0.09495500475168228, "3775": 0.09317722171545029, "3853": 0.12642613053321838, "3893": 0.012615402229130268, "3896": 0.14686977863311768, "3965": 0.12986256182193756, "4023": 0.7333439588546753, "4127": 0.3191637098789215, "4176": 0.09672962874174118, "4195": 0.07884006202220917, "4280": 0.11691460013389587, "4286": 0.26446542143821716, "4295": 0.6960725784301758, "4426": 0.056018441915512085, "4442": 0.5324648022651672, "4491": 0.014542185701429844, "4539": 0.9256220459938049, "4630": 0.6583697199821472, "4668": 0.19541899859905243, "4671": 0.05417001247406006, "4786": 0.07884006202220917, "4945": 0.659380316734314, "4962": 0.0752234235405922, "5034": 0.8475768566131592, "5094": 0.029824240133166313, "5228": 0.09406650811433792, "5250": 0.6363908052444458, "5260": 0.5104349255561829, "5292": 0.07159364968538284, "5320": 0.7028654217720032, "5326": 0.31132611632347107, "5360": 0.04860413447022438, "5387": 0.4818955361843109, "5739": 0.5822374224662781, "5799": 0.02887592278420925, "5812": 0.42990362644195557, "5876": 0.5827828645706177, "5939": 0.5685047507286072, "6038": 1.0207915306091309, "6562": 0.8885661959648132, "6882": 0.06612417846918106, "6887": 0.022212404757738113, "6914": 0.09850110858678818, "6968": 0.6075552701950073, "7096": 0.1710275560617447, "7137": 0.05694137513637543, "7337": 0.13157635927200317, "7352": 0.7028654217720032, "7356": 0.030771657824516296, "7361": 0.7086513638496399, "7457": 0.3027053773403168, "7461": 0.22937409579753876, "7570": 0.6149744987487793, "7591": 0.15693697333335876, "7694": 0.4487839937210083, "7711": 0.04394211992621422, "7716": 0.6265231370925903, "7770": 0.11517547070980072, "7870": 0.5370414853096008, "7889": 0.8600510358810425, "8000": 0.9783848524093628, "8171": 0.5517725944519043, "8246": 0.17431432008743286, "8285": 0.8666408061981201, "8319": 0.42225050926208496, "8360": 0.7229714393615723, "8449": 0.7086513638496399, "8458": 1.0601204633712769, "8553": 0.7182208299636841, "8670": 0.15275461971759796, "8715": 0.011650617234408855, "8870": 0.11343330889940262, "8878": 1.018678069114685, "8939": 0.0174254160374403, "9002": 0.13071982562541962, "9006": 0.4950772523880005, "9007": 0.4002431631088257, "9113": 0.10993985831737518, "9350": 0.05970508232712746, "9412": 0.07341018319129944, "9413": 0.20739519596099854, "9416": 0.5596157908439636, "9447": 0.014542185701429844, "9495": 0.1212492436170578, "9654": 0.25845035910606384, "10085": 0.35677260160446167, "10223": 0.014542185701429844, "10448": 0.045809537172317505, "10509": 0.6654226183891296, "10572": 0.1685553640127182, "10611": 0.013579257763922215, "10737": 0.436867892742157, "11158": 0.31845372915267944, "11265": 0.7934166193008423, "11290": 0.36086538434028625, "11311": 0.4580921530723572, "11320": 1.1469062566757202, "11390": 0.27934664487838745, "11432": 0.24631060659885406, "11595": 0.2478361576795578, "11598": 0.20660123229026794, "11709": 0.5534584522247314, "11778": 0.151916041970253, "11867": 0.6064908504486084, "11923": 0.11517547070980072, "12031": 0.5800528526306152, "12115": 0.08064348995685577, "12123": 0.1212492436170578, "12170": 0.015504186972975731, "12207": 1.439538836479187, "12322": 0.8332487344741821, "12328": 1.258327841758728, "12650": 0.06703783571720123, "13045": 0.6999598741531372, "13153": 0.03266380727291107, "13330": 0.09228714555501938, "13356": 0.4412745535373688, "13791": 0.9115922451019287, "13871": 0.129004567861557, "13874": 0.2160874605178833, "13922": 0.5472630262374878, "14067": 0.14518201351165771, "14126": 0.45870962738990784, "14164": 0.8264343738555908, "14234": 1.3813996315002441, "14778": 0.9944084882736206, "14863": 0.1477125883102417, "15277": 0.8161250352859497, "15403": 0.0009760859538801014, "15420": 0.2561853528022766, "15428": 0.04953393340110779, "15527": 0.04394211992621422, "15663": 0.2667117714881897, "15909": 0.14686977863311768, "16221": 0.1946154683828354, "16257": 0.8349450826644897, "16285": 0.15442965924739838, "16381": 0.35950297117233276, "16389": 0.09050461649894714, "16416": 0.684319257736206, "16605": 0.28155985474586487, "17250": 0.6916812658309937, "17379": 0.15860503911972046, "17441": 0.49030399322509766, "17926": 0.05786345899105072, "17996": 0.5415972471237183, "18714": 0.03925827145576477, "18757": 0.18492233753204346, "18900": 0.791648268699646, "18941": 0.045809537172317505, "19021": 1.2797396183013916, "19466": 1.12241530418396, "19500": 0.16442140936851501, "19620": 0.23710809648036957, "19653": 0.14518201351165771, "20187": 0.2470736801624298, "20194": 0.5220900774002075, "20226": 0.06977381557226181, "20544": 0.6563454270362854, "20582": 1.0001721382141113, "20620": 0.176772341132164, "20766": 0.03925827145576477, "20960": 0.3560888469219208, "21032": 0.12470348179340363, "21297": 0.20102575421333313, "21466": 0.2026219218969345, "21890": 0.1358480453491211, "21903": 1.1089750528335571, "21967": 0.11778303235769272, "22184": 0.0019512200960889459, "22575": 1.039613962173462, "22643": 1.3998736143112183, "22694": 0.018384648486971855, "22889": 1.17624831199646, "22930": 0.10467668622732162, "22931": 1.3998736143112183, "23041": 0.5635144114494324, "23150": 0.11168810725212097, "23216": 0.08961215615272522, "23340": 0.22937409579753876, "23586": 0.040196798741817474, "23713": 1.0881409645080566, "23900": 0.10291612148284912, "24054": 0.13243216276168823, "24129": 1.17624831199646, "24269": 0.0029254043474793434, "24335": 0.8383291959762573, "24374": 0.10203468054533005, "24471": 0.17759032547473907, "24952": 0.6358738541603088, "25125": 0.6926587820053101, "25194": 0.1970241367816925, "25761": 0.2667117714881897, "26089": 0.0770333781838417, "26402": 0.14686977863311768, "26651": 0.26146242022514343, "26688": 1.0285027027130127, "26835": 0.034552380442619324, "26986": 0.06886265426874161, "27099": 0.06520967930555344, "27391": 0.9929623603820801, "27641": 0.37371641397476196, "27781": 1.1846466064453125, "27854": 0.7907629609107971, "28156": 0.3963087201118469, "28389": 0.07341018319129944, "28788": 0.4938860833644867, "28873": 1.057410478591919} | 12670680 | In systemic lupus erythematosus (SLE), self-reactive antibodies can target the kidney (lupus nephritis), leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE causes their homing to lymph nodes, promoting T helper type 2 (T(H)2) cell differentiation and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in mice lacking the Src family protein tyrosine kinase Lyn (Lyn(-/-) mice). Individuals with SLE also have elevated serum IgE, self-reactive IgEs and activated basophils that express CD62 ligand (CD62L) and the major histocompatibility complex (MHC) class II molecule human leukocyte antigen-DR (HLA-DR), parameters that are associated with increased disease activity and active lupus nephritis. Basophils were also present in the lymph nodes and spleen of subjects with SLE. Thus, in Lyn(-/-) mice, basophils and IgE autoantibodies amplify autoantibody production that leads to lupus nephritis, and in individuals with SLE IgE autoantibodies and activated basophils are factors associated with disease activity and nephritis. | BASOPHILS AND THE T HELPER 2 ENVIRONMENT CAN PROMOTE THE DEVELOPMENT OF LUPUS NEPHRITIS |
{"1004": 0.045809537172317505, "1019": 0.03360854089260101, "1020": 0.17431432008743286, "1040": 0.07431721687316895, "1041": 0.012615402229130268, "2000": 0.10291612148284912, "2001": 0.16110190749168396, "2005": 0.07250232994556427, "2015": 0.5461324453353882, "2020": 0.07341018319129944, "2022": 0.09672962874174118, "2039": 0.13499516248703003, "2043": 0.1873544454574585, "2051": 0.4837033152580261, "2058": 0.6764062643051147, "2062": 0.15442965924739838, "2064": 0.22157983481884003, "2071": 0.03266380727291107, "2084": 0.45994341373443604, "2086": 0.2447827309370041, "2090": 0.07431721687316895, "2095": 0.1873544454574585, "2106": 0.0752234235405922, "2111": 0.05786345899105072, "2116": 0.24859806895256042, "2140": 0.07250232994556427, "2146": 0.8567397594451904, "2172": 0.2470736801624298, "2177": 0.41840189695358276, "2179": 0.10555581003427505, "2184": 0.10818854719400406, "2202": 0.1212492436170578, "2206": 0.27044451236724854, "2227": 0.5822374224662781, "2230": 0.04394211992621422, "2249": 0.7201237678527832, "2260": 0.22548456490039825, "2278": 0.052318159490823746, "2287": 0.007782140281051397, "2290": 0.4624064862728119, "2297": 0.5290185213088989, "2302": 0.417115718126297, "2312": 0.1485546976327896, "2321": 0.19782574474811554, "2323": 0.1384023278951645, "2325": 0.009718249551951885, "2335": 0.15943801403045654, "2382": 0.09228714555501938, "2389": 0.42096930742263794, "2405": 0.4855078160762787, "2411": 0.38574060797691345, "2415": 0.4374985992908478, "2416": 0.0009760859538801014, "2421": 0.30917787551879883, "2443": 0.4556184411048889, "2470": 0.77198725938797, "2484": 0.05046287178993225, "2491": 0.40351006388664246, "2532": 0.1718502640724182, "2537": 0.09761575609445572, "2550": 0.4132472574710846, "2551": 0.11604541540145874, "2556": 0.15023678541183472, "2558": 0.06337817758321762, "2560": 0.11604541540145874, "2565": 0.23864774405956268, "2566": 0.4926934838294983, "2574": 0.016465263441205025, "2578": 0.11343330889940262, "2590": 0.3297532796859741, "2625": 0.05694137513637543, "2628": 0.27934664487838745, "2689": 0.21372433006763458, "2695": 0.39696553349494934, "2706": 0.6897233724594116, "2711": 0.34922540187835693, "2729": 0.7791815400123596, "2731": 0.5914691090583801, "2733": 0.5920094847679138, "2740": 0.25845035910606384, "2777": 0.27044451236724854, "2779": 0.3141832649707794, "2781": 0.6420594453811646, "2812": 0.2501201331615448, "2817": 0.6233867406845093, "2846": 0.8332487344741821, "2847": 0.11778303235769272, "2864": 0.04674193635582924, "2871": 0.043007105588912964, "2894": 0.3381449282169342, "2902": 0.2881702482700348, "2904": 0.07884006202220917, "2913": 0.6112717390060425, "2918": 0.1602703034877777, "2923": 0.5324648022651672, "2936": 0.2741633653640747, "2939": 0.23864774405956268, "2943": 0.6970458030700684, "2946": 0.0019512200960889459, "2951": 0.1710275560617447, "2966": 0.35745587944984436, "2967": 0.3141832649707794, "2968": 0.10291612148284912, "3024": 0.2822965085506439, "3042": 0.49864232540130615, "3073": 0.12642613053321838, "3078": 1.0868242979049683, "3091": 0.2741633653640747, "3112": 0.053244512528181076, "3115": 0.007782140281051397, "3134": 0.3897167444229126, "3144": 0.00875066313892603, "3150": 0.6064908504486084, "3151": 0.6343214511871338, "3156": 0.28082266449928284, "3161": 0.04394211992621422, "3204": 0.45499902963638306, "3218": 0.23633737862110138, "3227": 0.43623676896095276, "3273": 0.25239890813827515, "3278": 0.06977381557226181, "3279": 1.0305955410003662, "3319": 0.7701805830001831, "3328": 0.3554046154022217, "3345": 0.38441169261932373, "3350": 0.04207121208310127, "3353": 0.27342069149017334, "3366": 0.5707147121429443, "3371": 0.36426326632499695, "3378": 0.4770587682723999, "3431": 0.24859806895256042, "3435": 0.07793712615966797, "3445": 0.46117570996284485, "3450": 0.20580662786960602, "3460": 0.0019512200960889459, "3463": 0.2145126610994339, "3465": 0.030771657824516296, "3466": 0.08064348995685577, "3469": 0.1212492436170578, "3497": 0.27342069149017334, "3508": 0.22079704701900482, "3517": 0.10555581003427505, "3550": 0.27786844968795776, "3558": 0.6823468804359436, "3563": 0.3423145115375519, "3582": 0.7960633039474487, "3591": 0.043007105588912964, "3593": 0.5347557663917542, "3618": 0.30989447236061096, "3623": 0.29619070887565613, "3635": 1.175042748451233, "3653": 0.25239890813827515, "3695": 0.06246116757392883, "3737": 0.6734226942062378, "3742": 0.15275461971759796, "3788": 0.6679295301437378, "3841": 0.36086538434028625, "3867": 0.053244512528181076, "3891": 0.06246116757392883, "3905": 0.026976587250828743, "3949": 0.7105726003646851, "3965": 0.18573370575904846, "3970": 0.030771657824516296, "3974": 0.4337083101272583, "3979": 0.8161250352859497, "4012": 0.055094651877880096, "4023": 0.5110208988189697, "4050": 0.0770333781838417, "4076": 0.22548456490039825, "4081": 0.23710809648036957, "4102": 0.2105647772550583, "4106": 0.5751199722290039, "4146": 0.20501139760017395, "4225": 0.16607704758644104, "4227": 0.25239890813827515, "4229": 0.029824240133166313, "4233": 0.014542185701429844, "4263": 0.7342816591262817, "4292": 0.3283478021621704, "4328": 0.053244512528181076, "4346": 0.1751343309879303, "4359": 0.36426326632499695, "4391": 0.28670501708984375, "4558": 0.5651806592941284, "4621": 0.2689530849456787, "4642": 0.8989537954330444, "4654": 0.1011524572968483, "4705": 0.8534175157546997, "4738": 0.8433839678764343, "4758": 0.4709797203540802, "4772": 0.00875066313892603, "4844": 0.8109301924705505, "4866": 0.41840189695358276, "4882": 0.2786078155040741, "5002": 0.06703783571720123, "5009": 0.05694137513637543, "5022": 0.6543170213699341, "5068": 0.28890204429626465, "5099": 0.06154331564903259, "5114": 0.6410312056541443, "5130": 0.49864232540130615, "5134": 0.16359257698059082, "5155": 0.06154331564903259, "5171": 0.12728634476661682, "5197": 0.49030399322509766, "5219": 0.8383291959762573, "5232": 0.15275461971759796, "5248": 0.8981585502624512, "5344": 0.12556517124176025, "5359": 0.6492279767990112, "5427": 0.2652147710323334, "5468": 0.26820653676986694, "5531": 0.0842406153678894, "5547": 0.36426326632499695, "5555": 0.6244332790374756, "5739": 0.1913948506116867, "5761": 0.1332872211933136, "5776": 0.6970458030700684, "5790": 0.7144040465354919, "5808": 0.16524957120418549, "5845": 0.10291612148284912, "5983": 0.20501139760017395, "6022": 0.07341018319129944, "6075": 0.05694137513637543, "6078": 0.09228714555501938, "6083": 0.11430477350950241, "6177": 0.53589928150177, "6204": 0.22001366317272186, "6226": 0.603290855884552, "6245": 0.14095009863376617, "6388": 0.06703783571720123, "6401": 0.5489565134048462, "6430": 0.2852376699447632, "6431": 0.08064348995685577, "6521": 0.9546096324920654, "6577": 0.16690383851528168, "6591": 0.4938860833644867, "6592": 0.49686139822006226, "6612": 0.804835319519043, "6638": 0.6877616047859192, "6689": 0.30917787551879883, "6721": 0.6112717390060425, "6742": 0.1913948506116867, "6747": 0.06246116757392883, "6749": 0.11430477350950241, "6758": 0.5995445251464844, "6808": 0.5629584193229675, "6818": 0.7951818704605103, "6825": 0.2800849378108978, "6912": 0.7028654217720032, "6922": 0.43053874373435974, "6939": 0.13071982562541962, "6950": 0.06977381557226181, "6959": 0.40741631388664246, "7012": 0.9225212931632996, "7017": 0.27786844968795776, "7026": 0.7067264318466187, "7038": 0.23402166366577148, "7058": 0.2501201331615448, "7091": 0.3262358605861664, "7233": 0.15359249711036682, "7242": 0.9754437208175659, "7274": 0.018384648486971855, "7312": 0.23710809648036957, "7375": 0.30558720231056213, "7435": 0.040196798741817474, "7438": 0.24859806895256042, "7457": 0.029824240133166313, "7473": 0.16359257698059082, "7478": 0.045809537172317505, "7522": 0.520350456237793, "7551": 0.03925827145576477, "7583": 0.7258110046386719, "7594": 0.45994341373443604, "7667": 0.11081436276435852, "7711": 0.03925827145576477, "7748": 0.2990913391113281, "7784": 0.23710809648036957, "7810": 0.5729197263717651, "7831": 0.0770333781838417, "7848": 0.3353555500507355, "7861": 0.4462870955467224, "7863": 0.9591107368469238, "7879": 0.053244512528181076, "7885": 0.07159364968538284, "8015": 0.11691460013389587, "8077": 0.21372433006763458, "8082": 0.18978065252304077, "8116": 0.42735910415649414, "8117": 0.04674193635582924, "8152": 0.07884006202220917, "8155": 0.06977381557226181, "8161": 0.1064341589808464, "8182": 0.44753631949424744, "8186": 0.10555581003427505, "8317": 0.304147332906723, "8381": 0.3127557039260864, "8483": 0.38374659419059753, "8487": 0.052318159490823746, "8564": 0.016465263441205025, "8586": 0.5729197263717651, "8599": 0.8492490649223328, "8606": 0.026025565341114998, "8733": 0.7500885725021362, "8738": 0.6793810129165649, "8778": 0.10379679501056671, "8822": 0.020300358533859253, "8830": 1.0172666311264038, "8832": 0.08961215615272522, "8930": 0.30989447236061096, "9031": 0.3956514894962311, "9044": 0.0029254043474793434, "9047": 0.7647408246994019, "9164": 0.6634125709533691, "9181": 0.5893046259880066, "9276": 0.5729197263717651, "9312": 0.25995752215385437, "9349": 0.3963087201118469, "9367": 0.5968599319458008, "9517": 0.8109301924705505, "9556": 0.6563454270362854, "9560": 0.12038381397724152, "9723": 0.0770333781838417, "9726": 0.0317181795835495, "9740": 0.17922431230545044, "9871": 0.17020416259765625, "9885": 0.0029254043474793434, "9987": 0.34922540187835693, "10061": 0.46363574266433716, "10174": 0.12814582884311676, "10238": 0.06795065850019455, "10250": 0.3963087201118469, "10365": 0.26446542143821716, "10408": 0.13157635927200317, "10426": 0.009718249551951885, "10429": 0.04487626627087593, "10502": 0.8272887468338013, "10516": 0.2478361576795578, "10552": 0.12642613053321838, "10572": 0.6155022978782654, "10753": 0.0038986403960734606, "10802": 0.1913948506116867, "10903": 0.2607102394104004, "10906": 0.32905077934265137, "10975": 0.07068414986133575, "11100": 0.4914994537830353, "11110": 0.2659635543823242, "11179": 1.0655186176300049, "11252": 0.14686977863311768, "11433": 0.2089812457561493, "11572": 0.36900100111961365, "11594": 0.6265231370925903, "11709": 0.004870930220931768, "11778": 0.6410312056541443, "11806": 1.018678069114685, "12154": 0.14349138736724854, "12353": 0.3723714053630829, "12412": 0.10906458646059036, "12421": 0.347847044467926, "12435": 0.0174254160374403, "12719": 0.0009760859538801014, "12771": 0.2223619967699051, "12832": 0.15860503911972046, "12879": 0.19782574474811554, "13024": 0.26146242022514343, "13033": 0.7047978043556213, "13046": 0.1873544454574585, "13102": 0.31204116344451904, "13105": 0.26296505331993103, "13180": 0.5925496220588684, "13247": 0.0752234235405922, "13441": 0.4145384132862091, "13467": 0.08513788133859634, "13483": 0.13499516248703003, "13822": 0.6118015646934509, "13866": 0.14518201351165771, "14210": 0.6793810129165649, "14260": 1.076228141784668, "14266": 0.5063233375549316, "14300": 0.5506471395492554, "14354": 0.04487626627087593, "14357": 0.4349733293056488, "14613": 0.20421554148197174, "14617": 0.956112265586853, "14667": 0.3070250153541565, "14671": 0.4158279001712799, "15034": 0.2800849378108978, "15058": 0.7746911644935608, "15243": 0.4067663550376892, "15252": 0.28670501708984375, "15272": 1.094698429107666, "15306": 0.5523349046707153, "15354": 0.13925230503082275, "15578": 1.0546929836273193, "15592": 0.49864232540130615, "15680": 0.46608972549438477, "15844": 0.42096930742263794, "15849": 0.09495500475168228, "15871": 0.7827593088150024, "15945": 0.8459017872810364, "15946": 0.22548456490039825, "16029": 0.33325836062431335, "16048": 0.011650617234408855, "16053": 0.14095009863376617, "16068": 0.34508460760116577, "16134": 0.08692999184131622, "16250": 0.5427330136299133, "16302": 0.417115718126297, "16530": 0.09050461649894714, "16593": 0.3743882179260254, "16755": 0.13157635927200317, "16838": 0.46363574266433716, "16924": 0.04674193635582924, "17003": 0.00875066313892603, "17041": 1.2330384254455566, "17042": 0.732405424118042, "17208": 0.1212492436170578, "17220": 0.7809720039367676, "17261": 0.39762192964553833, "17473": 0.20977331697940826, "17503": 0.06886265426874161, "17544": 0.1685553640127182, "17785": 0.025073638185858727, "17908": 0.23787821829319, "17980": 0.11168810725212097, "18058": 0.007782140281051397, "18089": 0.06795065850019455, "18154": 0.05970508232712746, "18215": 0.09584271162748337, "18224": 0.3601844012737274, "18678": 0.4248080551624298, "18742": 0.823009729385376, "18793": 0.15693697333335876, "18857": 0.5156965255737305, "18886": 0.7018978595733643, "18909": 0.6338034868240356, "18923": 0.026976587250828743, "19037": 0.3170322775840759, "19229": 0.0029254043474793434, "19294": 0.6823468804359436, "19362": 0.1212492436170578, "19388": 1.0087559223175049, "19389": 0.07250232994556427, "19557": 0.2561853528022766, "19653": 0.8941729068756104, "19862": 0.20977331697940826, "19960": 0.5021947622299194, "20422": 0.12384103983640671, "20702": 0.18329764902591705, "20900": 0.6155022978782654, "20915": 0.07884006202220917, "20936": 0.23324857652187347, "21117": 0.6862877607345581, "21150": 0.3353555500507355, "21372": 0.08603433519601822, "21453": 0.05046287178993225, "21923": 0.46363574266433716, "22466": 0.35060185194015503, "23087": 0.33675122261047363, "23329": 0.08244366943836212, "24081": 0.09761575609445572, "24108": 0.37102460861206055, "24497": 0.3070250153541565, "24552": 1.0775588750839233, "24915": 0.2659635543823242, "24952": 0.055094651877880096, "25006": 0.055094651877880096, "25022": 0.4938860833644867, "25775": 0.009718249551951885, "26163": 0.8195732831954956, "26478": 0.06337817758321762, "26758": 0.0752234235405922, "27090": 0.42225050926208496, "27133": 0.13670019805431366, "27487": 0.32764431834220886, "27615": 1.2204381227493286, "27794": 0.1946154683828354, "27937": 0.12814582884311676, "28268": 0.09938567131757736, "28428": 0.47402387857437134, "28689": 0.9279413223266602, "29050": 0.684319257736206, "29234": 0.3676496744155884, "29290": 0.36290550231933594, "29336": 0.006812678650021553, "29464": 0.13157635927200317, "29474": 0.6155022978782654} | 12672066 | IMPORTANCE In 2011, the Centers for Medicare & Medicaid Services (CMS) approved intensive behavioral weight loss counseling for approximately 14 face-to-face, 10- to 15-minute sessions over 6 months for obese beneficiaries in primary care settings, when delivered by physicians and other CMS-defined primary care practitioners. OBJECTIVE To conduct a systematic review of behavioral counseling for overweight and obese patients recruited from primary care, as delivered by primary care practitioners working alone or with trained interventionists (eg, medical assistants, registered dietitians), or by trained interventionists working independently. EVIDENCE REVIEW We searched PubMed, CINAHL, and EMBASE for randomized controlled trials published between January 1980 and June 2014 that recruited overweight and obese patients from primary care; provided behavioral counseling (ie, diet, exercise, and behavioral therapy) for at least 3 months, with at least 6 months of postrandomization follow-up; included at least 15 participants per treatment group and objectively measured weights; and had a comparator, an intention-to-treat analysis, and attrition of less than 30% at 1 year or less than 40% at longer follow-up. FINDINGS Review of 3304 abstracts yielded 12 trials, involving 3893 participants, that met inclusion-exclusion criteria and prespecified quality ratings. No studies were found in which primary care practitioners delivered counseling that followed the CMS guidelines. Mean 6-month weight changes from baseline in the intervention groups ranged from a loss of 0.3 kg to 6.6 kg. In the control group, mean change ranged from a gain of 0.9 kg to a loss of 2.0 kg. Weight loss in both groups generally declined with longer follow-up (12-24 months). Interventions that prescribed both reduced energy intake (eg, ≥ 500 kcal/d) and increased physical activity (eg, ≥150 minutes a week of walking), with traditional behavioral therapy, generally produced larger weight loss than interventions without all 3 specific components. In the former trials, more treatment sessions, delivered in person or by telephone by trained interventionists, were associated with greater mean weight loss and likelihood of patients losing 5% or more of baseline weight. CONCLUSIONS AND RELEVANCE Intensive behavioral counseling can induce clinically meaningful weight loss, but there is little research on primary care practitioners providing such care. The present findings suggest that a range of trained interventionists, who deliver counseling in person or by telephone, could be considered for treating overweight or obesity in patients encountered in primary care settings. | Behavioral treatment of obesity in patients encountered in primary care settings: a systematic review. |
{"1015": 0.4879087805747986, "1039": 0.12728634476661682, "1041": 0.7809720039367676, "1043": 0.7845434546470642, "1052": 0.11517547070980072, "1061": 0.1808556467294693, "2002": 0.43812891840934753, "2005": 0.08782484382390976, "2007": 0.10731173306703568, "2011": 0.34370049834251404, "2025": 0.015504186972975731, "2028": 0.2539152204990387, "2029": 0.21530038118362427, "2034": 0.4770587682723999, "2046": 0.27342069149017334, "2058": 0.33675122261047363, "2063": 0.3622259199619293, "2083": 0.2800849378108978, "2087": 0.26146242022514343, "2090": 0.10731173306703568, "2099": 0.7163142561912537, "2152": 0.056018441915512085, "2213": 0.46608972549438477, "2239": 0.4444103240966797, "2240": 0.16524957120418549, "2278": 0.0174254160374403, "2290": 0.06977381557226181, "2361": 1.001607894897461, "2368": 0.2184450328350067, "2487": 1.0478670597076416, "2511": 0.255429208278656, "2515": 0.0842406153678894, "2529": 0.5461324453353882, "2535": 0.043007105588912964, "2734": 0.08961215615272522, "2817": 0.08154398202896118, "2838": 0.4374985992908478, "2859": 0.11691460013389587, "2863": 0.755608320236206, "2913": 0.026976587250828743, "2920": 0.17431432008743286, "2981": 0.803087055683136, "3081": 0.043007105588912964, "3117": 0.3870677351951599, "3130": 0.3656192123889923, "3141": 0.09228714555501938, "3161": 0.3374483287334442, "3210": 0.4450363218784332, "3223": 0.5860490798950195, "3258": 0.41065993905067444, "3273": 0.0354953333735466, "3283": 0.04953393340110779, "3284": 0.0752234235405922, "3351": 0.14433705806732178, "3378": 0.4002431631088257, "3384": 0.7398891448974609, "3444": 0.2607102394104004, "3445": 0.1677299439907074, "3450": 0.3034266233444214, "3461": 0.8633513450622559, "3466": 0.3916989266872406, "3491": 0.0009760859538801014, "3526": 0.7067264318466187, "3528": 0.014542185701429844, "3563": 0.07431721687316895, "3603": 0.1011524572968483, "3669": 0.5909284353256226, "3670": 1.0828639268875122, "3671": 0.04207121208310127, "3695": 0.42416930198669434, "3754": 0.43434104323387146, "3755": 0.1358480453491211, "3798": 0.2105647772550583, "3853": 0.5127768516540527, "3893": 0.36290550231933594, "3896": 0.34300774335861206, "3930": 1.0546929836273193, "4022": 0.5523349046707153, "4023": 0.6573580503463745, "4072": 0.18248429894447327, "4135": 0.3910386264324188, "4167": 0.9987343549728394, "4229": 0.0038986403960734606, "4242": 0.5045560002326965, "4286": 0.43875885009765625, "4315": 0.8682814836502075, "4321": 0.13499516248703003, "4383": 0.259204238653183, "4442": 0.7389566898345947, "4453": 0.5127768516540527, "4456": 0.757441520690918, "4523": 0.2719337046146393, "4539": 0.8091925978660583, "4649": 0.9178520441055298, "4659": 0.0317181795835495, "4671": 0.3077431619167328, "4703": 0.1913948506116867, "4742": 0.23324857652187347, "4800": 0.574020504951477, "4866": 0.6704301834106445, "4935": 0.026025565341114998, "4957": 0.35813871026039124, "4958": 0.7220231294631958, "4962": 0.7782850861549377, "4972": 0.2501201331615448, "4982": 0.043007105588912964, "5034": 0.43434104323387146, "5214": 0.12814582884311676, "5228": 0.6492279767990112, "5250": 0.9084475636482239, "5274": 1.1537069082260132, "5323": 0.045809537172317505, "5360": 0.37640097737312317, "5387": 0.9021284580230713, "5449": 0.12038381397724152, "5478": 0.2478361576795578, "5533": 0.45251765847206116, "5536": 1.0298984050750732, "5603": 0.23864774405956268, "5644": 0.08154398202896118, "5799": 0.39696553349494934, "5876": 0.39762192964553833, "5884": 0.6624060273170471, "5901": 0.19862671196460724, "5915": 0.5267143249511719, "5918": 0.10026945173740387, "5942": 0.2696990668773651, "5994": 0.2786078155040741, "6022": 0.3106105625629425, "6064": 0.41195443272590637, "6075": 0.27564704418182373, "6245": 0.020300358533859253, "6761": 0.07431721687316895, "6970": 0.7105726003646851, "6976": 0.5415972471237183, "7242": 0.3870677351951599, "7275": 0.11691460013389587, "7337": 0.23015019297599792, "7342": 0.07068414986133575, "7356": 0.6181373596191406, "7366": 0.11343330889940262, "7403": 0.9178520441055298, "7461": 0.5827828645706177, "7512": 1.0073304176330566, "7539": 0.02887592278420925, "7645": 0.17267228662967682, "7711": 0.21214580535888672, "7755": 0.030771657824516296, "7790": 0.02412080205976963, "7816": 0.3963087201118469, "7889": 0.6892333030700684, "8000": 0.757441520690918, "8031": 1.0423725843429565, "8077": 0.3547199070453644, "8153": 0.16442140936851501, "8161": 0.04113444685935974, "8171": 0.841701865196228, "8185": 0.8091925978660583, "8281": 0.036437395960092545, "8290": 0.004870930220931768, "8319": 0.08871890604496002, "8360": 0.12642613053321838, "8675": 0.7969439625740051, "8878": 0.8699195384979248, "8991": 0.10555581003427505, "9007": 0.6043586730957031, "9031": 0.06977381557226181, "9067": 0.7389566898345947, "9113": 0.23402166366577148, "9165": 0.6064908504486084, "9174": 0.1970241367816925, "9253": 0.3777405619621277, "9308": 0.2918238639831543, "9335": 0.40351006388664246, "9350": 0.05417001247406006, "9412": 0.8057082891464233, "9416": 0.603290855884552, "9513": 0.8731874823570251, "9556": 0.23479416966438293, "9589": 0.7153595685958862, "9626": 0.15610189735889435, "9869": 0.30989447236061096, "10210": 0.7809720039367676, "10266": 0.1064341589808464, "10288": 0.5984715819358826, "10451": 0.04394211992621422, "10572": 0.803087055683136, "10738": 0.33675122261047363, "10769": 0.9240728616714478, "10803": 0.9886114001274109, "10836": 0.7565253376960754, "10924": 0.2689530849456787, "10976": 0.018384648486971855, "11022": 0.46363574266433716, "11099": 0.906871497631073, "11369": 0.18004031479358673, "11423": 0.4190443754196167, "11432": 0.16110190749168396, "11598": 0.5209306478500366, "11714": 0.6857960224151611, "11721": 0.4531385898590088, "11968": 0.7445381283760071, "11970": 0.2659635543823242, "12222": 0.4425300657749176, "12328": 1.0144377946853638, "12473": 0.06795065850019455, "12562": 0.02887592278420925, "12618": 0.25845035910606384, "12644": 0.014542185701429844, "12732": 0.7601850032806396, "12798": 1.2808253765106201, "12987": 0.8315495252609253, "13070": 0.09317722171545029, "13091": 0.0009760859538801014, "13100": 0.5191890001296997, "13248": 0.8707374930381775, "13330": 0.23324857652187347, "13458": 0.04207121208310127, "13531": 0.17020416259765625, "13567": 0.36967599391937256, "13656": 0.9929623603820801, "13776": 0.5685047507286072, "13791": 1.0887986421585083, "13806": 0.906871497631073, "13833": 0.8997484445571899, "13871": 0.09672962874174118, "13874": 0.32129061222076416, "13909": 0.32553088665008545, "13910": 0.6096806526184082, "13922": 0.13670019805431366, "14026": 0.18492233753204346, "14031": 0.3106105625629425, "14080": 0.04487626627087593, "14126": 0.3127557039260864, "14181": 0.6833335757255554, "14187": 0.34922540187835693, "14192": 0.7987030148506165, "14193": 0.9052929878234863, "14471": 0.38041436672210693, "14494": 0.7500885725021362, "14613": 0.006812678650021553, "14800": 0.10993985831737518, "14828": 0.7782850861549377, "14863": 0.04953393340110779, "14971": 0.05786345899105072, "15115": 0.755608320236206, "15176": 0.3883931338787079, "15453": 1.0874829292297363, "15527": 0.6011518239974976, "15543": 0.23633737862110138, "15663": 0.25694093108177185, "15698": 0.23864774405956268, "15756": 0.669430673122406, "15946": 0.956112265586853, "16007": 0.2160874605178833, "16026": 0.10818854719400406, "16033": 0.6583697199821472, "16081": 0.11168810725212097, "16221": 1.0001721382141113, "16238": 0.1970241367816925, "16285": 0.34577593207359314, "16351": 1.4094613790512085, "16389": 0.053244512528181076, "16505": 0.27044451236724854, "16570": 0.5336109399795532, "16902": 0.3810817003250122, "16910": 0.5701626539230347, "17076": 0.6674286723136902, "17132": 0.10379679501056671, "17261": 0.48430517315864563, "17347": 0.37907835841178894, "17379": 0.21293537318706512, "17441": 0.6212902665138245, "17503": 0.9209672808647156, "17657": 0.5370414853096008, "17703": 0.43623676896095276, "17820": 0.0913962796330452, "17890": 0.21922965347766876, "18208": 0.8357921838760376, "18259": 0.06886265426874161, "18260": 0.06977381557226181, "18439": 0.07612881064414978, "18445": 0.846739649772644, "18688": 1.022197961807251, "18714": 0.13157635927200317, "18900": 0.03925827145576477, "19092": 1.0409941673278809, "19136": 0.04953393340110779, "19335": 0.1602703034877777, "19341": 0.8135309815406799, "19345": 0.25845035910606384, "19601": 0.11256109178066254, "19653": 0.8074519634246826, "19707": 1.0361549854278564, "19739": 0.9827804565429688, "19811": 0.08782484382390976, "19872": 1.018678069114685, "20110": 0.6664261221885681, "20250": 1.0403043031692505, "20350": 0.053244512528181076, "20360": 0.5347557663917542, "20544": 0.75193190574646, "20766": 0.02316705882549286, "20817": 0.35060185194015503, "20858": 0.07341018319129944, "20879": 0.4203280806541443, "21081": 0.14686977863311768, "21104": 1.024303913116455, "21434": 0.9225212931632996, "21466": 0.18573370575904846, "21520": 0.1332872211933136, "21572": 0.5596157908439636, "21575": 0.26296505331993103, "21618": 0.7647408246994019, "21833": 0.0038986403960734606, "21903": 1.1720224618911743, "21919": 0.40741631388664246, "21967": 0.14433705806732178, "22025": 1.1038070917129517, "22248": 0.0797421783208847, "22275": 0.055094651877880096, "22415": 0.28963330388069153, "22422": 0.07793712615966797, "22520": 0.9287132620811462, "22694": 0.6317287683486938, "22931": 0.13499516248703003, "23079": 0.21687394380569458, "23130": 0.07612881064414978, "23216": 0.05694137513637543, "23388": 0.5495203733444214, "23536": 0.3883931338787079, "23586": 0.4974553883075714, "23713": 0.953857421875, "23737": 0.8600510358810425, "23892": 0.04674193635582924, "23900": 0.8152611255645752, "23924": 0.77198725938797, "24054": 0.6502478122711182, "24269": 0.2247048318386078, "24278": 0.3170322775840759, "24324": 0.5607312321662903, "24396": 0.2561853528022766, "24434": 0.06795065850019455, "24554": 0.24018502235412598, "24848": 0.007782140281051397, "24983": 0.15610189735889435, "25117": 0.0058422754518687725, "25194": 0.4126010537147522, "25409": 0.28670501708984375, "25456": 0.440646231174469, "25644": 0.46363574266433716, "25708": 1.4075511693954468, "25714": 0.9240728616714478, "25761": 0.3012613356113434, "26402": 0.9515975713729858, "26419": 0.2184450328350067, "26512": 0.009718249551951885, "26520": 0.27342069149017334, "26524": 0.018384648486971855, "26773": 0.48670899868011475, "26785": 0.4926934838294983, "26986": 0.2749055027961731, "27295": 0.11951763927936554, "27427": 0.47584590315818787, "27781": 0.052318159490823746, "27814": 0.022212404757738113, "27854": 0.2837681770324707, "28156": 0.12556517124176025, "28177": 0.015504186972975731, "28522": 0.8699195384979248, "28644": 0.12642613053321838, "28674": 0.5127768516540527, "28848": 0.13071982562541962, "28873": 0.07884006202220917, "28976": 0.2689530849456787, "29107": 0.026025565341114998, "29166": 0.7380234599113464, "29290": 0.5186077356338501, "29295": 0.30917787551879883, "29480": 0.3757305145263672, "29543": 0.7546905279159546} | 12685434 | Although GBP1 (guanylate binding protein 1) was among the first interferon-inducible proteins identified, its function is still largely unknown. Epidermal growth factor receptor (EGFR) activation by amplification or mutation is one of the most frequent genetic lesions in a variety of human tumors. These include glioblastoma multiforme (GBM), which is characterized by independent but interrelated features of extensive invasion into normal brain parenchyma, rapid growth, necrosis, and angiogenesis. In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of mice. GBP1 expression was high and positively correlated with EGFR expression in human GBM tumors and cell lines, particularly those of the neural subtype. Together, these findings establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion. | Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastoma |
{"1011": 0.34508460760116577, "1043": 0.12556517124176025, "1050": 0.22548456490039825, "1052": 0.007782140281051397, "1996": 0.29473719000816345, "1997": 0.06246116757392883, "2007": 0.4337083101272583, "2008": 0.04953393340110779, "2011": 0.3084607720375061, "2015": 0.2160874605178833, "2025": 0.15275461971759796, "2029": 0.4041621685028076, "2043": 0.15275461971759796, "2046": 0.3750596046447754, "2048": 0.33675122261047363, "2050": 0.036437395960092545, "2064": 0.013579257763922215, "2076": 0.21293537318706512, "2079": 0.11256109178066254, "2083": 0.41195443272590637, "2135": 0.09850110858678818, "2139": 0.19782574474811554, "2140": 0.4349733293056488, "2179": 0.3304552733898163, "2298": 0.01934296265244484, "2302": 0.53589928150177, "2322": 0.7370892763137817, "2330": 0.42608439922332764, "2361": 0.4673144817352295, "2401": 0.10906458646059036, "2441": 0.2881702482700348, "2490": 0.28082266449928284, "2515": 0.08782484382390976, "2523": 0.7295845746994019, "2535": 0.1358480453491211, "2538": 0.43053874373435974, "2539": 0.7096124291419983, "2556": 0.05046287178993225, "2588": 0.35403475165367126, "2647": 0.09495500475168228, "2649": 0.08244366943836212, "2656": 0.8567397594451904, "2676": 0.3656192123889923, "2698": 0.35745587944984436, "2714": 0.010684899985790253, "2744": 0.6573580503463745, "2828": 0.020300358533859253, "2863": 0.11081436276435852, "2885": 0.08154398202896118, "2894": 0.6260011196136475, "2920": 0.23247487843036652, "2943": 0.5562619566917419, "2947": 0.1485546976327896, "2983": 0.025073638185858727, "3031": 0.07884006202220917, "3098": 0.8152611255645752, "3174": 0.8004589080810547, "3223": 0.31132611632347107, "3252": 0.77198725938797, "3311": 0.15442965924739838, "3320": 0.04487626627087593, "3356": 0.3554046154022217, "3366": 0.2711893916130066, "3375": 1.223315715789795, "3378": 0.6000806093215942, "3408": 0.2822965085506439, "3418": 0.08154398202896118, "3491": 0.5244048833847046, "3499": 0.09228714555501938, "3526": 0.1970241367816925, "3544": 0.5080875158309937, "3569": 0.371698260307312, "3614": 0.6950984001159668, "3625": 0.1913948506116867, "3665": 0.13071982562541962, "3690": 0.05046287178993225, "3708": 0.06429435312747955, "3711": 0.38041436672210693, "3853": 0.49030399322509766, "3983": 0.21214580535888672, "4013": 0.8567397594451904, "4017": 0.26296505331993103, "4135": 0.5773153901100159, "4195": 0.13925230503082275, "4211": 0.29400965571403503, "4304": 0.3588210940361023, "4360": 0.18654440343379974, "4442": 0.043007105588912964, "4443": 0.4974553883075714, "4444": 0.34508460760116577, "4473": 0.18004031479358673, "4607": 0.26146242022514343, "4637": 0.026976587250828743, "4652": 0.21687394380569458, "4691": 0.41840189695358276, "4748": 0.8666408061981201, "4796": 1.1870332956314087, "4895": 0.4311734735965729, "4958": 0.013579257763922215, "4962": 0.3127557039260864, "4972": 0.319873183965683, "4987": 0.0752234235405922, "5090": 0.5584990978240967, "5127": 0.014542185701429844, "5158": 0.4568560719490051, "5243": 0.2689530849456787, "5250": 0.7845434546470642, "5258": 0.5936289429664612, "5391": 0.10731173306703568, "5422": 0.004870930220931768, "5449": 0.33605360984802246, "5478": 0.4831010699272156, "5482": 0.5936289429664612, "5498": 0.5701626539230347, "5669": 0.016465263441205025, "5738": 0.05139094591140747, "5741": 0.10467668622732162, "5867": 0.25845035910606384, "5942": 0.47463157773017883, "6064": 0.3784096837043762, "6090": 1.579300880432129, "6178": 0.7818660736083984, "6310": 0.1229778528213501, "6459": 0.0913962796330452, "6494": 0.175953671336174, "6541": 1.0073304176330566, "6641": 0.23710809648036957, "6643": 0.004870930220931768, "6673": 0.7969439625740051, "6679": 0.5301685929298401, "6733": 0.9333322048187256, "6753": 0.4330752193927765, "6999": 0.6476961374282837, "7077": 0.20739519596099854, "7327": 0.9650808572769165, "7337": 0.3656192123889923, "7356": 0.016465263441205025, "7366": 0.20977331697940826, "7398": 0.055094651877880096, "7480": 0.3870677351951599, "7635": 0.6096806526184082, "7645": 0.36290550231933594, "7677": 0.4158279001712799, "7783": 0.06703783571720123, "7816": 0.6054253578186035, "7861": 0.5534584522247314, "7905": 1.2146576642990112, "7939": 0.6006163358688354, "7980": 0.13670019805431366, "8031": 0.9485763907432556, "8039": 0.11168810725212097, "8115": 0.20739519596099854, "8171": 0.8973627090454102, "8290": 0.06703783571720123, "8332": 0.4067663550376892, "8360": 0.15693697333335876, "8462": 0.3106105625629425, "8464": 0.11168810725212097, "8516": 0.11168810725212097, "8524": 0.1510767638683319, "8552": 0.07431721687316895, "8621": 0.05786345899105072, "8729": 0.08064348995685577, "8878": 0.08064348995685577, "8915": 0.23787821829319, "8924": 0.6634125709533691, "9007": 1.0533316135406494, "9034": 0.12814582884311676, "9096": 0.1602703034877777, "9099": 0.7728893756866455, "9112": 0.0354953333735466, "9165": 0.05417001247406006, "9228": 0.5438674688339233, "9232": 0.022212404757738113, "9309": 0.4067663550376892, "9335": 0.5773153901100159, "9597": 0.07250232994556427, "9700": 0.41840189695358276, "9739": 0.6086184978485107, "10066": 0.0317181795835495, "10210": 0.3409265875816345, "10266": 0.14179791510105133, "10327": 0.4190443754196167, "10341": 0.013579257763922215, "10371": 0.5483922958374023, "10442": 1.0389231443405151, "10445": 0.0770333781838417, "10496": 0.9052929878234863, "10572": 0.12642613053321838, "10595": 0.03360854089260101, "10671": 0.5838727951049805, "10719": 1.072225570678711, "10737": 0.2576959431171417, "10738": 0.9857001900672913, "10769": 0.1889725625514984, "10811": 0.42735910415649414, "10956": 0.3027053773403168, "10980": 0.40546512603759766, "11022": 1.1641268730163574, "11211": 0.15359249711036682, "11387": 0.17840765416622162, "11610": 0.3464667797088623, "11835": 0.20580662786960602, "11909": 0.32270604372024536, "11977": 0.03925827145576477, "12126": 0.16359257698059082, "12165": 0.029824240133166313, "12222": 0.6410312056541443, "12319": 0.12986256182193756, "12554": 0.23402166366577148, "12649": 1.4085067510604858, "12702": 0.2881702482700348, "12745": 0.37035053968429565, "12921": 0.5033760666847229, "12950": 0.1718502640724182, "12987": 0.28743788599967957, "13014": 0.32764431834220886, "13100": 0.03831886500120163, "13248": 0.0770333781838417, "13496": 0.176772341132164, "13540": 0.5551415085792542, "13595": 0.007782140281051397, "13791": 0.0354953333735466, "13833": 0.38374659419059753, "13876": 0.20818853378295898, "13880": 0.22157983481884003, "13922": 0.1677299439907074, "14045": 0.960606575012207, "14173": 0.04394211992621422, "14187": 0.6578640341758728, "14193": 0.28963330388069153, "14449": 0.06886265426874161, "14480": 0.08603433519601822, "14709": 0.12986256182193756, "14774": 0.06703783571720123, "14828": 0.03360854089260101, "14935": 0.4431571960449219, "14997": 0.11168810725212097, "15057": 0.176772341132164, "15176": 0.4400174915790558, "15262": 0.14433705806732178, "15420": 0.8748174905776978, "15439": 0.19381128251552582, "15745": 0.11865071207284927, "15778": 0.16276304423809052, "16061": 0.02412080205976963, "16181": 0.12038381397724152, "16263": 0.469759464263916, "16280": 0.5191890001296997, "16285": 0.9409833550453186, "16291": 0.2983669638633728, "16298": 0.18978065252304077, "16305": 0.7665573358535767, "16307": 0.3757305145263672, "16556": 0.32764431834220886, "16627": 0.8450632095336914, "16706": 0.3297532796859741, "16731": 0.10026945173740387, "16771": 0.21922965347766876, "17341": 0.0797421783208847, "17344": 0.15359249711036682, "17820": 0.19782574474811554, "18260": 0.32129061222076416, "18410": 0.07250232994556427, "18479": 1.0628231763839722, "18670": 0.07341018319129944, "18903": 0.0606246218085289, "18946": 0.791648268699646, "19137": 0.06612417846918106, "19241": 0.8682814836502075, "19476": 0.08871890604496002, "19547": 0.07341018319129944, "19601": 1.0702182054519653, "19653": 0.46117570996284485, "20228": 0.21214580535888672, "20307": 0.08961215615272522, "20403": 0.7647408246994019, "20544": 0.0797421783208847, "20817": 0.7463917136192322, "20858": 0.03360854089260101, "20960": 0.18816383183002472, "21162": 0.21372433006763458, "21197": 0.9531047344207764, "21252": 0.022212404757738113, "21508": 0.9240728616714478, "21575": 0.46608972549438477, "21618": 0.4938860833644867, "21716": 0.05694137513637543, "21755": 0.49626702070236206, "21770": 0.1619328260421753, "21903": 0.2954642176628113, "21957": 0.004870930220931768, "21996": 1.1695996522903442, "22159": 0.1808556467294693, "22476": 0.12384103983640671, "22644": 0.6322478652000427, "22864": 0.983511209487915, "23079": 0.3464667797088623, "23150": 0.15860503911972046, "23216": 0.7342816591262817, "23274": 0.06977381557226181, "23535": 0.24401791393756866, "23725": 0.8289952278137207, "23797": 0.12986256182193756, "23833": 0.6048921346664429, "23943": 0.2539152204990387, "23959": 1.0409941673278809, "24004": 1.0298984050750732, "24137": 0.0842406153678894, "24169": 0.0038986403960734606, "24170": 0.9052929878234863, "24277": 0.22626367211341858, "24279": 0.6212902665138245, "24312": 1.0802149772644043, "24635": 0.6902132034301758, "25002": 0.29328158497810364, "25117": 0.7286425232887268, "25178": 0.07431721687316895, "25194": 0.38574060797691345, "25354": 1.0257055759429932, "25426": 0.3547199070453644, "25458": 0.10818854719400406, "25644": 0.2881702482700348, "26131": 0.40806588530540466, "26244": 0.2918238639831543, "26282": 0.055094651877880096, "26313": 0.535327672958374, "26394": 1.018678069114685, "26396": 0.10026945173740387, "26402": 0.22859740257263184, "26517": 0.35745587944984436, "26520": 0.1889725625514984, "26534": 0.12642613053321838, "26773": 0.37371641397476196, "26874": 0.15693697333335876, "27058": 1.0920805931091309, "27074": 1.0881409645080566, "27169": 0.0842406153678894, "27295": 0.14433705806732178, "27642": 0.09584271162748337, "27777": 0.12556517124176025, "27854": 0.0174254160374403, "28105": 0.06429435312747955, "28173": 0.058784693479537964, "28424": 0.053244512528181076, "28470": 0.1485546976327896, "28507": 0.23633737862110138, "28691": 0.2976420819759369, "28808": 0.9348671436309814, "28835": 0.2089812457561493, "29060": 0.012615402229130268, "29105": 0.7342816591262817} | 12691537 | The archaeal ATPase complex PAN, the homolog of the eukaryotic 26S proteasome-regulatory ATPases, was shown to associate transiently with the 20S proteasome upon binding of ATP or ATPgammaS, but not ADP. By electron microscopy (EM), PAN appears as a two-ring structure, capping the 20S, and resembles two densities in the 19S complex. The N termini of the archaeal 20S alpha subunits were found to function as a gate that prevents entry of seven-residue peptides but allows entry of tetrapeptides. Upon association with the 20S particle, PAN stimulates gate opening. Although degradation of globular proteins requires ATP hydrolysis, the PAN-20S complex with ATPgammaS translocates and degrades unfolded and denatured proteins. Rabbit 26S proteasomes also degrade these unfolded proteins upon ATP binding, without hydrolysis. Thus, although unfolding requires energy from ATP hydrolysis, ATP binding alone supports ATPase-20S association, gate opening, and translocation of unfolded substrates into the proteasome, which can occur by facilitated diffusion through the ATPase. | ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins. |
{"1011": 0.15526613593101501, "1050": 0.4812922179698944, "1052": 0.33953672647476196, "1056": 0.5805994272232056, "1164": 0.22157983481884003, "1999": 0.2018241584300995, "2003": 0.006812678650021553, "2005": 0.1808556467294693, "2029": 0.06520967930555344, "2035": 0.015504186972975731, "2050": 0.18978065252304077, "2076": 0.015504186972975731, "2079": 0.02412080205976963, "2109": 0.3170322775840759, "2232": 0.1485546976327896, "2243": 0.7163142561912537, "2378": 0.11604541540145874, "2430": 0.6583697199821472, "2470": 0.056018441915512085, "2497": 0.056018441915512085, "2515": 0.12986256182193756, "2529": 0.35334911942481995, "2535": 0.9893379211425781, "2537": 0.021256839856505394, "2546": 0.18248429894447327, "2590": 0.151916041970253, "2691": 0.18978065252304077, "2705": 0.06246116757392883, "2764": 0.014542185701429844, "2783": 0.09672962874174118, "2832": 0.0797421783208847, "2895": 0.0606246218085289, "2913": 0.2231435477733612, "2920": 0.48068851232528687, "2925": 0.09938567131757736, "3012": 0.11691460013389587, "3161": 0.05694137513637543, "3170": 0.4849066734313965, "3270": 1.0471819639205933, "3273": 0.09495500475168228, "3305": 0.05694137513637543, "3378": 0.14518201351165771, "3424": 0.8272887468338013, "3466": 0.011650617234408855, "3526": 0.38374659419059753, "3625": 0.13157635927200317, "3652": 0.09228714555501938, "3716": 0.34577593207359314, "3720": 0.1685553640127182, "3796": 0.8925741910934448, "3800": 0.043007105588912964, "3853": 0.2652147710323334, "3949": 0.37304413318634033, "4005": 0.6054253578186035, "4200": 0.35745587944984436, "4245": 0.5255602598190308, "4286": 0.40220460295677185, "4295": 0.39893341064453125, "4319": 0.24631060659885406, "4395": 0.7601850032806396, "4403": 0.05786345899105072, "4442": 0.3622259199619293, "4456": 0.6634125709533691, "4539": 0.3084607720375061, "4824": 0.5596157908439636, "4852": 0.2622140049934387, "4949": 0.7370892763137817, "4972": 0.0029254043474793434, "5072": 0.34370049834251404, "5197": 0.03360854089260101, "5257": 0.0174254160374403, "5267": 0.07341018319129944, "5298": 0.26446542143821716, "5387": 1.0037577152252197, "5705": 0.32129061222076416, "5714": 0.75193190574646, "5850": 0.46670228242874146, "5875": 0.24859806895256042, "5876": 0.39762192964553833, "5911": 0.4879087805747986, "5991": 0.6624060273170471, "6074": 0.7009293437004089, "6541": 0.9857001900672913, "6612": 0.175953671336174, "6624": 0.0317181795835495, "6845": 0.4286321699619293, "6848": 0.1064341589808464, "6882": 0.3850763738155365, "6897": 0.5069117546081543, "6904": 0.3034266233444214, "6936": 0.17840765416622162, "7011": 1.1720224618911743, "7076": 0.13157635927200317, "7096": 0.21372433006763458, "7242": 0.8550800085067749, "7337": 0.16690383851528168, "7366": 0.20977331697940826, "7438": 0.129004567861557, "7461": 0.0606246218085289, "7870": 0.3191637098789215, "7889": 0.34508460760116577, "8049": 0.083342544734478, "8089": 0.47827014327049255, "8213": 0.2231435477733612, "8285": 1.2175520658493042, "8322": 0.1685553640127182, "8534": 0.27934664487838745, "8865": 0.14349138736724854, "8878": 0.0797421783208847, "9007": 0.11691460013389587, "9125": 0.036437395960092545, "9349": 0.2447827309370041, "9416": 0.3464667797088623, "9420": 0.25088030099868774, "9824": 0.22626367211341858, "10354": 0.15526613593101501, "10586": 0.7710843086242676, "10722": 0.5800528526306152, "10737": 0.3297532796859741, "10744": 0.004870930220931768, "10851": 0.846739649772644, "11001": 0.41195443272590637, "11311": 0.8949713706970215, "12141": 0.304147332906723, "12207": 0.18492233753204346, "12248": 0.12642613053321838, "13046": 0.36900100111961365, "13341": 0.05786345899105072, "13441": 0.05139094591140747, "13625": 0.05139094591140747, "13656": 0.7665573358535767, "13922": 0.29109421372413635, "14126": 0.22001366317272186, "14228": 0.48970574140548706, "14277": 1.108330488204956, "14667": 0.5562619566917419, "14949": 0.680370569229126, "14971": 0.04767346754670143, "15403": 0.5607312321662903, "15615": 0.7182208299636841, "16000": 1.1506214141845703, "16007": 0.04953393340110779, "16012": 0.3656192123889923, "16746": 0.5278670787811279, "17252": 0.055094651877880096, "17261": 0.5893046259880066, "17379": 0.24401791393756866, "17404": 0.5517725944519043, "18178": 0.0752234235405922, "18714": 0.2786078155040741, "18715": 1.4812493324279785, "19466": 0.0606246218085289, "19857": 0.09495500475168228, "20187": 0.8567397594451904, "20233": 0.15693697333335876, "20360": 0.9363996982574463, "20369": 0.08064348995685577, "20467": 0.23864774405956268, "20752": 0.16524957120418549, "20900": 0.38041436672210693, "20992": 0.469759464263916, "21434": 0.554580807685852, "21472": 0.022212404757738113, "21709": 0.19862671196460724, "21733": 0.6823468804359436, "21890": 0.2247048318386078, "21903": 0.4041621685028076, "22025": 1.0506030321121216, "22330": 1.185243844985962, "22401": 0.6420594453811646, "22931": 0.6613984704017639, "23041": 1.1425544023513794, "23467": 0.18004031479358673, "23692": 0.28890204429626465, "23833": 0.06246116757392883, "23924": 0.11951763927936554, "24054": 0.25239890813827515, "24063": 0.034552380442619324, "24395": 0.4450363218784332, "24434": 0.06429435312747955, "25409": 0.034552380442619324, "25456": 0.09584271162748337, "25605": 0.1889725625514984, "26402": 0.09406650811433792, "26785": 0.9147270321846008, "27144": 0.04207121208310127, "27641": 0.2478361576795578, "27781": 0.46608972549438477, "27814": 0.1693800985813141, "28286": 1.0023250579833984, "28873": 0.4002431631088257, "28896": 0.4400174915790558, "29166": 1.0641717910766602} | 12705056 | The increasing understanding of the role of cytokines in autoimmunity, and the observation that tumour necrosis factor alpha (TNFalpha) is central to the inflammatory and destructive process common to several human autoimmune diseases, has led to a new generation of therapeutics, the TNFalpha blocking agents. In this article, we review the current knowledge of the role of cytokines in autoimmunity as unravelled by studies both in the laboratory and the clinic. In addition, we discuss future prospects of the anti-TNFalpha therapy that may involve combination therapy with other anti-cytokine or anti-T cell biologicals, or the use of small chemicals targeting molecules involved in TNFalpha production such as NF-kappaB and p38 MAPK. The future developments of anti-TNFalpha and anti-cytokine therapy in general will be interesting. | Cytokines and anti-cytokine biologicals in autoimmunity: present and future. |
{"1014": 0.31489628553390503, "1021": 0.34715715050697327, "1051": 0.4734157919883728, "2007": 0.06795065850019455, "2035": 0.3248254358768463, "2051": 0.1384023278951645, "2053": 0.08692999184131622, "2086": 0.2026219218969345, "2089": 0.1064341589808464, "2090": 0.1734936386346817, "2092": 0.0752234235405922, "2095": 0.07068414986133575, "2111": 0.08692999184131622, "2116": 0.10203468054533005, "2120": 0.3297532796859741, "2137": 0.21922965347766876, "2166": 0.5734702348709106, "2167": 0.4286321699619293, "2193": 0.09495500475168228, "2203": 0.567397952079773, "2206": 0.04674193635582924, "2268": 0.34370049834251404, "2273": 0.48670899868011475, "2289": 0.2493593990802765, "2308": 0.4794800877571106, "2310": 0.3956514894962311, "2313": 0.39893341064453125, "2323": 0.026025565341114998, "2331": 1.0409941673278809, "2351": 0.4673144817352295, "2364": 0.1677299439907074, "2426": 0.12038381397724152, "2444": 0.01934296265244484, "2450": 0.27044451236724854, "2470": 0.2447827309370041, "2511": 0.4879087805747986, "2512": 0.8649974465370178, "2515": 0.24325250089168549, "2522": 0.39893341064453125, "2523": 0.8901712894439697, "2526": 0.42735910415649414, "2540": 0.4673144817352295, "2566": 0.0913962796330452, "2590": 0.41065993905067444, "2599": 0.1602703034877777, "2628": 0.2160874605178833, "2640": 0.4938860833644867, "2641": 0.38441169261932373, "2660": 0.12814582884311676, "2730": 0.129004567861557, "2740": 0.5517725944519043, "2765": 0.29255300760269165, "2812": 0.03266380727291107, "2817": 0.6456501483917236, "2833": 0.36290550231933594, "2913": 0.4950772523880005, "2931": 0.08154398202896118, "2944": 0.0019512200960889459, "2951": 0.08603433519601822, "3141": 0.2822965085506439, "3160": 0.07159364968538284, "3268": 0.20102575421333313, "3273": 0.21372433006763458, "3276": 0.9045027494430542, "3278": 0.8074519634246826, "3279": 0.15943801403045654, "3280": 0.6291293501853943, "3287": 0.3916989266872406, "3303": 0.17840765416622162, "3350": 0.8212929964065552, "3378": 0.8383291959762573, "3406": 0.8212929964065552, "3426": 0.49626702070236206, "3446": 0.7674643993377686, "3463": 0.5244048833847046, "3466": 0.25845035910606384, "3517": 0.0913962796330452, "3556": 0.10379679501056671, "3563": 0.7445381283760071, "3567": 0.06520967930555344, "3582": 0.5968599319458008, "3695": 0.5033760666847229, "3726": 0.757441520690918, "3767": 0.3982778787612915, "3808": 0.056018441915512085, "3867": 0.1677299439907074, "3891": 0.5232481360435486, "3896": 0.32764431834220886, "4003": 0.42735910415649414, "4012": 0.007782140281051397, "4081": 0.25467249751091003, "4100": 0.6461620330810547, "4102": 0.619189441204071, "4106": 0.7076893448829651, "4117": 0.5629584193229675, "4254": 0.22157983481884003, "4292": 0.5478278398513794, "4295": 0.3443928062915802, "4328": 0.3777405619621277, "4359": 0.42544642090797424, "4453": 0.3141832649707794, "4456": 0.4617912769317627, "4521": 0.0038986403960734606, "4795": 0.18492233753204346, "4841": 0.05417001247406006, "4895": 0.06886265426874161, "4945": 0.0019512200960889459, "4957": 0.12556517124176025, "5002": 0.018384648486971855, "5066": 0.6754127144813538, "5197": 0.5370414853096008, "5248": 0.129004567861557, "5320": 0.2531573474407196, "5345": 0.6813592314720154, "5362": 0.17020416259765625, "5393": 0.08244366943836212, "5402": 0.07159364968538284, "5418": 0.7764897346496582, "5443": 0.47402387857437134, "5468": 0.2852376699447632, "5504": 0.6223390698432922, "5547": 0.2800849378108978, "5617": 0.0019512200960889459, "5709": 0.07250232994556427, "5717": 0.12642613053321838, "5761": 0.045809537172317505, "5769": 0.06154331564903259, "5776": 0.09938567131757736, "5788": 0.09672962874174118, "5790": 0.014542185701429844, "5799": 0.3191637098789215, "5920": 0.1221139207482338, "5950": 0.6764062643051147, "5983": 0.4950772523880005, "5986": 0.12728634476661682, "5996": 0.3757305145263672, "6022": 0.20660123229026794, "6075": 0.5197699069976807, "6083": 0.4764525294303894, "6086": 0.2447827309370041, "6165": 0.5795059204101562, "6240": 0.34922540187835693, "6289": 0.5729197263717651, "6365": 0.09850110858678818, "6409": 0.16690383851528168, "6421": 0.29255300760269165, "6431": 0.27044451236724854, "6463": 0.7629209756851196, "6535": 0.3870677351951599, "6550": 0.41065993905067444, "6592": 0.49864232540130615, "6612": 0.13670019805431366, "6677": 0.8135309815406799, "6721": 0.0058422754518687725, "6747": 0.43812891840934753, "6767": 1.0881409645080566, "6818": 0.6405166387557983, "6937": 0.06612417846918106, "6961": 0.12384103983640671, "7012": 0.129004567861557, "7017": 0.42225050926208496, "7060": 0.8475768566131592, "7080": 0.007782140281051397, "7091": 0.2516399025917053, "7099": 0.23247487843036652, "7108": 0.0354953333735466, "7189": 0.4158279001712799, "7312": 0.5010119676589966, "7461": 0.12814582884311676, "7524": 0.6096806526184082, "7550": 0.1011524572968483, "7667": 0.13499516248703003, "7691": 0.6882523894309998, "7778": 0.12728634476661682, "7784": 0.4437839686870575, "7831": 0.5010119676589966, "7863": 0.9944084882736206, "7882": 0.31845372915267944, "7965": 0.1905880719423294, "8161": 0.030771657824516296, "8168": 0.04394211992621422, "8290": 0.1384023278951645, "8353": 0.014542185701429844, "8381": 0.18248429894447327, "8606": 0.5957841277122498, "8664": 0.19220098853111267, "8733": 0.30486753582954407, "8738": 0.8442239761352539, "8924": 0.680370569229126, "8995": 0.2786078155040741, "9002": 0.022212404757738113, "9104": 0.14433705806732178, "9252": 0.043007105588912964, "9312": 0.4568560719490051, "9336": 0.48670899868011475, "9363": 1.0894558429718018, "9530": 0.26446542143821716, "9556": 0.3027053773403168, "9560": 0.7286425232887268, "9574": 1.1720224618911743, "9580": 0.6902132034301758, "9582": 0.20102575421333313, "9614": 0.018384648486971855, "9756": 0.26446542143821716, "9967": 0.026025565341114998, "10085": 0.28082266449928284, "10266": 0.03831886500120163, "10383": 0.02316705882549286, "10426": 0.4926934838294983, "10427": 0.1358480453491211, "10548": 0.029824240133166313, "10611": 0.7067264318466187, "10788": 0.4067663550376892, "10817": 0.3601844012737274, "10831": 0.1212492436170578, "11100": 0.6456501483917236, "11119": 0.755608320236206, "11156": 0.6022219061851501, "11326": 0.015504186972975731, "11467": 0.2223619967699051, "11487": 0.3070250153541565, "11522": 0.6573580503463745, "11656": 0.5127768516540527, "11704": 0.08692999184131622, "11709": 0.018384648486971855, "11825": 0.014542185701429844, "12044": 0.7647408246994019, "12199": 0.7863243818283081, "12353": 0.036437395960092545, "12407": 0.07068414986133575, "12421": 0.3750596046447754, "12435": 0.1477125883102417, "12462": 0.05786345899105072, "12763": 0.1602703034877777, "12765": 0.06795065850019455, "12826": 0.12642613053321838, "12878": 0.036437395960092545, "13105": 0.7370892763137817, "13122": 0.14349138736724854, "13180": 0.3903779089450836, "13356": 1.2555493116378784, "13494": 0.045809537172317505, "13599": 0.23556606471538544, "13613": 0.05139094591140747, "13896": 0.034552380442619324, "14155": 0.23479416966438293, "14234": 0.35334911942481995, "14243": 0.34508460760116577, "14266": 0.2918238639831543, "14267": 0.9769153594970703, "14343": 0.14686977863311768, "14358": 0.24631060659885406, "14671": 0.1930064558982849, "14876": 0.7258110046386719, "14971": 0.025073638185858727, "15050": 0.5324648022651672, "15306": 0.4879087805747986, "15316": 0.14179791510105133, "15354": 0.5033760666847229, "15431": 0.7537717819213867, "15509": 0.319873183965683, "15559": 0.8315495252609253, "15643": 0.0019512200960889459, "15671": 0.11691460013389587, "15680": 0.10731173306703568, "15873": 0.5573811531066895, "15942": 1.3695534467697144, "15945": 0.7934166193008423, "15982": 0.8109301924705505, "16014": 0.10906458646059036, "16149": 0.1212492436170578, "16157": 0.4228905141353607, "16330": 0.4932899475097656, "16515": 0.12556517124176025, "16902": 0.6714286804199219, "17062": 0.4067663550376892, "17080": 0.07431721687316895, "17119": 0.4950772523880005, "17237": 0.056018441915512085, "17245": 0.007782140281051397, "17464": 0.6941232681274414, "17547": 0.09584271162748337, "17760": 0.28743788599967957, "17826": 0.2830325961112976, "17850": 0.16690383851528168, "17908": 0.23864774405956268, "18150": 0.7592713832855225, "18609": 0.06886265426874161, "18731": 0.20580662786960602, "18749": 1.024303913116455, "18949": 0.3824150264263153, "19037": 0.2034190446138382, "19064": 0.24631060659885406, "19546": 0.0797421783208847, "19699": 0.1693800985813141, "19830": 0.011650617234408855, "19862": 0.4158279001712799, "20155": 0.565735399723053, "20166": 0.13499516248703003, "20272": 0.1485546976327896, "20427": 0.3923587501049042, "20569": 0.07068414986133575, "20576": 0.15442965924739838, "20589": 0.35128939151763916, "20824": 0.6275664567947388, "20871": 0.2976420819759369, "21150": 0.12470348179340363, "21371": 0.2501201331615448, "21449": 0.21135559678077698, "21539": 0.07793712615966797, "21557": 0.15023678541183472, "21604": 0.15943801403045654, "21877": 0.6989894509315491, "21879": 0.5696102976799011, "21923": 0.6989894509315491, "21961": 0.040196798741817474, "22010": 0.6833335757255554, "22084": 0.05786345899105072, "22423": 0.02887592278420925, "22684": 0.21214580535888672, "22935": 0.9271688461303711, "22963": 0.07341018319129944, "23062": 0.37974658608436584, "23208": 0.15023678541183472, "23260": 0.09050461649894714, "23329": 0.13414156436920166, "23444": 0.9045027494430542, "23521": 0.6275664567947388, "23566": 1.3950450420379639, "23900": 0.42096930742263794, "24117": 0.016465263441205025, "24232": 0.43244171142578125, "24552": 0.3683255612850189, "25006": 0.603290855884552, "25022": 0.3325583338737488, "25095": 0.3443928062915802, "25121": 0.09850110858678818, "25125": 0.7201237678527832, "25176": 0.16110190749168396, "25331": 0.11778303235769272, "25451": 0.06703783571720123, "25696": 1.2975058555603027, "25937": 0.013579257763922215, "26163": 0.36900100111961365, "26226": 0.3248254358768463, "26237": 1.0815403461456299, "26243": 0.045809537172317505, "26462": 0.500420093536377, "26642": 0.16524957120418549, "26906": 0.30558720231056213, "27204": 0.018384648486971855, "27354": 0.053244512528181076, "27794": 1.0271050930023193, "28093": 0.22859740257263184, "28102": 0.12384103983640671, "28268": 0.4512746334075928, "28321": 0.44753631949424744, "28369": 0.8400169610977173, "28689": 0.2089812457561493, "29299": 0.3177432417869568} | 12709184 | IMPORTANCE Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and mortality. DESIGN Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. SETTING Adventist Health Study 2 (AHS-2), a large North American cohort. PARTICIPANTS A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73,308 participants remained after exclusions. EXPOSURES Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. MAIN OUTCOME AND MEASURE The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. RESULTS There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82-6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. CONCLUSIONS AND RELEVANCE Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance. | Vegetarian dietary patterns and mortality in Adventist Health Study 2. |
{"1011": 0.03360854089260101, "1061": 0.3784096837043762, "1999": 0.004870930220931768, "2004": 0.08244366943836212, "2005": 0.31845372915267944, "2006": 0.6054253578186035, "2008": 0.03831886500120163, "2011": 0.40546512603759766, "2029": 0.25995752215385437, "2033": 0.35745587944984436, "2063": 0.1510767638683319, "2076": 0.083342544734478, "2079": 0.07793712615966797, "2094": 0.9340999722480774, "2098": 0.09850110858678818, "2109": 0.10379679501056671, "2155": 0.9021284580230713, "2361": 1.1312761306762695, "2377": 0.036437395960092545, "2470": 0.055094651877880096, "2511": 0.083342544734478, "2515": 0.18411032855510712, "2529": 0.45870962738990784, "2535": 0.5914691090583801, "2590": 0.4126010537147522, "2734": 0.28670501708984375, "2817": 0.21293537318706512, "2852": 0.25694093108177185, "2865": 1.0165601968765259, "2891": 0.5404602885246277, "2913": 0.304147332906723, "2920": 0.3519764244556427, "2945": 0.5381823778152466, "2953": 0.6608943343162537, "3064": 0.06795065850019455, "3081": 0.009718249551951885, "3211": 0.6270449161529541, "3223": 0.5914691090583801, "3248": 0.09495500475168228, "3273": 0.11517547070980072, "3276": 0.20977331697940826, "3378": 0.20580662786960602, "3436": 0.32199856638908386, "3466": 0.009718249551951885, "3495": 0.08692999184131622, "3508": 0.02412080205976963, "3522": 0.045809537172317505, "3526": 0.6223390698432922, "3597": 0.6999598741531372, "3622": 0.469759464263916, "3625": 0.2531573474407196, "3652": 0.034552380442619324, "3670": 0.812664806842804, "3796": 0.026025565341114998, "3853": 0.4444103240966797, "3930": 0.823009729385376, "4072": 0.5301685929298401, "4130": 0.02412080205976963, "4227": 0.1994270235300064, "4263": 0.7463917136192322, "4286": 0.4400174915790558, "4395": 0.5197699069976807, "4442": 0.5489565134048462, "4453": 0.6186635494232178, "4456": 0.8492490649223328, "4502": 0.010684899985790253, "4523": 0.5404602885246277, "4539": 0.9076598286628723, "4671": 0.007782140281051397, "4742": 0.0606246218085289, "4758": 0.10467668622732162, "4958": 0.1619328260421753, "4962": 1.147526502609253, "4972": 0.3012613356113434, "4982": 0.2719337046146393, "5054": 0.7096124291419983, "5099": 0.950843095779419, "5197": 0.052318159490823746, "5228": 0.3106105625629425, "5250": 0.27564704418182373, "5280": 0.025073638185858727, "5387": 0.8492490649223328, "5393": 0.09672962874174118, "5449": 0.21293537318706512, "5478": 0.2247048318386078, "5537": 0.0029254043474793434, "5572": 1.4560681581497192, "5603": 0.08513788133859634, "5668": 0.4337083101272583, "5799": 0.13414156436920166, "5876": 0.7987030148506165, "5918": 0.2018241584300995, "5942": 0.2954642176628113, "6064": 0.4794800877571106, "6177": 0.04953393340110779, "6591": 0.6907027959823608, "6593": 0.32199856638908386, "6653": 0.7096124291419983, "6700": 0.009718249551951885, "6709": 0.08603433519601822, "6827": 0.7755908370018005, "6873": 1.0546929836273193, "6887": 0.4794800877571106, "6897": 0.6608943343162537, "6914": 0.7746911644935608, "6922": 0.34715715050697327, "7337": 0.2667117714881897, "7366": 0.5116065740585327, "7403": 0.7987030148506165, "7591": 0.016465263441205025, "7645": 0.3930181860923767, "7711": 0.10026945173740387, "7790": 0.8332487344741821, "7816": 0.34508460760116577, "7885": 0.030771657824516296, "7889": 0.7629209756851196, "8018": 0.12814582884311676, "8038": 1.564702033996582, "8050": 0.08513788133859634, "8095": 0.6389714479446411, "8153": 0.2089812457561493, "8171": 0.07884006202220917, "8303": 0.22626367211341858, "8360": 0.4267219603061676, "8458": 0.34577593207359314, "8651": 0.7086513638496399, "8878": 0.176772341132164, "8939": 0.6144463419914246, "8991": 0.2026219218969345, "9007": 0.6729245185852051, "9067": 0.20501139760017395, "9095": 0.11865071207284927, "9099": 0.43244171142578125, "9165": 1.024303913116455, "9416": 0.5629584193229675, "9495": 0.15526613593101501, "10253": 0.861702561378479, "10266": 0.029824240133166313, "10572": 0.7305257320404053, "10580": 0.175953671336174, "10738": 0.4487839937210083, "10769": 0.11604541540145874, "10938": 0.2852376699447632, "11423": 0.32341301441192627, "11444": 0.7389566898345947, "11469": 0.12814582884311676, "11714": 0.5903874635696411, "12115": 0.14179791510105133, "12222": 0.1946154683828354, "12359": 0.025073638185858727, "12562": 0.2852376699447632, "12618": 0.00875066313892603, "12732": 0.8829278349876404, "12789": 0.03831886500120163, "12987": 0.5506471395492554, "13070": 0.11778303235769272, "13248": 0.02316705882549286, "13458": 0.3297532796859741, "13490": 0.27786844968795776, "13656": 0.7827593088150024, "13712": 0.4196864068508148, "13776": 0.5762182474136353, "13791": 0.10555581003427505, "13806": 0.04113444685935974, "13833": 0.24018502235412598, "13922": 0.18654440343379974, "14031": 0.17020416259765625, "14126": 0.37707099318504333, "14193": 1.3969792127609253, "14270": 0.09850110858678818, "14471": 0.3723714053630829, "14494": 0.029824240133166313, "14536": 0.05694137513637543, "14800": 0.12642613053321838, "14828": 0.5074998140335083, "14931": 0.7809720039367676, "15115": 0.0029254043474793434, "15176": 0.011650617234408855, "15527": 0.18004031479358673, "15543": 0.6054253578186035, "15663": 0.22937409579753876, "15946": 0.03925827145576477, "16007": 0.15526613593101501, "16012": 0.5033760666847229, "16081": 1.1524739265441895, "16221": 0.3027053773403168, "16285": 0.30989447236061096, "16288": 0.00875066313892603, "16341": 0.7500885725021362, "16505": 0.7683706283569336, "16515": 0.14686977863311768, "16691": 0.0752234235405922, "16706": 0.3170322775840759, "16910": 0.669430673122406, "16969": 0.19541899859905243, "17175": 0.03831886500120163, "17181": 0.04674193635582924, "17379": 0.26296505331993103, "17459": 0.48670899868011475, "17666": 0.2719337046146393, "17903": 0.07431721687316895, "18714": 0.2018241584300995, "19137": 0.45251765847206116, "19601": 0.040196798741817474, "19653": 0.5876781344413757, "19824": 0.05970508232712746, "19872": 0.5027855634689331, "19995": 0.5729197263717651, "20250": 0.23092569410800934, "20353": 0.016465263441205025, "20360": 0.07793712615966797, "20467": 0.7683706283569336, "20544": 0.0770333781838417, "20806": 0.15442965924739838, "21081": 0.1332872211933136, "21197": 0.5957841277122498, "21230": 0.2247048318386078, "21434": 0.535327672958374, "21618": 0.3269403576850891, "21865": 0.3656192123889923, "21903": 0.14686977863311768, "21919": 0.09761575609445572, "22166": 0.3499138653278351, "22248": 0.016465263441205025, "22422": 0.176772341132164, "23216": 0.13755162060260773, "23586": 0.6634125709533691, "23713": 0.38441169261932373, "23737": 0.5427330136299133, "23924": 0.15860503911972046, "23934": 0.08244366943836212, "24004": 0.8534175157546997, "24051": 0.37102460861206055, "24054": 0.7239188551902771, "24169": 0.42608439922332764, "24174": 0.6744182109832764, "24277": 0.01934296265244484, "24278": 0.24631060659885406, "24529": 0.11951763927936554, "24587": 0.5925496220588684, "25194": 0.006812678650021553, "25206": 0.07250232994556427, "25409": 0.6011518239974976, "25456": 0.5139457583427429, "25708": 1.216395378112793, "26083": 0.8715548515319824, "26223": 0.02316705882549286, "26244": 0.07431721687316895, "26402": 1.0423725843429565, "26435": 0.24018502235412598, "26512": 0.19541899859905243, "26520": 0.06246116757392883, "26534": 0.40806588530540466, "26773": 0.23556606471538544, "26775": 0.5540198087692261, "26786": 0.05046287178993225, "26986": 0.8957691192626953, "27854": 0.020300358533859253, "28086": 0.04394211992621422, "28155": 0.7987030148506165, "28935": 0.02792670577764511, "29206": 0.2689530849456787, "29290": 0.3464667797088623} | 12737132 | The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP. | TEAD mediates YAP-dependent gene induction and growth control. |
{"1009": 0.32058215141296387, "1011": 0.45623743534088135, "1019": 0.0019512200960889459, "1043": 0.28670501708984375, "1044": 0.3191637098789215, "2003": 0.025073638185858727, "2004": 0.0752234235405922, "2013": 0.46853771805763245, "2020": 0.11865071207284927, "2024": 0.2786078155040741, "2029": 0.23247487843036652, "2031": 0.18248429894447327, "2038": 0.129004567861557, "2046": 0.39762192964553833, "2057": 0.025073638185858727, "2063": 0.04674193635582924, "2064": 0.2531573474407196, "2071": 0.2837681770324707, "2078": 0.9021284580230713, "2079": 0.1913948506116867, "2109": 0.0029254043474793434, "2128": 0.08961215615272522, "2140": 0.12728634476661682, "2153": 0.055094651877880096, "2179": 0.13414156436920166, "2239": 0.022212404757738113, "2265": 0.11778303235769272, "2278": 0.2247048318386078, "2291": 0.23015019297599792, "2309": 0.7105726003646851, "2313": 0.3070250153541565, "2320": 0.058784693479537964, "2410": 0.1710275560617447, "2430": 0.8383291959762573, "2509": 0.4494072198867798, "2515": 0.0174254160374403, "2529": 0.7163142561912537, "2535": 0.025073638185858727, "2546": 0.03360854089260101, "2549": 0.12642613053321838, "2583": 0.46055975556373596, "2629": 0.12384103983640671, "2696": 0.3464667797088623, "2825": 0.15275461971759796, "2828": 0.1873544454574585, "2944": 0.055094651877880096, "2969": 1.1350497007369995, "2999": 0.4093637466430664, "3001": 0.040196798741817474, "3065": 0.14095009863376617, "3161": 0.08244366943836212, "3200": 0.05970508232712746, "3209": 0.3864043951034546, "3226": 0.6265231370925903, "3231": 0.0606246218085289, "3273": 0.13071982562541962, "3302": 0.6502478122711182, "3336": 0.3127557039260864, "3370": 0.36900100111961365, "3372": 0.24018502235412598, "3429": 0.2447827309370041, "3491": 0.3519764244556427, "3495": 0.7076893448829651, "3526": 1.1102628707885742, "3603": 0.052318159490823746, "3619": 1.3655734062194824, "3622": 0.2674594223499298, "3630": 0.24171993136405945, "3662": 0.24018502235412598, "3668": 0.21135559678077698, "3674": 0.036437395960092545, "3729": 1.0312920808792114, "3754": 0.3423145115375519, "3811": 0.7057625651359558, "3853": 0.24171993136405945, "3930": 0.045809537172317505, "3977": 0.029824240133166313, "4013": 0.43244171142578125, "4022": 1.0423725843429565, "4053": 0.4673144817352295, "4066": 0.6102113127708435, "4090": 0.47463157773017883, "4127": 0.16442140936851501, "4167": 1.0001721382141113, "4176": 0.0174254160374403, "4179": 0.7314660549163818, "4182": 0.31132611632347107, "4245": 0.09406650811433792, "4270": 0.8187123537063599, "4286": 0.5751199722290039, "4310": 0.02887592278420925, "4423": 0.777387797832489, "4442": 1.2129170894622803, "4509": 0.23479416966438293, "4651": 0.15275461971759796, "4663": 0.08244366943836212, "4760": 0.015504186972975731, "4800": 0.7881022095680237, "4840": 0.5393219590187073, "4928": 0.04767346754670143, "4935": 0.38441169261932373, "4962": 0.24325250089168549, "4964": 0.011650617234408855, "5067": 0.058784693479537964, "5144": 0.6070231795310974, "5214": 0.2478361576795578, "5591": 0.7898768186569214, "5643": 0.009718249551951885, "5644": 0.27934664487838745, "5672": 0.8264343738555908, "5740": 0.040196798741817474, "5809": 0.38174858689308167, "5812": 0.013579257763922215, "5852": 0.07250232994556427, "6061": 0.1734936386346817, "6064": 0.0606246218085289, "6091": 1.004473328590393, "6110": 0.6512666940689087, "6388": 0.27342069149017334, "6418": 0.03925827145576477, "6419": 0.5244048833847046, "6459": 0.2470736801624298, "6522": 0.07159364968538284, "6529": 0.08513788133859634, "6551": 0.006812678650021553, "6632": 0.8004589080810547, "6887": 0.3269403576850891, "6914": 0.6512666940689087, "7028": 0.004870930220931768, "7065": 0.2969166338443756, "7080": 0.1602703034877777, "7159": 0.03360854089260101, "7192": 0.981317400932312, "7275": 1.004473328590393, "7337": 0.06429435312747955, "7356": 0.014542185701429844, "7366": 0.2800849378108978, "7403": 0.10026945173740387, "7531": 0.8425432443618774, "7551": 0.04767346754670143, "7578": 0.034552380442619324, "7645": 0.4879087805747986, "7677": 0.010684899985790253, "7712": 0.030771657824516296, "7818": 0.6568518877029419, "7856": 0.272677481174469, "7872": 1.4161186218261719, "7885": 0.11430477350950241, "7949": 0.15777134895324707, "8000": 0.8592242002487183, "8040": 0.8756314516067505, "8081": 0.09050461649894714, "8153": 0.8091925978660583, "8168": 0.025073638185858727, "8469": 0.11691460013389587, "8578": 0.7701805830001831, "8651": 0.11081436276435852, "8713": 0.1332872211933136, "8873": 0.4132472574710846, "8878": 0.8366385698318481, "8907": 0.08782484382390976, "8980": 0.10906458646059036, "9007": 0.22157983481884003, "9100": 0.5925496220588684, "9113": 0.7942996621131897, "9114": 0.19862671196460724, "9186": 0.38041436672210693, "9230": 0.8212929964065552, "9239": 0.3297532796859741, "9280": 0.14686977863311768, "9350": 0.35334911942481995, "9412": 0.2089812457561493, "9859": 0.14349138736724854, "9972": 0.3374483287334442, "10003": 0.05139094591140747, "10015": 0.14264501631259918, "10032": 0.1685553640127182, "10047": 0.4500300884246826, "10244": 0.9798521995544434, "10295": 0.08064348995685577, "10315": 0.6734226942062378, "10336": 0.46608972549438477, "10527": 0.2667117714881897, "10572": 0.2976420819759369, "10580": 0.319873183965683, "10627": 0.5313173532485962, "10673": 0.27044451236724854, "10744": 0.15860503911972046, "10834": 0.07068414986133575, "10938": 0.08871890604496002, "10956": 0.2089812457561493, "10976": 0.7463917136192322, "11005": 0.14686977863311768, "11020": 0.16359257698059082, "11156": 0.007782140281051397, "11265": 0.5827828645706177, "11311": 0.037378571927547455, "11432": 0.43244171142578125, "11601": 0.42225050926208496, "11649": 0.5584990978240967, "11792": 0.10993985831737518, "11901": 0.07159364968538284, "12115": 0.469759464263916, "12328": 1.1089750528335571, "12356": 0.18167030811309814, "12402": 0.5596157908439636, "12477": 0.757441520690918, "12521": 0.4728073179721832, "12562": 0.28670501708984375, "12735": 0.255429208278656, "12898": 0.053244512528181076, "12955": 0.006812678650021553, "13447": 0.0913962796330452, "13490": 0.1873544454574585, "13595": 0.09050461649894714, "13671": 0.9170717000961304, "13708": 0.011650617234408855, "13776": 0.7610978484153748, "13791": 0.38174858689308167, "13806": 0.3070250153541565, "13874": 0.3963087201118469, "13918": 0.03925827145576477, "13922": 0.02316705882549286, "13923": 0.259204238653183, "14095": 0.5528968572616577, "14313": 0.3560888469219208, "14332": 0.5415972471237183, "14340": 0.13414156436920166, "14524": 1.094698429107666, "14584": 0.0354953333735466, "14591": 0.1685553640127182, "14828": 0.00875066313892603, "14882": 0.04113444685935974, "15698": 0.9546096324920654, "15756": 0.7827593088150024, "15887": 0.07793712615966797, "15923": 0.037378571927547455, "16221": 0.06977381557226181, "16231": 0.9162907600402832, "16285": 0.03360854089260101, "16360": 0.8281423449516296, "16387": 0.6553317308425903, "16487": 0.09672962874174118, "16505": 1.2152372598648071, "16515": 0.7115318179130554, "16530": 0.20580662786960602, "16558": 0.7445381283760071, "16691": 0.3034266233444214, "16731": 1.072225570678711, "16834": 0.7665573358535767, "16932": 0.0058422754518687725, "16992": 0.4093637466430664, "17059": 0.010684899985790253, "17134": 0.861702561378479, "17175": 1.2883929014205933, "17351": 0.045809537172317505, "17441": 0.2026219218969345, "17487": 0.7201237678527832, "17598": 0.2561853528022766, "17815": 0.007782140281051397, "17820": 0.841701865196228, "17890": 0.6118015646934509, "17903": 0.045809537172317505, "17926": 0.05139094591140747, "18340": 0.021256839856505394, "18439": 0.2576959431171417, "18479": 0.5478278398513794, "18514": 0.0913962796330452, "18595": 0.007782140281051397, "18715": 0.0174254160374403, "18827": 0.7969439625740051, "18845": 0.09495500475168228, "18856": 0.979118824005127, "19098": 0.1401015669107437, "19444": 0.018384648486971855, "19476": 0.13499516248703003, "19481": 0.15275461971759796, "19601": 0.2516399025917053, "19616": 1.0101795196533203, "19653": 0.37907835841178894, "19723": 0.3560888469219208, "19847": 0.6502478122711182, "19852": 0.05139094591140747, "19857": 0.6160298585891724, "19885": 0.4487839937210083, "19961": 1.2516462802886963, "20011": 0.11256109178066254, "20030": 1.0464962720870972, "20045": 0.7845434546470642, "20116": 0.16359257698059082, "20250": 0.8091925978660583, "20282": 0.05694137513637543, "20544": 0.15023678541183472, "20582": 1.0894558429718018, "20662": 0.6022219061851501, "20687": 0.9732321500778198, "20736": 0.4437839686870575, "20875": 0.10203468054533005, "20958": 0.1358480453491211, "20972": 0.0029254043474793434, "21017": 0.7172679901123047, "21032": 0.6358738541603088, "21150": 0.004870930220931768, "21181": 0.861702561378479, "21230": 0.10906458646059036, "21371": 0.0797421783208847, "21376": 0.0354953333735466, "21472": 0.3519764244556427, "21486": 0.3956514894962311, "21508": 0.05786345899105072, "21707": 0.013579257763922215, "21967": 0.021256839856505394, "22022": 1.351516842842102, "22025": 0.04953393340110779, "22131": 0.7809720039367676, "22160": 0.35745587944984436, "22184": 0.6254787445068359, "22210": 1.0464962720870972, "22248": 0.15526613593101501, "22262": 0.18816383183002472, "22291": 0.9805850982666016, "22394": 0.38574060797691345, "22407": 0.1734936386346817, "22806": 0.5729197263717651, "22931": 0.7220231294631958, "22932": 0.4500300884246826, "23041": 0.6764062643051147, "23130": 0.39433568716049194, "23402": 0.8583967685699463, "23499": 0.0752234235405922, "23700": 0.29109421372413635, "23737": 0.77198725938797, "23777": 0.35334911942481995, "23874": 1.1798561811447144, "23924": 0.5827828645706177, "23936": 0.18167030811309814, "24084": 0.034552380442619324, "24269": 0.1808556467294693, "24278": 0.6970458030700684, "24374": 0.6064908504486084, "24501": 0.02412080205976963, "24545": 0.22704219818115234, "24978": 0.07250232994556427, "25202": 0.839173436164856, "25540": 0.5696102976799011, "25714": 0.30989447236061096, "25972": 1.0172666311264038, "26236": 0.1889725625514984, "26296": 0.8143964409828186, "26305": 0.07884006202220917, "26616": 0.4145384132862091, "26786": 0.02316705882549286, "27009": 0.5021947622299194, "27086": 0.7592713832855225, "27152": 0.7067264318466187, "27159": 0.15943801403045654, "27166": 0.8004589080810547, "27226": 0.6244332790374756, "27321": 0.13414156436920166, "27343": 0.007782140281051397, "27480": 0.0913962796330452, "27528": 0.6699305176734924, "27698": 0.025073638185858727, "27710": 0.053244512528181076, "27781": 0.47827014327049255, "27815": 0.7018978595733643, "28024": 0.15442965924739838, "28086": 0.4734157919883728, "28156": 0.34577593207359314, "28636": 0.14433705806732178, "28788": 0.29255300760269165, "29206": 0.18978065252304077} | 12742164 | Stem cells, which are clonogenic cells with self-renewal and multilineage differentiation properties, have the potential to replace or repair damaged tissue. We have directly isolated clonogenic human central nervous system stem cells (hCNS-SC) from fresh human fetal brain tissue, using antibodies to cell surface markers and fluorescence-activated cell sorting. These hCNS-SC are phenotypically 5F3 (CD133)(+), 5E12(+), CD34(-), CD45(-), and CD24(-/lo). Single CD133(+) CD34(-) CD45(-) sorted cells initiated neurosphere cultures, and the progeny of clonogenic cells could differentiate into both neurons and glial cells. Single cells from neurosphere cultures initiated from CD133(+) CD34(-) CD45(-) cells were again replated as single cells and were able to reestablish neurosphere cultures, demonstrating the self-renewal potential of this highly enriched population. Upon transplantation into brains of immunodeficient neonatal mice, the sorted/expanded hCNS-SC showed potent engraftment, proliferation, migration, and neural differentiation. | Direct isolation of human central nervous system stem cells. |
{"1011": 0.151916041970253, "1016": 0.22704219818115234, "1022": 0.2493593990802765, "1041": 0.6244332790374756, "1048": 0.31489628553390503, "1051": 0.3381449282169342, "1052": 0.7629209756851196, "1998": 0.10555581003427505, "2007": 0.31845372915267944, "2011": 0.1751343309879303, "2015": 0.5021947622299194, "2020": 0.010684899985790253, "2029": 0.3519764244556427, "2038": 0.009718249551951885, "2048": 0.0019512200960889459, "2062": 0.04487626627087593, "2072": 0.401551216840744, "2084": 0.27044451236724854, "2087": 0.06795065850019455, "2092": 0.37304413318634033, "2099": 0.7436100244522095, "2119": 0.3127557039260864, "2135": 0.12556517124176025, "2140": 0.6533012986183167, "2166": 0.004870930220931768, "2168": 0.08244366943836212, "2265": 0.3283478021621704, "2274": 0.3297532796859741, "2278": 0.7701805830001831, "2309": 0.5069117546081543, "2324": 0.7105726003646851, "2378": 0.6892333030700684, "2389": 0.2223619967699051, "2403": 0.37371641397476196, "2410": 0.2786078155040741, "2459": 0.4926934838294983, "2470": 0.19782574474811554, "2475": 0.34922540187835693, "2482": 0.3554046154022217, "2483": 0.9271688461303711, "2487": 0.5968599319458008, "2497": 0.16359257698059082, "2553": 0.5410289764404297, "2556": 0.41840189695358276, "2566": 0.16690383851528168, "2592": 0.12470348179340363, "2606": 0.05046287178993225, "2620": 0.9092346429824829, "2676": 0.5244048833847046, "2714": 0.2689530849456787, "2765": 0.34370049834251404, "2771": 0.7889899015426636, "2804": 0.2689530849456787, "2809": 0.38574060797691345, "2817": 0.5990082025527954, "2828": 0.436867892742157, "2863": 0.5512100458145142, "2881": 0.0038986403960734606, "2913": 0.5914691090583801, "2920": 0.05970508232712746, "2951": 0.3012613356113434, "3020": 0.1889725625514984, "3065": 0.2561853528022766, "3231": 0.26296505331993103, "3273": 0.37640097737312317, "3334": 0.6603899002075195, "3351": 0.02792670577764511, "3370": 0.5151132941246033, "3378": 0.5734702348709106, "3406": 0.678390383720398, "3445": 0.5662899017333984, "3450": 0.07159364968538284, "3463": 0.5528968572616577, "3491": 0.45251765847206116, "3495": 0.4938860833644867, "3526": 0.7809720039367676, "3532": 0.18654440343379974, "3540": 0.06703783571720123, "3563": 0.06337817758321762, "3572": 0.8281423449516296, "3623": 0.39893341064453125, "3662": 0.4145384132862091, "3670": 1.1413075923919678, "3672": 1.0868242979049683, "3739": 0.15860503911972046, "3893": 0.8764448165893555, "3930": 0.8682814836502075, "3979": 0.04767346754670143, "4008": 0.5324648022651672, "4013": 0.6902132034301758, "4023": 0.47827014327049255, "4081": 0.08244366943836212, "4102": 0.6451379656791687, "4106": 0.5696102976799011, "4118": 0.304147332906723, "4127": 0.3995884954929352, "4146": 0.0058422754518687725, "4174": 0.04487626627087593, "4355": 0.6624060273170471, "4442": 0.8748174905776978, "4456": 1.1230508089065552, "4489": 0.021256839856505394, "4588": 0.4974553883075714, "4598": 0.4286321699619293, "4647": 0.9131608605384827, "4668": 0.6270449161529541, "4671": 0.47584590315818787, "4677": 0.8525851964950562, "4725": 0.495672345161438, "4760": 0.18654440343379974, "4812": 0.3547199070453644, "4839": 0.12470348179340363, "4958": 0.48430517315864563, "4962": 0.9363996982574463, "4997": 0.8083226680755615, "5072": 0.09495500475168228, "5182": 0.07341018319129944, "5187": 0.34715715050697327, "5228": 0.7239188551902771, "5250": 0.6931471824645996, "5387": 0.8039615154266357, "5410": 0.7898768186569214, "5604": 0.016465263441205025, "5643": 0.7408206462860107, "5688": 0.10203468054533005, "5769": 0.151916041970253, "5852": 0.14179791510105133, "5876": 0.5051454305648804, "5887": 1.3086495399475098, "5950": 0.9553611874580383, "5966": 0.20102575421333313, "6022": 0.10555581003427505, "6064": 0.4145384132862091, "6079": 0.18573370575904846, "6083": 0.0770333781838417, "6168": 0.19220098853111267, "6169": 0.2018241584300995, "6370": 0.23556606471538544, "6377": 0.19220098853111267, "6388": 0.2184450328350067, "6459": 0.3930181860923767, "6461": 0.11081436276435852, "6592": 0.4412745535373688, "6614": 0.7755908370018005, "6761": 0.37640097737312317, "6819": 0.7656494975090027, "6845": 0.13243216276168823, "6887": 0.7463917136192322, "6906": 0.9886114001274109, "6936": 0.13071982562541962, "7012": 0.176772341132164, "7020": 0.8039615154266357, "7076": 0.11865071207284927, "7093": 0.48068851232528687, "7096": 0.7863243818283081, "7312": 0.4849066734313965, "7356": 0.053244512528181076, "7361": 0.7454653382301331, "7388": 1.1369311809539795, "7403": 0.6358738541603088, "7457": 0.26296505331993103, "7485": 0.06520967930555344, "7551": 0.08782484382390976, "7578": 0.2105647772550583, "7629": 0.8877626657485962, "7645": 0.2969166338443756, "7718": 0.1212492436170578, "7763": 0.3248254358768463, "7783": 1.024303913116455, "7831": 0.6102113127708435, "7863": 0.1873544454574585, "7872": 1.2627575397491455, "7885": 0.3012613356113434, "7900": 0.151916041970253, "7987": 0.18654440343379974, "8000": 0.2105647772550583, "8153": 0.25694093108177185, "8156": 0.10467668622732162, "8171": 0.7314660549163818, "8247": 0.0058422754518687725, "8281": 0.11081436276435852, "8319": 0.11256109178066254, "8335": 0.4728073179721832, "8449": 0.9194108247756958, "8556": 0.34715715050697327, "8704": 0.2830325961112976, "8720": 0.0038986403960734606, "8859": 0.19541899859905243, "8873": 0.6573580503463745, "8909": 1.039613962173462, "8920": 0.5450005531311035, "8939": 0.8091925978660583, "8991": 0.22001366317272186, "9007": 0.25845035910606384, "9165": 0.8433839678764343, "9171": 0.12642613053321838, "9250": 0.026025565341114998, "9253": 0.10291612148284912, "9312": 0.5517725944519043, "9335": 0.14433705806732178, "9336": 0.1619328260421753, "9358": 0.4849066734313965, "9413": 0.7408206462860107, "9468": 0.011650617234408855, "9556": 0.14095009863376617, "9597": 0.5267143249511719, "9706": 0.5784112811088562, "9996": 0.6096806526184082, "10020": 0.04394211992621422, "10047": 0.319873183965683, "10210": 0.7987030148506165, "10509": 0.2478361576795578, "10556": 0.053244512528181076, "10641": 0.20977331697940826, "10708": 0.006812678650021553, "10722": 0.45251765847206116, "10744": 0.0752234235405922, "10755": 0.3560888469219208, "10769": 1.001607894897461, "10847": 0.6714286804199219, "11022": 0.35060185194015503, "11100": 0.13670019805431366, "11156": 0.1946154683828354, "11226": 0.6006163358688354, "11234": 0.09938567131757736, "11251": 0.5573811531066895, "11311": 0.1064341589808464, "11320": 0.8989537954330444, "11423": 0.562402069568634, "11487": 0.02412080205976963, "11538": 0.19541899859905243, "11628": 0.3170322775840759, "11631": 0.5920094847679138, "11657": 0.1510767638683319, "11709": 0.9455460906028748, "12115": 0.6583697199821472, "12319": 0.2763880789279938, "12328": 0.055094651877880096, "12402": 0.31204116344451904, "12435": 0.3870677351951599, "12562": 0.011650617234408855, "12596": 0.17840765416622162, "12650": 0.25995752215385437, "12682": 0.6064908504486084, "12826": 0.4196864068508148, "12955": 0.3027053773403168, "12987": 0.1221139207482338, "13458": 0.2689530849456787, "13599": 0.48430517315864563, "13625": 0.030771657824516296, "13656": 0.7047978043556213, "13659": 0.14939609169960022, "13791": 0.10291612148284912, "13833": 0.987156867980957, "13874": 1.04512357711792, "14026": 0.3443928062915802, "14031": 0.23015019297599792, "14119": 0.23864774405956268, "14155": 0.33675122261047363, "14163": 0.12814582884311676, "14193": 0.35128939151763916, "14298": 0.06886265426874161, "14358": 0.15860503911972046, "14402": 0.10993985831737518, "14471": 0.14264501631259918, "14494": 0.9702757596969604, "14760": 0.20739519596099854, "14800": 0.05786345899105072, "14828": 0.10203468054533005, "15113": 0.1221139207482338, "15136": 1.0999135971069336, "15172": 0.31560876965522766, "15370": 0.29400965571403503, "15429": 0.11430477350950241, "15509": 0.7047978043556213, "15527": 0.7583568692207336, "15543": 0.09938567131757736, "15863": 0.3106105625629425, "15869": 0.5186077356338501, "16007": 0.08154398202896118, "16014": 0.020300358533859253, "16026": 0.32270604372024536, "16048": 0.319873183965683, "16134": 0.2696990668773651, "16147": 0.13755162060260773, "16157": 0.45623743534088135, "16221": 1.0775588750839233, "16238": 0.3262358605861664, "16285": 0.083342544734478, "16330": 0.6970458030700684, "16381": 0.6744182109832764, "16387": 0.8091925978660583, "16515": 1.0655186176300049, "16576": 0.08603433519601822, "16578": 0.06520967930555344, "16677": 0.14433705806732178, "16706": 0.1602703034877777, "16745": 0.8731874823570251, "16902": 0.03266380727291107, "16932": 0.9170717000961304, "17245": 0.09228714555501938, "17782": 0.7601850032806396, "17908": 0.32129061222076416, "18078": 0.22859740257263184, "18178": 0.10026945173740387, "18195": 0.06703783571720123, "18260": 0.14518201351165771, "18275": 0.18248429894447327, "18514": 0.8022117614746094, "18539": 0.1873544454574585, "18595": 0.045809537172317505, "18700": 0.20660123229026794, "18714": 0.4734157919883728, "18715": 1.0960047245025635, "18720": 1.1481462717056274, "19539": 1.0271050930023193, "19762": 0.12986256182193756, "19824": 0.2561853528022766, "20155": 0.14349138736724854, "20214": 0.7898768186569214, "20360": 0.7863243818283081, "20483": 0.9470623731613159, "20504": 1.035461664199829, "20576": 0.1751343309879303, "20582": 1.151856780052185, "20752": 0.4002431631088257, "20806": 0.25995752215385437, "20842": 0.14264501631259918, "21032": 0.4556184411048889, "21081": 0.9371650815010071, "21181": 0.09584271162748337, "21434": 0.5887627601623535, "21472": 0.34922540187835693, "21486": 0.012615402229130268, "21775": 0.021256839856505394, "21781": 0.16359257698059082, "21903": 0.5506471395492554, "21906": 1.018678069114685, "22025": 0.11865071207284927, "22203": 0.12470348179340363, "22260": 0.05046287178993225, "22275": 1.3862943649291992, "22311": 1.175042748451233, "22330": 0.7295845746994019, "22394": 0.1485546976327896, "22407": 0.45499902963638306, "22419": 0.02316705882549286, "22504": 0.04674193635582924, "22694": 0.0752234235405922, "22868": 0.08961215615272522, "22907": 0.09938567131757736, "22916": 0.0009760859538801014, "22931": 0.24325250089168549, "22963": 0.45994341373443604, "22991": 0.8731874823570251, "23041": 0.6872705817222595, "23065": 0.1221139207482338, "23079": 0.1401015669107437, "23150": 0.052318159490823746, "23169": 0.14095009863376617, "23186": 0.7009293437004089, "23191": 0.20660123229026794, "23208": 0.0606246218085289, "23245": 0.9256220459938049, "23616": 1.2688164710998535, "23737": 0.08871890604496002, "23758": 0.8666408061981201, "23777": 0.24401791393756866, "23833": 0.021256839856505394, "23892": 0.2954642176628113, "23900": 0.27934664487838745, "24012": 0.21687394380569458, "24229": 0.8550800085067749, "24374": 0.8845420479774475, "24587": 0.8109301924705505, "24594": 0.15610189735889435, "24759": 0.2231435477733612, "25006": 0.08692999184131622, "25086": 0.24859806895256042, "25206": 0.09938567131757736, "25331": 0.3388410806655884, "25409": 0.7638313174247742, "25708": 1.195341944694519, "25714": 0.1734936386346817, "25746": 0.06337817758321762, "25778": 0.03360854089260101, "25937": 0.15693697333335876, "26179": 0.8349450826644897, "26305": 0.6867793202400208, "26572": 0.53589928150177, "26601": 0.18654440343379974, "26741": 0.08513788133859634, "27009": 0.43623676896095276, "27144": 0.040196798741817474, "27216": 0.2969166338443756, "27354": 0.014542185701429844, "27531": 0.1751343309879303, "27781": 0.03360854089260101, "27814": 0.21214580535888672, "27854": 0.1873544454574585, "27881": 0.06246116757392883, "28086": 0.31560876965522766, "28522": 0.2247048318386078, "28691": 0.013579257763922215, "28873": 0.45499902963638306, "29107": 0.18978065252304077, "29206": 0.06154331564903259, "29299": 0.6322478652000427, "29610": 0.03925827145576477} | 12762485 | AIM Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information. METHODS The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP). RESULTS Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression. CONCLUSIONS These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded. | p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin. |
{"1014": 0.2576959431171417, "1019": 0.176772341132164, "1021": 0.07341018319129944, "1023": 0.11081436276435852, "1038": 0.5805994272232056, "1039": 0.15610189735889435, "1044": 0.12384103983640671, "1053": 0.026025565341114998, "1058": 0.05786345899105072, "1999": 0.12814582884311676, "2004": 0.11081436276435852, "2007": 0.1994270235300064, "2020": 0.02887592278420925, "2026": 0.46486347913742065, "2039": 0.05139094591140747, "2053": 0.09228714555501938, "2058": 0.5415972471237183, "2062": 0.12728634476661682, "2065": 0.083342544734478, "2075": 0.1332872211933136, "2076": 0.2990913391113281, "2084": 0.1693800985813141, "2086": 0.38574060797691345, "2094": 0.7239188551902771, "2095": 0.3297532796859741, "2106": 0.014542185701429844, "2109": 0.0029254043474793434, "2146": 0.07612881064414978, "2152": 0.5607312321662903, "2158": 0.5936289429664612, "2166": 0.20102575421333313, "2182": 0.45623743534088135, "2206": 0.1873544454574585, "2229": 0.37035053968429565, "2273": 0.9115922451019287, "2285": 0.21293537318706512, "2287": 0.7845434546470642, "2303": 0.4349733293056488, "2313": 0.05694137513637543, "2321": 0.30989447236061096, "2323": 0.04394211992621422, "2324": 0.15860503911972046, "2331": 0.6197150945663452, "2339": 0.0842406153678894, "2351": 0.1946154683828354, "2358": 0.1384023278951645, "2364": 0.2719337046146393, "2381": 0.469759464263916, "2383": 0.11778303235769272, "2408": 0.4974553883075714, "2421": 0.07884006202220917, "2443": 0.23402166366577148, "2465": 0.630689799785614, "2470": 0.26820653676986694, "2504": 0.6754127144813538, "2511": 0.026025565341114998, "2515": 0.2478361576795578, "2522": 0.26146242022514343, "2523": 0.08244366943836212, "2529": 0.03831886500120163, "2540": 0.6833335757255554, "2551": 0.2881702482700348, "2561": 0.38041436672210693, "2599": 0.175953671336174, "2625": 0.1970241367816925, "2628": 0.23247487843036652, "2639": 0.07159364968538284, "2641": 0.14349138736724854, "2659": 0.22392450273036957, "2668": 0.5045560002326965, "2675": 0.4425300657749176, "2682": 0.07159364968538284, "2687": 0.7124901413917542, "2711": 0.016465263441205025, "2717": 0.12642613053321838, "2722": 0.3262358605861664, "2727": 0.08692999184131622, "2731": 0.22079704701900482, "2740": 0.3676496744155884, "2753": 0.47158926725387573, "2756": 0.06795065850019455, "2765": 0.27044451236724854, "2777": 0.029824240133166313, "2812": 0.29328158497810364, "2817": 0.6492279767990112, "2836": 0.03925827145576477, "2846": 0.0174254160374403, "2861": 0.1602703034877777, "2896": 0.42225050926208496, "2913": 0.4673144817352295, "2944": 0.6317287683486938, "2951": 0.4286321699619293, "2966": 0.3757305145263672, "2981": 0.8366385698318481, "2998": 0.026025565341114998, "3020": 0.7018978595733643, "3141": 0.2576959431171417, "3160": 0.4788752794265747, "3161": 0.20739519596099854, "3180": 0.5438674688339233, "3189": 0.12986256182193756, "3231": 0.5925496220588684, "3251": 0.3325583338737488, "3265": 0.25239890813827515, "3273": 0.27342069149017334, "3276": 0.5415972471237183, "3278": 0.2409527748823166, "3280": 0.3318578004837036, "3284": 0.040196798741817474, "3287": 0.6244332790374756, "3334": 0.2918238639831543, "3359": 0.6389714479446411, "3366": 0.5838727951049805, "3378": 0.9115922451019287, "3426": 0.05786345899105072, "3435": 0.40285754203796387, "3439": 0.3170322775840759, "3445": 0.3877306580543518, "3446": 0.052318159490823746, "3450": 0.1946154683828354, "3452": 0.14264501631259918, "3463": 0.5506471395492554, "3466": 0.22079704701900482, "3471": 0.022212404757738113, "3486": 0.38905516266822815, "3517": 0.12384103983640671, "3549": 0.1332872211933136, "3556": 0.2822965085506439, "3558": 0.9076598286628723, "3582": 0.5947071313858032, "3618": 0.6202403903007507, "3623": 0.18492233753204346, "3633": 0.3723714053630829, "3635": 0.9029204845428467, "3647": 0.08692999184131622, "3671": 0.623910129070282, "3695": 0.7076893448829651, "3742": 0.5947071313858032, "3767": 0.38574060797691345, "3778": 0.6563454270362854, "3798": 0.7445381283760071, "3808": 0.12814582884311676, "3867": 0.129004567861557, "3891": 0.9333322048187256, "3896": 0.304147332906723, "3963": 0.009718249551951885, "3979": 0.12038381397724152, "3980": 0.47584590315818787, "3997": 0.043007105588912964, "4003": 0.9485763907432556, "4023": 0.6286086440086365, "4029": 0.4067663550376892, "4090": 0.12986256182193756, "4094": 0.1384023278951645, "4098": 0.14939609169960022, "4101": 0.6960725784301758, "4102": 0.6679295301437378, "4106": 0.2852376699447632, "4117": 0.04394211992621422, "4118": 0.1808556467294693, "4146": 0.4654768109321594, "4206": 0.3601844012737274, "4244": 0.3485364317893982, "4254": 0.06429435312747955, "4262": 0.6527929902076721, "4275": 0.3777405619621277, "4280": 0.33953672647476196, "4281": 0.6080870032310486, "4295": 0.7755908370018005, "4328": 1.104454517364502, "4453": 0.2478361576795578, "4456": 0.06886265426874161, "4555": 0.49864232540130615, "4578": 0.672426164150238, "4654": 0.18329764902591705, "4696": 0.23633737862110138, "4705": 0.6487176418304443, "4725": 0.31489628553390503, "4795": 0.3339579105377197, "4906": 0.7854343056678772, "4945": 0.16442140936851501, "5022": 0.007782140281051397, "5159": 0.35060185194015503, "5188": 0.0317181795835495, "5292": 0.10379679501056671, "5329": 0.007782140281051397, "5345": 0.956112265586853, "5360": 0.015504186972975731, "5423": 0.21765978634357452, "5443": 0.040196798741817474, "5468": 0.7408206462860107, "5490": 0.08513788133859634, "5505": 0.21293537318706512, "5514": 0.018384648486971855, "5531": 0.3554046154022217, "5547": 0.04487626627087593, "5563": 0.3464667797088623, "5566": 0.007782140281051397, "5570": 0.18492233753204346, "5579": 0.0752234235405922, "5604": 0.32764431834220886, "5610": 0.4041621685028076, "5646": 0.030771657824516296, "5675": 0.052318159490823746, "5699": 0.46363574266433716, "5717": 0.015504186972975731, "5761": 0.5629584193229675, "5769": 0.10555581003427505, "5776": 0.11343330889940262, "5790": 0.045809537172317505, "5799": 0.2447827309370041, "5808": 0.34023189544677734, "5816": 0.0770333781838417, "5852": 0.24248650670051575, "5876": 0.175953671336174, "5950": 0.7314660549163818, "5986": 0.15693697333335876, "6001": 0.07884006202220917, "6022": 0.7987030148506165, "6086": 0.6583697199821472, "6336": 0.13071982562541962, "6337": 0.004870930220931768, "6388": 0.03360854089260101, "6420": 0.026025565341114998, "6431": 0.14518201351165771, "6444": 0.014542185701429844, "6463": 0.9225212931632996, "6550": 0.040196798741817474, "6551": 0.016465263441205025, "6558": 0.12728634476661682, "6612": 0.05786345899105072, "6638": 0.3930181860923767, "6677": 0.5197699069976807, "6687": 0.08154398202896118, "6740": 0.06246116757392883, "6747": 0.3034266233444214, "6818": 0.07884006202220917, "6849": 0.0009760859538801014, "6909": 0.762009859085083, "6912": 1.001607894897461, "7012": 0.15693697333335876, "7017": 0.42353010177612305, "7023": 1.1128336191177368, "7091": 0.7124901413917542, "7189": 0.4500300884246826, "7236": 0.3191637098789215, "7274": 0.05139094591140747, "7355": 0.14939609169960022, "7457": 0.07341018319129944, "7461": 0.24631060659885406, "7505": 0.2561853528022766, "7524": 0.9225212931632996, "7535": 0.0174254160374403, "7542": 0.021256839856505394, "7551": 0.18411032855510712, "7576": 0.0029254043474793434, "7594": 0.5104349255561829, "7644": 0.10906458646059036, "7667": 0.24401791393756866, "7691": 0.25239890813827515, "7718": 0.2652147710323334, "7749": 0.5450005531311035, "7778": 0.2837681770324707, "7810": 0.39762192964553833, "7831": 0.6353566646575928, "7863": 1.0137293338775635, "7870": 0.6254787445068359, "7885": 0.022212404757738113, "7965": 0.09495500475168228, "8015": 0.026976587250828743, "8089": 0.6892333030700684, "8155": 0.03831886500120163, "8186": 0.3141832649707794, "8187": 0.022212404757738113, "8197": 0.3499138653278351, "8316": 0.3750596046447754, "8319": 0.32058215141296387, "8345": 0.6275664567947388, "8380": 0.10467668622732162, "8609": 0.7854343056678772, "8729": 0.05694137513637543, "8757": 0.23710809648036957, "8781": 0.14179791510105133, "8783": 0.2652147710323334, "8822": 0.19381128251552582, "8873": 0.26146242022514343, "8920": 0.1718502640724182, "9002": 0.013579257763922215, "9031": 0.9776504039764404, "9098": 0.27934664487838745, "9174": 0.1619328260421753, "9367": 0.037378571927547455, "9410": 0.11343330889940262, "9420": 0.26146242022514343, "9422": 0.6664261221885681, "9488": 0.04113444685935974, "9556": 0.36900100111961365, "9560": 0.7086513638496399, "9657": 0.11865071207284927, "9723": 0.0058422754518687725, "9726": 0.8004589080810547, "9839": 0.1602703034877777, "9867": 0.9394577741622925, "9895": 0.013579257763922215, "9907": 0.77198725938797, "10173": 0.016465263441205025, "10174": 0.5662899017333984, "10354": 0.6754127144813538, "10381": 0.08871890604496002, "10415": 0.6155022978782654, "10426": 0.6492279767990112, "10516": 1.2991054058074951, "10569": 0.14939609169960022, "10611": 0.38441169261932373, "10744": 0.05694137513637543, "10788": 0.23864774405956268, "10817": 0.011650617234408855, "10831": 0.6149744987487793, "10857": 0.1677299439907074, "10903": 0.500420093536377, "11100": 0.6877616047859192, "11110": 0.3870677351951599, "11163": 0.08692999184131622, "11176": 0.0913962796330452, "11179": 0.9994535446166992, "11326": 0.13243216276168823, "11360": 0.3134697377681732, "11414": 0.10203468054533005, "11441": 0.5092619061470032, "11518": 0.12384103983640671, "11522": 0.6911921501159668, "11616": 0.25694093108177185, "11628": 0.11604541540145874, "11643": 0.44753631949424744, "11656": 0.28450319170951843, "11702": 0.04207121208310127, "11709": 0.1946154683828354, "11787": 0.2409527748823166, "12044": 0.07341018319129944, "12248": 0.08244366943836212, "12381": 0.13414156436920166, "12435": 0.3883931338787079, "12503": 0.0842406153678894, "12504": 0.14179791510105133, "12520": 0.08154398202896118, "12589": 0.034552380442619324, "12596": 0.0752234235405922, "12654": 0.0606246218085289, "12763": 0.1693800985813141, "12826": 0.35950297117233276, "12935": 0.2105647772550583, "13105": 0.6212902665138245, "13113": 0.7134475708007812, "13153": 0.3027053773403168, "13356": 1.0437490940093994, "13483": 1.070887804031372, "13592": 0.839173436164856, "13594": 0.012615402229130268, "13599": 0.5232481360435486, "13692": 0.47402387857437134, "13845": 0.17020416259765625, "13866": 0.255429208278656, "14025": 0.7163142561912537, "14142": 0.17922431230545044, "14144": 0.06977381557226181, "14155": 0.20977331697940826, "14171": 0.1064341589808464, "14198": 0.030771657824516296, "14267": 0.1510767638683319, "14280": 0.38174858689308167, "14358": 0.16690383851528168, "14372": 0.2667117714881897, "14396": 0.0174254160374403, "14451": 0.3077431619167328, "14671": 1.2819099426269531, "14912": 0.04113444685935974, "14967": 0.043007105588912964, "14971": 0.9886114001274109, "15001": 0.755608320236206, "15050": 0.7528522610664368, "15215": 0.016465263441205025, "15306": 0.5968599319458008, "15316": 0.03266380727291107, "15354": 0.5139457583427429, "15559": 0.9440274834632874, "15578": 0.8941729068756104, "15871": 0.32199856638908386, "16014": 0.3141832649707794, "16033": 0.6400018334388733, "16134": 0.40285754203796387, "16175": 0.672426164150238, "16228": 0.013579257763922215, "16259": 0.861702561378479, "16268": 0.14349138736724854, "16480": 0.5232481360435486, "16515": 0.05139094591140747, "16519": 0.28155985474586487, "16872": 0.1510767638683319, "16902": 0.6011518239974976, "16991": 0.04674193635582924, "17042": 0.38041436672210693, "17062": 0.09672962874174118, "17208": 0.5685047507286072, "17245": 0.08782484382390976, "17345": 0.12038381397724152, "17371": 0.7389566898345947, "17464": 0.6482070088386536, "17531": 0.34715715050697327, "17547": 0.04674193635582924, "17563": 0.021256839856505394, "17651": 0.4318077862262726, "17760": 0.34370049834251404, "17785": 0.2145126610994339, "17943": 0.13071982562541962, "18095": 0.29473719000816345, "18118": 0.22782009840011597, "18133": 0.34922540187835693, "18253": 0.09495500475168228, "18315": 0.004870930220931768, "18422": 0.44753631949424744, "18423": 0.8383291959762573, "18440": 0.857568621635437, "18518": 0.052318159490823746, "18539": 0.176772341132164, "18561": 0.11343330889940262, "18596": 0.15442965924739838, "18609": 0.016465263441205025, "18643": 0.44753631949424744, "18647": 0.22157983481884003, "18857": 0.5284429788589478, "18949": 0.07612881064414978, "18994": 0.02316705882549286, "19037": 0.41065993905067444, "19064": 0.417115718126297, "19158": 0.06977381557226181, "19188": 0.2501201331615448, "19289": 0.2145126610994339, "19300": 0.014542185701429844, "19332": 0.10467668622732162, "19389": 0.20660123229026794, "19470": 0.40806588530540466, "19518": 0.175953671336174, "19830": 0.14349138736724854, "19912": 0.2470736801624298, "19942": 0.37907835841178894, "20134": 0.5301685929298401, "20155": 0.5267143249511719, "20177": 0.3027053773403168, "20272": 0.10555581003427505, "20282": 0.15777134895324707, "20311": 1.0755622386932373, "20446": 0.04767346754670143, "20482": 0.045809537172317505, "20500": 0.26296505331993103, "20569": 0.2018241584300995, "20647": 0.04113444685935974, "20713": 0.016465263441205025, "20915": 1.076228141784668, "21150": 0.009718249551951885, "21371": 0.8247235417366028, "21374": 0.014542185701429844, "21449": 0.20977331697940826, "21453": 0.12556517124176025, "21557": 0.1808556467294693, "21813": 0.08513788133859634, "21877": 0.3070250153541565, "21879": 0.7889899015426636, "21887": 0.26296505331993103, "22010": 0.5827828645706177, "22084": 0.27044451236724854, "22360": 0.007782140281051397, "22597": 0.4574742913246155, "22828": 0.2539152204990387, "22935": 1.126855492591858, "22939": 0.15777134895324707, "22963": 0.3163207769393921, "23260": 0.0038986403960734606, "23760": 0.12384103983640671, "23891": 0.14264501631259918, "23900": 0.6011518239974976, "23969": 0.1718502640724182, "24081": 0.13157635927200317, "24110": 0.7969439625740051, "24316": 0.0019512200960889459, "24353": 0.13925230503082275, "24501": 0.12038381397724152, "24552": 0.8796916007995605, "24710": 0.07250232994556427, "24714": 0.030771657824516296, "24755": 0.7239188551902771, "24757": 0.013579257763922215, "24915": 0.0009760859538801014, "25070": 0.5139457583427429, "25086": 0.26446542143821716, "25185": 0.20580662786960602, "25346": 0.7105726003646851, "25353": 0.46055975556373596, "25613": 0.0019512200960889459, "25937": 0.3601844012737274, "26163": 0.09317722171545029, "26189": 0.1229778528213501, "26226": 1.1425544023513794, "26236": 0.10731173306703568, "26237": 0.24248650670051575, "26319": 0.0913962796330452, "26462": 0.18492233753204346, "26745": 0.1994270235300064, "26786": 0.09495500475168228, "26906": 0.1229778528213501, "27054": 0.1401015669107437, "27090": 0.637939989566803, "27133": 0.08782484382390976, "27351": 0.6317287683486938, "27354": 0.15860503911972046, "27615": 0.07250232994556427, "27651": 0.3070250153541565, "27671": 0.38574060797691345, "27794": 0.9317949414253235, "27833": 1.0587663650512695, "28093": 0.3615458607673645, "28125": 0.04953393340110779, "28353": 0.33115679025650024, "28428": 0.6471850275993347, "28436": 0.20739519596099854, "28489": 0.016465263441205025, "28697": 0.0354953333735466, "28828": 0.10203468054533005, "28879": 0.20022670924663544, "29048": 0.3923587501049042, "29160": 0.817850649356842, "29166": 0.08154398202896118, "29278": 0.006812678650021553, "29295": 0.1064341589808464, "29299": 0.417115718126297, "29305": 0.17267228662967682, "29361": 0.10379679501056671, "29458": 0.0606246218085289} | 12770738 | BACKGROUND Questions remain as to whether higher levels of cardiorespiratory fitness, a measure of regular physical activity, are associated with lower risk of cardiovascular disease (CVD) mortality in overweight and obese individuals with diabetes. Our objective was to quantify the independent and joint relations of cardiorespiratory fitness (hereafter, fitness) and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with CVD mortality in men with diabetes. METHODS This study was conducted using prospective observational data from the Aerobics Center Longitudinal Study. Study participants comprised 2316 men with no history of stroke or myocardial infarction and who were diagnosed as having diabetes (mean [SD] age, 50 [10] years); had a medical examination, including a maximal exercise test during 1970 to 1997 with mortality surveillance to December 31, 1998; and had a BMI of 18.5 or greater and less than 35.0. The main outcome measure was CVD mortality across levels of fitness with stratification by BMI. RESULTS We identified 179 CVD deaths during a mean (SD) follow-up of 15.9 (7.9) years and 36,710 man-years of exposure. In a model containing age, examination year, fasting glucose level, systolic blood pressure, parental history of premature CVD, total cholesterol level, cigarette smoking, abnormal resting, and exercise electrocardiograms, a significantly higher adjusted risk of mortality was observed in men with a low fitness level who were normal weight (hazard ratio, 2.7 [95% confidence interval, 1.3-5.7]), overweight (hazard ratio, 2.7 [95% confidence interval, 1.4-5.1]), and class 1 obese (hazard ratio, 2.8 [95% confidence interval, 1.4-5.1]) compared with normal weight men with a high fitness level. CONCLUSION In this cohort of men with diabetes, low fitness level was associated with increased risk of CVD mortality within normal weight, overweight, and class 1 obese weight categories. | Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes. |
{"1003": 0.043007105588912964, "1018": 0.08871890604496002, "1019": 0.15693697333335876, "1023": 0.08782484382390976, "1039": 0.36967599391937256, "1058": 0.021256839856505394, "2001": 0.3248254358768463, "2013": 0.176772341132164, "2018": 0.21687394380569458, "2038": 0.25088030099868774, "2042": 0.18978065252304077, "2043": 0.3170322775840759, "2051": 0.06795065850019455, "2058": 0.1685553640127182, "2062": 0.0797421783208847, "2084": 0.3269403576850891, "2086": 0.40481385588645935, "2091": 0.38905516266822815, "2095": 0.4400174915790558, "2106": 0.48430517315864563, "2109": 0.11604541540145874, "2111": 0.28963330388069153, "2116": 0.45870962738990784, "2129": 0.08513788133859634, "2138": 0.1718502640724182, "2141": 0.1229778528213501, "2144": 0.5651806592941284, "2146": 0.23556606471538544, "2166": 0.36697331070899963, "2172": 0.1685553640127182, "2176": 0.1913948506116867, "2177": 0.24554696679115295, "2193": 0.4879087805747986, "2197": 0.021256839856505394, "2214": 0.13414156436920166, "2246": 0.018384648486971855, "2263": 0.007782140281051397, "2274": 0.08782484382390976, "2287": 0.8349450826644897, "2308": 0.7408206462860107, "2313": 0.6553317308425903, "2316": 0.18978065252304077, "2329": 0.007782140281051397, "2331": 0.857568621635437, "2335": 0.0354953333735466, "2339": 0.35334911942481995, "2348": 0.036437395960092545, "2349": 0.3077431619167328, "2351": 0.6358738541603088, "2381": 0.2409527748823166, "2383": 0.14264501631259918, "2411": 0.015504186972975731, "2414": 0.11778303235769272, "2439": 0.175953671336174, "2450": 0.49626702070236206, "2515": 0.10379679501056671, "2522": 0.5162794589996338, "2541": 0.0009760859538801014, "2558": 0.07612881064414978, "2563": 0.638455867767334, "2589": 0.10993985831737518, "2615": 0.1718502640724182, "2625": 0.06612417846918106, "2627": 0.2976420819759369, "2639": 0.07884006202220917, "2659": 0.23015019297599792, "2660": 0.00875066313892603, "2687": 0.5021947622299194, "2689": 0.5092619061470032, "2691": 0.0770333781838417, "2722": 0.9379299283027649, "2727": 1.0285027027130127, "2730": 0.3262358605861664, "2765": 0.10993985831737518, "2779": 0.0842406153678894, "2786": 0.5838727951049805, "2807": 0.4132472574710846, "2826": 0.7863243818283081, "2844": 0.6223390698432922, "2857": 0.469759464263916, "2866": 0.6451379656791687, "2885": 0.0913962796330452, "2889": 0.06612417846918106, "2896": 0.37035053968429565, "2901": 0.151916041970253, "2904": 0.5092619061470032, "2908": 0.09761575609445572, "2931": 0.2983669638633728, "2944": 0.3963087201118469, "2951": 0.6170841455459595, "2967": 0.3443928062915802, "2979": 0.1212492436170578, "2991": 0.27044451236724854, "3025": 0.13670019805431366, "3041": 0.006812678650021553, "3047": 0.16690383851528168, "3054": 0.09584271162748337, "3057": 0.004870930220931768, "3062": 0.27044451236724854, "3107": 0.2184450328350067, "3112": 0.06977381557226181, "3163": 0.026025565341114998, "3231": 0.09584271162748337, "3268": 0.1873544454574585, "3278": 0.10291612148284912, "3280": 0.8238670229911804, "3285": 0.08244366943836212, "3300": 0.14686977863311768, "3303": 0.37707099318504333, "3333": 0.6096806526184082, "3336": 0.11865071207284927, "3426": 0.23556606471538544, "3431": 0.37707099318504333, "3439": 0.05046287178993225, "3445": 0.1970241367816925, "3446": 0.5080875158309937, "3466": 0.861702561378479, "3540": 0.10731173306703568, "3563": 0.39893341064453125, "3572": 0.04860413447022438, "3575": 0.7836518287658691, "3616": 0.1685553640127182, "3623": 0.21135559678077698, "3653": 0.18573370575904846, "3725": 0.43244171142578125, "3747": 0.15023678541183472, "3801": 0.19381128251552582, "3867": 0.5255602598190308, "3885": 0.17020416259765625, "3891": 0.35950297117233276, "3896": 0.8247235417366028, "3898": 0.7191727757453918, "3997": 0.04674193635582924, "4030": 0.15275461971759796, "4102": 0.39367714524269104, "4125": 0.09317722171545029, "4134": 0.18167030811309814, "4146": 0.10203468054533005, "4182": 0.8893690705299377, "4212": 0.3485364317893982, "4236": 0.2983669638633728, "4254": 0.650757372379303, "4275": 0.06703783571720123, "4295": 0.06612417846918106, "4328": 0.17267228662967682, "4358": 0.319873183965683, "4456": 1.0506030321121216, "4481": 0.04953393340110779, "4523": 0.016465263441205025, "4530": 0.4311734735965729, "4621": 0.27934664487838745, "4634": 0.574020504951477, "4647": 0.14179791510105133, "4691": 0.0019512200960889459, "4852": 0.04860413447022438, "4996": 0.2749055027961731, "5068": 0.08961215615272522, "5105": 0.1064341589808464, "5278": 0.34300774335861206, "5320": 0.18816383183002472, "5357": 0.31132611632347107, "5360": 0.6265231370925903, "5468": 0.0354953333735466, "5476": 0.28670501708984375, "5579": 0.40546512603759766, "5604": 0.030771657824516296, "5646": 0.03831886500120163, "5737": 0.7845434546470642, "5770": 0.2652147710323334, "5876": 0.03831886500120163, "5901": 0.29109421372413635, "5915": 0.535327672958374, "5920": 0.052318159490823746, "5986": 0.33605360984802246, "5989": 0.08064348995685577, "5996": 0.7881022095680237, "6022": 0.18167030811309814, "6075": 0.0019512200960889459, "6081": 0.05970508232712746, "6118": 0.15860503911972046, "6124": 0.2317005842924118, "6165": 0.5045560002326965, "6179": 0.25467249751091003, "6195": 0.0009760859538801014, "6261": 0.045809537172317505, "6405": 0.05046287178993225, "6428": 0.1808556467294693, "6430": 0.32764431834220886, "6522": 0.29619070887565613, "6551": 0.02887592278420925, "6576": 0.4500300884246826, "6643": 0.14095009863376617, "6666": 0.34370049834251404, "6677": 0.5914691090583801, "6689": 0.5893046259880066, "6698": 0.03925827145576477, "6721": 0.04394211992621422, "6747": 0.6223390698432922, "6784": 0.13925230503082275, "6819": 0.14686977863311768, "6873": 0.030771657824516296, "6875": 0.24171993136405945, "7017": 0.6674286723136902, "7039": 0.06246116757392883, "7080": 0.16524957120418549, "7108": 0.026025565341114998, "7277": 0.021256839856505394, "7461": 0.6848117709159851, "7473": 0.16524957120418549, "7510": 0.4093637466430664, "7691": 0.29255300760269165, "7790": 0.4286321699619293, "7809": 0.18492233753204346, "7868": 0.2034190446138382, "8023": 0.009718249551951885, "8092": 0.055094651877880096, "8137": 0.21293537318706512, "8197": 0.04953393340110779, "8289": 0.28082266449928284, "8292": 0.6492279767990112, "8353": 0.1401015669107437, "8358": 0.1332872211933136, "8386": 0.38041436672210693, "8465": 0.2852376699447632, "8649": 0.13499516248703003, "8664": 0.00875066313892603, "8819": 0.41840189695358276, "9010": 0.09672962874174118, "9035": 0.043007105588912964, "9336": 0.0842406153678894, "9426": 0.12470348179340363, "9560": 0.09761575609445572, "9574": 0.07068414986133575, "9654": 0.1685553640127182, "9671": 0.4228905141353607, "9765": 0.23247487843036652, "9783": 0.08871890604496002, "9867": 0.24401791393756866, "9874": 0.5696102976799011, "9885": 0.2089812457561493, "9888": 0.15943801403045654, "10032": 0.29400965571403503, "10035": 0.3824150264263153, "10149": 0.12038381397724152, "10173": 0.1873544454574585, "10174": 0.4944818615913391, "10197": 0.45870962738990784, "10262": 0.3012613356113434, "10426": 0.5162794589996338, "10473": 0.17431432008743286, "10548": 0.3027053773403168, "10611": 0.4151833653450012, "10788": 0.0606246218085289, "11213": 0.10555581003427505, "11326": 1.1431772708892822, "11643": 0.3248254358768463, "11656": 0.44566190242767334, "12099": 0.2576959431171417, "12117": 0.26446542143821716, "12238": 0.7057625651359558, "12353": 0.2317005842924118, "12430": 0.11430477350950241, "12473": 0.24171993136405945, "12504": 0.034552380442619324, "12520": 0.16276304423809052, "12530": 0.10555581003427505, "12637": 0.09228714555501938, "12878": 0.5238267183303833, "13105": 0.20818853378295898, "13356": 1.0326838493347168, "13494": 0.19622190296649933, "13531": 0.5045560002326965, "13594": 0.09850110858678818, "13993": 0.3262358605861664, "14440": 0.49923527240753174, "14644": 0.2184450328350067, "14670": 0.4158279001712799, "15189": 0.5849615335464478, "15354": 0.07884006202220917, "15584": 0.09672962874174118, "15643": 0.10291612148284912, "15704": 0.02316705882549286, "15982": 0.371698260307312, "16014": 0.2800849378108978, "16227": 0.029824240133166313, "16311": 0.083342544734478, "16515": 0.14349138736724854, "16922": 0.05417001247406006, "16989": 0.012615402229130268, "17062": 0.08064348995685577, "17208": 0.3134697377681732, "17237": 0.13157635927200317, "17547": 0.05970508232712746, "17568": 0.06429435312747955, "17913": 0.0029254043474793434, "18133": 0.04113444685935974, "18182": 0.053244512528181076, "18250": 0.20977331697940826, "18422": 0.32905077934265137, "18509": 0.01934296265244484, "18687": 0.21530038118362427, "18755": 0.08692999184131622, "18949": 0.29036402702331543, "19064": 0.0606246218085289, "19209": 0.2531573474407196, "19518": 0.5990082025527954, "19824": 0.129004567861557, "19833": 0.05046287178993225, "19879": 0.056018441915512085, "20177": 0.2852376699447632, "20272": 0.2447827309370041, "20576": 0.0752234235405922, "20588": 0.2089812457561493, "20592": 0.2786078155040741, "20598": 0.32129061222076416, "20662": 0.04394211992621422, "20876": 0.09938567131757736, "21040": 0.11517547070980072, "21081": 0.40741631388664246, "21371": 0.015504186972975731, "21539": 0.10993985831737518, "22822": 0.17840765416622162, "22835": 0.35334911942481995, "22865": 0.10906458646059036, "23364": 0.638455867767334, "23676": 0.1229778528213501, "23900": 0.1685553640127182, "24133": 0.06429435312747955, "24155": 0.2247048318386078, "24410": 0.13157635927200317, "24422": 0.2607102394104004, "24528": 0.3615458607673645, "24552": 0.007782140281051397, "24710": 0.32341301441192627, "24965": 0.26296505331993103, "25022": 0.06795065850019455, "25409": 0.6353566646575928, "25437": 0.6754127144813538, "25638": 0.04207121208310127, "26226": 0.2018241584300995, "26319": 0.3464667797088623, "26451": 0.056018441915512085, "26462": 0.2637155055999756, "26572": 0.05046287178993225, "27162": 0.09228714555501938, "27794": 1.1198691129684448, "28093": 0.1510767638683319, "28207": 0.11168810725212097, "28321": 0.2852376699447632, "28436": 0.27044451236724854, "28687": 0.3106105625629425, "28711": 1.4741191864013672, "28892": 0.6833335757255554, "29458": 0.20818853378295898} | 12779444 | The number of women dying from cervical cancer in 1997 was 7% lower than in 1996 and has fallen by over 25% since 1992.1 Such rapid change must be at least partly due to cervical screening, although strong cohort effects have caused large fluctuations in cervical mortality in the past.2 We modelled mortality data, taking into account the effects of age and year of birth and looking for trends in time within four age groups to estimate the beneficial effects of cervical screening. We obtained mortality data, in 5 year age bands, from death registrations in England and Wales and calculated rates using mid-year population estimates. Mortality since 1993 was adjusted upwards by 4% because of changes in classification of cause of death.3 We modelled the data assuming that the age specific mortality is the product of a smoothly varying age effect, birth cohort effect, and age dependent … | Effect of screening on cervical cancer mortality in England and Wales: analysis of trends with an age period cohort model. |
{"1017": 0.13157635927200317, "1040": 0.2089812457561493, "1042": 0.5860490798950195, "1043": 0.3982778787612915, "1047": 0.36967599391937256, "1050": 0.18654440343379974, "1055": 0.1477125883102417, "1155": 0.17840765416622162, "1999": 0.03925827145576477, "2004": 0.6553317308425903, "2007": 0.4248080551624298, "2011": 0.3084607720375061, "2015": 0.22626367211341858, "2029": 0.18978065252304077, "2038": 0.05786345899105072, "2064": 0.015504186972975731, "2076": 0.03266380727291107, "2079": 0.3248254358768463, "2089": 0.14264501631259918, "2109": 0.007782140281051397, "2110": 0.022212404757738113, "2140": 0.32058215141296387, "2155": 1.1281205415725708, "2163": 0.3784096837043762, "2177": 0.05046287178993225, "2179": 0.272677481174469, "2220": 0.055094651877880096, "2243": 1.2873153686523438, "2247": 0.021256839856505394, "2278": 0.7800771594047546, "2366": 0.06154331564903259, "2367": 0.15442965924739838, "2377": 0.41389304399490356, "2389": 0.4002431631088257, "2391": 0.5795059204101562, "2430": 0.8492490649223328, "2475": 0.6327666640281677, "2485": 0.11951763927936554, "2509": 0.7314660549163818, "2515": 0.2763880789279938, "2535": 0.7201237678527832, "2552": 0.16607704758644104, "2571": 0.3381449282169342, "2685": 0.006812678650021553, "2701": 0.732405424118042, "2817": 0.06246116757392883, "2832": 0.14179791510105133, "2850": 1.001607894897461, "2891": 0.4462870955467224, "2895": 0.11951763927936554, "2912": 0.22157983481884003, "2913": 0.34922540187835693, "2920": 0.791648268699646, "2945": 0.6430866718292236, "2951": 0.04767346754670143, "2953": 0.0913962796330452, "3081": 0.07793712615966797, "3117": 0.26820653676986694, "3149": 0.4374985992908478, "3161": 0.5336109399795532, "3170": 0.2493593990802765, "3248": 0.34370049834251404, "3273": 0.04113444685935974, "3283": 0.16359257698059082, "3370": 0.23710809648036957, "3372": 0.2447827309370041, "3375": 0.5092619061470032, "3378": 0.7528522610664368, "3433": 0.05970508232712746, "3450": 0.3910386264324188, "3466": 0.056018441915512085, "3491": 0.3723714053630829, "3495": 0.10818854719400406, "3526": 0.3683255612850189, "3544": 0.09672962874174118, "3622": 0.3304552733898163, "3625": 0.2160874605178833, "3674": 0.6921701431274414, "3683": 0.2478361576795578, "3694": 0.08244366943836212, "3710": 0.53589928150177, "3774": 0.09761575609445572, "3798": 0.2516399025917053, "3799": 0.03266380727291107, "3800": 0.04767346754670143, "3818": 0.3784096837043762, "3853": 0.5168620347976685, "3930": 0.7229714393615723, "4023": 0.7881022095680237, "4167": 0.32553088665008545, "4187": 0.7067264318466187, "4240": 0.45870962738990784, "4395": 0.6553317308425903, "4442": 0.16442140936851501, "4490": 0.12470348179340363, "4539": 0.1477125883102417, "4667": 0.8109301924705505, "4742": 0.34023189544677734, "4758": 0.3304552733898163, "4796": 0.8941729068756104, "4801": 0.1510767638683319, "4876": 0.49626702070236206, "4939": 0.13499516248703003, "4962": 0.18978065252304077, "4972": 0.46117570996284485, "5034": 1.2330384254455566, "5117": 0.03266380727291107, "5250": 0.7286425232887268, "5283": 0.14095009863376617, "5299": 0.7445381283760071, "5302": 0.2800849378108978, "5387": 0.401551216840744, "5398": 0.1221139207482338, "5449": 0.17840765416622162, "5482": 0.45994341373443604, "5484": 0.0174254160374403, "5488": 0.015504186972975731, "5536": 0.4728073179721832, "5589": 0.12642613053321838, "5668": 0.19541899859905243, "5705": 1.244919776916504, "5799": 0.083342544734478, "5843": 0.9783848524093628, "5876": 0.5450005531311035, "5884": 0.77198725938797, "5939": 0.669430673122406, "5994": 0.037378571927547455, "6038": 0.6275664567947388, "6091": 0.9037119746208191, "6169": 0.2667117714881897, "6194": 0.0009760859538801014, "6377": 0.016465263441205025, "6459": 0.030771657824516296, "6540": 0.5290185213088989, "6541": 0.2531573474407196, "6593": 0.030771657824516296, "6624": 0.22157983481884003, "6711": 0.1229778528213501, "6733": 0.38174858689308167, "6833": 0.5174443125724792, "6834": 0.06886265426874161, "6887": 0.4349733293056488, "6895": 0.6022219061851501, "6970": 0.6823468804359436, "7020": 0.0029254043474793434, "7336": 0.2786078155040741, "7337": 0.7182208299636841, "7352": 1.0641717910766602, "7366": 0.175953671336174, "7461": 0.09317722171545029, "7568": 0.007782140281051397, "7591": 0.026025565341114998, "7645": 0.4531385898590088, "7711": 0.4673144817352295, "7755": 0.28155985474586487, "7816": 0.7818660736083984, "7824": 0.5517725944519043, "7842": 0.129004567861557, "7878": 0.0354953333735466, "8000": 0.0913962796330452, "8031": 0.7182208299636841, "8113": 0.6512666940689087, "8171": 0.6265231370925903, "8176": 0.19381128251552582, "8290": 0.7647408246994019, "8327": 0.15777134895324707, "8360": 0.029824240133166313, "8676": 0.2689530849456787, "8878": 0.817850649356842, "8883": 0.42608439922332764, "9007": 0.9409833550453186, "9096": 0.0913962796330452, "9113": 0.6451379656791687, "9125": 0.40285754203796387, "9211": 0.7610978484153748, "9226": 1.1089750528335571, "9228": 0.3106105625629425, "9350": 0.053244512528181076, "9468": 0.0038986403960734606, "9488": 0.09584271162748337, "9495": 0.22626367211341858, "9527": 0.8583967685699463, "9530": 0.2852376699447632, "9556": 0.015504186972975731, "9777": 0.08154398202896118, "10163": 0.5336109399795532, "10266": 0.9576126337051392, "10318": 0.417115718126297, "10572": 0.5483922958374023, "10580": 0.11951763927936554, "10595": 0.6664261221885681, "10627": 0.31204116344451904, "10637": 0.0174254160374403, "10708": 0.006812678650021553, "10737": 0.5979346632957458, "10738": 0.4093637466430664, "10744": 0.1930064558982849, "10769": 1.0001721382141113, "10976": 0.2696990668773651, "11113": 0.7047978043556213, "11211": 0.9710156321525574, "11223": 0.6317287683486938, "11265": 0.4734157919883728, "11835": 0.6669275164604187, "12222": 0.6867793202400208, "12247": 0.03925827145576477, "12259": 0.7934166193008423, "12319": 0.0038986403960734606, "12328": 0.10906458646059036, "12352": 0.10467668622732162, "12562": 0.4950772523880005, "12732": 0.7500885725021362, "13100": 0.8666408061981201, "13221": 0.9769153594970703, "13330": 0.04394211992621422, "13791": 1.0165601968765259, "13808": 0.2409527748823166, "13833": 1.0668635368347168, "13922": 0.4450363218784332, "14021": 1.2851567268371582, "14187": 0.26146242022514343, "14193": 0.06246116757392883, "14262": 0.38574060797691345, "14270": 0.18167030811309814, "14828": 0.9115922451019287, "14889": 0.5151132941246033, "14958": 0.5180262327194214, "15115": 0.09317722171545029, "15176": 0.8315495252609253, "15420": 0.27786844968795776, "15431": 0.841701865196228, "15698": 0.609149694442749, "15756": 0.04394211992621422, "15946": 0.07793712615966797, "15956": 0.25239890813827515, "16000": 0.04767346754670143, "16238": 0.029824240133166313, "16285": 0.7647408246994019, "16305": 0.7028654217720032, "16420": 1.2835346460342407, "16599": 0.17840765416622162, "16690": 0.02316705882549286, "16691": 0.06246116757392883, "16771": 0.5151132941246033, "16910": 0.8583967685699463, "16952": 0.0019512200960889459, "17146": 0.030771657824516296, "17257": 0.12470348179340363, "17351": 0.15526613593101501, "17371": 0.025073638185858727, "17379": 0.2659635543823242, "17441": 0.7445381283760071, "17703": 0.015504186972975731, "17820": 0.2145126610994339, "17856": 0.2394166737794876, "18044": 0.08064348995685577, "18260": 0.9287132620811462, "18549": 0.12470348179340363, "18714": 0.15943801403045654, "18715": 0.16276304423809052, "18861": 0.151916041970253, "19143": 0.7546905279159546, "19220": 0.0797421783208847, "19362": 0.9162907600402832, "19601": 0.0317181795835495, "19653": 0.812664806842804, "19680": 0.3547199070453644, "19780": 0.47036975622177124, "19872": 0.3027053773403168, "19962": 0.040196798741817474, "20275": 0.24171993136405945, "20350": 0.26146242022514343, "20461": 0.5244048833847046, "20467": 0.083342544734478, "20528": 0.8600510358810425, "20544": 0.7987030148506165, "20752": 0.10993985831737518, "20766": 0.18492233753204346, "20817": 0.4093637466430664, "20858": 0.25845035910606384, "21017": 0.9092346429824829, "21466": 0.27342069149017334, "21575": 0.5662899017333984, "21618": 0.4356052577495575, "21890": 0.5045560002326965, "21903": 1.6187692880630493, "21919": 0.5186077356338501, "21935": 0.29981520771980286, "21967": 0.1751343309879303, "21976": 0.8475768566131592, "22214": 0.20022670924663544, "22332": 0.14264501631259918, "22684": 0.3877306580543518, "22922": 0.4177590310573578, "22930": 0.3485364317893982, "23041": 0.2394166737794876, "23212": 0.09850110858678818, "23216": 0.7969439625740051, "23217": 0.3723714053630829, "23586": 0.2976420819759369, "23616": 0.47158926725387573, "23725": 0.5290185213088989, "23758": 0.7629209756851196, "23900": 0.1889725625514984, "24054": 0.32129061222076416, "24137": 0.10993985831737518, "24169": 0.3012613356113434, "24255": 0.007782140281051397, "24312": 0.029824240133166313, "24774": 0.022212404757738113, "24848": 0.15442965924739838, "25003": 0.7791815400123596, "25194": 0.512191891670227, "25456": 0.06886265426874161, "25644": 0.1913948506116867, "25761": 0.14686977863311768, "26243": 0.13670019805431366, "26244": 1.0628231763839722, "26402": 0.36426326632499695, "26534": 0.010684899985790253, "26721": 0.7276995778083801, "26773": 0.817850649356842, "26886": 0.3027053773403168, "27099": 0.056018441915512085, "27118": 0.5215105414390564, "27166": 0.42225050926208496, "27295": 0.3963087201118469, "27790": 0.08692999184131622, "27854": 0.8281423449516296, "28247": 0.4337083101272583, "28314": 1.1481462717056274, "28696": 0.1510767638683319, "29290": 0.347847044467926} | 12785130 | Src family kinases (SFKs) play critical roles in the regulation of many cellular functions by growth factors, G-protein-coupled receptors and ligand-gated ion channels. Recent data have shown that SFKs serve as a convergent point of multiple signaling pathways regulating N-methyl-d-aspartate (NMDA) receptors in the central nervous system. Multiple SFK molecules, such as Src and Fyn, closely associate with their substrate, NMDA receptors, via indirect and direct binding mechanisms. The NMDA receptor is associated with an SFK signaling complex consisting of SFKs; the SFK-activating phosphatase, protein tyrosine phosphatase α; and the SFK-inactivating kinase, C-terminal Src kinase. Early studies have demonstrated that intramolecular interactions with the SH2 or SH3 domain lock SFKs in a closed conformation. Disruption of the interdomain interactions can induce the activation of SFKs with multiple signaling pathways involved in regulation of this process. The enzyme activity of SFKs appears 'graded', exhibiting different levels coinciding with activation states. It has also been proposed that the SH2 and SH3 domains may stimulate catalytic activity of protein tyrosine kinases, such as Abl. Recently, it has been found that the enzyme activity of neuronal Src protein is associated with its stability, and that the SH2 and SH3 domain interactions may act not only to constrain the activation of neuronal Src, but also to regulate the enzyme activity of active neuronal Src. Collectively, these findings demonstrate novel mechanisms underlying the regulation of SFKs. | The regulation of N-methyl-D-aspartate receptors by Src kinase. |
{"1011": 0.1332872211933136, "1053": 0.014542185701429844, "1997": 0.09228714555501938, "2003": 0.10818854719400406, "2005": 0.2247048318386078, "2008": 0.04953393340110779, "2029": 0.11256109178066254, "2038": 0.0009760859538801014, "2047": 0.16442140936851501, "2057": 0.055094651877880096, "2064": 0.11081436276435852, "2072": 1.2364475727081299, "2079": 0.0174254160374403, "2083": 0.3949938118457794, "2091": 0.7647408246994019, "2092": 0.43623676896095276, "2109": 0.39762192964553833, "2129": 0.06429435312747955, "2152": 0.1751343309879303, "2182": 0.17267228662967682, "2190": 0.05786345899105072, "2224": 0.25845035910606384, "2241": 0.07159364968538284, "2312": 0.680370569229126, "2330": 0.18167030811309814, "2396": 0.46055975556373596, "2441": 0.35128939151763916, "2458": 0.3248254358768463, "2470": 0.5472630262374878, "2478": 0.2026219218969345, "2483": 0.3995884954929352, "2502": 0.083342544734478, "2529": 0.6086184978485107, "2535": 0.03925827145576477, "2565": 0.1685553640127182, "2589": 0.15526613593101501, "2590": 0.6425731778144836, "2622": 0.0770333781838417, "2640": 0.5021947622299194, "2649": 0.030771657824516296, "2651": 0.007782140281051397, "2747": 0.09228714555501938, "2764": 0.21293537318706512, "2783": 0.4932899475097656, "2817": 0.2800849378108978, "2825": 0.011650617234408855, "2832": 0.2018241584300995, "2864": 0.30989447236061096, "2878": 0.5209306478500366, "2881": 0.6410312056541443, "2913": 0.3381449282169342, "2922": 0.3191637098789215, "2944": 0.6348392367362976, "2951": 0.3070250153541565, "2974": 0.31489628553390503, "3075": 0.04767346754670143, "3089": 0.16442140936851501, "3098": 0.08154398202896118, "3107": 0.0058422754518687725, "3112": 0.6348392367362976, "3144": 0.6064908504486084, "3231": 0.6461620330810547, "3278": 0.06337817758321762, "3284": 0.14179791510105133, "3463": 0.03831886500120163, "3469": 0.13414156436920166, "3490": 0.2018241584300995, "3526": 0.5584990978240967, "3594": 0.11256109178066254, "3669": 0.09317722171545029, "3670": 0.11778303235769272, "3800": 0.15610189735889435, "3811": 0.08871890604496002, "3898": 1.2210142612457275, "3921": 0.6867793202400208, "3935": 0.16110190749168396, "3979": 0.08603433519601822, "4007": 0.16276304423809052, "4045": 0.10555581003427505, "4072": 0.11256109178066254, "4094": 0.9256220459938049, "4106": 0.7009293437004089, "4111": 0.4574742913246155, "4118": 0.4425300657749176, "4127": 0.1229778528213501, "4146": 0.2231435477733612, "4176": 0.41065993905067444, "4235": 0.043007105588912964, "4275": 0.5010119676589966, "4286": 0.5278670787811279, "4313": 0.1011524572968483, "4328": 0.010684899985790253, "4442": 0.5871354341506958, "4473": 0.0009760859538801014, "4495": 0.05694137513637543, "4503": 0.11168810725212097, "4556": 0.34023189544677734, "4621": 0.0797421783208847, "4632": 0.7546905279159546, "4638": 0.16359257698059082, "4685": 0.09761575609445572, "4710": 0.777387797832489, "4719": 0.043007105588912964, "4725": 0.500420093536377, "4726": 0.03360854089260101, "4812": 0.1011524572968483, "4866": 0.08064348995685577, "4962": 1.1635169982910156, "4975": 0.14686977863311768, "5002": 0.6882523894309998, "5070": 0.03266380727291107, "5097": 0.07068414986133575, "5147": 0.20818853378295898, "5197": 0.684319257736206, "5214": 0.06612417846918106, "5461": 0.7482418417930603, "5468": 0.1384023278951645, "5537": 0.1693800985813141, "5577": 0.012615402229130268, "5604": 0.6764062643051147, "5617": 0.3127557039260864, "5656": 0.015504186972975731, "5693": 0.1358480453491211, "5761": 0.15023678541183472, "5833": 0.21214580535888672, "5852": 0.472198486328125, "5906": 0.3519764244556427, "5911": 0.25088030099868774, "5963": 0.4002431631088257, "5997": 0.25995752215385437, "6028": 0.987156867980957, "6064": 0.8400169610977173, "6123": 0.1734936386346817, "6137": 0.6149744987487793, "6162": 0.11343330889940262, "6176": 0.06246116757392883, "6179": 0.18654440343379974, "6235": 0.0842406153678894, "6279": 0.10731173306703568, "6337": 0.10026945173740387, "6349": 0.06795065850019455, "6364": 0.04767346754670143, "6388": 0.48850810527801514, "6529": 0.04207121208310127, "6573": 0.966567873954773, "6602": 0.2852376699447632, "6666": 0.05417001247406006, "6786": 0.3034266233444214, "6845": 0.39893341064453125, "6848": 0.040196798741817474, "6887": 0.1994270235300064, "6897": 0.7537717819213867, "6911": 0.2852376699447632, "6914": 0.6022219061851501, "6936": 0.058784693479537964, "6994": 0.1685553640127182, "7012": 0.1913948506116867, "7099": 0.006812678650021553, "7103": 0.07612881064414978, "7248": 0.10731173306703568, "7300": 0.12814582884311676, "7324": 1.4113680124282837, "7366": 0.6970458030700684, "7403": 1.229617714881897, "7480": 0.20977331697940826, "7551": 0.6054253578186035, "7613": 0.2969166338443756, "7646": 0.05139094591140747, "7698": 1.1506214141845703, "7709": 0.23247487843036652, "7718": 0.2247048318386078, "7784": 0.18492233753204346, "7860": 0.0009760859538801014, "7882": 0.10993985831737518, "7885": 0.7408206462860107, "8077": 0.03925827145576477, "8080": 0.3777405619621277, "8107": 0.77198725938797, "8168": 0.15860503911972046, "8228": 0.010684899985790253, "8361": 0.0606246218085289, "8382": 0.1677299439907074, "8778": 0.09584271162748337, "8991": 0.5668440461158752, "9007": 0.1401015669107437, "9041": 0.1685553640127182, "9124": 0.010684899985790253, "9165": 0.9783848524093628, "9312": 0.06612417846918106, "9320": 0.33115679025650024, "9447": 0.2822965085506439, "9487": 0.5909284353256226, "9510": 0.1212492436170578, "9539": 0.31845372915267944, "9859": 0.12642613053321838, "9896": 0.29036402702331543, "9942": 0.28890204429626465, "10015": 0.1602703034877777, "10071": 0.011650617234408855, "10327": 0.026025565341114998, "10438": 0.040196798741817474, "10591": 1.0668635368347168, "10788": 0.2689530849456787, "10990": 0.46853771805763245, "11038": 0.8004589080810547, "11160": 0.1677299439907074, "11326": 1.180456280708313, "11369": 0.8004589080810547, "11487": 0.1751343309879303, "11619": 0.03925827145576477, "11643": 0.603290855884552, "11767": 0.613389253616333, "12030": 0.07250232994556427, "12117": 1.1166772842407227, "12126": 0.0058422754518687725, "12221": 0.04767346754670143, "12238": 0.8442239761352539, "12265": 0.75193190574646, "12322": 0.1358480453491211, "12353": 0.1229778528213501, "12482": 0.1751343309879303, "12504": 0.29109421372413635, "12530": 0.08782484382390976, "12562": 0.09228714555501938, "12637": 0.1889725625514984, "12687": 0.0058422754518687725, "12697": 0.2470736801624298, "12702": 0.23479416966438293, "12789": 0.26146242022514343, "12876": 0.20501139760017395, "12941": 0.31560876965522766, "12978": 0.15275461971759796, "12987": 1.5092722177505493, "13458": 0.5528968572616577, "13594": 0.4374985992908478, "13625": 0.21135559678077698, "13685": 0.0029254043474793434, "13722": 0.26146242022514343, "13792": 0.25694093108177185, "14152": 0.175953671336174, "14193": 0.2719337046146393, "14471": 0.890972912311554, "14800": 0.2652147710323334, "15078": 0.03925827145576477, "15113": 0.28670501708984375, "15410": 0.05417001247406006, "15873": 0.01934296265244484, "15923": 0.5729197263717651, "16012": 0.6482070088386536, "16134": 0.5450005531311035, "16221": 0.27786844968795776, "16227": 0.2247048318386078, "16281": 0.1808556467294693, "16474": 0.15359249711036682, "16478": 0.11951763927936554, "16505": 0.15693697333335876, "16515": 0.6813592314720154, "16578": 0.12814582884311676, "16776": 0.07612881064414978, "16803": 0.034552380442619324, "17431": 0.18654440343379974, "17523": 0.06703783571720123, "17592": 0.4734157919883728, "17826": 0.841701865196228, "17841": 0.14686977863311768, "17908": 0.5903874635696411, "18082": 0.08961215615272522, "18182": 0.5882205963134766, "18589": 0.0019512200960889459, "18780": 0.9263957738876343, "18953": 0.3916989266872406, "19345": 0.535327672958374, "19518": 0.3012613356113434, "19654": 0.24631060659885406, "20001": 0.009718249551951885, "20155": 0.32199856638908386, "20253": 0.1401015669107437, "20302": 0.19622190296649933, "20353": 0.43875885009765625, "20600": 0.04113444685935974, "20794": 0.0058422754518687725, "20859": 0.4248080551624298, "20906": 0.23864774405956268, "21046": 0.014542185701429844, "21145": 0.5410289764404297, "21230": 0.045809537172317505, "21470": 0.11256109178066254, "21477": 0.3248254358768463, "21685": 0.3346569836139679, "21770": 0.04113444685935974, "21934": 0.15442965924739838, "22026": 0.25239890813827515, "22834": 0.0317181795835495, "22916": 0.9092346429824829, "22945": 0.007782140281051397, "23186": 0.37907835841178894, "23233": 0.025073638185858727, "23521": 0.37974658608436584, "24004": 0.8315495252609253, "24010": 0.022212404757738113, "24410": 0.3381449282169342, "24558": 0.3949938118457794, "24635": 0.6734226942062378, "24710": 0.3464667797088623, "24854": 0.0029254043474793434, "25095": 0.2501201331615448, "25169": 0.4374985992908478, "25437": 0.6989894509315491, "25455": 0.24018502235412598, "25524": 0.6312094330787659, "25711": 0.08961215615272522, "25714": 0.18004031479358673, "26282": 0.0009760859538801014, "27404": 0.07793712615966797, "27927": 0.0058422754518687725, "28406": 0.08064348995685577, "28637": 0.29255300760269165, "28848": 0.49030399322509766, "29105": 0.6578640341758728, "29490": 0.5833279490470886} | 12787125 | The remarkable gene knockdown technique of RNAi has opened exciting new avenues for genetic screens in model organisms and human cells. Here we describe the current state of the art for RNAi screening, and stress the importance of well-designed assays and of analytical approaches for large-scale screening experiments, from high-throughput screens using simplified homogenous assays to microscopy and whole-animal experiments. Like classical genetic screens in the past, the success of large-scale RNAi surveys depends on a careful development of phenotypic assays and their interpretation in a relevant biological context. | The art and design of genetic screens: RNA interference |
{"1037": 0.022212404757738113, "1039": 0.04207121208310127, "1058": 0.09228714555501938, "2000": 0.2145126610994339, "2022": 0.11691460013389587, "2039": 0.055094651877880096, "2046": 0.06977381557226181, "2052": 0.10818854719400406, "2062": 0.3547199070453644, "2064": 0.38041436672210693, "2071": 0.11865071207284927, "2079": 0.1212492436170578, "2082": 0.8340972661972046, "2083": 0.25995752215385437, "2088": 0.06612417846918106, "2089": 0.18492233753204346, "2090": 0.04767346754670143, "2097": 0.47827014327049255, "2109": 0.3485364317893982, "2118": 0.6338034868240356, "2121": 0.07431721687316895, "2126": 0.15943801403045654, "2129": 0.2493593990802765, "2191": 0.2447827309370041, "2204": 0.4437839686870575, "2224": 0.5261374711990356, "2227": 0.06977381557226181, "2235": 0.2531573474407196, "2241": 0.6527929902076721, "2267": 0.5186077356338501, "2275": 0.34370049834251404, "2320": 0.06703783571720123, "2323": 0.09672962874174118, "2339": 0.6769026517868042, "2342": 0.09850110858678818, "2415": 0.0058422754518687725, "2437": 0.012615402229130268, "2442": 0.04953393340110779, "2451": 0.1332872211933136, "2458": 0.36426326632499695, "2465": 0.1913948506116867, "2468": 0.09761575609445572, "2475": 0.40611594915390015, "2478": 0.4891071021556854, "2488": 0.4568560719490051, "2490": 0.09317722171545029, "2493": 0.7398891448974609, "2495": 0.9621002674102783, "2515": 0.18978065252304077, "2525": 0.08692999184131622, "2529": 0.5086748600006104, "2533": 0.06429435312747955, "2553": 0.07068414986133575, "2565": 0.1693800985813141, "2582": 0.12384103983640671, "2583": 0.014542185701429844, "2590": 0.0842406153678894, "2592": 0.4794800877571106, "2607": 0.5139457583427429, "2671": 0.014542185701429844, "2709": 0.21530038118362427, "2729": 0.2983669638633728, "2731": 0.4437839686870575, "2740": 0.3485364317893982, "2755": 0.02412080205976963, "2801": 0.04394211992621422, "2803": 0.5033760666847229, "2804": 0.11691460013389587, "2816": 0.6343214511871338, "2817": 0.4679262638092041, "2825": 0.469759464263916, "2832": 0.1930064558982849, "2846": 0.5718178153038025, "2850": 0.5707147121429443, "2852": 0.20102575421333313, "2866": 0.3269403576850891, "2877": 0.6613984704017639, "2898": 0.5756692886352539, "2902": 0.7220231294631958, "2925": 0.16607704758644104, "2934": 0.40089741349220276, "2951": 0.0606246218085289, "2966": 0.9754437208175659, "2971": 0.4450363218784332, "2974": 0.7800771594047546, "2995": 0.2696990668773651, "3014": 0.13157635927200317, "3020": 0.5590575933456421, "3076": 0.7210738658905029, "3078": 0.4041621685028076, "3084": 0.20102575421333313, "3095": 0.04767346754670143, "3107": 0.43053874373435974, "3125": 0.6075552701950073, "3144": 0.1064341589808464, "3167": 0.45932671427726746, "3171": 0.2089812457561493, "3176": 0.4855078160762787, "3229": 0.5568217039108276, "3253": 0.3750596046447754, "3265": 0.11865071207284927, "3274": 1.0992631912231445, "3275": 0.30486753582954407, "3289": 0.5347557663917542, "3327": 0.04113444685935974, "3341": 0.9217445850372314, "3352": 0.2852376699447632, "3356": 0.0354953333735466, "3375": 0.4494072198867798, "3391": 0.09672962874174118, "3401": 0.04394211992621422, "3445": 0.02792670577764511, "3460": 0.4412745535373688, "3465": 0.5267143249511719, "3466": 0.007782140281051397, "3482": 0.6389714479446411, "3497": 0.7951818704605103, "3517": 0.176772341132164, "3550": 0.24325250089168549, "3569": 0.2852376699447632, "3572": 0.24248650670051575, "3591": 0.6338034868240356, "3594": 0.15526613593101501, "3606": 0.8349450826644897, "3617": 0.1011524572968483, "3623": 0.11256109178066254, "3697": 0.23710809648036957, "3698": 0.10906458646059036, "3716": 0.08871890604496002, "3721": 0.6970458030700684, "3737": 0.4412745535373688, "3740": 0.3409265875816345, "3746": 0.2018241584300995, "3749": 0.4349733293056488, "3784": 0.8298473954200745, "3793": 0.25239890813827515, "3800": 0.08961215615272522, "3818": 0.14518201351165771, "3834": 0.12728634476661682, "3836": 0.14433705806732178, "3921": 0.0029254043474793434, "3968": 0.4041621685028076, "3971": 0.1734936386346817, "3995": 0.8861536383628845, "4007": 0.42353010177612305, "4012": 0.11604541540145874, "4022": 0.4574742913246155, "4036": 0.0842406153678894, "4037": 0.10467668622732162, "4041": 0.129004567861557, "4072": 0.05139094591140747, "4083": 1.0775588750839233, "4094": 0.5936289429664612, "4107": 0.053244512528181076, "4111": 0.38041436672210693, "4162": 0.0913962796330452, "4163": 0.06337817758321762, "4176": 0.22079704701900482, "4200": 0.46486347913742065, "4227": 0.02316705882549286, "4235": 0.05786345899105072, "4252": 0.4770587682723999, "4274": 0.4920966327190399, "4279": 0.08961215615272522, "4280": 0.3170322775840759, "4286": 0.18492233753204346, "4292": 0.14433705806732178, "4297": 0.31560876965522766, "4310": 0.39893341064453125, "4345": 0.2531573474407196, "4346": 0.09050461649894714, "4359": 0.1994270235300064, "4423": 0.34370049834251404, "4436": 0.0029254043474793434, "4469": 0.1221139207482338, "4481": 0.4400174915790558, "4495": 0.05694137513637543, "4547": 0.7144040465354919, "4553": 0.6563454270362854, "4610": 0.38308101892471313, "4621": 0.6430866718292236, "4636": 0.46670228242874146, "4646": 0.736154317855835, "4651": 0.053244512528181076, "4653": 0.15275461971759796, "4659": 0.52266925573349, "4681": 0.1011524572968483, "4719": 0.14349138736724854, "4729": 0.15023678541183472, "4730": 0.01934296265244484, "4773": 0.3723714053630829, "4804": 0.2918238639831543, "4863": 0.14686977863311768, "4871": 0.22548456490039825, "4935": 0.34370049834251404, "4955": 0.3723714053630829, "4957": 0.4203280806541443, "5022": 0.23247487843036652, "5029": 0.129004567861557, "5056": 1.061472773551941, "5071": 0.24554696679115295, "5082": 0.5427330136299133, "5084": 0.6931471824645996, "5097": 0.7389566898345947, "5107": 0.05139094591140747, "5114": 0.007782140281051397, "5121": 0.15359249711036682, "5145": 0.0770333781838417, "5161": 0.1685553640127182, "5275": 0.1905880719423294, "5292": 0.3381449282169342, "5301": 0.3750596046447754, "5335": 0.4177590310573578, "5352": 0.5914691090583801, "5366": 0.043007105588912964, "5375": 0.07068414986133575, "5378": 0.5795059204101562, "5410": 0.10906458646059036, "5478": 0.18573370575904846, "5514": 0.02316705882549286, "5534": 0.35060185194015503, "5543": 0.029824240133166313, "5547": 0.5324648022651672, "5562": 0.6931471824645996, "5566": 0.32199856638908386, "5567": 0.3027053773403168, "5574": 0.04394211992621422, "5656": 0.15777134895324707, "5702": 0.3416208028793335, "5724": 0.4450363218784332, "5739": 0.1710275560617447, "5770": 0.650757372379303, "5776": 0.37371641397476196, "5799": 0.029824240133166313, "5860": 0.3388410806655884, "6025": 0.6102113127708435, "6061": 0.034552380442619324, "6082": 0.2822965085506439, "6129": 0.05417001247406006, "6149": 0.24325250089168549, "6162": 0.37035053968429565, "6179": 0.10818854719400406, "6194": 0.2576959431171417, "6296": 0.3547199070453644, "6364": 0.06612417846918106, "6393": 0.42735910415649414, "6428": 0.0029254043474793434, "6464": 0.2561853528022766, "6509": 0.5914691090583801, "6570": 0.0770333781838417, "6612": 0.24325250089168549, "6627": 0.34300774335861206, "6648": 0.4812922179698944, "6666": 0.6970458030700684, "6685": 0.6872705817222595, "6704": 0.14939609169960022, "6753": 0.0009760859538801014, "6785": 0.0770333781838417, "6786": 0.42990362644195557, "6787": 0.29400965571403503, "6801": 0.6674286723136902, "6851": 0.1685553640127182, "6871": 0.5718178153038025, "6897": 0.04860413447022438, "6975": 0.8400169610977173, "6987": 0.28082266449928284, "7047": 0.5773153901100159, "7153": 0.1212492436170578, "7197": 1.2082605361938477, "7203": 0.49626702070236206, "7209": 0.8247235417366028, "7277": 0.11604541540145874, "7297": 0.5540198087692261, "7312": 0.007782140281051397, "7366": 0.19541899859905243, "7375": 0.013579257763922215, "7435": 0.28450319170951843, "7473": 0.45623743534088135, "7475": 0.2741633653640747, "7478": 0.13071982562541962, "7484": 1.2889312505722046, "7522": 0.22937409579753876, "7543": 0.5033760666847229, "7583": 0.11430477350950241, "7588": 0.848413348197937, "7620": 0.1510767638683319, "7801": 0.3339579105377197, "7818": 0.6512666940689087, "7843": 0.056018441915512085, "7863": 0.25694093108177185, "7868": 0.3824150264263153, "7899": 0.07250232994556427, "7926": 0.4537591338157654, "7949": 0.17922431230545044, "7976": 0.2247048318386078, "8048": 0.27564704418182373, "8065": 0.0913962796330452, "8114": 0.4624064862728119, "8122": 0.24171993136405945, "8153": 0.8442239761352539, "8161": 0.176772341132164, "8192": 0.0038986403960734606, "8277": 0.0752234235405922, "8286": 0.0317181795835495, "8312": 0.9363996982574463, "8323": 0.6466736793518066, "8324": 1.004473328590393, "8329": 0.2026219218969345, "8377": 0.011650617234408855, "8378": 0.39893341064453125, "8402": 0.06337817758321762, "8497": 0.14349138736724854, "8702": 0.1602703034877777, "8758": 0.19622190296649933, "8835": 0.5261374711990356, "8882": 0.21214580535888672, "8893": 0.01934296265244484, "8908": 0.04487626627087593, "8921": 0.31132611632347107, "8941": 0.41840189695358276, "8969": 0.4752389192581177, "8970": 0.6420594453811646, "8990": 0.4425300657749176, "9108": 0.16442140936851501, "9147": 0.33953672647476196, "9154": 0.5415972471237183, "9162": 0.8780695199966431, "9186": 0.4873090982437134, "9229": 0.08692999184131622, "9251": 0.2018241584300995, "9279": 0.5168620347976685, "9280": 0.21530038118362427, "9308": 0.23402166366577148, "9349": 0.3141832649707794, "9355": 0.4831010699272156, "9377": 0.5979346632957458, "9412": 0.8559102416038513, "9450": 0.2852376699447632, "9539": 0.06886265426874161, "9544": 0.20022670924663544, "9585": 0.0842406153678894, "9723": 0.02316705882549286, "9798": 0.791648268699646, "9823": 0.3777405619621277, "9871": 0.41001203656196594, "9918": 0.19782574474811554, "9958": 0.791648268699646, "10015": 0.05139094591140747, "10056": 0.26146242022514343, "10262": 0.33325836062431335, "10408": 0.12814582884311676, "10439": 0.46608972549438477, "10449": 0.4481603503227234, "10467": 0.23864774405956268, "10580": 0.12728634476661682, "10660": 0.46117570996284485, "10886": 0.3656192123889923, "10897": 0.27934664487838745, "10910": 0.1677299439907074, "10956": 0.02412080205976963, "10990": 0.5898461937904358, "11213": 0.839173436164856, "11553": 0.7942996621131897, "11598": 0.7201237678527832, "11788": 0.012615402229130268, "11806": 0.4041621685028076, "12016": 0.2659635543823242, "12126": 0.19782574474811554, "12191": 0.3027053773403168, "12333": 0.1011524572968483, "12353": 0.49030399322509766, "12379": 0.3423145115375519, "12504": 0.42735910415649414, "12637": 0.9650808572769165, "12655": 0.401551216840744, "12702": 0.3588210940361023, "12823": 0.3170322775840759, "13024": 0.012615402229130268, "13087": 0.20739519596099854, "13149": 0.00875066313892603, "13318": 0.01934296265244484, "13416": 0.1734936386346817, "13418": 0.7220231294631958, "13425": 0.11691460013389587, "13494": 0.15359249711036682, "13553": 0.2501201331615448, "13696": 0.3283478021621704, "13746": 0.7144040465354919, "13908": 0.00875066313892603, "13951": 0.06977381557226181, "13999": 0.14179791510105133, "14095": 0.4938860833644867, "14118": 0.40806588530540466, "14206": 0.29981520771980286, "14613": 0.23710809648036957, "14679": 0.5718178153038025, "14776": 0.12642613053321838, "14972": 0.0029254043474793434, "15007": 0.08961215615272522, "15078": 0.08782484382390976, "15189": 0.3622259199619293, "15192": 0.42096930742263794, "15411": 0.38174858689308167, "15413": 0.011650617234408855, "15438": 0.28450319170951843, "15596": 0.42353010177612305, "15645": 0.1477125883102417, "15850": 0.5336109399795532, "15863": 0.45251765847206116, "15869": 0.6853039860725403, "15965": 0.08871890604496002, "15980": 0.10731173306703568, "16004": 0.12728634476661682, "16012": 0.6684301495552063, "16166": 0.013579257763922215, "16269": 0.018384648486971855, "16307": 0.2394166737794876, "16462": 0.1970241367816925, "16599": 0.13499516248703003, "16746": 0.1734936386346817, "16911": 0.06246116757392883, "16941": 0.319873183965683, "16957": 0.1710275560617447, "16991": 0.16359257698059082, "17146": 0.06154331564903259, "17158": 0.35677260160446167, "17239": 0.5127768516540527, "17319": 0.09317722171545029, "17362": 0.5186077356338501, "17453": 0.0354953333735466, "17566": 0.02316705882549286, "17568": 0.5573811531066895, "17592": 0.056018441915512085, "17771": 0.5290185213088989, "17938": 0.5461324453353882, "17993": 0.16607704758644104, "18014": 0.3910386264324188, "18100": 0.12642613053321838, "18216": 0.5860490798950195, "18420": 0.05417001247406006, "18726": 0.20102575421333313, "18730": 0.6461620330810547, "18900": 0.10467668622732162, "19206": 0.004870930220931768, "19293": 0.16524957120418549, "19335": 0.21922965347766876, "19601": 0.3443928062915802, "19727": 0.09317722171545029, "19922": 0.10291612148284912, "19960": 0.7239188551902771, "20026": 0.5438674688339233, "20116": 0.4437839686870575, "20125": 0.3683255612850189, "20226": 0.29619070887565613, "20353": 0.32129061222076416, "20502": 0.5517725944519043, "20528": 0.045809537172317505, "20906": 0.3850763738155365, "21050": 0.6950984001159668, "21150": 0.030771657824516296, "21186": 0.5816917419433594, "21268": 0.26146242022514343, "21416": 0.1602703034877777, "21685": 0.18816383183002472, "21800": 0.14179791510105133, "21877": 0.5562619566917419, "21890": 0.5573811531066895, "22415": 0.6254787445068359, "22419": 0.040196798741817474, "22602": 0.06612417846918106, "22605": 0.0009760859538801014, "22911": 0.06246116757392883, "22945": 0.06886265426874161, "23019": 0.1808556467294693, "23614": 0.018384648486971855, "23761": 0.23864774405956268, "24010": 0.0913962796330452, "24191": 0.25694093108177185, "24229": 0.10379679501056671, "24270": 0.15526613593101501, "24484": 0.9915141463279724, "24545": 0.45499902963638306, "24710": 0.21293537318706512, "24840": 0.043007105588912964, "24899": 0.08692999184131622, "25088": 0.1619328260421753, "25169": 0.07159364968538284, "25891": 0.23247487843036652, "26154": 0.9005423784255981, "26262": 0.6487176418304443, "26396": 0.48008447885513306, "26715": 0.6950984001159668, "27142": 0.3318578004837036, "27292": 0.020300358533859253, "27554": 0.13670019805431366, "27605": 0.129004567861557, "27830": 0.3163207769393921, "28049": 0.034552380442619324, "28578": 0.8169882297515869, "28926": 0.2539152204990387, "29536": 0.12470348179340363} | 12789595 | It is becoming “a truth universally acknowledged” that the education of undergraduate medical students will be enhanced through the use of computer assisted learning. Access to the wide range of online options illustrated in the figure must surely make learning more exciting, effective, and likely to be retained. This assumption is potentially but by no means inevitably correct. ### Box 1: Why fund computer assisted learning? Computer assisted learning is inevitable —Individual lecturers and departments are already beginning to introduce a wide range of computer based applications, sometimes in a haphazard way. Planned and coordinated development is better than indiscriminate expansion It is convenient and flexible —Courses supported by computer assisted learning applications may require fewer face to face lectures and seminars and place fewer geographical and temporal constraints on staff and students. Students at peripheral hospitals or primary care centres may benefit in particular Unique presentational benefits —Computer presentation is particularly suited to subjects that are visually intensive, detail oriented, and difficult to conceptualise, such as complex biochemical processes or microscopic images.1 Furthermore, “virtual” cases may reduce the need to use animal or human tissue in learning Personalised learning —Each learner can progress at his or her preferred pace. They can repeat, interrupt, and resume at will, which may have particular advantages for weaker students Economies of scale —Once an application has been set up, the incremental cost of offering it to additional students is relatively small Competitive advantage —Potential applicants may use the quality of information technology to discriminate between medical schools. A “leading edge” virtual campus is likely to attract good students Achieves the ultimate goal of higher education —The goal is to link people into learning communities. Computer applications, especially the internet and world wide web, are an extremely efficient way of doing this2 Expands pedagogical horizons —The most controversial argument for … RETURN TO TEXT | Computer assisted learning in undergraduate medical education. |
{"1014": 0.43812891840934753, "1018": 0.3381449282169342, "1039": 0.7314660549163818, "1048": 0.31560876965522766, "1061": 0.8238670229911804, "1998": 0.32199856638908386, "2015": 0.1889725625514984, "2035": 0.5500838756561279, "2039": 0.02412080205976963, "2043": 0.0029254043474793434, "2044": 0.14686977863311768, "2048": 0.09495500475168228, "2053": 0.0009760859538801014, "2090": 0.417115718126297, "2095": 0.13071982562541962, "2108": 0.0029254043474793434, "2111": 0.4093637466430664, "2116": 0.09672962874174118, "2154": 0.28670501708984375, "2158": 0.6389714479446411, "2166": 0.5562619566917419, "2169": 0.25694093108177185, "2176": 0.6522845029830933, "2177": 0.09761575609445572, "2204": 0.0354953333735466, "2206": 0.083342544734478, "2214": 0.18248429894447327, "2236": 0.6823468804359436, "2273": 0.8780695199966431, "2287": 1.0822023153305054, "2294": 0.4512746334075928, "2303": 0.5427330136299133, "2308": 0.8567397594451904, "2313": 0.9576126337051392, "2322": 0.10203468054533005, "2323": 0.0317181795835495, "2331": 0.9108069539070129, "2340": 0.037378571927547455, "2351": 0.31845372915267944, "2362": 0.10555581003427505, "2389": 0.4974553883075714, "2391": 0.11517547070980072, "2402": 0.11691460013389587, "2403": 0.2394166737794876, "2414": 0.09317722171545029, "2423": 0.1332872211933136, "2444": 0.304147332906723, "2450": 0.7047978043556213, "2451": 0.812664806842804, "2465": 0.7370892763137817, "2470": 0.3910386264324188, "2515": 0.08871890604496002, "2522": 0.17759032547473907, "2523": 0.22704219818115234, "2529": 0.2531573474407196, "2538": 0.13071982562541962, "2539": 0.10555581003427505, "2540": 0.011650617234408855, "2542": 0.5685047507286072, "2554": 0.401551216840744, "2561": 0.3676496744155884, "2563": 0.29473719000816345, "2581": 0.45499902963638306, "2591": 0.8973627090454102, "2628": 0.20022670924663544, "2660": 0.1685553640127182, "2685": 0.2881702482700348, "2711": 0.20580662786960602, "2722": 0.23864774405956268, "2730": 0.11256109178066254, "2733": 0.37707099318504333, "2740": 1.0236024856567383, "2753": 0.347847044467926, "2757": 0.05046287178993225, "2765": 0.04113444685935974, "2779": 0.5255602598190308, "2817": 0.603290855884552, "2825": 0.037378571927547455, "2844": 0.2018241584300995, "2846": 0.4500300884246826, "2857": 0.20501139760017395, "2866": 0.6583697199821472, "2879": 0.014542185701429844, "2885": 0.013579257763922215, "2913": 0.5267143249511719, "2931": 0.5313173532485962, "2951": 0.2852376699447632, "2959": 0.21135559678077698, "2966": 0.04674193635582924, "2983": 0.3499138653278351, "3057": 0.05417001247406006, "3131": 0.3325583338737488, "3141": 0.39367714524269104, "3189": 0.0317181795835495, "3195": 0.4145384132862091, "3197": 0.39367714524269104, "3227": 0.0797421783208847, "3268": 0.23247487843036652, "3273": 0.3560888469219208, "3276": 0.8893690705299377, "3278": 0.03266380727291107, "3279": 0.11778303235769272, "3280": 0.5278670787811279, "3287": 0.6425731778144836, "3303": 0.0797421783208847, "3337": 0.12038381397724152, "3348": 0.6548244953155518, "3350": 0.7491656541824341, "3378": 0.2830325961112976, "3426": 0.5074998140335083, "3429": 0.5045560002326965, "3446": 0.1229778528213501, "3450": 0.18411032855510712, "3452": 0.24248650670051575, "3461": 0.45870962738990784, "3463": 0.3353555500507355, "3466": 0.5295937061309814, "3497": 0.11691460013389587, "3517": 0.08154398202896118, "3529": 0.2837681770324707, "3549": 0.15860503911972046, "3556": 0.7239188551902771, "3558": 0.09495500475168228, "3582": 0.5957841277122498, "3635": 0.255429208278656, "3643": 0.014542185701429844, "3647": 0.02792670577764511, "3679": 0.2409527748823166, "3725": 0.2493593990802765, "3742": 0.6075552701950073, "3747": 0.9178520441055298, "3767": 0.5930894017219543, "3801": 0.5021947622299194, "3867": 0.0842406153678894, "3885": 0.0058422754518687725, "3891": 0.8567397594451904, "3896": 0.5381823778152466, "3920": 0.2576959431171417, "3963": 0.46486347913742065, "3997": 0.02887592278420925, "4022": 0.7105726003646851, "4023": 0.19862671196460724, "4094": 0.22157983481884003, "4102": 0.5324648022651672, "4106": 0.34370049834251404, "4117": 0.9123768210411072, "4118": 0.176772341132164, "4146": 0.09761575609445572, "4230": 0.055094651877880096, "4254": 1.1134753227233887, "4262": 0.14686977863311768, "4279": 0.5701626539230347, "4280": 0.48008447885513306, "4281": 0.6793810129165649, "4286": 0.17267228662967682, "4295": 0.678885817527771, "4328": 0.31845372915267944, "4358": 0.5461324453353882, "4364": 0.009718249551951885, "4392": 0.010684899985790253, "4424": 0.2741633653640747, "4456": 0.7881022095680237, "4464": 0.2696990668773651, "4489": 0.15943801403045654, "4511": 0.11865071207284927, "4531": 0.10291612148284912, "4577": 0.29400965571403503, "4725": 0.3519764244556427, "4747": 0.7295845746994019, "4793": 0.3262358605861664, "4795": 0.1930064558982849, "4882": 0.11430477350950241, "4957": 0.20102575421333313, "4969": 0.015504186972975731, "5002": 0.6430866718292236, "5105": 0.6389714479446411, "5248": 1.0137293338775635, "5257": 0.42161011695861816, "5320": 0.42096930742263794, "5345": 0.6882523894309998, "5360": 0.3615458607673645, "5387": 0.6400018334388733, "5404": 0.020300358533859253, "5443": 0.08603433519601822, "5468": 0.18329764902591705, "5486": 0.09317722171545029, "5531": 0.21687394380569458, "5535": 0.12728634476661682, "5610": 0.18411032855510712, "5646": 0.09495500475168228, "5662": 0.18329764902591705, "5717": 0.8600510358810425, "5739": 0.02316705882549286, "5790": 0.21687394380569458, "5799": 0.3519764244556427, "5816": 0.7210738658905029, "5818": 0.3325583338737488, "5876": 0.9037119746208191, "5907": 0.4568560719490051, "5909": 0.6070231795310974, "5919": 0.045809537172317505, "5948": 0.35813871026039124, "5950": 0.6989894509315491, "5966": 0.1401015669107437, "5983": 0.2516399025917053, "5986": 0.014542185701429844, "5996": 0.1718502640724182, "6001": 0.20022670924663544, "6022": 0.14264501631259918, "6063": 0.24631060659885406, "6180": 0.3134697377681732, "6383": 0.24248650670051575, "6428": 0.0009760859538801014, "6431": 0.18167030811309814, "6463": 0.12556517124176025, "6480": 0.1873544454574585, "6535": 0.2976420819759369, "6544": 0.8100618124008179, "6550": 0.6139179468154907, "6553": 0.0058422754518687725, "6677": 0.7683706283569336, "6747": 0.48430517315864563, "6818": 0.6353566646575928, "6825": 0.45994341373443604, "6897": 0.034552380442619324, "6911": 0.06154331564903259, "6950": 0.007782140281051397, "7012": 0.18573370575904846, "7017": 0.3963087201118469, "7023": 0.9680526852607727, "7080": 0.5640701055526733, "7091": 0.24171993136405945, "7108": 0.1064341589808464, "7189": 0.603290855884552, "7355": 0.33953672647476196, "7386": 0.12556517124176025, "7461": 0.6466736793518066, "7551": 0.10555581003427505, "7594": 0.1477125883102417, "7644": 0.42990362644195557, "7645": 0.04487626627087593, "7666": 0.03925827145576477, "7667": 0.013579257763922215, "7691": 0.3743882179260254, "7729": 0.036437395960092545, "7778": 0.32341301441192627, "7790": 0.08154398202896118, "7810": 0.1602703034877777, "7831": 0.5139457583427429, "7870": 0.574020504951477, "7965": 0.7389566898345947, "8023": 0.06337817758321762, "8092": 0.7934166193008423, "8186": 0.29109421372413635, "8290": 0.21687394380569458, "8317": 0.4311734735965729, "8335": 0.5433003902435303, "8339": 0.04207121208310127, "8353": 0.15442965924739838, "8381": 0.6317287683486938, "8384": 0.0606246218085289, "8465": 0.3588210940361023, "8554": 0.10203468054533005, "8599": 0.2247048318386078, "8609": 0.3995884954929352, "8738": 0.20102575421333313, "8777": 0.5762182474136353, "8787": 0.11951763927936554, "8832": 0.4002431631088257, "8902": 0.14433705806732178, "8920": 0.1384023278951645, "8924": 0.05417001247406006, "8995": 0.19862671196460724, "9031": 0.0009760859538801014, "9084": 0.022212404757738113, "9098": 0.19220098853111267, "9164": 1.059443712234497, "9280": 0.10818854719400406, "9289": 0.014542185701429844, "9420": 0.0058422754518687725, "9422": 0.45251765847206116, "9556": 0.755608320236206, "9560": 0.26146242022514343, "9580": 1.104454517364502, "9723": 0.23247487843036652, "9740": 0.010684899985790253, "9750": 0.19862671196460724, "9777": 0.083342544734478, "9871": 0.3141832649707794, "9874": 0.839173436164856, "9895": 0.02792670577764511, "9967": 0.08603433519601822, "10035": 0.3956514894962311, "10173": 0.574020504951477, "10174": 0.15526613593101501, "10197": 0.27786844968795776, "10202": 0.24171993136405945, "10238": 0.19862671196460724, "10266": 0.20022670924663544, "10383": 0.01934296265244484, "10426": 0.5795059204101562, "10427": 0.5238267183303833, "10473": 0.3070250153541565, "10611": 0.2954642176628113, "10640": 0.03266380727291107, "10671": 0.5472630262374878, "10744": 0.09938567131757736, "10827": 0.29109421372413635, "10831": 0.4938860833644867, "10847": 0.13925230503082275, "10857": 0.46853771805763245, "10962": 0.31204116344451904, "11179": 0.16442140936851501, "11207": 0.05786345899105072, "11506": 0.2763880789279938, "11507": 0.151916041970253, "11546": 0.175953671336174, "11566": 0.35813871026039124, "11628": 0.04394211992621422, "11656": 0.5313173532485962, "11678": 0.020300358533859253, "11709": 0.13157635927200317, "11765": 0.11168810725212097, "12123": 0.39367714524269104, "12265": 0.5127768516540527, "12353": 0.09584271162748337, "12435": 0.26146242022514343, "12473": 0.09495500475168228, "12490": 0.040196798741817474, "12520": 0.42353010177612305, "12530": 0.29981520771980286, "12596": 0.0174254160374403, "12654": 0.006812678650021553, "12826": 0.13755162060260773, "12876": 0.2026219218969345, "12878": 0.6882523894309998, "12955": 0.06886265426874161, "13105": 0.5336109399795532, "13180": 0.34715715050697327, "13181": 0.06520967930555344, "13356": 1.197703242301941, "13483": 0.7276995778083801, "13494": 0.3995884954929352, "13506": 0.10379679501056671, "13531": 0.40220460295677185, "13585": 0.06795065850019455, "13599": 0.25694093108177185, "13798": 0.02316705882549286, "13818": 0.06612417846918106, "13822": 0.7537717819213867, "14025": 0.6296497583389282, "14243": 0.5629584193229675, "14246": 0.015504186972975731, "14260": 0.8853482007980347, "14267": 0.09672962874174118, "14286": 0.7370892763137817, "14343": 0.29109421372413635, "14354": 0.1229778528213501, "14396": 0.14939609169960022, "14670": 0.7898768186569214, "14671": 0.22157983481884003, "14813": 0.4891071021556854, "15001": 0.2089812457561493, "15050": 0.2018241584300995, "15077": 0.0606246218085289, "15087": 0.08871890604496002, "15258": 0.08603433519601822, "15306": 0.5773153901100159, "15354": 0.5156965255737305, "15415": 0.4794800877571106, "15509": 0.27342069149017334, "15559": 0.11604541540145874, "15592": 0.7969439625740051, "15596": 0.1808556467294693, "15671": 0.18329764902591705, "15982": 0.3163207769393921, "16014": 0.8682814836502075, "16134": 0.3423145115375519, "16211": 0.11691460013389587, "16330": 0.0354953333735466, "16389": 0.5197699069976807, "16483": 0.1619328260421753, "16515": 0.1889725625514984, "16582": 0.23402166366577148, "16678": 0.18978065252304077, "16902": 0.8550800085067749, "17062": 0.06612417846918106, "17208": 0.025073638185858727, "17237": 0.32058215141296387, "17464": 0.6754127144813538, "17522": 0.3601844012737274, "17537": 0.04487626627087593, "17547": 0.6107416749000549, "17606": 0.03831886500120163, "17631": 0.19220098853111267, "17663": 0.7845434546470642, "17680": 0.08871890604496002, "17908": 0.0019512200960889459, "18224": 0.26146242022514343, "18422": 0.09495500475168228, "18509": 0.08871890604496002, "18539": 0.1212492436170578, "18700": 0.4158279001712799, "18909": 0.07068414986133575, "18949": 0.3339579105377197, "19037": 0.1751343309879303, "19064": 0.3241194784641266, "19188": 0.20501139760017395, "19205": 0.3034266233444214, "19209": 0.6714286804199219, "19389": 0.4831010699272156, "19939": 0.18573370575904846, "19982": 0.15275461971759796, "20134": 0.036437395960092545, "20155": 0.5209306478500366, "20272": 0.4356052577495575, "20390": 0.0606246218085289, "20435": 0.11256109178066254, "20576": 0.6867793202400208, "20752": 0.056018441915512085, "20828": 0.08692999184131622, "20871": 0.043007105588912964, "20932": 0.3923587501049042, "21024": 0.07884006202220917, "21371": 0.14686977863311768, "22137": 0.011650617234408855, "22886": 0.2531573474407196, "22935": 0.8861536383628845, "22963": 0.12986256182193756, "23260": 0.47158926725387573, "23284": 0.058784693479537964, "23382": 0.0797421783208847, "23444": 0.22937409579753876, "23472": 0.9432673454284668, "23900": 0.6038249135017395, "24110": 0.7389566898345947, "24155": 0.09938567131757736, "24319": 0.12642613053321838, "24552": 0.43244171142578125, "24658": 0.48068851232528687, "24757": 0.22782009840011597, "25331": 0.02316705882549286, "25409": 0.30989447236061096, "25428": 0.02887592278420925, "25519": 0.5979346632957458, "25582": 0.09584271162748337, "25604": 0.5629584193229675, "25613": 0.11081436276435852, "25860": 0.44691193103790283, "25870": 0.48430517315864563, "26163": 0.6338034868240356, "26226": 0.40351006388664246, "26237": 0.03925827145576477, "26266": 0.07884006202220917, "26462": 0.5528968572616577, "26786": 0.0842406153678894, "26906": 0.371698260307312, "27204": 0.026976587250828743, "27351": 0.6348392367362976, "27794": 0.022212404757738113, "27896": 0.04207121208310127, "28093": 0.28082266449928284, "28268": 0.12986256182193756, "28321": 0.23324857652187347, "28403": 0.006812678650021553, "28436": 0.14518201351165771, "29299": 0.40285754203796387, "29458": 0.5707147121429443} | 12794099 | BACKGROUND There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community. METHODS AND FINDINGS We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45-79 y with no known cardiovascular disease or cancer at baseline survey in 1993-1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1-14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass-, and social class-adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21-1.60), 1.95 (1.70--2.25), 2.52 (2.13-3.00), and 4.04 (2.95-5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age. CONCLUSIONS Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age. | Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study |
{"1019": 0.176772341132164, "1020": 0.2089812457561493, "1022": 0.013579257763922215, "1023": 0.10818854719400406, "1054": 0.5789587497711182, "1061": 0.3283478021621704, "2003": 0.07250232994556427, "2012": 0.016465263441205025, "2026": 0.8349450826644897, "2044": 0.18004031479358673, "2046": 0.5816917419433594, "2064": 0.1212492436170578, "2075": 0.45870962738990784, "2076": 0.06337817758321762, "2078": 0.33115679025650024, "2079": 0.20501139760017395, "2090": 0.8509185314178467, "2094": 0.05694137513637543, "2098": 0.4938860833644867, "2129": 0.1873544454574585, "2135": 0.30989447236061096, "2166": 0.43938836455345154, "2247": 0.4926934838294983, "2274": 0.0770333781838417, "2282": 0.12556517124176025, "2303": 0.34508460760116577, "2334": 0.9944084882736206, "2339": 0.2667117714881897, "2362": 0.034552380442619324, "2364": 0.3547199070453644, "2407": 0.8109301924705505, "2408": 0.8169882297515869, "2416": 0.026025565341114998, "2426": 0.13755162060260773, "2458": 0.5646255612373352, "2462": 0.43938836455345154, "2475": 0.1358480453491211, "2515": 0.1751343309879303, "2535": 0.21372433006763458, "2556": 0.06612417846918106, "2562": 0.09406650811433792, "2597": 0.38374659419059753, "2764": 0.07341018319129944, "2765": 0.5805994272232056, "2832": 0.05694137513637543, "2852": 0.6296497583389282, "2856": 0.17759032547473907, "2892": 0.036437395960092545, "2933": 0.18248429894447327, "2944": 0.6043586730957031, "2953": 0.6522845029830933, "3029": 0.16524957120418549, "3073": 0.013579257763922215, "3223": 0.1221139207482338, "3252": 0.14939609169960022, "3267": 0.1930064558982849, "3273": 0.011650617234408855, "3303": 0.06612417846918106, "3341": 0.05970508232712746, "3358": 0.8004589080810547, "3399": 0.09228714555501938, "3433": 0.25995752215385437, "3442": 0.9447870850563049, "3445": 0.40285754203796387, "3463": 0.5313173532485962, "3464": 0.20818853378295898, "3466": 0.52266925573349, "3488": 0.28450319170951843, "3491": 0.16607704758644104, "3526": 0.9317949414253235, "3558": 0.7295845746994019, "3584": 0.10906458646059036, "3588": 0.4709797203540802, "3595": 0.7463917136192322, "3623": 0.5822374224662781, "3639": 0.17759032547473907, "3640": 0.013579257763922215, "3670": 0.8074519634246826, "3675": 0.49686139822006226, "3739": 0.3743882179260254, "3778": 0.15023678541183472, "3800": 0.06977381557226181, "3853": 0.23092569410800934, "3930": 0.6793810129165649, "3975": 0.03925827145576477, "4013": 0.9455460906028748, "4041": 0.04487626627087593, "4055": 0.32129061222076416, "4066": 0.3526630103588104, "4072": 0.10818854719400406, "4111": 0.5364705324172974, "4114": 0.7105726003646851, "4176": 0.5139457583427429, "4195": 0.07884006202220917, "4237": 0.11256109178066254, "4275": 0.4158279001712799, "4305": 0.848413348197937, "4363": 0.29400965571403503, "4373": 0.8264343738555908, "4389": 0.04953393340110779, "4442": 0.8829278349876404, "4460": 0.23556606471538544, "4503": 0.1064341589808464, "4504": 0.20501139760017395, "4525": 0.2018241584300995, "4629": 0.7463917136192322, "4667": 0.2184450328350067, "4671": 0.045809537172317505, "4675": 0.6369074583053589, "4742": 0.5784112811088562, "4777": 0.8641747236251831, "4800": 0.02792670577764511, "4852": 0.13071982562541962, "4942": 1.0546929836273193, "4962": 0.04674193635582924, "4975": 0.10203468054533005, "4982": 0.15610189735889435, "5009": 0.4067663550376892, "5144": 0.0009760859538801014, "5153": 0.255429208278656, "5158": 0.03360854089260101, "5224": 0.5751199722290039, "5228": 0.2749055027961731, "5250": 0.6223390698432922, "5258": 0.05786345899105072, "5320": 0.25694093108177185, "5377": 0.03925827145576477, "5412": 0.004870930220931768, "5416": 1.013020396232605, "5418": 0.8764448165893555, "5441": 0.8083226680755615, "5459": 0.016465263441205025, "5478": 0.24171993136405945, "5649": 0.04394211992621422, "5656": 0.9485763907432556, "5668": 0.4891071021556854, "5680": 0.37371641397476196, "5787": 0.08692999184131622, "5908": 0.2741633653640747, "5942": 0.3381449282169342, "6028": 0.052318159490823746, "6032": 0.49626702070236206, "6129": 0.29981520771980286, "6143": 0.28155985474586487, "6192": 1.2341761589050293, "6194": 0.0009760859538801014, "6228": 0.47584590315818787, "6377": 0.083342544734478, "6459": 0.12470348179340363, "6537": 0.3388410806655884, "6540": 0.37371641397476196, "6605": 0.08692999184131622, "6622": 0.8323994874954224, "6645": 0.4337083101272583, "6741": 0.0009760859538801014, "6774": 0.10203468054533005, "6806": 0.6420594453811646, "6897": 0.15860503911972046, "6911": 0.11343330889940262, "6958": 0.06154331564903259, "6970": 0.2145126610994339, "6980": 1.2633098363876343, "6999": 0.7737906575202942, "7060": 0.6312094330787659, "7246": 0.7028654217720032, "7336": 0.04767346754670143, "7337": 0.947819709777832, "7356": 0.026976587250828743, "7358": 0.01934296265244484, "7366": 0.5871354341506958, "7372": 1.2198615074157715, "7375": 0.401551216840744, "7403": 0.05694137513637543, "7411": 0.2531573474407196, "7457": 0.43812891840934753, "7461": 0.009718249551951885, "7528": 0.1221139207482338, "7645": 0.4624064862728119, "7755": 0.7229714393615723, "7790": 0.75193190574646, "7816": 0.0317181795835495, "7894": 0.19220098853111267, "7926": 0.18167030811309814, "7964": 0.19782574474811554, "7969": 0.030771657824516296, "8031": 0.29473719000816345, "8153": 1.0748957395553589, "8156": 0.47402387857437134, "8171": 0.7426811456680298, "8186": 0.22782009840011597, "8278": 0.8788808584213257, "8290": 0.2561853528022766, "8332": 0.04394211992621422, "8335": 0.03266380727291107, "8346": 0.12728634476661682, "8486": 0.6578640341758728, "8498": 0.7978238463401794, "8524": 0.14433705806732178, "8546": 0.2976420819759369, "8638": 0.15359249711036682, "8745": 0.19862671196460724, "8790": 0.1718502640724182, "8803": 0.09850110858678818, "8880": 0.08961215615272522, "8902": 0.20421554148197174, "9007": 0.3106105625629425, "9014": 0.00875066313892603, "9138": 0.17020416259765625, "9211": 0.33605360984802246, "9249": 0.2689530849456787, "9250": 0.38905516266822815, "9279": 0.16110190749168396, "9319": 0.6892333030700684, "9547": 0.8780695199966431, "9560": 0.10818854719400406, "9623": 0.34922540187835693, "9635": 0.25239890813827515, "9662": 0.04487626627087593, "9677": 0.10731173306703568, "9728": 0.14179791510105133, "9760": 0.036437395960092545, "9855": 0.1710275560617447, "9884": 0.6619023680686951, "9885": 0.4679262638092041, "9942": 0.8109301924705505, "10039": 0.04767346754670143, "10178": 0.08513788133859634, "10232": 0.2689530849456787, "10266": 0.31560876965522766, "10327": 0.02792670577764511, "10351": 0.6338034868240356, "10371": 0.26146242022514343, "10408": 0.05786345899105072, "10467": 0.0770333781838417, "10480": 0.6446255445480347, "10514": 0.3995884954929352, "10521": 0.15860503911972046, "10548": 0.4709797203540802, "10580": 0.46302130818367004, "10595": 0.8973627090454102, "10599": 0.3615458607673645, "10624": 0.4349733293056488, "10671": 1.0802149772644043, "10744": 0.10291612148284912, "10785": 0.03831886500120163, "10789": 0.08244366943836212, "10804": 0.19220098853111267, "10863": 0.7047978043556213, "10939": 0.7314660549163818, "10949": 0.23092569410800934, "11113": 0.0913962796330452, "11124": 0.6853039860725403, "11356": 0.06337817758321762, "11423": 0.45870962738990784, "11443": 0.38374659419059753, "11643": 0.47766464948654175, "11657": 0.6128603219985962, "11718": 0.06429435312747955, "11767": 0.24171993136405945, "11983": 0.016465263441205025, "12016": 0.030771657824516296, "12228": 0.2034190446138382, "12247": 0.056018441915512085, "12328": 0.08064348995685577, "12468": 0.24018502235412598, "12477": 0.0009760859538801014, "12504": 0.6950984001159668, "12530": 0.02792670577764511, "12562": 0.4286321699619293, "12702": 0.46608972549438477, "12725": 0.06520967930555344, "12745": 0.7124901413917542, "12761": 0.6096806526184082, "12823": 0.38041436672210693, "13007": 0.05417001247406006, "13105": 0.055094651877880096, "13136": 0.7827593088150024, "13153": 0.04674193635582924, "13296": 0.06977381557226181, "13490": 0.3077431619167328, "13530": 0.24018502235412598, "13571": 0.07159364968538284, "13665": 0.817850649356842, "13734": 0.05786345899105072, "13791": 0.052318159490823746, "13833": 0.1332872211933136, "13908": 0.5151132941246033, "13912": 0.3485364317893982, "14095": 0.9425065517425537, "14206": 0.045809537172317505, "14313": 0.25845035910606384, "14405": 0.66441810131073, "14442": 0.14095009863376617, "14443": 0.26820653676986694, "14462": 0.3443928062915802, "14648": 0.006812678650021553, "14774": 0.043007105588912964, "14828": 0.41065993905067444, "14905": 0.026976587250828743, "14991": 0.05694137513637543, "15012": 0.2719337046146393, "15172": 0.6492279767990112, "15224": 0.08871890604496002, "15273": 1.420846700668335, "15439": 0.7124901413917542, "15509": 0.8731874823570251, "15923": 0.2089812457561493, "16012": 0.04953393340110779, "16023": 0.37974658608436584, "16127": 0.036437395960092545, "16259": 0.11865071207284927, "16285": 0.17431432008743286, "16691": 0.2659635543823242, "16703": 0.3897167444229126, "16882": 0.09228714555501938, "17034": 0.17840765416622162, "17079": 0.7692760229110718, "17258": 1.1281205415725708, "17439": 0.29473719000816345, "17913": 0.19782574474811554, "17970": 0.0770333781838417, "18330": 0.05417001247406006, "18514": 0.18004031479358673, "18600": 0.11256109178066254, "18622": 0.7601850032806396, "18711": 0.11865071207284927, "18771": 0.11343330889940262, "18829": 0.8658194541931152, "18908": 0.472198486328125, "19012": 0.8074519634246826, "19120": 0.17267228662967682, "19137": 0.5370414853096008, "19202": 0.25694093108177185, "19269": 0.030771657824516296, "19293": 0.19541899859905243, "19389": 0.06612417846918106, "19449": 0.6441128253936768, "19476": 0.500420093536377, "19518": 0.16110190749168396, "19616": 0.4500300884246826, "19706": 0.7389566898345947, "19717": 0.14939609169960022, "19780": 0.19541899859905243, "19852": 0.4494072198867798, "19872": 0.043007105588912964, "19882": 0.8973627090454102, "19894": 0.8957691192626953, "19995": 1.0560526847839355, "20049": 0.9732321500778198, "20125": 0.07793712615966797, "20155": 0.5816917419433594, "20250": 0.24171993136405945, "20370": 0.1685553640127182, "20487": 0.20739519596099854, "20567": 0.20501139760017395, "20582": 0.2516399025917053, "20607": 0.11865071207284927, "20679": 0.07612881064414978, "20886": 0.4158279001712799, "21245": 0.13499516248703003, "21471": 0.29328158497810364, "21486": 0.11168810725212097, "21508": 0.20022670924663544, "21628": 0.3084607720375061, "21642": 0.19381128251552582, "21685": 0.05417001247406006, "21758": 0.1510767638683319, "21903": 1.0881409645080566, "21919": 0.24631060659885406, "22013": 0.5751199722290039, "22147": 0.5174443125724792, "22210": 0.841701865196228, "22248": 0.1734936386346817, "22574": 0.18654440343379974, "22663": 0.10467668622732162, "22869": 0.3723714053630829, "22933": 0.4518963396549225, "23169": 0.006812678650021553, "23267": 0.09495500475168228, "23303": 0.2576959431171417, "23586": 0.31204116344451904, "23589": 0.3241194784641266, "23599": 0.16607704758644104, "23737": 0.2394166737794876, "23959": 0.07250232994556427, "24012": 0.25995752215385437, "24054": 0.7163142561912537, "24094": 0.3547199070453644, "24110": 0.19862671196460724, "24117": 0.13925230503082275, "24269": 0.03925827145576477, "24314": 0.2607102394104004, "24388": 0.9613537192344666, "24587": 0.01934296265244484, "24710": 0.8666408061981201, "24848": 0.29255300760269165, "24879": 0.4419025182723999, "24899": 0.012615402229130268, "24939": 0.15860503911972046, "25292": 0.040196798741817474, "25336": 0.37102460861206055, "25456": 0.5336109399795532, "25608": 0.10906458646059036, "25700": 0.06795065850019455, "25714": 0.025073638185858727, "26083": 0.9531047344207764, "26402": 0.36358460783958435, "26462": 0.11604541540145874, "26524": 0.08871890604496002, "26633": 0.02887592278420925, "26694": 0.1011524572968483, "26721": 0.1332872211933136, "26832": 0.05694137513637543, "26989": 0.5990082025527954, "27169": 0.25694093108177185, "27508": 0.3134697377681732, "27697": 0.33325836062431335, "27749": 0.11951763927936554, "27777": 0.02412080205976963, "27790": 0.5729197263717651, "27846": 0.33115679025650024, "27998": 1.341864824295044, "28086": 0.19541899859905243, "28424": 0.18004031479358673, "28568": 0.11691460013389587, "28637": 0.07159364968538284, "28715": 0.1930064558982849, "28893": 0.16524957120418549, "28964": 0.1619328260421753} | 12800122 | Subdividing proliferating tissues into compartments is an evolutionarily conserved strategy of animal development [1-6]. Signals across boundaries between compartments can result in local expression of secreted proteins organizing growth and patterning of tissues [1-6]. Sharp and straight interfaces between compartments are crucial for stabilizing the position of such organizers and therefore for precise implementation of body plans. Maintaining boundaries in proliferating tissues requires mechanisms to counteract cell rearrangements caused by cell division; however, the nature of such mechanisms remains unclear. Here we quantitatively analyzed cell morphology and the response to the laser ablation of cell bonds in the vicinity of the anteroposterior compartment boundary in developing Drosophila wings. We found that mechanical tension is approximately 2.5-fold increased on cell bonds along this compartment boundary as compared to the remaining tissue. Cell bond tension is decreased in the presence of Y-27632 [7], an inhibitor of Rho-kinase whose main effector is Myosin II [8]. Simulations using a vertex model [9] demonstrate that a 2.5-fold increase in local cell bond tension suffices to guide the rearrangement of cells after cell division to maintain compartment boundaries. Our results provide a physical mechanism in which the local increase in Myosin II-dependent cell bond tension directs cell sorting at compartment boundaries. | Increased Cell Bond Tension Governs Cell Sorting at the Drosophila Anteroposterior Compartment Boundary |
{"2004": 0.46608972549438477, "2005": 0.37371641397476196, "2013": 0.6522845029830933, "2015": 0.32270604372024536, "2031": 0.018384648486971855, "2038": 0.15777134895324707, "2040": 0.22859740257263184, "2042": 0.04113444685935974, "2045": 0.2667117714881897, "2054": 0.1873544454574585, "2064": 0.04207121208310127, "2070": 0.029824240133166313, "2071": 0.32553088665008545, "2079": 0.2145126610994339, "2085": 0.07431721687316895, "2092": 0.0752234235405922, "2109": 0.7248653769493103, "2116": 0.025073638185858727, "2144": 0.09672962874174118, "2179": 0.11168810725212097, "2224": 0.5284429788589478, "2270": 0.401551216840744, "2339": 0.175953671336174, "2342": 0.11778303235769272, "2389": 0.37371641397476196, "2393": 0.10203468054533005, "2419": 0.24859806895256042, "2458": 0.13243216276168823, "2470": 0.306306391954422, "2478": 0.3127557039260864, "2530": 0.6332852244377136, "2535": 0.05786345899105072, "2559": 0.02412080205976963, "2599": 0.7755908370018005, "2632": 0.34508460760116577, "2641": 0.2145126610994339, "2651": 0.11865071207284927, "2667": 0.2026219218969345, "2671": 0.2447827309370041, "2734": 0.040196798741817474, "2740": 0.2145126610994339, "2747": 0.22001366317272186, "2753": 0.11517547070980072, "2764": 0.5174443125724792, "2783": 0.46363574266433716, "2800": 0.4980490207672119, "2817": 0.36697331070899963, "2825": 0.03831886500120163, "2833": 0.040196798741817474, "2852": 0.2160874605178833, "2877": 0.3241194784641266, "2890": 0.11604541540145874, "2902": 0.018384648486971855, "2913": 0.41195443272590637, "2923": 0.055094651877880096, "2934": 0.2247048318386078, "2937": 0.3499138653278351, "2966": 0.5838727951049805, "2969": 0.5925496220588684, "2993": 0.09584271162748337, "3011": 0.46363574266433716, "3019": 0.6358738541603088, "3112": 0.11168810725212097, "3120": 0.2741633653640747, "3144": 0.13670019805431366, "3151": 0.6425731778144836, "3200": 0.04953393340110779, "3209": 0.4311734735965729, "3217": 0.7342816591262817, "3252": 0.1619328260421753, "3267": 0.07612881064414978, "3269": 1.1786550283432007, "3273": 0.3963087201118469, "3319": 0.07159364968538284, "3424": 0.9650808572769165, "3436": 0.26446542143821716, "3460": 0.5855054259300232, "3522": 0.010684899985790253, "3593": 0.1064341589808464, "3594": 0.7163142561912537, "3628": 0.2478361576795578, "3652": 0.0029254043474793434, "3688": 0.48430517315864563, "3727": 0.37707099318504333, "3785": 0.1384023278951645, "3800": 0.11343330889940262, "3802": 0.5712664127349854, "3867": 0.27786844968795776, "3904": 0.17020416259765625, "3905": 0.5450005531311035, "3945": 0.53589928150177, "3949": 0.49864232540130615, "4005": 0.02792670577764511, "4031": 0.4349733293056488, "4045": 0.3588210940361023, "4073": 0.14349138736724854, "4138": 0.13755162060260773, "4163": 0.10906458646059036, "4200": 0.8315495252609253, "4264": 1.2737466096878052, "4295": 0.4734157919883728, "4315": 0.15610189735889435, "4319": 0.6989894509315491, "4383": 0.4190443754196167, "4503": 0.21372433006763458, "4621": 0.41647201776504517, "4652": 0.4487839937210083, "4663": 0.015504186972975731, "4761": 0.014542185701429844, "4810": 0.2852376699447632, "4839": 0.1510767638683319, "4852": 0.037378571927547455, "4870": 0.31560876965522766, "4895": 0.1718502640724182, "4975": 0.2409527748823166, "5022": 0.4196864068508148, "5072": 0.36967599391937256, "5130": 0.07250232994556427, "5136": 0.015504186972975731, "5144": 0.49626702070236206, "5173": 1.0533316135406494, "5260": 0.8004589080810547, "5555": 0.5568217039108276, "5682": 0.00875066313892603, "5776": 0.3723714053630829, "5802": 0.07068414986133575, "5845": 0.10555581003427505, "5850": 0.8247235417366028, "5901": 0.15777134895324707, "5911": 0.1212492436170578, "6074": 0.37102460861206055, "6179": 0.3423145115375519, "6370": 0.6000806093215942, "6529": 0.5903874635696411, "6546": 0.12038381397724152, "6575": 0.2576959431171417, "6612": 0.42096930742263794, "6666": 0.1384023278951645, "6779": 0.32764431834220886, "6845": 0.07341018319129944, "6887": 0.7067264318466187, "6897": 0.3170322775840759, "6950": 0.10993985831737518, "6964": 0.11168810725212097, "7017": 0.23633737862110138, "7053": 0.10467668622732162, "7066": 0.66441810131073, "7117": 0.15777134895324707, "7155": 0.6522845029830933, "7242": 0.11865071207284927, "7295": 0.7220231294631958, "7328": 0.5882205963134766, "7361": 0.33605360984802246, "7366": 0.25845035910606384, "7374": 0.2409527748823166, "7435": 0.3883931338787079, "7438": 0.5057345628738403, "7522": 0.1946154683828354, "7547": 0.5404602885246277, "7583": 0.1889725625514984, "7616": 0.010684899985790253, "7680": 0.3526630103588104, "7712": 0.7038320899009705, "7849": 0.14179791510105133, "7870": 0.5244048833847046, "7872": 0.04860413447022438, "8100": 0.26146242022514343, "8167": 0.6970458030700684, "8280": 0.3353555500507355, "8325": 0.4067663550376892, "8332": 0.02412080205976963, "8387": 0.14686977863311768, "8465": 0.14602625370025635, "8519": 0.07159364968538284, "8662": 0.7028654217720032, "8729": 0.0797421783208847, "8738": 0.08961215615272522, "8765": 0.24171993136405945, "8907": 0.6149744987487793, "8985": 0.6482070088386536, "9022": 0.07884006202220917, "9092": 0.37907835841178894, "9314": 0.06612417846918106, "9349": 0.6754127144813538, "9526": 0.6451379656791687, "9727": 0.011650617234408855, "9740": 0.1011524572968483, "9754": 0.08064348995685577, "9777": 0.7018978595733643, "9821": 0.4132472574710846, "9871": 0.12814582884311676, "10072": 0.5404602885246277, "10088": 0.45499902963638306, "10099": 0.6471850275993347, "10327": 0.562402069568634, "10372": 0.06154331564903259, "10723": 0.010684899985790253, "10727": 0.7592713832855225, "10847": 0.043007105588912964, "10867": 0.175953671336174, "11005": 0.42225050926208496, "11088": 0.06886265426874161, "11311": 0.129004567861557, "11326": 0.12384103983640671, "11343": 0.31489628553390503, "11390": 0.026976587250828743, "11431": 0.6563454270362854, "11483": 0.5607312321662903, "11546": 0.18004031479358673, "11572": 0.08603433519601822, "11647": 0.006812678650021553, "11704": 0.5805994272232056, "11767": 0.2918238639831543, "11837": 0.6410312056541443, "12030": 0.021256839856505394, "12141": 0.29619070887565613, "12153": 0.3423145115375519, "12222": 0.013579257763922215, "12318": 0.19782574474811554, "12353": 0.4574742913246155, "12402": 0.036437395960092545, "12448": 0.5903874635696411, "12550": 0.10203468054533005, "12553": 0.026025565341114998, "12637": 0.04767346754670143, "12681": 0.3615458607673645, "12702": 0.6674286723136902, "12810": 0.4145384132862091, "12902": 0.8212929964065552, "12929": 0.7510106563568115, "13109": 0.46608972549438477, "13194": 1.1128336191177368, "13367": 0.1011524572968483, "13434": 0.2976420819759369, "13441": 0.4228905141353607, "13494": 0.0354953333735466, "13807": 0.04674193635582924, "13819": 0.058784693479537964, "13859": 0.9455460906028748, "13882": 0.5381823778152466, "13978": 0.05694137513637543, "14152": 0.08782484382390976, "14386": 0.21687394380569458, "14613": 0.25467249751091003, "14617": 0.12814582884311676, "14667": 0.8187123537063599, "14685": 0.28155985474586487, "14817": 0.10731173306703568, "14956": 0.5495203733444214, "15007": 0.05970508232712746, "15059": 0.0038986403960734606, "15189": 0.08154398202896118, "15245": 0.6522845029830933, "15345": 0.2089812457561493, "15415": 0.3588210940361023, "15535": 0.804835319519043, "15744": 0.21765978634357452, "15869": 0.0354953333735466, "15900": 0.1677299439907074, "15901": 0.17922431230545044, "15923": 0.13243216276168823, "16012": 0.3241194784641266, "16204": 0.34300774335861206, "16250": 0.1677299439907074, "16263": 0.08064348995685577, "16462": 0.030771657824516296, "16514": 0.9348671436309814, "16670": 0.3923587501049042, "16886": 0.6744182109832764, "16942": 0.09317722171545029, "17018": 0.7144040465354919, "17086": 0.4356052577495575, "17098": 0.9635916948318481, "17175": 0.7086513638496399, "17193": 0.22001366317272186, "17261": 0.3499138653278351, "17341": 0.4248080551624298, "17463": 0.28670501708984375, "17473": 0.28743788599967957, "17561": 0.4400174915790558, "17631": 0.10906458646059036, "17663": 0.24171993136405945, "17830": 0.34300774335861206, "17865": 0.2976420819759369, "17901": 0.11256109178066254, "17985": 0.056018441915512085, "18191": 0.14939609169960022, "18447": 0.20022670924663544, "18452": 0.10555581003427505, "18547": 0.7601850032806396, "18738": 0.5162794589996338, "18804": 0.43244171142578125, "19176": 0.1913948506116867, "19783": 0.7610978484153748, "19960": 0.7809720039367676, "20017": 0.10906458646059036, "20219": 0.0038986403960734606, "20233": 0.7629209756851196, "20282": 0.07431721687316895, "20353": 0.32553088665008545, "20422": 0.10555581003427505, "20435": 0.11343330889940262, "20632": 0.6941232681274414, "20906": 0.3070250153541565, "20992": 0.6823468804359436, "21102": 0.969535231590271, "21150": 0.3910386264324188, "21162": 0.23556606471538544, "21376": 0.11604541540145874, "21391": 0.36494144797325134, "21477": 0.3757305145263672, "21529": 0.2231435477733612, "21647": 0.07793712615966797, "21685": 0.4950772523880005, "21759": 0.1913948506116867, "22123": 1.013020396232605, "22423": 0.6338034868240356, "22522": 0.38041436672210693, "22641": 0.4400174915790558, "22863": 0.6022219061851501, "22911": 0.6212902665138245, "23041": 0.4158279001712799, "23086": 0.022212404757738113, "23150": 0.1401015669107437, "23444": 0.5607312321662903, "23555": 1.035461664199829, "23572": 0.25088030099868774, "23610": 0.030771657824516296, "24093": 0.10906458646059036, "24229": 0.4113073945045471, "24269": 0.8400169610977173, "24278": 0.11951763927936554, "24473": 0.45623743534088135, "24479": 0.5952457785606384, "24757": 0.02412080205976963, "24759": 0.021256839856505394, "24797": 1.013020396232605, "24848": 0.9371650815010071, "25274": 0.08244366943836212, "25654": 0.755608320236206, "25714": 0.5324648022651672, "25969": 0.2576959431171417, "26235": 0.23787821829319, "26282": 0.5718178153038025, "26591": 0.6563454270362854, "26835": 0.5063233375549316, "27144": 0.04207121208310127, "27292": 0.6882523894309998, "27348": 0.016465263441205025, "27761": 0.6107416749000549, "27849": 0.3554046154022217, "28024": 0.4537591338157654, "28774": 0.5528968572616577, "29090": 0.3170322775840759, "29217": 0.13499516248703003, "29234": 0.12384103983640671, "29280": 0.2184450328350067, "29451": 0.025073638185858727, "29494": 0.02792670577764511} | 12801438 | The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and "leads" which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations. | Plant products as antimicrobial agents. |
{"2003": 0.19862671196460724, "2054": 0.26820653676986694, "2070": 0.09761575609445572, "2075": 0.175953671336174, "2079": 0.09761575609445572, "2166": 0.07068414986133575, "2287": 0.18329764902591705, "2319": 0.06246116757392883, "2339": 0.28670501708984375, "2358": 0.8658194541931152, "2458": 0.33675122261047363, "2504": 0.2786078155040741, "2515": 0.18004031479358673, "2535": 0.23402166366577148, "2537": 0.129004567861557, "2550": 0.012615402229130268, "2590": 0.5450005531311035, "2599": 0.12384103983640671, "2618": 0.0770333781838417, "2740": 0.02316705882549286, "2791": 0.13071982562541962, "2832": 0.8100618124008179, "2877": 0.21687394380569458, "2897": 0.5116065740585327, "2919": 0.306306391954422, "2944": 0.06977381557226181, "3252": 0.36494144797325134, "3278": 0.19622190296649933, "3291": 0.021256839856505394, "3366": 0.13071982562541962, "3370": 0.23556606471538544, "3378": 0.05046287178993225, "3399": 0.02887592278420925, "3426": 0.004870930220931768, "3431": 0.1619328260421753, "3433": 0.4444103240966797, "3463": 0.056018441915512085, "3466": 0.3485364317893982, "3508": 0.20739519596099854, "3526": 0.7638313174247742, "3544": 0.2674594223499298, "3558": 0.15359249711036682, "3559": 0.04953393340110779, "3625": 0.24554696679115295, "3647": 0.020300358533859253, "3663": 0.18329764902591705, "3670": 1.5614286661148071, "3711": 0.2184450328350067, "3785": 0.05417001247406006, "3798": 0.5127768516540527, "3800": 0.0009760859538801014, "3853": 0.5139457583427429, "3891": 0.034552380442619324, "3896": 0.41065993905067444, "3989": 0.06520967930555344, "4023": 0.1011524572968483, "4044": 0.14349138736724854, "4053": 0.07884006202220917, "4072": 0.12642613053321838, "4106": 0.03831886500120163, "4176": 0.0842406153678894, "4254": 0.3777405619621277, "4264": 0.020300358533859253, "4371": 0.05139094591140747, "4442": 0.5844172835350037, "4456": 0.15943801403045654, "4506": 0.03831886500120163, "4654": 0.3883931338787079, "4671": 0.906871497631073, "4765": 0.05139094591140747, "4783": 0.2034190446138382, "4795": 0.319873183965683, "4962": 1.5841201543807983, "4972": 0.3388410806655884, "4975": 0.013579257763922215, "4997": 0.1873544454574585, "5090": 0.1064341589808464, "5158": 0.12470348179340363, "5197": 0.32199856638908386, "5228": 1.0382318496704102, "5248": 0.04953393340110779, "5250": 0.6872705817222595, "5258": 0.02316705882549286, "5260": 0.06795065850019455, "5320": 0.20580662786960602, "5360": 0.07250232994556427, "5402": 0.5232481360435486, "5418": 0.0029254043474793434, "5421": 0.28597161173820496, "5449": 0.9531047344207764, "5770": 0.35745587944984436, "5834": 0.28155985474586487, "6064": 0.8247235417366028, "6075": 0.15526613593101501, "6123": 0.11865071207284927, "6125": 0.3676496744155884, "6179": 0.29036402702331543, "6194": 0.6265231370925903, "6210": 0.23710809648036957, "6214": 0.00875066313892603, "6245": 0.04953393340110779, "6348": 0.02887592278420925, "6364": 0.20739519596099854, "6459": 0.5707147121429443, "6666": 0.4574742913246155, "6721": 0.9546096324920654, "6844": 0.7898768186569214, "6897": 0.40871503949165344, "6911": 0.7086513638496399, "6958": 0.15359249711036682, "6962": 0.49626702070236206, "7060": 0.14264501631259918, "7337": 0.1994270235300064, "7356": 0.2394166737794876, "7366": 0.5290185213088989, "7386": 0.4356052577495575, "7403": 1.2082605361938477, "7461": 0.32553088665008545, "7551": 0.056018441915512085, "7711": 0.02792670577764511, "7784": 0.1751343309879303, "7790": 0.5104349255561829, "7816": 0.3012613356113434, "7965": 0.015504186972975731, "8023": 0.3615458607673645, "8050": 0.03266380727291107, "8092": 0.021256839856505394, "8137": 0.29036402702331543, "8146": 0.3262358605861664, "8153": 0.0038986403960734606, "8171": 0.5483922958374023, "8185": 0.02412080205976963, "8281": 0.47827014327049255, "8332": 0.25239890813827515, "8349": 0.2317005842924118, "8358": 0.75193190574646, "8360": 0.2105647772550583, "8386": 0.8004589080810547, "8465": 0.6629094481468201, "8677": 0.3262358605861664, "8776": 0.09850110858678818, "8991": 0.9084475636482239, "9031": 0.16110190749168396, "9041": 0.5990082025527954, "9099": 0.2034190446138382, "9165": 1.3979449272155762, "9247": 0.11256109178066254, "9260": 0.2247048318386078, "9375": 0.030771657824516296, "9426": 0.06795065850019455, "9509": 0.39696553349494934, "9670": 0.04767346754670143, "9671": 0.28155985474586487, "10074": 0.2659635543823242, "10288": 0.25088030099868774, "10327": 0.5238267183303833, "10595": 0.11604541540145874, "10636": 0.034552380442619324, "10738": 0.19622190296649933, "10857": 0.08603433519601822, "10960": 0.0317181795835495, "11160": 0.4500300884246826, "11423": 1.1356772184371948, "11643": 0.0797421783208847, "11663": 0.9650808572769165, "11692": 0.7182208299636841, "11704": 0.10467668622732162, "11709": 0.5607312321662903, "11767": 0.757441520690918, "12260": 0.036437395960092545, "12332": 0.07793712615966797, "12359": 0.09761575609445572, "12456": 0.18654440343379974, "12520": 0.5640701055526733, "12530": 0.755608320236206, "12562": 0.6764062643051147, "12589": 0.1994270235300064, "12681": 0.7067264318466187, "12702": 0.812664806842804, "12709": 0.17020416259765625, "12789": 0.259204238653183, "12800": 0.6492279767990112, "12955": 0.13414156436920166, "12987": 0.8408597707748413, "13105": 0.08692999184131622, "13458": 0.5909284353256226, "13494": 0.6533012986183167, "13531": 0.15442965924739838, "13791": 0.15610189735889435, "13908": 0.3084607720375061, "13938": 0.04674193635582924, "13995": 0.2105647772550583, "14026": 0.7969439625740051, "14048": 0.3027053773403168, "14080": 0.07884006202220917, "14120": 0.03831886500120163, "14192": 0.2667117714881897, "14193": 1.1192315816879272, "14471": 0.935633659362793, "14494": 0.2018241584300995, "14670": 0.3070250153541565, "14800": 0.34922540187835693, "14817": 0.09406650811433792, "15011": 0.045809537172317505, "15176": 0.052318159490823746, "15189": 0.7408206462860107, "15543": 0.034552380442619324, "15615": 0.025073638185858727, "15923": 0.7134475708007812, "16012": 0.6709295511245728, "16221": 0.25239890813827515, "16238": 0.21372433006763458, "16381": 0.2409527748823166, "16505": 0.1889725625514984, "16515": 0.07431721687316895, "16530": 0.12556517124176025, "16705": 0.11430477350950241, "16706": 0.026976587250828743, "16774": 0.00875066313892603, "16783": 0.48850810527801514, "16796": 0.09761575609445572, "16803": 0.34577593207359314, "16820": 0.1751343309879303, "16882": 0.040196798741817474, "16984": 0.02316705882549286, "17341": 0.1718502640724182, "17630": 0.3084607720375061, "17631": 0.7610978484153748, "17637": 0.10467668622732162, "17760": 0.22548456490039825, "17900": 0.38374659419059753, "17926": 0.05694137513637543, "18046": 0.06886265426874161, "18078": 0.2317005842924118, "18089": 0.5139457583427429, "18154": 0.6773988008499146, "18275": 0.17759032547473907, "18647": 0.1808556467294693, "18804": 0.603290855884552, "19209": 0.04767346754670143, "19304": 0.0019512200960889459, "19345": 0.25845035910606384, "19389": 0.1873544454574585, "19500": 0.1751343309879303, "19539": 0.1873544454574585, "19762": 0.052318159490823746, "19852": 0.13157635927200317, "20353": 0.2223619967699051, "20875": 1.1537069082260132, "20906": 0.03360854089260101, "21208": 0.0174254160374403, "21425": 0.1751343309879303, "21446": 0.22937409579753876, "21453": 0.2983669638633728, "21466": 0.021256839856505394, "21685": 0.056018441915512085, "21759": 0.1619328260421753, "22026": 0.10818854719400406, "22422": 0.12470348179340363, "22570": 0.4132472574710846, "22694": 0.015504186972975731, "23077": 0.15693697333335876, "23079": 0.38574060797691345, "23284": 0.26446542143821716, "23302": 0.8022117614746094, "23563": 0.11343330889940262, "23737": 0.1221139207482338, "23807": 0.19782574474811554, "23924": 0.07341018319129944, "24051": 0.22157983481884003, "24670": 0.7124901413917542, "24908": 0.043007105588912964, "25206": 0.12642613053321838, "25300": 0.00875066313892603, "25323": 0.2478361576795578, "25524": 0.4462870955467224, "26134": 0.22001366317272186, "26282": 0.04953393340110779, "26775": 0.07250232994556427, "26835": 0.02792670577764511, "27226": 0.22079704701900482, "27617": 0.22001366317272186, "27989": 0.043007105588912964, "28086": 0.013579257763922215, "28436": 0.6086184978485107, "28637": 0.15023678541183472, "28848": 0.8691008687019348, "28892": 0.36358460783958435, "29129": 0.011650617234408855, "29172": 0.3248254358768463, "29206": 0.3381449282169342} | 12804937 | Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure. Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others. These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging. | Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences |
{"1011": 0.2105647772550583, "1018": 0.15860503911972046, "1039": 0.07341018319129944, "1052": 0.045809537172317505, "1060": 0.757441520690918, "1156": 0.27342069149017334, "2002": 0.4709797203540802, "2005": 0.15442965924739838, "2008": 0.06977381557226181, "2011": 0.09672962874174118, "2020": 0.09495500475168228, "2024": 0.0797421783208847, "2029": 0.1710275560617447, "2033": 0.08513788133859634, "2048": 0.23015019297599792, "2076": 0.02792670577764511, "2079": 0.2576959431171417, "2099": 1.0868242979049683, "2107": 0.0029254043474793434, "2109": 0.015504186972975731, "2152": 0.05139094591140747, "2166": 0.347847044467926, "2176": 0.007782140281051397, "2179": 0.17840765416622162, "2239": 0.255429208278656, "2349": 0.15275461971759796, "2460": 0.09761575609445572, "2483": 0.10993985831737518, "2491": 0.7463917136192322, "2515": 0.21135559678077698, "2521": 0.7845434546470642, "2535": 0.5267143249511719, "2566": 0.3777405619621277, "2581": 0.23479416966438293, "2590": 0.46486347913742065, "2618": 0.24248650670051575, "2683": 0.19782574474811554, "2714": 0.4487839937210083, "2750": 0.07068414986133575, "2765": 0.09672962874174118, "2828": 0.05970508232712746, "2869": 1.17624831199646, "2897": 0.6054253578186035, "2906": 0.9470623731613159, "2920": 0.4673144817352295, "2938": 0.304147332906723, "2943": 1.0229004621505737, "2953": 0.45499902963638306, "3001": 0.14518201351165771, "3085": 0.31560876965522766, "3117": 0.24401791393756866, "3132": 0.37035053968429565, "3145": 0.036437395960092545, "3273": 0.07159364968538284, "3276": 0.3027053773403168, "3283": 0.07159364968538284, "3366": 0.36967599391937256, "3378": 0.17922431230545044, "3406": 0.5952457785606384, "3433": 0.08692999184131622, "3449": 0.4248080551624298, "3450": 0.2652147710323334, "3463": 0.04113444685935974, "3466": 0.11865071207284927, "3491": 0.11778303235769272, "3603": 0.2184450328350067, "3605": 0.1602703034877777, "3625": 0.09850110858678818, "3635": 0.056018441915512085, "3670": 0.75193190574646, "3671": 0.026025565341114998, "3747": 0.011650617234408855, "3768": 0.13157635927200317, "3800": 0.006812678650021553, "3853": 0.25239890813827515, "3896": 0.05694137513637543, "3949": 0.42225050926208496, "3972": 0.5381823778152466, "4013": 0.4126010537147522, "4017": 0.2184450328350067, "4023": 0.2822965085506439, "4078": 0.49982786178588867, "4127": 0.22001366317272186, "4168": 0.3248254358768463, "4176": 0.06337817758321762, "4180": 0.34370049834251404, "4295": 0.34023189544677734, "4359": 0.44753631949424744, "4395": 0.41389304399490356, "4442": 0.04487626627087593, "4502": 0.5822374224662781, "4504": 0.02792670577764511, "4517": 1.2862366437911987, "4539": 0.846739649772644, "4639": 0.4518963396549225, "4648": 0.47402387857437134, "4700": 0.24631060659885406, "4724": 0.13670019805431366, "4749": 1.335720419883728, "4758": 0.5696102976799011, "4824": 0.23864774405956268, "4903": 0.997294545173645, "4919": 0.021256839856505394, "4957": 0.14264501631259918, "4962": 1.0257055759429932, "4973": 0.03925827145576477, "5197": 0.24631060659885406, "5228": 0.30989447236061096, "5267": 0.9635916948318481, "5387": 0.5990082025527954, "5423": 0.24248650670051575, "5441": 0.3547199070453644, "5512": 0.5033760666847229, "5537": 0.4158279001712799, "5547": 0.22157983481884003, "5585": 0.16524957120418549, "5648": 0.25995752215385437, "5666": 0.6603899002075195, "5668": 0.4974553883075714, "5703": 0.42990362644195557, "5799": 0.5330380201339722, "5845": 0.043007105588912964, "5876": 0.39367714524269104, "6001": 0.3297532796859741, "6064": 0.21135559678077698, "6125": 0.6578640341758728, "6187": 0.13157635927200317, "6388": 0.5033760666847229, "6459": 0.021256839856505394, "6540": 0.0354953333735466, "6622": 0.4891071021556854, "6638": 1.1586239337921143, "6887": 0.37907835841178894, "6897": 0.6420594453811646, "7035": 0.43053874373435974, "7108": 0.018384648486971855, "7242": 0.034552380442619324, "7312": 0.056018441915512085, "7337": 0.35677260160446167, "7366": 0.4494072198867798, "7403": 0.5903874635696411, "7438": 0.4500300884246826, "7461": 0.09495500475168228, "7473": 0.27934664487838745, "7551": 0.16690383851528168, "7591": 0.10818854719400406, "7645": 0.11081436276435852, "7711": 0.8264343738555908, "7816": 0.7105726003646851, "7870": 0.4374985992908478, "7875": 0.3170322775840759, "7885": 0.2447827309370041, "7889": 0.9546096324920654, "8000": 0.08692999184131622, "8156": 0.11604541540145874, "8192": 0.20421554148197174, "8247": 0.2659635543823242, "8319": 0.3163207769393921, "8381": 0.777387797832489, "8469": 0.09938567131757736, "8486": 0.23015019297599792, "8487": 0.4412745535373688, "8498": 0.05786345899105072, "8516": 0.5162794589996338, "8677": 0.15359249711036682, "8776": 0.11778303235769272, "8821": 0.12556517124176025, "8878": 0.8004589080810547, "8898": 0.28743788599967957, "9007": 0.5952457785606384, "9125": 0.037378571927547455, "9165": 0.9131608605384827, "9314": 0.5033760666847229, "9319": 0.29981520771980286, "9412": 0.08154398202896118, "9416": 0.4950772523880005, "9513": 0.16524957120418549, "9556": 0.27044451236724854, "9593": 0.036437395960092545, "9756": 0.36900100111961365, "9869": 0.44753631949424744, "9950": 0.034552380442619324, "10071": 0.1602703034877777, "10202": 0.3560888469219208, "10266": 0.0354953333735466, "10391": 0.04113444685935974, "10464": 0.8658194541931152, "10480": 0.12470348179340363, "10548": 0.06246116757392883, "10595": 0.09317722171545029, "10737": 0.053244512528181076, "10738": 1.0641717910766602, "10769": 1.3610767126083374, "10785": 0.39696553349494934, "10867": 0.18167030811309814, "10924": 0.6907027959823608, "11179": 0.3588210940361023, "11290": 1.0841858386993408, "11369": 1.0519683361053467, "11423": 0.14179791510105133, "11486": 0.255429208278656, "11636": 0.4891071021556854, "11650": 1.351516842842102, "11659": 0.03925827145576477, "11993": 0.6011518239974976, "12016": 0.4067663550376892, "12042": 0.12038381397724152, "12222": 0.7009293437004089, "12247": 0.014542185701429844, "12319": 0.10379679501056671, "12369": 0.2659635543823242, "12546": 0.05139094591140747, "12641": 0.5990082025527954, "12649": 0.0752234235405922, "12732": 0.6674286723136902, "12737": 0.09495500475168228, "12761": 0.1905880719423294, "12859": 0.6096806526184082, "13100": 0.04487626627087593, "13441": 0.1994270235300064, "13458": 0.17267228662967682, "13502": 0.47827014327049255, "13530": 0.11168810725212097, "13617": 0.045809537172317505, "13791": 0.3560888469219208, "13833": 1.436757206916809, "13874": 0.609149694442749, "13907": 0.1064341589808464, "14048": 0.12384103983640671, "14080": 0.19782574474811554, "14126": 0.22079704701900482, "14206": 0.6155022978782654, "14402": 0.17759032547473907, "14471": 0.15777134895324707, "14494": 0.009718249551951885, "14671": 0.8715548515319824, "14798": 0.1602703034877777, "14828": 0.2447827309370041, "14956": 0.18004031479358673, "15176": 0.47402387857437134, "15330": 0.10467668622732162, "15460": 0.02887592278420925, "15485": 0.9084475636482239, "15509": 0.7969439625740051, "15527": 0.10203468054533005, "15543": 0.04394211992621422, "15578": 0.5517725944519043, "16012": 0.4673144817352295, "16026": 0.5601736903190613, "16030": 0.2667117714881897, "16221": 0.19381128251552582, "16253": 0.9680526852607727, "16259": 1.0389231443405151, "16285": 0.6902132034301758, "16344": 0.1677299439907074, "16371": 0.22937409579753876, "16515": 0.8509185314178467, "16678": 0.2830325961112976, "16910": 0.7791815400123596, "16913": 0.8013357520103455, "17086": 0.23556606471538544, "17241": 0.00875066313892603, "17379": 0.03925827145576477, "17441": 0.05046287178993225, "17544": 0.3676496744155884, "17669": 0.022212404757738113, "17815": 0.06246116757392883, "18089": 1.211173415184021, "18114": 0.010684899985790253, "18234": 0.6118015646934509, "18423": 0.014542185701429844, "18452": 0.021256839856505394, "18647": 0.14264501631259918, "18699": 1.589713454246521, "18714": 1.167778730392456, "18804": 0.1734936386346817, "18924": 0.672426164150238, "18969": 0.17267228662967682, "19101": 0.9194108247756958, "19293": 0.05970508232712746, "19345": 0.5341835021972656, "19565": 1.005902886390686, "19577": 0.8845420479774475, "19795": 0.11517547070980072, "19802": 0.5209306478500366, "19852": 0.25694093108177185, "19995": 0.6430866718292236, "20062": 0.4673144817352295, "20120": 0.08603433519601822, "20155": 0.09938567131757736, "20287": 0.17840765416622162, "20307": 0.9455460906028748, "20350": 0.2622140049934387, "20544": 0.12384103983640671, "20624": 0.5607312321662903, "20752": 0.9958525896072388, "20915": 0.6970458030700684, "21208": 0.49030399322509766, "21257": 0.13755162060260773, "21453": 1.0423725843429565, "21477": 0.03925827145576477, "21575": 0.49686139822006226, "21618": 0.8780695199966431, "21903": 0.5168620347976685, "21919": 0.09938567131757736, "21967": 0.007782140281051397, "22069": 0.03360854089260101, "22597": 0.12038381397724152, "22610": 0.1619328260421753, "22718": 0.07884006202220917, "22769": 0.6744182109832764, "22930": 0.12986256182193756, "22939": 0.009718249551951885, "22943": 0.015504186972975731, "22991": 0.2976420819759369, "23060": 0.2516399025917053, "23079": 0.026025565341114998, "23150": 0.08154398202896118, "23194": 0.637939989566803, "23767": 0.2447827309370041, "23777": 0.06246116757392883, "23900": 0.05046287178993225, "24054": 0.0038986403960734606, "24171": 0.12814582884311676, "24552": 1.0546929836273193, "25032": 0.7028654217720032, "25172": 0.41840189695358276, "25206": 0.1384023278951645, "25236": 0.7276995778083801, "25311": 0.08961215615272522, "25476": 0.5324648022651672, "25502": 0.469759464263916, "25644": 0.6265231370925903, "25700": 0.04953393340110779, "25874": 0.7124901413917542, "26083": 0.18978065252304077, "26224": 1.0403043031692505, "26261": 0.8699195384979248, "26288": 0.2223619967699051, "26305": 0.11604541540145874, "26462": 0.3027053773403168, "26524": 1.156782865524292, "26534": 0.347847044467926, "26773": 0.5805994272232056, "27321": 0.3170322775840759, "27753": 0.18816383183002472, "27854": 0.3381449282169342, "28155": 0.6430866718292236, "28173": 0.02316705882549286, "28389": 0.0606246218085289} | 12805683 | Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs), precisely control energy metabolism. Consequently, these receptors are important targets for the treatment of metabolic diseases, including diabetes and obesity. A thorough understanding of NHR fat regulatory networks has been limited, however, by a lack of genetically tractable experimental systems. Here we show that deletion of the Caenorhabditis elegans NHR gene nhr-49 yielded worms with elevated fat content and shortened life span. Employing a quantitative RT-PCR screen, we found that nhr-49 influenced the expression of 13 genes involved in energy metabolism. Indeed, nhr-49 served as a key regulator of fat usage, modulating pathways that control the consumption of fat and maintain a normal balance of fatty acid saturation. We found that the two phenotypes of the nhr-49 knockout were linked to distinct pathways and were separable: The high-fat phenotype was due to reduced expression of enzymes in fatty acid β-oxidation, and the shortened adult life span resulted from impaired expression of a stearoyl-CoA desaturase. Despite its sequence relationship with the mammalian hepatocyte nuclear factor 4 receptor, the biological activities of nhr-49 were most similar to those of the mammalian PPARs, implying an evolutionarily conserved role for NHRs in modulating fat consumption and composition. Our findings in C. elegans provide novel insights into how NHR regulatory networks are coordinated to govern fat metabolism. | Nuclear Hormone Receptor NHR-49 Controls Fat Consumption and Fatty Acid Composition in C. elegans |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.