spalde-v3-lexical
stringlengths 4.95k
41.3k
| _id
stringlengths 4
9
| text
stringlengths 174
10k
| title
stringlengths 2
300
|
|---|---|---|---|
{"1040": 0.18167030811309814, "1059": 0.3923587501049042, "2005": 0.0019512200960889459, "2011": 0.10467668622732162, "2015": 0.6471850275993347, "2029": 0.07250232994556427, "2046": 0.2026219218969345, "2075": 0.2026219218969345, "2076": 0.5461324453353882, "2078": 0.42735910415649414, "2079": 0.011650617234408855, "2110": 0.5010119676589966, "2128": 0.822151780128479, "2129": 0.36358460783958435, "2135": 0.34508460760116577, "2139": 0.6568518877029419, "2153": 0.1710275560617447, "2163": 0.3084607720375061, "2182": 0.21922965347766876, "2203": 0.736154317855835, "2206": 0.02887592278420925, "2213": 0.5244048833847046, "2243": 0.4500300884246826, "2278": 0.3388410806655884, "2291": 0.14349138736724854, "2339": 0.08064348995685577, "2361": 0.7067264318466187, "2417": 0.05970508232712746, "2442": 0.014542185701429844, "2480": 0.987156867980957, "2504": 0.11604541540145874, "2515": 0.05970508232712746, "2535": 0.012615402229130268, "2594": 0.41195443272590637, "2689": 0.6086184978485107, "2734": 0.05694137513637543, "2747": 0.045809537172317505, "2819": 0.3269403576850891, "2832": 0.4574742913246155, "2864": 0.00875066313892603, "2904": 0.15860503911972046, "2920": 0.176772341132164, "2944": 0.7827593088150024, "3001": 0.08154398202896118, "3064": 0.1011524572968483, "3096": 0.23092569410800934, "3217": 0.7782850861549377, "3223": 0.3485364317893982, "3226": 0.5903874635696411, "3273": 0.020300358533859253, "3372": 0.5893046259880066, "3431": 0.6254787445068359, "3433": 0.1229778528213501, "3436": 0.5795059204101562, "3466": 0.13157635927200317, "3491": 0.19862671196460724, "3508": 0.1011524572968483, "3526": 0.9217445850372314, "3560": 0.27044451236724854, "3640": 0.006812678650021553, "3670": 0.6522845029830933, "3722": 0.3723714053630829, "3787": 0.4145384132862091, "3853": 0.06246116757392883, "3896": 0.058784693479537964, "3930": 0.06703783571720123, "3973": 0.10203468054533005, "4032": 0.4431571960449219, "4044": 0.762009859085083, "4053": 0.7220231294631958, "4072": 0.2667117714881897, "4078": 0.0770333781838417, "4183": 0.5438674688339233, "4242": 0.04394211992621422, "4275": 0.6249561905860901, "4371": 0.17431432008743286, "4403": 0.1693800985813141, "4442": 0.8893690705299377, "4469": 0.7182208299636841, "4483": 0.30558720231056213, "4487": 0.5822374224662781, "4523": 0.02412080205976963, "4639": 0.7076893448829651, "4651": 0.021256839856505394, "4654": 0.12470348179340363, "4742": 0.23787821829319, "4758": 0.055094651877880096, "4821": 0.026976587250828743, "4958": 0.7144040465354919, "4962": 0.19782574474811554, "4989": 0.010684899985790253, "4991": 0.2983669638633728, "5017": 0.007782140281051397, "5034": 0.6624060273170471, "5072": 0.14095009863376617, "5158": 0.11256109178066254, "5159": 0.12038381397724152, "5228": 0.2674594223499298, "5250": 0.0019512200960889459, "5278": 0.3318578004837036, "5290": 0.3423145115375519, "5302": 0.40220460295677185, "5360": 0.38441169261932373, "5449": 0.18167030811309814, "5474": 0.2493593990802765, "5478": 0.5174443125724792, "5536": 0.02316705882549286, "5591": 0.6512666940689087, "5677": 0.20421554148197174, "5705": 0.05139094591140747, "5729": 0.4624064862728119, "5732": 0.0029254043474793434, "5741": 0.12470348179340363, "5783": 0.6369074583053589, "5788": 0.12814582884311676, "5809": 0.1677299439907074, "5812": 0.12556517124176025, "5854": 0.23864774405956268, "5918": 0.06886265426874161, "5942": 0.5838727951049805, "5967": 0.6624060273170471, "5996": 0.17267228662967682, "6001": 0.5267143249511719, "6025": 0.08782484382390976, "6028": 0.07612881064414978, "6194": 0.26296505331993103, "6215": 0.1485546976327896, "6308": 0.05139094591140747, "6310": 0.0058422754518687725, "6357": 1.0855059623718262, "6370": 0.02792670577764511, "6418": 0.45994341373443604, "6459": 0.056018441915512085, "6472": 0.11778303235769272, "6494": 0.8109301924705505, "6562": 0.8143964409828186, "6580": 1.2671676874160767, "6653": 0.9470623731613159, "6740": 0.029824240133166313, "6789": 1.0828639268875122, "6812": 0.26296505331993103, "6827": 0.6603899002075195, "6897": 0.10026945173740387, "6904": 0.7124901413917542, "6942": 0.045809537172317505, "6958": 0.0038986403960734606, "7065": 0.6176109313964844, "7178": 0.083342544734478, "7182": 0.35128939151763916, "7192": 0.20421554148197174, "7233": 0.46608972549438477, "7242": 0.2026219218969345, "7315": 1.0802149772644043, "7336": 0.2800849378108978, "7337": 0.4518963396549225, "7356": 0.6573580503463745, "7366": 0.3723714053630829, "7461": 0.3374483287334442, "7583": 0.31204116344451904, "7584": 0.5718178153038025, "7605": 0.7701805830001831, "7645": 0.4654768109321594, "7670": 0.037378571927547455, "7755": 0.21530038118362427, "7816": 0.09050461649894714, "7872": 0.777387797832489, "7885": 0.025073638185858727, "8000": 1.1051015853881836, "8038": 1.2134976387023926, "8082": 0.06703783571720123, "8153": 1.2381477355957031, "8184": 0.03266380727291107, "8185": 1.1629066467285156, "8281": 0.17840765416622162, "8347": 0.12728634476661682, "8469": 0.11430477350950241, "8578": 0.4500300884246826, "8590": 0.3269403576850891, "8651": 0.29400965571403503, "8710": 0.8829278349876404, "8735": 0.45251765847206116, "8760": 0.38441169261932373, "8776": 0.13071982562541962, "8778": 0.010684899985790253, "8790": 1.0144377946853638, "8878": 0.6911921501159668, "8898": 0.35677260160446167, "8902": 0.7934166193008423, "8907": 0.2231435477733612, "8939": 0.9515975713729858, "8980": 0.5174443125724792, "9007": 0.32553088665008545, "9031": 0.06154331564903259, "9034": 0.11865071207284927, "9035": 0.025073638185858727, "9100": 0.28670501708984375, "9114": 0.08871890604496002, "9125": 0.14179791510105133, "9239": 0.31132611632347107, "9247": 1.0519683361053467, "9331": 0.6563454270362854, "9350": 0.2852376699447632, "9412": 0.20580662786960602, "9513": 0.3622259199619293, "9662": 0.10731173306703568, "9869": 0.5712664127349854, "10032": 0.10291612148284912, "10058": 0.5104349255561829, "10461": 0.1718502640724182, "10463": 0.036437395960092545, "10467": 0.007782140281051397, "10525": 0.14602625370025635, "10570": 0.14433705806732178, "10572": 0.7782850861549377, "10580": 0.39893341064453125, "10595": 0.2231435477733612, "10599": 0.3381449282169342, "10803": 0.03360854089260101, "10814": 0.272677481174469, "10924": 0.7295845746994019, "10938": 0.04113444685935974, "10949": 0.6451379656791687, "10968": 1.3489859104156494, "11228": 0.2763880789279938, "11252": 0.18573370575904846, "11301": 0.17431432008743286, "11393": 1.09404456615448, "11423": 0.3084607720375061, "11432": 0.25239890813827515, "11477": 0.09672962874174118, "11643": 0.5104349255561829, "11937": 1.1128336191177368, "12115": 0.7163142561912537, "12328": 1.061472773551941, "12335": 0.0038986403960734606, "12394": 0.21214580535888672, "12402": 0.1889725625514984, "12448": 0.2034190446138382, "12452": 0.15777134895324707, "12504": 0.2317005842924118, "12562": 0.7889899015426636, "12662": 0.3269403576850891, "12702": 0.25995752215385437, "12719": 0.06886265426874161, "12732": 0.1677299439907074, "13113": 1.0236024856567383, "13365": 1.039613962173462, "13400": 0.0797421783208847, "13521": 0.013579257763922215, "13531": 0.09672962874174118, "13595": 0.23710809648036957, "13656": 0.053244512528181076, "13671": 0.08871890604496002, "13685": 0.21530038118362427, "13708": 0.07250232994556427, "13712": 0.20977331697940826, "13791": 0.9783848524093628, "13833": 0.04394211992621422, "13902": 0.0009760859538801014, "13918": 0.15023678541183472, "14080": 0.21293537318706512, "14095": 0.9232974052429199, "14206": 0.15693697333335876, "14313": 0.1905880719423294, "14440": 0.176772341132164, "14524": 0.5871354341506958, "14584": 0.1718502640724182, "14591": 0.47584590315818787, "14676": 0.040196798741817474, "14828": 0.7755908370018005, "14925": 0.732405424118042, "14996": 0.012615402229130268, "15059": 0.0354953333735466, "15581": 0.9186317324638367, "15770": 0.8255793452262878, "15924": 0.06337817758321762, "15946": 0.13243216276168823, "16012": 0.1913948506116867, "16036": 0.37371641397476196, "16081": 0.5784112811088562, "16233": 1.2432310581207275, "16285": 0.17759032547473907, "16341": 0.7500885725021362, "16360": 1.117316484451294, "16387": 0.8861536383628845, "16505": 0.036437395960092545, "16627": 0.2145126610994339, "16690": 0.026025565341114998, "16691": 0.28597161173820496, "16762": 0.2918238639831543, "16771": 0.09317722171545029, "16844": 1.2791962623596191, "16882": 0.8332487344741821, "16910": 0.1064341589808464, "16984": 0.18978065252304077, "17241": 0.9052929878234863, "17431": 0.12556517124176025, "17441": 0.4126010537147522, "17459": 0.7463917136192322, "17727": 0.7220231294631958, "17738": 0.31204116344451904, "17820": 0.02887592278420925, "17864": 0.0913962796330452, "17903": 0.23710809648036957, "17995": 0.1011524572968483, "18020": 0.0058422754518687725, "18094": 0.17840765416622162, "18322": 0.04674193635582924, "18340": 0.05139094591140747, "18714": 0.036437395960092545, "18969": 0.015504186972975731, "18976": 0.06246116757392883, "19293": 0.5347557663917542, "19335": 0.4151833653450012, "19341": 0.9425065517425537, "19362": 0.02792670577764511, "19518": 0.09406650811433792, "19653": 0.979118824005127, "19699": 0.02792670577764511, "19723": 1.3279863595962524, "19872": 0.16276304423809052, "20010": 0.12556517124176025, "20045": 1.6439902782440186, "20350": 0.055094651877880096, "20544": 0.6759096384048462, "20582": 0.7276995778083801, "20585": 0.7863243818283081, "20647": 1.1192315816879272, "20679": 0.9021284580230713, "20680": 0.007782140281051397, "20687": 0.5506471395492554, "20806": 0.7683706283569336, "21032": 0.09495500475168228, "21096": 0.20818853378295898, "21396": 0.6921701431274414, "21466": 0.1358480453491211, "21520": 0.6446255445480347, "21865": 0.07250232994556427, "21903": 0.09406650811433792, "21919": 0.3656192123889923, "21961": 0.19381128251552582, "21967": 0.30989447236061096, "22137": 0.29255300760269165, "22139": 0.0842406153678894, "22166": 1.013020396232605, "22170": 0.007782140281051397, "22303": 0.030771657824516296, "22415": 0.08782484382390976, "22422": 0.0797421783208847, "22471": 0.09850110858678818, "22618": 0.16110190749168396, "22663": 0.34370049834251404, "22785": 0.39893341064453125, "23150": 0.022212404757738113, "23216": 0.0606246218085289, "23339": 1.1249549388885498, "23737": 0.1602703034877777, "23818": 0.2034190446138382, "23858": 0.14433705806732178, "23924": 0.9650808572769165, "23946": 0.26446542143821716, "24054": 0.0354953333735466, "24104": 0.14939609169960022, "24269": 0.9944084882736206, "24278": 0.6128603219985962, "24374": 0.5816917419433594, "24454": 0.7791815400123596, "24501": 0.5827828645706177, "24576": 1.0101795196533203, "24587": 0.5914691090583801, "24710": 0.347847044467926, "24755": 0.20580662786960602, "24933": 0.2607102394104004, "25136": 0.26446542143821716, "25202": 0.15526613593101501, "25284": 0.02887592278420925, "25354": 1.0920805931091309, "25357": 0.6043586730957031, "25416": 0.1677299439907074, "25580": 0.03360854089260101, "25710": 0.05786345899105072, "25714": 0.5347557663917542, "25761": 0.24325250089168549, "25778": 0.07612881064414978, "25972": 0.9302552938461304, "26243": 0.46608972549438477, "26417": 0.5629584193229675, "26513": 0.1064341589808464, "26520": 0.06703783571720123, "26754": 1.0648454427719116, "27441": 1.3326339721679688, "27788": 0.16690383851528168, "27854": 0.8925741910934448, "27989": 0.13925230503082275, "28086": 0.1212492436170578, "28156": 0.39367714524269104, "28406": 0.09317722171545029, "28667": 0.7629209756851196, "29129": 0.12038381397724152, "29290": 0.5472630262374878} | 13481880 | Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous YAP/TAZ and induce conversion of cell fate. This provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element. | YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration |
{"1011": 0.19862671196460724, "1043": 0.7845434546470642, "1998": 0.19782574474811554, "1999": 0.053244512528181076, "2005": 0.16442140936851501, "2006": 0.20660123229026794, "2007": 0.31204116344451904, "2011": 0.2954642176628113, "2029": 0.29036402702331543, "2039": 0.04953393340110779, "2057": 0.04674193635582924, "2064": 0.0019512200960889459, "2071": 0.15359249711036682, "2076": 0.04207121208310127, "2078": 0.5151132941246033, "2090": 0.5584990978240967, "2104": 0.3615458607673645, "2109": 0.08692999184131622, "2112": 0.21687394380569458, "2119": 0.347847044467926, "2121": 0.19782574474811554, "2135": 0.7163142561912537, "2179": 0.036437395960092545, "2213": 0.9591107368469238, "2362": 0.06154331564903259, "2378": 0.18816383183002472, "2423": 0.28963330388069153, "2471": 0.13755162060260773, "2487": 0.6573580503463745, "2515": 0.08064348995685577, "2529": 0.37640097737312317, "2535": 0.05046287178993225, "2556": 0.0770333781838417, "2595": 0.03266380727291107, "2638": 0.37907835841178894, "2752": 0.14179791510105133, "2832": 0.23633737862110138, "2864": 0.3850763738155365, "2920": 0.08782484382390976, "2947": 0.15023678541183472, "2971": 0.06795065850019455, "2989": 0.8057082891464233, "2992": 0.43812891840934753, "3141": 0.4132472574710846, "3170": 0.034552380442619324, "3231": 0.1358480453491211, "3252": 0.36290550231933594, "3294": 0.030771657824516296, "3302": 0.8933739066123962, "3341": 0.5805994272232056, "3350": 0.791648268699646, "3370": 0.4770587682723999, "3375": 0.026025565341114998, "3378": 0.12728634476661682, "3424": 0.8957691192626953, "3445": 0.637939989566803, "3466": 0.18816383183002472, "3490": 0.3824150264263153, "3491": 0.1693800985813141, "3526": 0.8135309815406799, "3563": 0.08692999184131622, "3623": 0.6533012986183167, "3625": 0.6502478122711182, "3652": 0.026025565341114998, "3659": 0.9827804565429688, "3670": 0.9363996982574463, "3711": 0.09672962874174118, "3739": 0.6286086440086365, "3785": 0.4574742913246155, "3853": 0.3601844012737274, "3879": 0.02412080205976963, "3896": 0.01934296265244484, "3930": 0.08603433519601822, "3936": 0.11343330889940262, "4015": 0.03925827145576477, "4072": 0.2637155055999756, "4135": 0.08064348995685577, "4146": 0.09584271162748337, "4195": 0.4926934838294983, "4246": 0.8074519634246826, "4286": 0.29109421372413635, "4442": 0.9037119746208191, "4539": 0.10555581003427505, "4593": 0.3662964701652527, "4632": 0.6598852276802063, "4650": 0.1064341589808464, "4651": 0.036437395960092545, "4668": 0.2830325961112976, "4671": 0.2954642176628113, "4685": 0.1384023278951645, "4710": 0.46608972549438477, "4748": 0.8306987881660461, "4758": 0.2837681770324707, "4852": 0.24171993136405945, "4866": 0.1229778528213501, "4921": 1.0478670597076416, "4958": 0.5116065740585327, "4961": 0.6317287683486938, "4982": 0.21372433006763458, "5090": 0.10467668622732162, "5127": 0.0058422754518687725, "5159": 0.4067663550376892, "5228": 0.6533012986183167, "5244": 0.2607102394104004, "5250": 0.28450319170951843, "5333": 0.34508460760116577, "5449": 0.11604541540145874, "5498": 0.8298473954200745, "5548": 0.11691460013389587, "5566": 0.7737906575202942, "5699": 0.37907835841178894, "5769": 0.15023678541183472, "5967": 0.2223619967699051, "5994": 0.040196798741817474, "6083": 0.07793712615966797, "6135": 0.3883931338787079, "6177": 0.5528968572616577, "6194": 0.12038381397724152, "6274": 0.12728634476661682, "6296": 0.19622190296649933, "6310": 0.8813109993934631, "6592": 0.3241194784641266, "6637": 0.06154331564903259, "6657": 0.841701865196228, "6693": 0.7352184057235718, "6698": 0.9987343549728394, "6726": 0.7201237678527832, "6822": 0.2969166338443756, "6827": 0.48610860109329224, "6922": 0.3443928062915802, "6947": 0.3191637098789215, "6970": 0.7951818704605103, "6980": 0.029824240133166313, "7065": 0.2409527748823166, "7275": 0.0038986403960734606, "7297": 0.23556606471538544, "7337": 0.36290550231933594, "7356": 0.05970508232712746, "7366": 0.1889725625514984, "7457": 0.4764525294303894, "7461": 0.15943801403045654, "7542": 0.6862877607345581, "7551": 0.06612417846918106, "7645": 0.6482070088386536, "7704": 0.022212404757738113, "7711": 0.35677260160446167, "7772": 0.7537717819213867, "7816": 0.20818853378295898, "7885": 0.12470348179340363, "7901": 0.6624060273170471, "7926": 0.7755908370018005, "7934": 0.848413348197937, "7949": 0.23402166366577148, "8000": 0.034552380442619324, "8031": 0.9363996982574463, "8102": 1.3499990701675415, "8153": 0.28743788599967957, "8171": 0.13499516248703003, "8185": 0.9348671436309814, "8247": 0.9155091643333435, "8278": 0.25239890813827515, "8279": 0.0038986403960734606, "8290": 0.8357921838760376, "8319": 0.15023678541183472, "8332": 0.2719337046146393, "8360": 0.7951818704605103, "8458": 0.3930181860923767, "8553": 0.0913962796330452, "8663": 0.7755908370018005, "8776": 0.14686977863311768, "8878": 0.176772341132164, "8902": 1.0409941673278809, "8939": 0.75193190574646, "9007": 0.5427330136299133, "9308": 0.056018441915512085, "9359": 1.1089750528335571, "9412": 0.13925230503082275, "9597": 0.04953393340110779, "9972": 0.5778634548187256, "10085": 0.5651806592941284, "10266": 0.9857001900672913, "10358": 0.025073638185858727, "10496": 0.950843095779419, "10509": 0.034552380442619324, "10572": 0.8212929964065552, "10580": 0.2954642176628113, "10595": 0.016465263441205025, "10708": 0.0317181795835495, "10737": 0.00875066313892603, "10738": 0.01934296265244484, "10744": 0.08871890604496002, "10803": 0.7701805830001831, "10804": 1.034073829650879, "10985": 0.04953393340110779, "11156": 0.07250232994556427, "11211": 0.0029254043474793434, "11311": 0.21135559678077698, "11423": 0.35813871026039124, "11627": 0.16276304423809052, "11674": 0.8829278349876404, "11721": 0.10906458646059036, "11835": 0.6405166387557983, "11860": 0.41647201776504517, "11873": 0.13925230503082275, "11949": 0.04767346754670143, "12016": 0.23247487843036652, "12031": 0.013579257763922215, "12115": 0.02316705882549286, "12123": 0.12470348179340363, "12222": 0.684319257736206, "12328": 0.14518201351165771, "12562": 0.018384648486971855, "12719": 0.40351006388664246, "13070": 0.2667117714881897, "13275": 0.10291612148284912, "13330": 0.14179791510105133, "13341": 0.3141832649707794, "13423": 0.06246116757392883, "13594": 0.175953671336174, "13712": 0.7239188551902771, "13722": 0.4831010699272156, "13791": 0.19782574474811554, "13833": 0.1221139207482338, "13910": 0.8829278349876404, "13922": 0.1401015669107437, "14026": 0.5313173532485962, "14037": 0.0029254043474793434, "14061": 0.5461324453353882, "14080": 0.6684301495552063, "14187": 0.5069117546081543, "14190": 0.3170322775840759, "14234": 0.48850810527801514, "14313": 0.10379679501056671, "14449": 0.1905880719423294, "14613": 0.0174254160374403, "14774": 0.09672962874174118, "14905": 0.21135559678077698, "14997": 0.05786345899105072, "15057": 0.0354953333735466, "15115": 0.35060185194015503, "15176": 0.40089741349220276, "15191": 1.0560526847839355, "15423": 0.08244366943836212, "15431": 0.09228714555501938, "15453": 0.956112265586853, "15527": 0.15943801403045654, "15663": 0.36358460783958435, "15900": 0.037378571927547455, "15946": 0.10026945173740387, "16059": 0.10026945173740387, "16081": 0.6000806093215942, "16098": 0.04860413447022438, "16216": 0.029824240133166313, "16221": 0.1994270235300064, "16285": 0.2478361576795578, "16305": 0.04487626627087593, "16341": 0.49030399322509766, "16351": 1.2932277917861938, "16389": 0.13414156436920166, "16649": 0.0058422754518687725, "16691": 0.25845035910606384, "16783": 0.12642613053321838, "16882": 0.3325583338737488, "16930": 0.026976587250828743, "16983": 1.1255888938903809, "17009": 0.3464667797088623, "17250": 0.9194108247756958, "17379": 0.1994270235300064, "17491": 1.4847954511642456, "18142": 0.2531573474407196, "18259": 0.0174254160374403, "18411": 0.034552380442619324, "18423": 0.7987030148506165, "18622": 0.11517547070980072, "18714": 0.06703783571720123, "19157": 0.669430673122406, "19241": 0.11168810725212097, "19476": 1.0735615491867065, "19601": 0.05970508232712746, "19653": 0.7086513638496399, "19739": 0.0752234235405922, "19818": 0.26296505331993103, "19872": 0.9591107368469238, "19933": 0.1905880719423294, "20014": 0.6867793202400208, "20030": 0.03925827145576477, "20303": 1.2358801364898682, "20544": 0.04207121208310127, "20582": 0.2160874605178833, "20594": 0.4425300657749176, "20679": 0.9987343549728394, "20766": 0.03266380727291107, "20806": 0.2531573474407196, "20817": 0.609149694442749, "20861": 0.49864232540130615, "21101": 0.01934296265244484, "21104": 0.04953393340110779, "21297": 1.1971133947372437, "21412": 0.1401015669107437, "21466": 0.04953393340110779, "21471": 1.2916187047958374, "21520": 0.3388410806655884, "21575": 0.07431721687316895, "21579": 0.7445381283760071, "21670": 0.02792670577764511, "21766": 0.9333322048187256, "21778": 0.029824240133166313, "21877": 0.2689530849456787, "21903": 0.009718249551951885, "21935": 0.27342069149017334, "22014": 0.6729245185852051, "22476": 0.10906458646059036, "22500": 0.04394211992621422, "22658": 0.36358460783958435, "22916": 0.7258110046386719, "22931": 1.0641717910766602, "23041": 0.2493593990802765, "23150": 0.025073638185858727, "23163": 0.5438674688339233, "23216": 0.11604541540145874, "23277": 0.03266380727291107, "23316": 0.11778303235769272, "23586": 0.9591107368469238, "23758": 1.0409941673278809, "23797": 0.0009760859538801014, "23848": 0.6512666940689087, "24012": 0.7809720039367676, "24054": 0.7610978484153748, "24345": 0.2160874605178833, "24587": 0.8143964409828186, "24635": 0.7258110046386719, "24720": 0.11691460013389587, "24755": 1.12241530418396, "24879": 0.09317722171545029, "24972": 0.7047978043556213, "25194": 0.06703783571720123, "25238": 0.3662964701652527, "25276": 0.9621002674102783, "25293": 0.016465263441205025, "25456": 0.5827828645706177, "25714": 0.42735910415649414, "25817": 0.013579257763922215, "26228": 0.0174254160374403, "26244": 0.08782484382390976, "26396": 0.16524957120418549, "26402": 1.1070401668548584, "26419": 0.23556606471538544, "26651": 0.05786345899105072, "26723": 0.9363996982574463, "26773": 0.5267143249511719, "27169": 0.015504186972975731, "27321": 0.08692999184131622, "27391": 0.03925827145576477, "27633": 0.5957841277122498, "27781": 1.1456648111343384, "27895": 0.4113073945045471, "28031": 0.29328158497810364, "28041": 0.056018441915512085, "28309": 0.012615402229130268, "28579": 0.8195732831954956, "28788": 0.8965662121772766, "28873": 0.4400174915790558, "29090": 0.8091925978660583, "29105": 0.757441520690918, "29107": 0.20580662786960602, "29226": 0.06520967930555344, "29235": 0.44753631949424744, "29290": 0.3012613356113434, "29489": 0.15693697333335876, "29490": 0.34300774335861206} | 13492264 | Glomerular basement membrane (GBM) and podocalyxin are essential for podocyte morphology. We provide evidence of functional interconnections between basement membrane components (collagen IV and laminin), the expression of podocalyxin and the morphology of human glomerular epithelial cells (podocytes). We demonstrated that GBM and laminin, but not collagen IV, up-regulated the expression of podocalyxin. Scanning electron microscopy revealed that laminin induced a modified morphology of podocytes with process formation, which was more extensive in the presence of GBM. Under high magnification, podocytes appeared ruffled. Using transmission electron microscopy we observed that raised areas occurred in the basal cell surface. Furthermore, the presence of anti-podocalyxin antibody increased the extent of adhesion and spreading of podocytes to both collagen IV and laminin, thus podocalyxin apparently inhibits cell-matrix interactions. We also performed adhesion and spreading assays on podocytes grown under increased glucose concentration (25 mM). Under these conditions, the expression of podocalyxin was almost totally suppressed. The cells adhered and spread to basement membrane components but there was no increase in the extent of adhesion and spreading in the presence of anti-podocalyxin antibody, or ruffling of the cell edges. Additionally, in podocytes expressing podocalyxin, the presence of anti-podocalyxin antibody partially reversed the inhibition of adhesion to collagen IV provoked by anti-beta1 integrin antibody, thus podocalyxin should compete with beta1-related cell adhesion. We suggest that the observed podocalyxin-mediated inhibition of binding to the matrix could be in part responsible for the specialized conformation of the basal surface of podocytes. | Summary |
{"1012": 0.15777134895324707, "1013": 0.2516399025917053, "1049": 1.3118107318878174, "1054": 0.613389253616333, "2003": 0.469759464263916, "2015": 0.28155985474586487, "2033": 0.22704219818115234, "2054": 0.12556517124176025, "2079": 0.14686977863311768, "2088": 0.25845035910606384, "2109": 0.21765978634357452, "2140": 0.5827828645706177, "2171": 0.3519764244556427, "2213": 0.1619328260421753, "2224": 0.2034190446138382, "2226": 0.7398891448974609, "2309": 0.7276995778083801, "2326": 0.1734936386346817, "2339": 0.28670501708984375, "2361": 0.18329764902591705, "2378": 0.4574742913246155, "2451": 0.32764431834220886, "2460": 0.3269403576850891, "2470": 0.17431432008743286, "2478": 0.030771657824516296, "2515": 0.1913948506116867, "2532": 0.10906458646059036, "2565": 0.23015019297599792, "2578": 0.06246116757392883, "2592": 0.34922540187835693, "2609": 0.5370414853096008, "2671": 0.2983669638633728, "2720": 0.4412745535373688, "2771": 0.13414156436920166, "2777": 0.5162794589996338, "2800": 0.5267143249511719, "2819": 0.010684899985790253, "2838": 0.010684899985790253, "2892": 0.1930064558982849, "2897": 0.25845035910606384, "2898": 0.3810817003250122, "2943": 0.17431432008743286, "2951": 0.15860503911972046, "2974": 0.04487626627087593, "3024": 0.0606246218085289, "3073": 0.29473719000816345, "3075": 0.38174858689308167, "3085": 0.11865071207284927, "3120": 0.0019512200960889459, "3125": 0.4537591338157654, "3141": 0.1221139207482338, "3193": 0.18167030811309814, "3217": 0.7067264318466187, "3229": 0.7153595685958862, "3233": 0.011650617234408855, "3252": 0.7755908370018005, "3260": 0.1693800985813141, "3274": 0.3547199070453644, "3289": 0.25088030099868774, "3291": 0.14095009863376617, "3366": 0.058784693479537964, "3385": 0.1485546976327896, "3417": 0.6420594453811646, "3461": 0.4879087805747986, "3487": 0.03831886500120163, "3594": 0.016465263441205025, "3615": 0.10379679501056671, "3619": 0.20421554148197174, "3640": 0.2969166338443756, "3677": 0.26146242022514343, "3698": 0.1229778528213501, "3733": 0.6181373596191406, "3745": 0.1229778528213501, "3784": 0.1913948506116867, "3800": 0.5021947622299194, "3853": 0.08782484382390976, "3905": 0.9432673454284668, "3931": 0.3077431619167328, "3945": 0.18329764902591705, "3968": 0.8298473954200745, "3989": 0.6451379656791687, "4007": 1.013020396232605, "4014": 0.04674193635582924, "4037": 0.6754127144813538, "4045": 0.4444103240966797, "4089": 0.25694093108177185, "4132": 0.176772341132164, "4140": 0.5762182474136353, "4219": 0.022212404757738113, "4274": 0.6989894509315491, "4346": 0.10026945173740387, "4539": 0.13755162060260773, "4573": 0.4400174915790558, "4646": 0.7009293437004089, "4717": 0.09317722171545029, "4730": 0.2447827309370041, "4757": 0.14939609169960022, "4773": 1.2313295602798462, "4800": 0.2969166338443756, "4853": 0.09761575609445572, "4874": 0.0797421783208847, "4876": 0.5865923762321472, "4877": 0.052318159490823746, "4957": 0.3070250153541565, "4962": 0.31560876965522766, "5003": 0.3877306580543518, "5090": 0.40546512603759766, "5097": 0.6729245185852051, "5104": 0.09317722171545029, "5198": 0.043007105588912964, "5244": 0.1685553640127182, "5310": 0.38041436672210693, "5415": 0.08603433519601822, "5436": 0.5051454305648804, "5449": 0.31132611632347107, "5537": 0.5930894017219543, "5577": 0.19622190296649933, "5658": 0.043007105588912964, "5682": 0.026025565341114998, "5796": 0.5232481360435486, "5884": 0.28450319170951843, "5906": 0.11865071207284927, "6026": 0.3304552733898163, "6064": 0.987156867980957, "6075": 0.6588751673698425, "6082": 0.22937409579753876, "6093": 0.08782484382390976, "6131": 0.48068851232528687, "6179": 0.053244512528181076, "6235": 0.026025565341114998, "6299": 0.4349733293056488, "6412": 0.015504186972975731, "6434": 0.3084607720375061, "6529": 0.21293537318706512, "6614": 0.17431432008743286, "6648": 0.3077431619167328, "6742": 0.009718249551951885, "6804": 0.1384023278951645, "6851": 0.13157635927200317, "6897": 0.25239890813827515, "6971": 0.07159364968538284, "6994": 0.12038381397724152, "6999": 1.133164644241333, "7155": 0.09584271162748337, "7159": 0.18816383183002472, "7248": 0.011650617234408855, "7366": 0.43812891840934753, "7396": 0.38441169261932373, "7403": 0.2622140049934387, "7479": 0.5290185213088989, "7588": 0.040196798741817474, "7610": 0.17922431230545044, "7801": 0.4624064862728119, "7809": 0.6000806093215942, "7848": 0.09406650811433792, "7861": 0.06246116757392883, "7863": 0.9769153594970703, "7875": 0.0058422754518687725, "7908": 0.33675122261047363, "8010": 0.7220231294631958, "8031": 0.04207121208310127, "8043": 0.5313173532485962, "8059": 0.3547199070453644, "8171": 0.04674193635582924, "8197": 0.7683706283569336, "8241": 1.3149620294570923, "8278": 0.7239188551902771, "8299": 0.9363996982574463, "8316": 0.3743882179260254, "8332": 0.42353010177612305, "8382": 0.13157635927200317, "8545": 0.14518201351165771, "8553": 0.28670501708984375, "8704": 0.013579257763922215, "8737": 0.029824240133166313, "8756": 0.11778303235769272, "8778": 0.3297532796859741, "8831": 0.07068414986133575, "8833": 0.03925827145576477, "8860": 0.09850110858678818, "8893": 0.9021284580230713, "8917": 0.23556606471538544, "9007": 0.13243216276168823, "9108": 0.2501201331615448, "9140": 0.08782484382390976, "9189": 0.052318159490823746, "9292": 0.09495500475168228, "9388": 0.18248429894447327, "9445": 0.9240728616714478, "9447": 0.2852376699447632, "9586": 0.014542185701429844, "9587": 0.011650617234408855, "9625": 0.562402069568634, "9628": 0.07068414986133575, "9710": 0.1477125883102417, "9936": 0.53589928150177, "10047": 0.11081436276435852, "10057": 0.0058422754518687725, "10071": 0.5074998140335083, "10343": 0.3241194784641266, "10371": 1.6439902782440186, "10439": 0.4873090982437134, "10539": 0.3723714053630829, "10566": 0.052318159490823746, "10629": 0.2493593990802765, "10636": 0.0019512200960889459, "10671": 1.1115491390228271, "10732": 0.07431721687316895, "10737": 0.006812678650021553, "10752": 0.16524957120418549, "10856": 0.014542185701429844, "10923": 0.3622259199619293, "11022": 0.1685553640127182, "11028": 0.036437395960092545, "11038": 0.11604541540145874, "11047": 0.5930894017219543, "11089": 0.13755162060260773, "11100": 0.6405166387557983, "11157": 0.12470348179340363, "11226": 0.5707147121429443, "11338": 0.469759464263916, "11343": 0.38041436672210693, "11460": 0.22626367211341858, "11603": 0.03266380727291107, "11744": 0.23710809648036957, "11890": 0.6828403472900391, "11909": 0.5209306478500366, "11985": 0.12728634476661682, "12066": 0.7018978595733643, "12105": 0.14095009863376617, "12395": 0.3601844012737274, "12504": 0.053244512528181076, "12616": 0.2696990668773651, "12702": 0.09672962874174118, "12737": 0.35334911942481995, "12745": 1.2070930004119873, "12789": 0.11517547070980072, "12868": 0.3141832649707794, "12987": 1.173231601715088, "13103": 0.0019512200960889459, "13139": 0.2800849378108978, "13159": 0.06429435312747955, "13164": 0.2822965085506439, "13221": 0.14264501631259918, "13434": 0.10026945173740387, "13458": 0.3883931338787079, "13523": 0.10379679501056671, "13578": 0.25845035910606384, "13704": 0.1946154683828354, "13759": 0.5404602885246277, "13922": 0.0913962796330452, "13972": 0.1510767638683319, "14048": 0.13157635927200317, "14119": 0.42225050926208496, "14160": 0.14518201351165771, "14163": 0.0354953333735466, "14193": 0.28597161173820496, "14336": 0.30486753582954407, "14471": 0.0174254160374403, "14540": 0.1751343309879303, "14719": 0.053244512528181076, "14811": 0.7305257320404053, "14851": 0.0770333781838417, "14876": 0.8298473954200745, "14903": 1.1051015853881836, "14966": 0.13499516248703003, "14981": 0.10291612148284912, "15006": 0.06703783571720123, "15058": 0.16607704758644104, "15148": 0.043007105588912964, "15258": 0.6872705817222595, "15338": 0.4425300657749176, "15439": 0.8492490649223328, "15577": 0.9037119746208191, "15895": 0.36697331070899963, "16001": 0.1602703034877777, "16012": 0.8973627090454102, "16014": 0.25088030099868774, "16129": 0.3877306580543518, "16137": 0.5151132941246033, "16281": 0.016465263441205025, "16285": 0.14433705806732178, "16403": 0.06429435312747955, "16602": 0.5696102976799011, "16706": 0.02412080205976963, "16744": 0.052318159490823746, "16770": 0.40611594915390015, "16914": 0.512191891670227, "17012": 0.05786345899105072, "17547": 0.5272908806800842, "17592": 0.4145384132862091, "17782": 0.04767346754670143, "17928": 0.2881702482700348, "18150": 0.10993985831737518, "18589": 0.034552380442619324, "18726": 0.23092569410800934, "19287": 0.09317722171545029, "19386": 0.5584990978240967, "19464": 0.15610189735889435, "19500": 0.04860413447022438, "19587": 0.1677299439907074, "19706": 0.4926934838294983, "19842": 0.4788752794265747, "19875": 0.40285754203796387, "19968": 0.0797421783208847, "20137": 0.19622190296649933, "20236": 0.41195443272590637, "20287": 0.44566190242767334, "20353": 0.5528968572616577, "20470": 0.10026945173740387, "20477": 0.33605360984802246, "20528": 0.09850110858678818, "20699": 0.20739519596099854, "20906": 0.35403475165367126, "20932": 0.22157983481884003, "20950": 0.0770333781838417, "21021": 0.35813871026039124, "21025": 0.011650617234408855, "21186": 0.5438674688339233, "21197": 0.07159364968538284, "21246": 0.09495500475168228, "21477": 0.07159364968538284, "21508": 1.0901126861572266, "21647": 0.41840189695358276, "22026": 0.11168810725212097, "22318": 0.08603433519601822, "22409": 0.34300774335861206, "22419": 0.06703783571720123, "22498": 0.6254787445068359, "22747": 0.26296505331993103, "22822": 0.15860503911972046, "23376": 0.319873183965683, "23561": 0.12556517124176025, "23767": 0.777387797832489, "23848": 0.030771657824516296, "23947": 0.29400965571403503, "23959": 0.5947071313858032, "24098": 0.04767346754670143, "24203": 0.13755162060260773, "24471": 0.9739698171615601, "24540": 0.06703783571720123, "24558": 0.5393219590187073, "24635": 0.22079704701900482, "25003": 0.23092569410800934, "25022": 0.21214580535888672, "25426": 0.0770333781838417, "25524": 0.36967599391937256, "25525": 0.7809720039367676, "25551": 0.36494144797325134, "25743": 0.13670019805431366, "25856": 0.18411032855510712, "26098": 0.04674193635582924, "26458": 0.9739698171615601, "26601": 0.23247487843036652, "26703": 0.00875066313892603, "27347": 0.0009760859538801014, "27388": 0.6048921346664429, "27650": 0.176772341132164, "28247": 0.23556606471538544, "28433": 0.12642613053321838, "28616": 0.175953671336174, "28848": 0.4891071021556854, "29061": 0.3416208028793335, "29098": 0.04767346754670143, "29458": 0.3810817003250122} | 13494853 | The abbreviated name, 'mfold web server', describes a number of closely related software applications available on the World Wide Web (WWW) for the prediction of the secondary structure of single stranded nucleic acids. The objective of this web server is to provide easy access to RNA and DNA folding and hybridization software to the scientific community at large. By making use of universally available web GUIs (Graphical User Interfaces), the server circumvents the problem of portability of this software. Detailed output, in the form of structure plots with or without reliability information, single strand frequency plots and 'energy dot plots', are available for the folding of single sequences. A variety of 'bulk' servers give less information, but in a shorter time and for up to hundreds of sequences at once. The portal for the mfold web server is http://www.bioinfo.rpi.edu/applications/mfold. This URL will be referred to as 'MFOLDROOT'. | Mfold web server for nucleic acid folding and hybridization prediction |
{"1050": 0.32270604372024536, "2022": 0.08871890604496002, "2043": 0.23402166366577148, "2058": 0.020300358533859253, "2086": 0.5438674688339233, "2088": 0.045809537172317505, "2095": 0.1751343309879303, "2109": 0.07612881064414978, "2111": 0.20660123229026794, "2119": 0.24401791393756866, "2129": 0.056018441915512085, "2146": 0.3883931338787079, "2157": 0.42416930198669434, "2158": 0.5701626539230347, "2166": 0.5607312321662903, "2187": 0.5364705324172974, "2192": 1.3144375085830688, "2214": 0.6011518239974976, "2217": 0.28963330388069153, "2273": 0.7827593088150024, "2287": 1.1941591501235962, "2303": 0.48008447885513306, "2308": 0.8649974465370178, "2313": 0.12384103983640671, "2322": 0.5903874635696411, "2323": 0.0842406153678894, "2373": 0.0354953333735466, "2382": 0.06612417846918106, "2398": 1.1994705200195312, "2408": 0.401551216840744, "2421": 0.07884006202220917, "2443": 0.05417001247406006, "2450": 0.7445381283760071, "2462": 0.037378571927547455, "2470": 0.30558720231056213, "2478": 0.16110190749168396, "2486": 0.1358480453491211, "2502": 0.04113444685935974, "2529": 0.3346569836139679, "2575": 0.43875885009765625, "2583": 0.151916041970253, "2592": 0.23402166366577148, "2595": 0.26146242022514343, "2597": 0.45251765847206116, "2607": 0.36426326632499695, "2608": 0.7163142561912537, "2611": 0.04767346754670143, "2641": 0.01934296265244484, "2660": 0.12814582884311676, "2676": 0.36900100111961365, "2682": 0.07341018319129944, "2710": 0.7863243818283081, "2711": 0.10818854719400406, "2740": 0.15526613593101501, "2756": 0.1734936386346817, "2779": 0.40806588530540466, "2812": 0.1619328260421753, "2817": 0.5795059204101562, "2819": 0.11256109178066254, "2825": 0.26446542143821716, "2828": 0.15023678541183472, "2844": 0.9455460906028748, "2846": 0.8450632095336914, "2849": 0.9379299283027649, "2898": 0.3381449282169342, "2907": 0.1685553640127182, "2913": 0.43244171142578125, "2931": 0.6338034868240356, "2937": 0.24018502235412598, "2946": 0.603290855884552, "2951": 0.5995445251464844, "3010": 0.5562619566917419, "3026": 0.020300358533859253, "3057": 0.055094651877880096, "3080": 0.2223619967699051, "3082": 0.06795065850019455, "3091": 0.7201237678527832, "3093": 0.7647408246994019, "3115": 0.24859806895256042, "3125": 0.06337817758321762, "3133": 0.030771657824516296, "3141": 0.0842406153678894, "3174": 0.151916041970253, "3231": 0.18411032855510712, "3244": 0.1510767638683319, "3273": 0.2607102394104004, "3276": 0.30917787551879883, "3284": 0.36290550231933594, "3287": 0.5033760666847229, "3289": 0.07431721687316895, "3337": 0.06977381557226181, "3348": 0.4419025182723999, "3362": 0.1064341589808464, "3378": 0.0752234235405922, "3401": 0.03266380727291107, "3463": 0.3883931338787079, "3486": 0.5336109399795532, "3491": 0.12556517124176025, "3512": 0.3353555500507355, "3556": 0.7408206462860107, "3558": 0.06977381557226181, "3563": 0.417115718126297, "3593": 0.37640097737312317, "3617": 0.4500300884246826, "3621": 0.17020416259765625, "3635": 0.7827593088150024, "3643": 0.7295845746994019, "3671": 0.255429208278656, "3742": 0.5893046259880066, "3747": 0.5789587497711182, "3767": 0.46363574266433716, "3800": 0.5893046259880066, "3801": 0.5887627601623535, "3867": 0.08154398202896118, "3893": 0.6027565002441406, "3928": 0.27934664487838745, "3977": 0.11865071207284927, "3991": 0.1930064558982849, "3997": 1.2910817861557007, "4007": 0.42416930198669434, "4012": 0.18329764902591705, "4029": 0.48430517315864563, "4090": 0.1064341589808464, "4094": 0.30989447236061096, "4098": 0.025073638185858727, "4102": 0.37304413318634033, "4106": 0.4412745535373688, "4118": 0.43244171142578125, "4139": 0.0752234235405922, "4146": 0.05786345899105072, "4206": 0.37371641397476196, "4245": 0.5506471395492554, "4286": 0.1913948506116867, "4292": 0.24171993136405945, "4340": 0.18167030811309814, "4344": 0.6128603219985962, "4358": 0.06429435312747955, "4375": 0.6075552701950073, "4389": 0.2696990668773651, "4424": 0.08871890604496002, "4431": 0.777387797832489, "4503": 0.16110190749168396, "4523": 0.11604541540145874, "4555": 0.2493593990802765, "4561": 0.1221139207482338, "4577": 0.043007105588912964, "4578": 0.4337083101272583, "4601": 0.2954642176628113, "4607": 0.022212404757738113, "4639": 0.7791815400123596, "4646": 0.006812678650021553, "4672": 0.5461324453353882, "4700": 0.6011518239974976, "4705": 0.7960633039474487, "4725": 0.5584990978240967, "4749": 0.35334911942481995, "4781": 0.03925827145576477, "4793": 0.603290855884552, "5012": 0.1229778528213501, "5047": 0.09050461649894714, "5105": 0.11256109178066254, "5159": 0.15023678541183472, "5300": 0.5562619566917419, "5306": 0.010684899985790253, "5340": 0.37707099318504333, "5345": 0.6613984704017639, "5387": 0.5685047507286072, "5410": 0.18816383183002472, "5447": 0.680370569229126, "5468": 0.6857960224151611, "5535": 0.4770587682723999, "5548": 0.06154331564903259, "5566": 0.016465263441205025, "5604": 0.09406650811433792, "5646": 0.4518963396549225, "5682": 0.18248429894447327, "5761": 0.4248080551624298, "5790": 0.2607102394104004, "5876": 0.6533012986183167, "5907": 1.0073304176330566, "5950": 0.6793810129165649, "6001": 0.9287132620811462, "6011": 0.26146242022514343, "6020": 0.07612881064414978, "6022": 0.1693800985813141, "6024": 0.3241194784641266, "6146": 0.38574060797691345, "6179": 0.43244171142578125, "6218": 1.27701997756958, "6321": 0.2576959431171417, "6333": 0.0038986403960734606, "6383": 0.04767346754670143, "6428": 0.7018978595733643, "6459": 0.7389566898345947, "6463": 0.6456501483917236, "6480": 0.4248080551624298, "6584": 0.0058422754518687725, "6601": 0.4067663550376892, "6612": 0.14518201351165771, "6614": 0.5707147121429443, "6638": 0.2539152204990387, "6650": 0.009718249551951885, "6705": 0.11778303235769272, "6721": 0.02316705882549286, "6723": 0.045809537172317505, "6747": 0.2247048318386078, "6749": 0.22079704701900482, "6817": 0.20660123229026794, "6914": 0.5584990978240967, "6950": 0.045809537172317505, "6970": 0.6286086440086365, "7017": 0.3464667797088623, "7023": 0.1905880719423294, "7038": 0.0913962796330452, "7066": 0.5151132941246033, "7091": 0.14179791510105133, "7142": 0.1384023278951645, "7172": 0.0770333781838417, "7189": 0.18654440343379974, "7223": 0.9115922451019287, "7345": 0.4425300657749176, "7361": 0.2501201331615448, "7444": 0.8813109993934631, "7446": 0.19381128251552582, "7461": 0.04953393340110779, "7551": 0.28743788599967957, "7594": 0.6793810129165649, "7604": 0.2576959431171417, "7633": 0.03925827145576477, "7639": 0.6613984704017639, "7644": 0.6165571808815002, "7704": 0.39367714524269104, "7718": 0.18492233753204346, "7778": 0.19622190296649933, "7809": 0.045809537172317505, "7823": 0.09850110858678818, "7831": 0.7683706283569336, "7863": 0.5523349046707153, "7885": 0.12642613053321838, "7965": 0.6118015646934509, "8023": 0.6286086440086365, "8092": 0.2969166338443756, "8093": 0.7809720039367676, "8137": 0.3262358605861664, "8186": 0.02887592278420925, "8213": 0.40481385588645935, "8281": 0.40481385588645935, "8321": 0.7737906575202942, "8358": 0.4770587682723999, "8386": 0.6027565002441406, "8483": 0.5057345628738403, "8487": 0.15860503911972046, "8522": 0.45623743534088135, "8553": 0.3381449282169342, "8599": 0.14602625370025635, "8699": 0.77198725938797, "8704": 0.06703783571720123, "8787": 0.7987030148506165, "8991": 0.0606246218085289, "8992": 0.036437395960092545, "8999": 0.28963330388069153, "9044": 0.05786345899105072, "9211": 0.13157635927200317, "9312": 0.013579257763922215, "9349": 0.21372433006763458, "9381": 0.151916041970253, "9397": 0.0058422754518687725, "9398": 0.04113444685935974, "9463": 0.06246116757392883, "9486": 0.2447827309370041, "9539": 0.036437395960092545, "9556": 0.2409527748823166, "9646": 0.1808556467294693, "9671": 0.18248429894447327, "9672": 0.3339579105377197, "9723": 0.08782484382390976, "9750": 0.4794800877571106, "9765": 0.19381128251552582, "9854": 0.3262358605861664, "10035": 0.09317722171545029, "10173": 0.6086184978485107, "10174": 0.2184450328350067, "10197": 0.2231435477733612, "10238": 0.15526613593101501, "10426": 0.6170841455459595, "10473": 0.7105726003646851, "10502": 0.7978238463401794, "10539": 0.27786844968795776, "10616": 0.861702561378479, "10629": 0.02316705882549286, "10640": 0.7791815400123596, "10651": 0.3241194784641266, "10702": 0.04860413447022438, "10742": 0.19782574474811554, "10817": 0.030771657824516296, "10826": 0.16524957120418549, "10843": 0.3318578004837036, "10857": 0.7408206462860107, "10903": 0.6634125709533691, "11025": 0.02316705882549286, "11100": 0.36358460783958435, "11179": 0.5069117546081543, "11207": 0.0038986403960734606, "11251": 0.18654440343379974, "11265": 0.637939989566803, "11373": 0.0317181795835495, "11380": 0.5341835021972656, "11433": 0.22157983481884003, "11514": 1.036847710609436, "11647": 0.004870930220931768, "11702": 0.4855078160762787, "11709": 0.812664806842804, "11718": 0.02792670577764511, "11774": 0.18004031479358673, "11802": 0.22782009840011597, "11875": 0.28890204429626465, "11890": 0.5438674688339233, "12150": 0.6202403903007507, "12177": 0.14518201351165771, "12332": 0.10026945173740387, "12435": 0.3297532796859741, "12515": 0.11691460013389587, "12520": 0.41840189695358276, "12589": 0.4950772523880005, "12596": 0.25694093108177185, "12826": 0.3325583338737488, "12832": 0.34370049834251404, "12848": 0.7827593088150024, "12919": 0.42608439922332764, "12955": 0.28597161173820496, "13015": 0.6461620330810547, "13373": 0.10818854719400406, "13483": 0.025073638185858727, "13513": 0.42990362644195557, "13599": 0.347847044467926, "13690": 0.17759032547473907, "13811": 1.1381834745407104, "13912": 0.7115318179130554, "13940": 0.7500885725021362, "14125": 0.2837681770324707, "14155": 0.04767346754670143, "14161": 0.1889725625514984, "14171": 0.42608439922332764, "14267": 0.17840765416622162, "14273": 0.1602703034877777, "14280": 0.10731173306703568, "14343": 0.22782009840011597, "14375": 0.22704219818115234, "14405": 0.9186317324638367, "14409": 0.06154331564903259, "14412": 0.22859740257263184, "14639": 0.021256839856505394, "14761": 0.8013357520103455, "14798": 0.25845035910606384, "14983": 0.12038381397724152, "15020": 0.10993985831737518, "15141": 0.16442140936851501, "15258": 0.3777405619621277, "15291": 0.06886265426874161, "15295": 0.23247487843036652, "15306": 0.4537591338157654, "15457": 0.5232481360435486, "15486": 0.16607704758644104, "15502": 0.0606246218085289, "15517": 0.0842406153678894, "15578": 0.6734226942062378, "15596": 0.029824240133166313, "15871": 0.1358480453491211, "15873": 0.24018502235412598, "15913": 0.3485364317893982, "15995": 0.10467668622732162, "16003": 0.18492233753204346, "16014": 0.9178520441055298, "16083": 0.31489628553390503, "16111": 0.3163207769393921, "16134": 0.4679262638092041, "16148": 1.160461664199829, "16330": 0.2493593990802765, "16367": 0.7925328612327576, "16381": 0.6212902665138245, "16406": 0.034552380442619324, "16485": 0.3127557039260864, "16515": 0.2394166737794876, "16523": 1.0742288827896118, "16578": 0.23247487843036652, "16755": 0.28082266449928284, "16784": 0.21765978634357452, "16824": 0.3622259199619293, "16902": 0.981317400932312, "17042": 0.6867793202400208, "17205": 1.130645751953125, "17208": 0.2689530849456787, "17547": 0.9052929878234863, "17603": 0.040196798741817474, "17606": 0.4203280806541443, "17643": 0.07884006202220917, "17882": 0.004870930220931768, "17908": 0.46670228242874146, "18212": 0.12038381397724152, "18422": 0.3005385100841522, "18539": 0.2317005842924118, "18678": 0.45870962738990784, "18721": 0.1994270235300064, "18857": 0.6674286723136902, "19037": 0.7028654217720032, "19046": 0.02792670577764511, "19064": 0.4673144817352295, "19113": 0.129004567861557, "19120": 0.1889725625514984, "19158": 0.24554696679115295, "19198": 0.08603433519601822, "19319": 0.43244171142578125, "19879": 0.020300358533859253, "19939": 0.3170322775840759, "20155": 0.08692999184131622, "20177": 0.08244366943836212, "20272": 0.15777134895324707, "20349": 0.05970508232712746, "20480": 0.29109421372413635, "20692": 0.8039615154266357, "20828": 0.8281423449516296, "20854": 0.4487839937210083, "20932": 0.7134475708007812, "21024": 0.5162794589996338, "21155": 0.3304552733898163, "21230": 0.11517547070980072, "21243": 0.0913962796330452, "21374": 0.2696990668773651, "21499": 0.2105647772550583, "21879": 0.47827014327049255, "22006": 0.176772341132164, "22254": 0.7258110046386719, "22828": 0.6233867406845093, "22835": 0.13071982562541962, "22963": 0.1011524572968483, "22991": 0.2749055027961731, "23073": 0.3554046154022217, "23368": 0.08513788133859634, "23608": 0.3757305145263672, "23900": 0.7701805830001831, "24081": 0.47827014327049255, "24155": 0.05786345899105072, "24327": 0.11081436276435852, "24552": 0.9194108247756958, "24665": 0.38374659419059753, "24758": 0.5767669677734375, "25022": 0.3526630103588104, "25523": 0.8109301924705505, "25524": 0.34508460760116577, "25808": 0.22079704701900482, "25870": 0.012615402229130268, "25937": 0.14602625370025635, "26163": 0.574020504951477, "26237": 0.9194108247756958, "26264": 0.08603433519601822, "26319": 0.14518201351165771, "26364": 0.2659635543823242, "26404": 0.07793712615966797, "26462": 0.6435998678207397, "26721": 0.8143964409828186, "26786": 0.09761575609445572, "26906": 0.14518201351165771, "27029": 0.10906458646059036, "27292": 0.20739519596099854, "27323": 0.7737906575202942, "27354": 0.0038986403960734606, "27534": 0.026976587250828743, "27947": 0.004870930220931768, "28108": 0.2786078155040741, "28203": 0.8500841856002808, "28329": 0.029824240133166313, "28436": 0.40546512603759766, "28488": 0.42161011695861816, "28591": 0.10906458646059036, "28648": 0.4093637466430664, "28689": 0.574020504951477, "28892": 0.03266380727291107, "28993": 0.7995813488960266, "29299": 0.3897167444229126, "29443": 0.57457035779953, "29458": 0.6857960224151611} | 13496853 | PURPOSE The aim of this study was to update reference data of handgrip strength for healthy adults of both genders spanning a wide age range and to analyze possible factors of influence. METHODS Intraindividual and interindividual variations of grip strength and their relation to several anthropometric factors were analyzed in a standardized manner for 769 healthy adults (women, n = 403; men, n = 366) aged between 20 years and 95 years. Measurements were done in neutral position of arm, forearm, and wrist on setting II of a Baseline digital hydraulic dynamometer (NexGen Ergonomics Inc. Quebec, Canada). RESULTS Mean strength was about 41% less in women (right 29 kg; left 27 kg) than in men (right 49 kg; left 47 kg) resulting in a ratio of left to right hand slightly above .95 in both genders. During the course of life, hand strength develops comparably in both genders peaking at 35 years of age and decreasing continuously further on. Anthropometric variables such as forearm circumference and length, hand size, or body mass showed a positive correlation with grip strength. Body mass index, type of work, and hand dominance showed only a partial positive correlation or no correlation with grip strength. Gender and age, followed by parameters representing body length and obesity, were observed to have the highest predictive value for handgrip strength and were therefore entered into the generation of prediction equations. CONCLUSIONS We recommend side adjustment of measured values for intraindividual comparison and inclusion of information regarding anthropometric characteristics, as well as using gender- and age-adjusted reference values, whereas hand dominance can be neglected. The regression equations we generated might prove to be useful for clinicians or for those who use normative values within software to provide more accurate predictions of strength scores for specific applications. | Grip strength in healthy caucasian adults: reference values. |
{"1003": 0.3241194784641266, "1020": 0.319873183965683, "1025": 0.17267228662967682, "1038": 0.3850763738155365, "1042": 0.8567397594451904, "1050": 0.5057345628738403, "1051": 0.7286425232887268, "1999": 0.06977381557226181, "2000": 0.2763880789279938, "2004": 0.176772341132164, "2007": 0.06703783571720123, "2029": 0.129004567861557, "2043": 0.04113444685935974, "2044": 0.6482070088386536, "2051": 0.45932671427726746, "2058": 0.33325836062431335, "2086": 0.2478361576795578, "2090": 0.2674594223499298, "2095": 0.007782140281051397, "2109": 0.18978065252304077, "2121": 0.2837681770324707, "2146": 0.4132472574710846, "2152": 0.5882205963134766, "2179": 0.012615402229130268, "2181": 0.04860413447022438, "2184": 0.08064348995685577, "2193": 0.21214580535888672, "2197": 0.27342069149017334, "2206": 0.09850110858678818, "2214": 0.10555581003427505, "2220": 0.41840189695358276, "2226": 0.32270604372024536, "2232": 0.8349450826644897, "2233": 0.37974658608436584, "2260": 0.6139179468154907, "2263": 0.6059582233428955, "2273": 0.34370049834251404, "2287": 0.9248477816581726, "2302": 0.15943801403045654, "2303": 0.08603433519601822, "2308": 0.8022117614746094, "2313": 0.2231435477733612, "2317": 0.36426326632499695, "2335": 0.08603433519601822, "2355": 0.5255602598190308, "2367": 0.20580662786960602, "2381": 0.13925230503082275, "2382": 0.4248080551624298, "2383": 0.2576959431171417, "2389": 0.20977331697940826, "2397": 0.8608771562576294, "2416": 0.06977381557226181, "2421": 0.0174254160374403, "2426": 0.32905077934265137, "2443": 0.3346569836139679, "2445": 0.09317722171545029, "2450": 0.6332852244377136, "2470": 0.22157983481884003, "2478": 0.0058422754518687725, "2491": 0.3191637098789215, "2504": 0.6425731778144836, "2515": 0.00875066313892603, "2522": 0.4624064862728119, "2523": 0.6674286723136902, "2545": 0.4849066734313965, "2546": 0.09495500475168228, "2549": 0.47584590315818787, "2558": 0.6867793202400208, "2561": 0.3662964701652527, "2572": 0.672426164150238, "2590": 0.42096930742263794, "2628": 0.2089812457561493, "2640": 0.45623743534088135, "2641": 0.040196798741817474, "2659": 0.4228905141353607, "2667": 0.5318912267684937, "2668": 0.6420594453811646, "2679": 0.40285754203796387, "2706": 0.2470736801624298, "2714": 0.018384648486971855, "2750": 0.037378571927547455, "2753": 0.037378571927547455, "2765": 0.42353010177612305, "2771": 0.6769026517868042, "2783": 0.49030399322509766, "2812": 0.18978065252304077, "2817": 0.6118015646934509, "2825": 0.11778303235769272, "2846": 0.3353555500507355, "2896": 0.09228714555501938, "2913": 0.5461324453353882, "2931": 0.4673144817352295, "2937": 0.6000806093215942, "2951": 0.06977381557226181, "3020": 0.19220098853111267, "3041": 0.022212404757738113, "3046": 0.3283478021621704, "3057": 0.01934296265244484, "3058": 0.32905077934265137, "3078": 0.5313173532485962, "3112": 0.1913948506116867, "3144": 0.04394211992621422, "3231": 0.8212929964065552, "3246": 0.14264501631259918, "3273": 0.3353555500507355, "3276": 0.20102575421333313, "3278": 0.28743788599967957, "3284": 0.2918238639831543, "3334": 0.14686977863311768, "3336": 0.06429435312747955, "3348": 0.21135559678077698, "3350": 0.4812922179698944, "3366": 0.5174443125724792, "3367": 0.14686977863311768, "3378": 0.6471850275993347, "3382": 0.3963087201118469, "3401": 0.8306987881660461, "3424": 0.6086184978485107, "3446": 0.030771657824516296, "3452": 0.14433705806732178, "3463": 0.6128603219985962, "3468": 0.07884006202220917, "3491": 0.06429435312747955, "3497": 0.4512746334075928, "3512": 0.6080870032310486, "3515": 0.41840189695358276, "3517": 0.36290550231933594, "3522": 0.2493593990802765, "3535": 0.9162907600402832, "3556": 0.2531573474407196, "3567": 0.06612417846918106, "3570": 0.5723689198493958, "3582": 0.5162794589996338, "3616": 0.036437395960092545, "3635": 0.5104349255561829, "3643": 0.7537717819213867, "3653": 0.2247048318386078, "3671": 0.791648268699646, "3742": 0.6075552701950073, "3755": 0.757441520690918, "3792": 0.09850110858678818, "3798": 0.5805994272232056, "3801": 0.4196864068508148, "3811": 0.045809537172317505, "3867": 0.4837033152580261, "3891": 0.33953672647476196, "3893": 0.9500881433486938, "3898": 0.03266380727291107, "3914": 1.2522047758102417, "3943": 0.18492233753204346, "3947": 0.02412080205976963, "3963": 0.8509185314178467, "3979": 0.08961215615272522, "3981": 0.3127557039260864, "4008": 0.567951500415802, "4022": 1.076228141784668, "4029": 0.39762192964553833, "4048": 0.6118015646934509, "4094": 0.004870930220931768, "4095": 1.09404456615448, "4102": 0.7220231294631958, "4106": 0.6233867406845093, "4146": 0.00875066313892603, "4182": 0.3177432417869568, "4225": 0.07341018319129944, "4292": 0.38441169261932373, "4293": 0.6181373596191406, "4340": 0.42990362644195557, "4358": 0.08244366943836212, "4376": 0.30989447236061096, "4403": 0.6548244953155518, "4456": 0.14518201351165771, "4621": 0.1693800985813141, "4692": 0.7124901413917542, "4710": 0.2954642176628113, "4712": 0.2800849378108978, "4740": 0.7818660736083984, "4793": 0.25239890813827515, "5147": 0.021256839856505394, "5179": 0.0174254160374403, "5197": 0.5618454217910767, "5246": 0.06154331564903259, "5300": 0.7889899015426636, "5306": 0.07159364968538284, "5326": 0.06977381557226181, "5345": 0.9702757596969604, "5401": 0.6064908504486084, "5402": 0.8853482007980347, "5443": 0.21530038118362427, "5468": 0.6654226183891296, "5604": 0.45870962738990784, "5610": 0.2881702482700348, "5617": 0.10203468054533005, "5646": 0.5174443125724792, "5700": 0.14264501631259918, "5761": 0.6149744987487793, "5764": 0.77198725938797, "5769": 0.013579257763922215, "5786": 0.8195732831954956, "5816": 0.6882523894309998, "5818": 0.3656192123889923, "5824": 0.10026945173740387, "5852": 0.43875885009765625, "5907": 0.1011524572968483, "5940": 0.27564704418182373, "5950": 0.6212902665138245, "5986": 0.19622190296649933, "5997": 0.08064348995685577, "6022": 0.8022117614746094, "6064": 0.20660123229026794, "6075": 0.1930064558982849, "6086": 0.25239890813827515, "6146": 0.014542185701429844, "6179": 0.2184450328350067, "6191": 0.20660123229026794, "6205": 0.3883931338787079, "6255": 0.08961215615272522, "6273": 0.2394166737794876, "6321": 0.07068414986133575, "6352": 0.05694137513637543, "6388": 0.006812678650021553, "6390": 0.24401791393756866, "6391": 0.5197699069976807, "6421": 0.5995445251464844, "6431": 0.09406650811433792, "6445": 0.5618454217910767, "6486": 0.3601844012737274, "6535": 0.5909284353256226, "6564": 0.3304552733898163, "6612": 0.0606246218085289, "6638": 0.04394211992621422, "6640": 0.42735910415649414, "6721": 0.15777134895324707, "6818": 0.5893046259880066, "6820": 0.7028654217720032, "6845": 0.03831886500120163, "6875": 1.0271050930023193, "6897": 0.2719337046146393, "6993": 0.15860503911972046, "7012": 0.18978065252304077, "7017": 0.6107416749000549, "7023": 0.2539152204990387, "7099": 0.5784112811088562, "7161": 0.4481603503227234, "7290": 0.036437395960092545, "7366": 0.06703783571720123, "7388": 0.06703783571720123, "7403": 0.24018502235412598, "7461": 0.04113444685935974, "7512": 0.8315495252609253, "7524": 0.6022219061851501, "7551": 0.12642613053321838, "7570": 0.2607102394104004, "7594": 0.5069117546081543, "7645": 0.04860413447022438, "7694": 0.05786345899105072, "7718": 0.35403475165367126, "7730": 0.12642613053321838, "7778": 0.14179791510105133, "7784": 0.49030399322509766, "7831": 0.6654226183891296, "7863": 1.0151457786560059, "7885": 0.015504186972975731, "7898": 0.06154331564903259, "7978": 0.011650617234408855, "8010": 0.22626367211341858, "8168": 0.38574060797691345, "8178": 0.02316705882549286, "8247": 0.0913962796330452, "8269": 0.9635916948318481, "8288": 0.05970508232712746, "8290": 0.1384023278951645, "8319": 0.41389304399490356, "8321": 0.11604541540145874, "8428": 0.6461620330810547, "8449": 0.009718249551951885, "8553": 0.8374842405319214, "8733": 0.5898461937904358, "8924": 0.6522845029830933, "8943": 0.7463917136192322, "9062": 0.07159364968538284, "9128": 0.083342544734478, "9235": 0.472198486328125, "9280": 0.3615458607673645, "9296": 0.5381823778152466, "9312": 0.04113444685935974, "9367": 0.15693697333335876, "9407": 0.05046287178993225, "9422": 0.5882205963134766, "9530": 0.5364705324172974, "9556": 0.15023678541183472, "9560": 0.6296497583389282, "9592": 0.1734936386346817, "9670": 0.01934296265244484, "9683": 0.9379299283027649, "9710": 0.35745587944984436, "9723": 1.1586239337921143, "9765": 0.2659635543823242, "9839": 0.09228714555501938, "9854": 0.053244512528181076, "9859": 0.01934296265244484, "10015": 0.1930064558982849, "10032": 1.2094266414642334, "10141": 0.7755908370018005, "10173": 0.7701805830001831, "10174": 0.09850110858678818, "10238": 0.23402166366577148, "10426": 0.5540198087692261, "10539": 0.0029254043474793434, "10640": 0.1221139207482338, "10665": 1.020087480545044, "10673": 0.07612881064414978, "10755": 1.0735615491867065, "10768": 0.5701626539230347, "10820": 0.9333322048187256, "10841": 0.5045560002326965, "10867": 0.3777405619621277, "10903": 0.3283478021621704, "11079": 0.0038986403960734606, "11100": 0.7389566898345947, "11156": 0.058784693479537964, "11179": 0.8074519634246826, "11234": 0.15610189735889435, "11324": 0.0354953333735466, "11326": 0.304147332906723, "11436": 0.06520967930555344, "11487": 0.045809537172317505, "11589": 0.26446542143821716, "11709": 0.0913962796330452, "12115": 0.9217445850372314, "12123": 0.3170322775840759, "12173": 0.07884006202220917, "12227": 0.34922540187835693, "12274": 0.7314660549163818, "12335": 0.43244171142578125, "12353": 0.255429208278656, "12381": 0.052318159490823746, "12407": 0.3423145115375519, "12435": 0.36086538434028625, "12461": 0.043007105588912964, "12515": 0.27712854743003845, "12596": 0.12728634476661682, "12709": 0.6833335757255554, "12826": 0.43875885009765625, "12835": 0.7683706283569336, "13024": 0.1751343309879303, "13105": 0.7629209756851196, "13120": 1.1616848707199097, "13180": 0.29619070887565613, "13316": 0.12038381397724152, "13331": 0.14179791510105133, "13490": 0.08603433519601822, "13599": 0.5209306478500366, "13757": 0.011650617234408855, "14067": 0.03831886500120163, "14127": 0.20102575421333313, "14155": 0.20977331697940826, "14171": 0.2026219218969345, "14194": 0.0038986403960734606, "14357": 0.19862671196460724, "14358": 0.09584271162748337, "14511": 0.7352184057235718, "14627": 0.6808650493621826, "14719": 0.09938567131757736, "14874": 0.17020416259765625, "14946": 0.5472630262374878, "14966": 0.7692760229110718, "15001": 0.18329764902591705, "15124": 1.0001721382141113, "15189": 0.06795065850019455, "15286": 0.35745587944984436, "15354": 0.5151132941246033, "15543": 0.04207121208310127, "15578": 0.7764897346496582, "15596": 0.3170322775840759, "15680": 0.31204116344451904, "15842": 0.5489565134048462, "15855": 0.1693800985813141, "15871": 0.05786345899105072, "15928": 0.129004567861557, "16012": 0.8117979168891907, "16014": 0.7500885725021362, "16026": 0.7426811456680298, "16118": 0.19862671196460724, "16227": 0.016465263441205025, "16330": 0.08064348995685577, "16387": 0.9084475636482239, "16463": 0.28963330388069153, "16478": 0.02316705882549286, "16515": 0.37371641397476196, "16593": 0.3723714053630829, "16731": 0.09584271162748337, "16902": 0.6022219061851501, "16989": 0.4349733293056488, "17042": 0.2918238639831543, "17245": 0.4568560719490051, "17266": 0.10379679501056671, "17371": 0.7827593088150024, "17376": 0.8475768566131592, "17441": 0.04674193635582924, "17464": 0.7692760229110718, "17489": 0.09495500475168228, "17547": 0.6654226183891296, "17826": 0.09672962874174118, "17908": 0.20660123229026794, "17996": 0.8877626657485962, "18047": 0.45623743534088135, "18260": 0.20421554148197174, "18422": 0.13755162060260773, "18436": 0.11081436276435852, "18539": 0.2478361576795578, "18714": 0.9754437208175659, "18724": 1.12432062625885, "19037": 0.46117570996284485, "19064": 0.1401015669107437, "19158": 0.38041436672210693, "19653": 0.1485546976327896, "19701": 0.0009760859538801014, "19722": 0.40220460295677185, "19761": 0.10731173306703568, "19822": 0.3897167444229126, "19841": 0.006812678650021553, "19875": 0.5021947622299194, "19939": 0.19541899859905243, "20069": 0.2689530849456787, "20100": 0.4487839937210083, "20155": 0.11951763927936554, "20162": 0.04860413447022438, "20194": 0.9650808572769165, "20353": 0.17759032547473907, "20367": 0.3304552733898163, "20390": 0.32129061222076416, "20482": 0.11517547070980072, "20589": 0.09850110858678818, "20752": 0.8633513450622559, "20858": 0.1693800985813141, "20906": 0.1011524572968483, "20921": 0.34508460760116577, "20932": 0.35060185194015503, "21150": 0.47463157773017883, "21183": 0.25239890813827515, "21371": 0.20580662786960602, "21376": 0.3615458607673645, "21412": 0.7934166193008423, "21539": 0.14686977863311768, "21608": 0.3949938118457794, "21639": 0.7500885725021362, "21778": 0.3262358605861664, "21799": 0.20977331697940826, "21891": 0.0009760859538801014, "22199": 0.09672962874174118, "22625": 0.22001366317272186, "22731": 0.3615458607673645, "22916": 0.04394211992621422, "22963": 0.4318077862262726, "22991": 0.5957841277122498, "23198": 0.20102575421333313, "23216": 0.3963087201118469, "23238": 0.03266380727291107, "23260": 0.9650808572769165, "23368": 0.16359257698059082, "23633": 0.0606246218085289, "23676": 0.09050461649894714, "23737": 0.1619328260421753, "23744": 0.0009760859538801014, "23900": 0.42544642090797424, "23944": 0.012615402229130268, "24077": 0.1710275560617447, "24081": 0.16690383851528168, "24110": 0.015504186972975731, "24176": 0.18329764902591705, "24226": 0.23402166366577148, "24396": 0.176772341132164, "24410": 0.12728634476661682, "24422": 0.5773153901100159, "24471": 0.5800528526306152, "24501": 0.025073638185858727, "24528": 0.7009293437004089, "24552": 0.6634125709533691, "24643": 0.25088030099868774, "24965": 0.0019512200960889459, "25022": 0.6989894509315491, "25086": 0.0606246218085289, "25128": 0.7463917136192322, "25389": 0.00875066313892603, "25714": 0.40481385588645935, "25833": 0.05786345899105072, "25855": 0.004870930220931768, "25937": 0.6573580503463745, "26462": 0.009718249551951885, "26563": 0.25467249751091003, "26877": 0.15610189735889435, "27159": 0.08154398202896118, "27295": 0.839173436164856, "27373": 0.6563454270362854, "27794": 1.0822023153305054, "28086": 0.15526613593101501, "28093": 0.13071982562541962, "28207": 0.4349733293056488, "28228": 0.03266380727291107, "28687": 0.8649974465370178, "28691": 0.14433705806732178, "29242": 0.31560876965522766, "29290": 0.10291612148284912, "29299": 0.3084607720375061, "29311": 0.010684899985790253, "29458": 0.6833335757255554} | 13497630 | Importance Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. Objective To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. Design, Setting, and Participants Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area. Exposures Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. Main Outcomes and Measures The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result. Results A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n = 69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n = 737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Conclusions and Relevance Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics. | Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age |
{"1011": 0.21765978634357452, "1013": 0.12986256182193756, "1038": 1.0409941673278809, "1039": 0.16690383851528168, "1041": 0.16359257698059082, "1043": 0.5865923762321472, "1051": 0.1970241367816925, "1156": 0.28890204429626465, "1996": 0.19220098853111267, "1998": 0.03266380727291107, "1999": 0.045809537172317505, "2008": 0.010684899985790253, "2011": 0.018384648486971855, "2029": 0.026025565341114998, "2041": 0.08064348995685577, "2046": 0.30486753582954407, "2076": 0.06886265426874161, "2079": 0.25467249751091003, "2109": 0.3409265875816345, "2135": 0.06703783571720123, "2182": 0.014542185701429844, "2213": 1.0257055759429932, "2291": 0.013579257763922215, "2350": 0.46363574266433716, "2475": 0.19381128251552582, "2491": 0.5133614540100098, "2503": 0.3656192123889923, "2511": 0.3897167444229126, "2515": 0.18816383183002472, "2535": 0.637939989566803, "2546": 0.5629584193229675, "2590": 0.4349733293056488, "2618": 0.7978238463401794, "2666": 0.7182208299636841, "2668": 0.26296505331993103, "2693": 0.34577593207359314, "2714": 0.17020416259765625, "2765": 0.15693697333335876, "2828": 0.4400174915790558, "2865": 0.14602625370025635, "2897": 0.6107416749000549, "2920": 0.1751343309879303, "2966": 0.04394211992621422, "3048": 0.058784693479537964, "3378": 0.021256839856505394, "3397": 0.2539152204990387, "3431": 0.175953671336174, "3433": 0.7881022095680237, "3457": 0.056018441915512085, "3463": 0.3106105625629425, "3466": 0.034552380442619324, "3526": 0.8941729068756104, "3563": 0.030771657824516296, "3605": 0.15526613593101501, "3625": 0.1734936386346817, "3665": 0.15610189735889435, "3670": 0.6197150945663452, "3674": 0.36900100111961365, "3774": 0.1229778528213501, "3800": 0.04113444685935974, "3853": 0.6296497583389282, "3930": 0.02887592278420925, "4013": 0.7047978043556213, "4127": 0.47584590315818787, "4167": 0.043007105588912964, "4187": 0.6902132034301758, "4306": 0.0174254160374403, "4371": 0.5914691090583801, "4395": 0.5021947622299194, "4442": 0.9827804565429688, "4539": 0.4537591338157654, "4588": 0.5438674688339233, "4668": 0.11343330889940262, "4671": 0.09317722171545029, "4748": 0.27342069149017334, "4757": 0.2852376699447632, "4758": 0.8450632095336914, "4945": 0.27786844968795776, "4962": 0.5562619566917419, "4972": 0.43938836455345154, "5197": 0.1946154683828354, "5228": 0.1751343309879303, "5244": 0.3127557039260864, "5250": 0.040196798741817474, "5292": 0.30558720231056213, "5323": 0.42225050926208496, "5383": 0.14095009863376617, "5387": 0.8731874823570251, "5393": 0.25088030099868774, "5449": 0.052318159490823746, "5666": 0.8829278349876404, "5668": 0.04207121208310127, "5701": 0.8893690705299377, "5769": 0.37907835841178894, "5812": 0.18329764902591705, "5838": 0.04860413447022438, "5876": 0.5607312321662903, "5923": 1.3449229001998901, "5944": 1.0172666311264038, "5970": 0.10731173306703568, "6091": 0.4891071021556854, "6125": 0.2689530849456787, "6164": 0.02887592278420925, "6169": 0.272677481174469, "6177": 0.4537591338157654, "6377": 0.11951763927936554, "6459": 0.09495500475168228, "6552": 0.02792670577764511, "6591": 0.04207121208310127, "6612": 0.6096806526184082, "6869": 0.46853771805763245, "6873": 0.9857001900672913, "6897": 0.10993985831737518, "6903": 0.05139094591140747, "6914": 0.5506471395492554, "6922": 0.6502478122711182, "6970": 0.0174254160374403, "7127": 0.1064341589808464, "7242": 0.0606246218085289, "7337": 0.23092569410800934, "7366": 0.21372433006763458, "7389": 0.535327672958374, "7403": 0.3070250153541565, "7411": 0.12728634476661682, "7461": 0.05417001247406006, "7473": 0.1930064558982849, "7485": 0.11604541540145874, "7645": 0.42990362644195557, "7711": 0.6989894509315491, "7816": 0.6744182109832764, "7872": 1.0464962720870972, "7889": 0.3084607720375061, "8000": 0.6086184978485107, "8071": 0.053244512528181076, "8092": 0.1808556467294693, "8153": 0.7701805830001831, "8185": 0.8893690705299377, "8246": 0.4093637466430664, "8247": 0.30917787551879883, "8278": 0.9225212931632996, "8290": 0.13499516248703003, "8346": 0.15359249711036682, "8355": 0.5517725944519043, "8360": 0.16690383851528168, "8523": 0.7969439625740051, "8560": 0.04953393340110779, "8676": 0.3283478021621704, "8681": 0.5215105414390564, "8737": 0.4837033152580261, "8878": 0.030771657824516296, "8988": 0.8004589080810547, "9007": 0.18573370575904846, "9031": 0.058784693479537964, "9113": 0.30989447236061096, "9141": 0.8039615154266357, "9165": 0.4812922179698944, "9230": 0.9178520441055298, "9319": 0.07884006202220917, "9416": 0.5415972471237183, "9513": 0.040196798741817474, "9568": 0.058784693479537964, "9597": 0.09495500475168228, "9677": 0.8780695199966431, "9687": 0.11256109178066254, "9756": 0.38574060797691345, "9808": 1.1217793226242065, "9869": 0.0797421783208847, "10085": 0.5483922958374023, "10266": 0.1477125883102417, "10448": 0.3170322775840759, "10509": 0.3106105625629425, "10572": 0.4734157919883728, "10580": 0.3283478021621704, "10610": 0.981317400932312, "10627": 0.0842406153678894, "10738": 0.5551415085792542, "10769": 0.5370414853096008, "10960": 0.4412745535373688, "11113": 0.5640701055526733, "11240": 1.0403043031692505, "11307": 0.09495500475168228, "11321": 0.75193190574646, "11423": 0.18978065252304077, "11432": 0.03925827145576477, "11486": 0.11865071207284927, "11539": 0.1930064558982849, "11601": 0.04953393340110779, "11627": 0.05694137513637543, "11707": 0.3622259199619293, "11896": 0.26146242022514343, "12123": 0.0354953333735466, "12222": 0.8187123537063599, "12247": 0.04113444685935974, "12328": 0.9500881433486938, "12402": 0.5162794589996338, "12435": 0.5104349255561829, "12458": 0.20739519596099854, "12540": 0.00875066313892603, "12562": 0.5751199722290039, "12604": 0.9131608605384827, "12863": 0.16442140936851501, "13026": 0.7665573358535767, "13433": 0.10906458646059036, "13447": 0.2409527748823166, "13461": 0.021256839856505394, "13490": 0.7028654217720032, "13526": 0.4412745535373688, "13791": 0.021256839856505394, "13833": 0.6249561905860901, "14048": 0.30558720231056213, "14095": 0.659380316734314, "14120": 0.44753631949424744, "14126": 0.2034190446138382, "14313": 0.02316705882549286, "14417": 0.19862671196460724, "15042": 1.4505887031555176, "15176": 0.9987343549728394, "15543": 0.22782009840011597, "15660": 0.9857001900672913, "15680": 0.04767346754670143, "15821": 0.1734936386346817, "15946": 0.04767346754670143, "16127": 0.40220460295677185, "16263": 0.04394211992621422, "16340": 0.06703783571720123, "16412": 0.2247048318386078, "16429": 0.6492279767990112, "16505": 0.18167030811309814, "16691": 0.20022670924663544, "16731": 0.04113444685935974, "16736": 0.38041436672210693, "16882": 0.09584271162748337, "16940": 0.7537717819213867, "17250": 0.9092346429824829, "17441": 0.3339579105377197, "17603": 0.9798521995544434, "17785": 0.1994270235300064, "17820": 0.04394211992621422, "18111": 1.596859097480774, "18260": 0.02316705882549286, "18349": 0.2990913391113281, "18622": 0.8853482007980347, "18714": 0.09938567131757736, "18845": 0.935633659362793, "19003": 0.010684899985790253, "19220": 0.02887592278420925, "19389": 0.8057082891464233, "19476": 0.5984715819358826, "19610": 0.9500881433486938, "19653": 0.7124901413917542, "19706": 0.5635144114494324, "19872": 0.16359257698059082, "20116": 0.9591107368469238, "20275": 0.18167030811309814, "20350": 0.4041621685028076, "20389": 0.35813871026039124, "20415": 1.0655186176300049, "20544": 0.0019512200960889459, "20752": 0.09406650811433792, "20858": 0.3325583338737488, "20936": 0.11256109178066254, "20960": 0.22548456490039825, "21009": 0.2478361576795578, "21252": 1.0158531665802002, "21520": 0.33675122261047363, "21575": 0.6476961374282837, "21618": 0.960606575012207, "21758": 0.17431432008743286, "21770": 0.06886265426874161, "21906": 0.0770333781838417, "22119": 0.4812922179698944, "22262": 0.14686977863311768, "22291": 0.3163207769393921, "22458": 0.05694137513637543, "22471": 0.41195443272590637, "22678": 0.2837681770324707, "22806": 0.8004589080810547, "23150": 0.1384023278951645, "23216": 0.4849066734313965, "23217": 0.1384023278951645, "23900": 0.040196798741817474, "23924": 0.014542185701429844, "24012": 0.2652147710323334, "24054": 0.0019512200960889459, "24365": 0.030771657824516296, "24848": 0.14686977863311768, "24960": 1.486563801765442, "25194": 0.07068414986133575, "25353": 0.6583697199821472, "25468": 0.3269403576850891, "25580": 0.5495203733444214, "25644": 0.9333322048187256, "25714": 0.1212492436170578, "26236": 1.0403043031692505, "26512": 0.053244512528181076, "26651": 0.2034190446138382, "26773": 0.9710156321525574, "26838": 0.3963087201118469, "27287": 0.817850649356842, "27295": 1.134421706199646, "27321": 0.8559102416038513, "27526": 0.20818853378295898, "27790": 0.034552380442619324, "27854": 0.0606246218085289, "28636": 0.30989447236061096, "28723": 0.03360854089260101, "28788": 1.0748957395553589, "28873": 0.08871890604496002, "29290": 0.24554696679115295} | 13509809 | The bone marrow (BM) niche comprises multiple cell types that regulate hematopoietic stem/progenitor cell (HSPC) migration out of the niche and into the circulation. Here, we demonstrate that osteocytes, the major cellular component of mature bone, are regulators of HSPC egress. Granulocyte colony-stimulating factor (G-CSF), used clinically to mobilize HSPCs, induces changes in the morphology and gene expression of the osteocytic network that precedes changes in osteoblasts. This rapid response is likely under control of the sympathetic nervous system, since osteocytes express the β2-adrenergic receptor and surgical sympathectomy prevents it. Mice with targeted ablation of osteocytes or a disrupted osteocyte network have comparable numbers of HSPCs in the BM but fail to mobilize HSPCs in response to G-CSF. Taken together, these results indicate that the BM/bone niche interface is critically controlled from inside of the bone matrix and establish an important physiological role for skeletal tissues in hematopoietic function. | Matrix-embedded osteocytes regulate mobilization of hematopoietic stem/progenitor cells. |
{"1011": 0.40611594915390015, "1044": 0.20022670924663544, "1051": 0.6793810129165649, "1998": 0.39762192964553833, "2002": 0.1685553640127182, "2005": 0.37907835841178894, "2008": 0.03831886500120163, "2011": 0.15275461971759796, "2013": 0.5341835021972656, "2022": 0.011650617234408855, "2029": 0.02412080205976963, "2038": 0.012615402229130268, "2046": 0.6301699280738831, "2063": 0.5629584193229675, "2064": 0.47584590315818787, "2079": 0.11778303235769272, "2083": 0.1930064558982849, "2109": 0.495672345161438, "2112": 0.5963221788406372, "2128": 0.0009760859538801014, "2131": 0.151916041970253, "2174": 0.026025565341114998, "2182": 0.018384648486971855, "2224": 0.20421554148197174, "2229": 1.134421706199646, "2278": 0.8500841856002808, "2444": 0.75193190574646, "2458": 0.15610189735889435, "2470": 0.0019512200960889459, "2515": 0.10555581003427505, "2535": 0.02412080205976963, "2537": 0.47158926725387573, "2542": 0.3012613356113434, "2550": 0.29036402702331543, "2572": 0.2822965085506439, "2583": 0.03925827145576477, "2734": 0.28082266449928284, "2764": 0.2689530849456787, "2765": 0.3106105625629425, "2771": 0.6212902665138245, "2825": 0.6451379656791687, "2828": 0.11865071207284927, "2832": 0.013579257763922215, "2864": 0.020300358533859253, "2915": 0.32764431834220886, "3081": 0.5795059204101562, "3085": 0.7352184057235718, "3112": 0.5261374711990356, "3120": 0.015504186972975731, "3144": 0.6714286804199219, "3189": 0.17840765416622162, "3231": 0.255429208278656, "3344": 0.7827593088150024, "3463": 0.36697331070899963, "3468": 0.7276995778083801, "3508": 0.4093637466430664, "3522": 0.3027053773403168, "3526": 1.0471819639205933, "3540": 0.12384103983640671, "3560": 0.4412745535373688, "3594": 0.1677299439907074, "3668": 0.30558720231056213, "3670": 0.10026945173740387, "3728": 0.28082266449928284, "3734": 0.23092569410800934, "3754": 0.23402166366577148, "3800": 0.1685553640127182, "3898": 0.4425300657749176, "3965": 0.176772341132164, "4005": 0.6400018334388733, "4072": 0.29981520771980286, "4106": 0.6296497583389282, "4111": 0.48670899868011475, "4118": 0.009718249551951885, "4127": 0.03360854089260101, "4176": 0.6989894509315491, "4179": 0.4145384132862091, "4195": 0.21293537318706512, "4245": 0.6773988008499146, "4287": 0.6907027959823608, "4351": 0.4444103240966797, "4442": 1.1858406066894531, "4473": 0.09050461649894714, "4503": 0.4145384132862091, "4539": 0.347847044467926, "4556": 0.2976420819759369, "4562": 0.6563454270362854, "4632": 0.014542185701429844, "4639": 0.47827014327049255, "4663": 0.6778947114944458, "4671": 0.34922540187835693, "4685": 0.022212404757738113, "4719": 0.1905880719423294, "4755": 0.43623676896095276, "4761": 0.14179791510105133, "4928": 0.0029254043474793434, "4962": 0.9842413663864136, "5147": 0.4267219603061676, "5155": 0.10818854719400406, "5173": 0.7018978595733643, "5214": 0.1510767638683319, "5224": 0.020300358533859253, "5228": 0.25995752215385437, "5267": 0.18573370575904846, "5292": 1.246605634689331, "5331": 0.15275461971759796, "5441": 0.2105647772550583, "5604": 0.3916989266872406, "5852": 0.053244512528181076, "5911": 0.037378571927547455, "6001": 0.5568217039108276, "6028": 0.055094651877880096, "6061": 0.4002431631088257, "6064": 0.8039615154266357, "6074": 0.5197699069976807, "6162": 0.11778303235769272, "6169": 0.960606575012207, "6179": 0.11081436276435852, "6459": 0.11168810725212097, "6468": 0.34577593207359314, "6529": 0.02316705882549286, "6576": 0.10203468054533005, "6822": 0.4914994537830353, "6855": 0.4926934838294983, "6897": 0.26446542143821716, "6914": 0.11081436276435852, "7013": 0.020300358533859253, "7171": 0.18411032855510712, "7218": 0.10993985831737518, "7297": 0.22782009840011597, "7366": 0.24554696679115295, "7403": 1.2671676874160767, "7570": 0.18978065252304077, "7645": 0.3676496744155884, "7718": 0.04207121208310127, "7818": 0.1510767638683319, "7872": 1.1394343376159668, "7883": 0.6218147873878479, "7885": 0.11778303235769272, "7889": 0.2719337046146393, "7900": 0.27342069149017334, "7949": 0.6420594453811646, "8000": 1.37795889377594, "8010": 0.27934664487838745, "8119": 0.1693800985813141, "8153": 0.3910386264324188, "8189": 1.0193830728530884, "8213": 0.4818955361843109, "8259": 0.20818853378295898, "8402": 0.36494144797325134, "8449": 0.15777134895324707, "8469": 0.5027855634689331, "8478": 0.28155985474586487, "8479": 0.9515975713729858, "8553": 0.4944818615913391, "8713": 0.817850649356842, "8885": 0.05786345899105072, "8908": 0.2822965085506439, "8991": 0.5162794589996338, "9124": 0.53589928150177, "9165": 0.791648268699646, "9285": 0.0317181795835495, "9314": 1.133164644241333, "9319": 0.23633737862110138, "9336": 0.052318159490823746, "9350": 0.6170841455459595, "9416": 0.28155985474586487, "9468": 0.09761575609445572, "9496": 0.3588210940361023, "9513": 0.06429435312747955, "9585": 0.5127768516540527, "9686": 0.861702561378479, "9699": 0.0606246218085289, "9878": 0.07612881064414978, "10003": 0.1994270235300064, "10085": 0.5990082025527954, "10222": 1.1005635261535645, "10442": 0.04674193635582924, "10448": 0.2026219218969345, "10580": 0.28597161173820496, "10752": 0.17922431230545044, "10768": 0.613389253616333, "10788": 0.052318159490823746, "10867": 0.4938860833644867, "11008": 0.5838727951049805, "11062": 0.07612881064414978, "11326": 0.7951818704605103, "11381": 0.1905880719423294, "11432": 0.6228629946708679, "11598": 0.02412080205976963, "11601": 0.24631060659885406, "11717": 0.08244366943836212, "11767": 0.28155985474586487, "11791": 0.025073638185858727, "11892": 0.02316705882549286, "11916": 0.4041621685028076, "11993": 0.46486347913742065, "12067": 0.39367714524269104, "12115": 0.347847044467926, "12153": 0.16359257698059082, "12238": 0.4673144817352295, "12328": 1.4413889646530151, "12402": 0.3982778787612915, "12562": 0.1485546976327896, "12599": 0.0058422754518687725, "12637": 0.1602703034877777, "12850": 0.006812678650021553, "12859": 0.8374842405319214, "12889": 0.09850110858678818, "12939": 0.5278670787811279, "12941": 0.043007105588912964, "12943": 1.067535400390625, "12955": 0.6598852276802063, "13103": 0.0913962796330452, "13341": 1.0051883459091187, "13369": 0.46363574266433716, "13458": 0.3127557039260864, "13595": 0.06703783571720123, "13819": 0.056018441915512085, "13908": 0.03831886500120163, "13931": 0.0770333781838417, "13938": 0.4926934838294983, "14126": 0.25694093108177185, "14213": 0.16359257698059082, "14471": 0.8247235417366028, "14627": 0.2607102394104004, "14800": 0.6254787445068359, "14817": 0.151916041970253, "14828": 0.03925827145576477, "14874": 0.39762192964553833, "14946": 0.8534175157546997, "14949": 0.06703783571720123, "15053": 0.007782140281051397, "15112": 0.8187123537063599, "15113": 0.04860413447022438, "15527": 0.22782009840011597, "15596": 0.17267228662967682, "15689": 0.018384648486971855, "15738": 0.9131608605384827, "15901": 0.025073638185858727, "15923": 0.45251765847206116, "15946": 0.0038986403960734606, "16012": 0.02792670577764511, "16026": 0.20818853378295898, "16216": 0.4286321699619293, "16221": 0.2223619967699051, "16387": 0.42608439922332764, "16505": 0.3499138653278351, "16510": 0.6989894509315491, "16515": 0.3070250153541565, "16530": 0.6522845029830933, "16578": 0.09938567131757736, "16670": 0.1710275560617447, "16691": 0.1718502640724182, "16706": 0.272677481174469, "16709": 0.02316705882549286, "16731": 0.29109421372413635, "16765": 0.04860413447022438, "17086": 0.7592713832855225, "17250": 0.7665573358535767, "17376": 0.2637155055999756, "17404": 0.1930064558982849, "17598": 0.5936289429664612, "17908": 0.5489565134048462, "18047": 0.13499516248703003, "18275": 0.4914994537830353, "18547": 0.5116065740585327, "18714": 0.15693697333335876, "18963": 0.009718249551951885, "19009": 0.8567397594451904, "19274": 0.13670019805431366, "19345": 0.8893690705299377, "19500": 0.11951763927936554, "19601": 0.026976587250828743, "19610": 0.41001203656196594, "19737": 0.6960725784301758, "19825": 0.19541899859905243, "20228": 0.35403475165367126, "20253": 0.11343330889940262, "20302": 0.05970508232712746, "20523": 0.15610189735889435, "20582": 0.3547199070453644, "20594": 0.08961215615272522, "20614": 0.6212902665138245, "21114": 1.034073829650879, "21197": 0.6363908052444458, "21376": 0.2830325961112976, "21770": 0.09317722171545029, "22026": 0.05139094591140747, "22069": 0.4093637466430664, "22731": 0.9263957738876343, "22943": 0.36086538434028625, "22945": 0.9379299283027649, "22991": 0.7737906575202942, "23072": 0.1510767638683319, "23572": 0.29109421372413635, "23737": 0.4909018874168396, "23767": 0.2501201331615448, "23924": 0.8013357520103455, "24004": 0.9013357162475586, "24010": 0.2852376699447632, "24051": 0.04207121208310127, "24203": 0.03925827145576477, "24269": 0.056018441915512085, "24278": 0.38574060797691345, "24286": 0.3601844012737274, "24418": 0.06429435312747955, "24759": 0.8298473954200745, "25437": 0.09406650811433792, "25476": 0.3464667797088623, "25714": 0.3241194784641266, "25829": 0.13243216276168823, "25972": 0.16276304423809052, "26236": 0.2969166338443756, "26305": 0.23015019297599792, "26524": 0.8534175157546997, "27268": 1.0116009712219238, "27321": 0.21765978634357452, "27642": 0.04394211992621422, "27710": 0.8567397594451904, "28024": 0.13157635927200317, "28086": 1.1665629148483276, "28156": 0.6674286723136902, "28228": 0.6456501483917236, "28290": 0.021256839856505394, "28637": 0.040196798741817474, "28667": 0.6916812658309937, "28788": 0.947819709777832, "28896": 0.0029254043474793434, "28901": 0.347847044467926, "28931": 0.2800849378108978, "29109": 0.2223619967699051, "29280": 0.7737906575202942} | 13513790 | Haploid cells are amenable for genetic analysis. Recent success in the derivation of mouse haploid embryonic stem cells (haESCs) via parthenogenesis has enabled genetic screening in mammalian cells. However, successful generation of live animals from these haESCs, which is needed to extend the genetic analysis to the organism level, has not been achieved. Here, we report the derivation of haESCs from androgenetic blastocysts. These cells, designated as AG-haESCs, partially maintain paternal imprints, express classical ESC pluripotency markers, and contribute to various tissues, including the germline, upon injection into diploid blastocysts. Strikingly, live mice can be obtained upon injection of AG-haESCs into MII oocytes, and these mice bear haESC-carried genetic traits and develop into fertile adults. Furthermore, gene targeting via homologous recombination is feasible in the AG-haESCs. Our results demonstrate that AG-haESCs can be used as a genetically tractable fertilization agent for the production of live animals via injection into oocytes. | Generation of Genetically Modified Mice by Oocyte Injection of Androgenetic Haploid Embryonic Stem Cells |
{"1011": 0.0752234235405922, "1014": 0.5318912267684937, "1044": 0.10731173306703568, "1047": 0.6558387279510498, "1052": 0.5191890001296997, "2002": 1.0165601968765259, "2007": 0.007782140281051397, "2010": 0.015504186972975731, "2015": 0.6223390698432922, "2025": 0.18329764902591705, "2029": 0.0058422754518687725, "2041": 0.27342069149017334, "2044": 0.06429435312747955, "2060": 0.12986256182193756, "2062": 0.11168810725212097, "2071": 0.2026219218969345, "2076": 0.25845035910606384, "2084": 0.500420093536377, "2094": 0.7537717819213867, "2102": 0.23864774405956268, "2109": 0.22001366317272186, "2116": 0.020300358533859253, "2146": 0.31489628553390503, "2166": 0.025073638185858727, "2168": 0.13243216276168823, "2179": 0.11604541540145874, "2184": 0.03925827145576477, "2201": 0.9907892942428589, "2203": 0.6999598741531372, "2214": 0.0606246218085289, "2217": 0.36494144797325134, "2224": 0.03925827145576477, "2244": 0.2531573474407196, "2287": 0.016465263441205025, "2313": 0.3877306580543518, "2321": 0.12814582884311676, "2322": 0.32553088665008545, "2330": 0.013579257763922215, "2367": 0.025073638185858727, "2378": 0.5010119676589966, "2391": 0.16690383851528168, "2394": 0.2969166338443756, "2403": 0.3416208028793335, "2430": 0.49030399322509766, "2439": 0.3339579105377197, "2446": 0.7201237678527832, "2470": 0.32270604372024536, "2475": 0.12814582884311676, "2488": 0.4462870955467224, "2491": 0.37371641397476196, "2515": 0.04860413447022438, "2540": 0.5822374224662781, "2581": 0.32270604372024536, "2594": 0.3191637098789215, "2625": 0.1994270235300064, "2668": 0.8289952278137207, "2714": 0.7491656541824341, "2729": 0.3916989266872406, "2732": 1.0828639268875122, "2734": 0.23402166366577148, "2750": 0.15777134895324707, "2762": 0.5404602885246277, "2765": 0.2822965085506439, "2812": 0.5151132941246033, "2817": 0.40285754203796387, "2818": 0.8949713706970215, "2846": 0.09761575609445572, "2850": 0.574020504951477, "2864": 0.02316705882549286, "2902": 0.9531047344207764, "2913": 0.46055975556373596, "2918": 0.12642613053321838, "2925": 0.2089812457561493, "2936": 0.009718249551951885, "2951": 0.5651806592941284, "2966": 0.07068414986133575, "2994": 0.7473171949386597, "3020": 0.34508460760116577, "3026": 0.04767346754670143, "3041": 0.02412080205976963, "3080": 0.6254787445068359, "3091": 0.5127768516540527, "3115": 0.6043586730957031, "3131": 0.48670899868011475, "3197": 0.32270604372024536, "3215": 0.6522845029830933, "3223": 0.5393219590187073, "3231": 0.06246116757392883, "3263": 0.47766464948654175, "3273": 0.23864774405956268, "3277": 0.37371641397476196, "3278": 0.16607704758644104, "3279": 0.9394577741622925, "3291": 0.1693800985813141, "3314": 0.6456501483917236, "3340": 0.37640097737312317, "3370": 0.4624064862728119, "3408": 0.3982778787612915, "3446": 0.04860413447022438, "3463": 0.5640701055526733, "3466": 0.755608320236206, "3471": 0.35060185194015503, "3491": 0.20977331697940826, "3522": 0.16359257698059082, "3550": 0.31204116344451904, "3556": 0.1229778528213501, "3558": 0.1734936386346817, "3635": 0.6059582233428955, "3643": 0.3423145115375519, "3647": 0.7105726003646851, "3791": 0.23402166366577148, "3808": 0.846739649772644, "3811": 0.0029254043474793434, "3867": 0.15860503911972046, "3872": 0.6075552701950073, "3896": 0.6624060273170471, "3938": 0.5512100458145142, "3974": 0.3662964701652527, "3979": 0.8813109993934631, "3989": 0.006812678650021553, "4002": 0.1619328260421753, "4003": 0.1994270235300064, "4090": 0.6522845029830933, "4094": 0.02887592278420925, "4102": 0.7510106563568115, "4106": 0.8764448165893555, "4118": 0.35060185194015503, "4162": 0.3070250153541565, "4187": 0.020300358533859253, "4236": 0.8583967685699463, "4245": 0.7898768186569214, "4254": 0.8400169610977173, "4270": 0.029824240133166313, "4298": 0.2493593990802765, "4370": 0.07068414986133575, "4464": 0.3910386264324188, "4489": 0.43623676896095276, "4558": 0.39893341064453125, "4587": 0.04394211992621422, "4621": 0.4145384132862091, "4720": 0.31560876965522766, "4725": 0.5027855634689331, "4758": 0.7791815400123596, "4795": 0.3177432417869568, "4866": 0.1401015669107437, "4914": 0.00875066313892603, "4921": 0.33675122261047363, "4928": 0.05139094591140747, "4955": 0.45251765847206116, "5022": 0.6075552701950073, "5068": 0.18248429894447327, "5084": 0.5990082025527954, "5139": 0.28082266449928284, "5159": 0.5045560002326965, "5292": 0.6608943343162537, "5300": 0.07884006202220917, "5333": 0.2470736801624298, "5345": 0.953857421875, "5360": 0.2478361576795578, "5400": 0.19862671196460724, "5403": 0.2786078155040741, "5428": 0.016465263441205025, "5443": 0.4914994537830353, "5478": 0.11168810725212097, "5511": 0.016465263441205025, "5531": 0.25694093108177185, "5576": 0.6960725784301758, "5604": 0.13071982562541962, "5662": 0.09938567131757736, "5688": 0.4914994537830353, "5709": 0.5209306478500366, "5717": 0.3443928062915802, "5757": 0.24018502235412598, "5770": 0.45499902963638306, "5772": 0.20501139760017395, "5776": 0.7473171949386597, "5790": 0.18004031479358673, "5850": 0.07612881064414978, "5918": 0.7009293437004089, "5942": 0.0019512200960889459, "5966": 0.2719337046146393, "5970": 0.8492490649223328, "5986": 0.013579257763922215, "6020": 0.26146242022514343, "6022": 0.7009293437004089, "6110": 0.32129061222076416, "6121": 1.0788878202438354, "6179": 0.026025565341114998, "6185": 0.04394211992621422, "6190": 0.22937409579753876, "6191": 0.5295937061309814, "6291": 0.08154398202896118, "6388": 0.31132611632347107, "6409": 0.5364705324172974, "6428": 0.1229778528213501, "6431": 0.6709295511245728, "6463": 0.06977381557226181, "6494": 0.7665573358535767, "6540": 0.19381128251552582, "6551": 0.10467668622732162, "6595": 0.06795065850019455, "6611": 0.25239890813827515, "6612": 0.21135559678077698, "6629": 0.0913962796330452, "6633": 0.417115718126297, "6648": 0.2659635543823242, "6660": 0.10026945173740387, "6666": 0.5876781344413757, "6702": 0.16690383851528168, "6709": 0.0019512200960889459, "6721": 0.6128603219985962, "6745": 0.2800849378108978, "6864": 0.053244512528181076, "7012": 0.9842413663864136, "7017": 0.3824150264263153, "7080": 0.5433003902435303, "7091": 0.5080875158309937, "7174": 0.1685553640127182, "7242": 0.02316705882549286, "7265": 0.3248254358768463, "7300": 0.6275664567947388, "7461": 0.46424978971481323, "7485": 0.15860503911972046, "7507": 0.21530038118362427, "7551": 0.13157635927200317, "7558": 0.5751199722290039, "7583": 0.6254787445068359, "7645": 0.21530038118362427, "7681": 0.6461620330810547, "7690": 0.19782574474811554, "7691": 0.1873544454574585, "7709": 0.19622190296649933, "7711": 0.1808556467294693, "7718": 0.06246116757392883, "7809": 0.5947071313858032, "7820": 0.23556606471538544, "7831": 0.7445381283760071, "7860": 0.0009760859538801014, "7861": 0.4462870955467224, "7885": 0.13670019805431366, "8122": 0.09050461649894714, "8211": 0.8074519634246826, "8213": 1.0137293338775635, "8280": 0.2659635543823242, "8290": 0.04767346754670143, "8323": 0.678390383720398, "8376": 0.9348671436309814, "8382": 0.5936289429664612, "8400": 0.3676496744155884, "8450": 0.15526613593101501, "8516": 0.7445381283760071, "8553": 0.10906458646059036, "8564": 0.006812678650021553, "8661": 0.14349138736724854, "8819": 0.007782140281051397, "8853": 0.14264501631259918, "8902": 0.9379299283027649, "8915": 0.9108069539070129, "8949": 0.3443928062915802, "8991": 0.0174254160374403, "9034": 0.018384648486971855, "9047": 0.8057082891464233, "9095": 0.4450363218784332, "9099": 0.8315495252609253, "9211": 0.015504186972975731, "9280": 0.016465263441205025, "9312": 0.28890204429626465, "9355": 0.14686977863311768, "9367": 0.3464667797088623, "9398": 0.018384648486971855, "9412": 0.036437395960092545, "9431": 0.22626367211341858, "9524": 0.14939609169960022, "9556": 0.33675122261047363, "9560": 0.0174254160374403, "9601": 0.2105647772550583, "9662": 0.03360854089260101, "9689": 0.14349138736724854, "9750": 0.18816383183002472, "9756": 0.05046287178993225, "9839": 0.15860503911972046, "10539": 0.025073638185858727, "10556": 0.08154398202896118, "10599": 0.37304413318634033, "10640": 0.0009760859538801014, "10708": 0.1064341589808464, "10742": 0.25845035910606384, "10771": 0.1677299439907074, "10859": 0.020300358533859253, "11031": 0.8796916007995605, "11179": 0.16524957120418549, "11234": 0.15023678541183472, "11704": 0.20501139760017395, "11707": 0.6006163358688354, "11709": 0.12470348179340363, "11714": 0.27934664487838745, "11806": 0.8550800085067749, "11949": 0.18978065252304077, "12033": 0.2145126610994339, "12044": 0.23324857652187347, "12058": 0.0913962796330452, "12123": 0.4412745535373688, "12237": 0.2822965085506439, "12319": 0.34370049834251404, "12353": 0.6275664567947388, "12435": 0.6165571808815002, "12503": 0.0019512200960889459, "12504": 0.0770333781838417, "12520": 0.043007105588912964, "12546": 0.014542185701429844, "12596": 0.22782009840011597, "12637": 0.19381128251552582, "12711": 0.32553088665008545, "12826": 0.4974553883075714, "12838": 0.25239890813827515, "12941": 0.2018241584300995, "13072": 0.129004567861557, "13105": 0.06520967930555344, "13341": 0.25467249751091003, "13356": 0.014542185701429844, "13494": 0.18248429894447327, "13531": 0.1064341589808464, "13595": 0.2034190446138382, "13599": 0.6254787445068359, "13726": 0.34370049834251404, "13922": 0.026025565341114998, "14115": 0.10379679501056671, "14117": 1.0986123085021973, "14155": 0.16276304423809052, "14402": 0.500420093536377, "14438": 0.7800771594047546, "14557": 0.1873544454574585, "14629": 0.06246116757392883, "14670": 0.3601844012737274, "14996": 0.4286321699619293, "15050": 0.7809720039367676, "15058": 0.777387797832489, "15189": 0.2918238639831543, "15306": 0.7445381283760071, "15316": 1.04512357711792, "15333": 0.31132611632347107, "15488": 0.8715548515319824, "15559": 0.12556517124176025, "15584": 0.00875066313892603, "15871": 0.42225050926208496, "16127": 0.2983669638633728, "16134": 0.4487839937210083, "16330": 0.6038249135017395, "16367": 0.2026219218969345, "16478": 0.2852376699447632, "16515": 0.1510767638683319, "16519": 0.0009760859538801014, "16578": 0.10731173306703568, "16731": 0.7305257320404053, "16940": 0.151916041970253, "17042": 0.24631060659885406, "17316": 0.48970574140548706, "17419": 1.0828639268875122, "17473": 0.22001366317272186, "17631": 0.27044451236724854, "17826": 0.1685553640127182, "17881": 0.18329764902591705, "17908": 0.5729197263717651, "18002": 0.15860503911972046, "18037": 0.8941729068756104, "18130": 0.47463157773017883, "18178": 0.35060185194015503, "18234": 0.7182208299636841, "18479": 0.987156867980957, "18539": 0.3374483287334442, "18687": 0.6054253578186035, "18804": 1.1217793226242065, "19064": 0.2763880789279938, "19209": 0.3423145115375519, "19389": 0.8666408061981201, "19802": 0.6112717390060425, "20162": 0.14179791510105133, "20253": 0.13414156436920166, "20302": 0.12556517124176025, "20363": 1.2392796277999878, "20389": 0.018384648486971855, "20502": 0.30989447236061096, "20523": 1.1356772184371948, "20679": 0.25995752215385437, "20828": 0.029824240133166313, "20885": 0.3353555500507355, "20960": 0.1229778528213501, "21117": 0.011650617234408855, "21150": 1.0437490940093994, "21325": 0.08603433519601822, "21371": 0.007782140281051397, "21500": 1.0868242979049683, "21778": 0.0019512200960889459, "22110": 1.1166772842407227, "22291": 0.3995884954929352, "22329": 0.846739649772644, "22423": 0.2674594223499298, "22935": 0.47463157773017883, "22963": 0.3723714053630829, "23150": 0.08513788133859634, "23316": 0.15023678541183472, "23320": 0.026025565341114998, "23484": 1.61021888256073, "23521": 0.022212404757738113, "23943": 0.06246116757392883, "24054": 0.03360854089260101, "24628": 0.5127768516540527, "24714": 0.10555581003427505, "24735": 0.33675122261047363, "24848": 1.1031591892242432, "25022": 0.6744182109832764, "25095": 0.03266380727291107, "25135": 0.22782009840011597, "25172": 0.5795059204101562, "25344": 0.006812678650021553, "25608": 0.46117570996284485, "25714": 0.17759032547473907, "25719": 0.026025565341114998, "25918": 0.15860503911972046, "26437": 0.07612881064414978, "26521": 0.5261374711990356, "27144": 0.4425300657749176, "27159": 0.14518201351165771, "27204": 1.1375575065612793, "27354": 0.0058422754518687725, "27531": 0.09228714555501938, "27710": 1.160461664199829, "28093": 0.04113444685935974, "28155": 0.8383291959762573, "28353": 0.04860413447022438, "28413": 0.058784693479537964, "28648": 0.1212492436170578, "28696": 0.9987343549728394, "28895": 0.10379679501056671, "29200": 0.5990082025527954, "29361": 0.10203468054533005, "29454": 0.11517547070980072, "29516": 0.12384103983640671} | 13514898 | INTRODUCTION Recent studies in septic patients showed that adverse effects of hydroxyethyl starches (HESs) possibly outweigh their benefits in severely impaired physiological haemostasis. It remains unclear whether this also applies to patient populations that are less vulnerable. In this meta-analysis, we evaluated the impact of various HES generations on safety and efficacy endpoints in patients undergoing cardiac surgery. METHODS We searched the PubMed, Embase and Cochrane Central Register of Controlled Trials databases for randomised controlled trials (RCTs) in the English or German language comparing the use of HES to any other colloid or crystalloid during open heart surgery. RESULTS Blood loss and transfusion requirements were higher for older starches with mean molecular weights more than 200 kDa compared to other volume substitutes. In contrast, this effect was not observed with latest-generation tetrastarches (130/0.4), which performed even better when compared to albumin (blood loss of tetrastarch versus albumin: standardised mean difference (SMD), -0.34; 95% CI, -0.63, -0.05; P = 0.02; versus gelatin: SMD, -0.06; 95% CI, -0.20, 0.08; P = 0.39; versus crystalloids: SMD, -0.05; 95% CI, -0.20, 0.10; P = 0.54). Similar results were found for transfusion needs. Lengths of stay in the intensive care unit or hospital were significantly shorter with tetrastarches compared to gelatin (intensive care unit: SMD, -0.10; 95% CI, -0.15, -0.05; P = 0.0002) and crystalloids (hospital: SMD, -0.52; 95% CI, -0.90, -0.14; P = 0.007). CONCLUSIONS In this meta-analysis of RCTs, we could not identify safety issues with tetrastarches compared with other colloid or crystalloid solutions in terms of blood loss, transfusion requirements or hospital length of stay in patients undergoing cardiac surgery. The safety data on coagulation with older starches raise some issues that need to be addressed in future trials. | The impact of hydroxyethyl starches in cardiac surgery: a meta-analysis |
{"1003": 0.35745587944984436, "1023": 0.00875066313892603, "1997": 0.3897167444229126, "1998": 0.022212404757738113, "1999": 0.6684301495552063, "2001": 0.1946154683828354, "2005": 0.27044451236724854, "2012": 0.6096806526184082, "2020": 0.09584271162748337, "2022": 0.055094651877880096, "2037": 0.07341018319129944, "2042": 0.272677481174469, "2043": 0.19862671196460724, "2058": 0.15610189735889435, "2062": 0.623910129070282, "2071": 0.04394211992621422, "2084": 0.5551415085792542, "2085": 0.11256109178066254, "2087": 0.3409265875816345, "2095": 0.1693800985813141, "2106": 0.25088030099868774, "2109": 0.11691460013389587, "2111": 0.5404602885246277, "2116": 0.09672962874174118, "2117": 0.6118015646934509, "2124": 0.20421554148197174, "2135": 0.1358480453491211, "2136": 0.2493593990802765, "2155": 0.48610860109329224, "2160": 0.2576959431171417, "2164": 0.2317005842924118, "2166": 0.8764448165893555, "2173": 0.9333322048187256, "2174": 0.22626367211341858, "2177": 0.40285754203796387, "2179": 0.13243216276168823, "2181": 0.3554046154022217, "2188": 1.130645751953125, "2203": 0.6492279767990112, "2206": 0.013579257763922215, "2215": 0.32270604372024536, "2236": 0.7436100244522095, "2241": 0.05417001247406006, "2270": 0.1808556467294693, "2313": 0.8674615025520325, "2323": 0.04394211992621422, "2326": 0.30917787551879883, "2331": 1.1287524700164795, "2339": 0.2607102394104004, "2342": 0.16359257698059082, "2348": 0.0752234235405922, "2350": 0.018384648486971855, "2351": 0.5822374224662781, "2359": 0.1873544454574585, "2381": 0.08154398202896118, "2405": 0.23402166366577148, "2414": 0.857568621635437, "2421": 0.4764525294303894, "2423": 0.19220098853111267, "2424": 0.12728634476661682, "2426": 0.5478278398513794, "2443": 0.38441169261932373, "2444": 0.15526613593101501, "2470": 0.6176109313964844, "2478": 0.151916041970253, "2485": 0.6892333030700684, "2511": 0.052318159490823746, "2515": 0.018384648486971855, "2517": 0.16276304423809052, "2531": 0.7009293437004089, "2542": 0.10291612148284912, "2563": 0.21293537318706512, "2578": 0.36290550231933594, "2590": 0.040196798741817474, "2592": 0.2674594223499298, "2593": 0.1602703034877777, "2639": 0.5990082025527954, "2640": 0.53589928150177, "2641": 0.0317181795835495, "2658": 0.3134697377681732, "2681": 0.0354953333735466, "2687": 0.1212492436170578, "2691": 0.6684301495552063, "2711": 0.09317722171545029, "2714": 0.055094651877880096, "2729": 1.0023250579833984, "2740": 0.24554696679115295, "2747": 0.4450363218784332, "2752": 0.20501139760017395, "2753": 0.3750596046447754, "2755": 0.14349138736724854, "2757": 0.18411032855510712, "2765": 0.19862671196460724, "2767": 0.8323994874954224, "2777": 0.083342544734478, "2783": 0.3381449282169342, "2803": 0.1734936386346817, "2812": 0.06977381557226181, "2814": 0.5696102976799011, "2817": 0.7863243818283081, "2844": 0.38174858689308167, "2846": 0.9029204845428467, "2866": 0.4914994537830353, "2872": 0.1970241367816925, "2881": 0.2317005842924118, "2902": 0.6317287683486938, "2913": 0.7898768186569214, "2945": 0.49030399322509766, "2951": 0.7134475708007812, "2966": 0.2447827309370041, "2967": 0.38441169261932373, "2983": 0.012615402229130268, "2988": 0.17840765416622162, "2994": 0.0029254043474793434, "3020": 0.22157983481884003, "3024": 0.036437395960092545, "3116": 0.2800849378108978, "3182": 0.3388410806655884, "3189": 0.3409265875816345, "3193": 0.29981520771980286, "3227": 0.10555581003427505, "3247": 0.06977381557226181, "3251": 0.1619328260421753, "3261": 0.06612417846918106, "3268": 0.14349138736724854, "3272": 0.42735910415649414, "3273": 0.4462870955467224, "3280": 0.9717550277709961, "3289": 0.0009760859538801014, "3301": 0.01934296265244484, "3319": 0.8567397594451904, "3325": 0.4914994537830353, "3326": 0.6054253578186035, "3343": 0.045809537172317505, "3344": 0.22782009840011597, "3350": 0.9287132620811462, "3416": 0.09938567131757736, "3433": 0.9493325352668762, "3446": 0.6165571808815002, "3463": 0.4974553883075714, "3466": 0.030771657824516296, "3476": 0.0009760859538801014, "3479": 0.25467249751091003, "3497": 0.08692999184131622, "3522": 0.3005385100841522, "3530": 0.32553088665008545, "3532": 0.12384103983640671, "3547": 0.5784112811088562, "3550": 0.01934296265244484, "3551": 0.17020416259765625, "3601": 0.53589928150177, "3725": 0.5370414853096008, "3726": 0.14686977863311768, "3728": 0.0058422754518687725, "3807": 0.0009760859538801014, "3866": 0.07159364968538284, "3867": 0.5930894017219543, "3906": 0.9425065517425537, "3935": 0.9857001900672913, "3945": 0.34370049834251404, "3979": 0.09584271162748337, "3997": 0.13243216276168823, "4094": 0.009718249551951885, "4102": 0.520350456237793, "4106": 0.5865923762321472, "4118": 0.6128603219985962, "4122": 0.14349138736724854, "4141": 0.31132611632347107, "4146": 0.2659635543823242, "4179": 0.7028654217720032, "4217": 0.09672962874174118, "4242": 0.39367714524269104, "4281": 0.8013357520103455, "4287": 0.16690383851528168, "4295": 0.15275461971759796, "4299": 0.6931471824645996, "4311": 0.15526613593101501, "4340": 0.2983669638633728, "4391": 0.46117570996284485, "4453": 0.5069117546081543, "4456": 1.04512357711792, "4531": 0.5495203733444214, "4566": 0.10818854719400406, "4568": 0.10731173306703568, "4663": 0.28082266449928284, "4671": 0.026025565341114998, "4703": 0.04953393340110779, "4706": 0.022212404757738113, "4719": 0.4400174915790558, "4725": 0.5833279490470886, "4749": 0.5925496220588684, "4792": 0.347847044467926, "4876": 0.07341018319129944, "5002": 0.500420093536377, "5014": 0.7510106563568115, "5022": 0.8281423449516296, "5083": 0.5893046259880066, "5084": 0.04674193635582924, "5228": 0.6476961374282837, "5281": 0.32905077934265137, "5301": 0.27342069149017334, "5328": 0.5860490798950195, "5335": 0.3027053773403168, "5368": 0.030771657824516296, "5393": 0.5197699069976807, "5427": 0.06246116757392883, "5443": 0.09495500475168228, "5454": 0.011650617234408855, "5468": 0.35745587944984436, "5531": 0.3339579105377197, "5536": 1.1255888938903809, "5605": 0.1710275560617447, "5617": 0.33325836062431335, "5646": 0.38441169261932373, "5647": 0.0009760859538801014, "5684": 0.6624060273170471, "5719": 0.272677481174469, "5723": 0.040196798741817474, "5724": 0.7124901413917542, "5739": 0.1677299439907074, "5761": 0.28743788599967957, "5769": 0.20580662786960602, "5776": 1.0587663650512695, "5790": 0.1221139207482338, "5816": 0.7201237678527832, "5838": 0.45994341373443604, "5856": 0.5376120805740356, "5920": 0.04860413447022438, "5921": 0.14433705806732178, "5993": 0.14939609169960022, "5996": 0.9515975713729858, "6022": 0.18816383183002472, "6075": 0.07341018319129944, "6162": 0.6022219061851501, "6165": 0.4437839686870575, "6257": 0.2881702482700348, "6299": 0.13243216276168823, "6319": 0.06337817758321762, "6322": 0.016465263441205025, "6388": 0.29109421372413635, "6405": 0.11951763927936554, "6428": 0.1930064558982849, "6431": 0.304147332906723, "6461": 0.03360854089260101, "6480": 0.22782009840011597, "6508": 0.4444103240966797, "6575": 0.15442965924739838, "6612": 0.07884006202220917, "6614": 0.7163142561912537, "6632": 0.0606246218085289, "6677": 0.39893341064453125, "6685": 0.05046287178993225, "6709": 0.11691460013389587, "6715": 0.2674594223499298, "6747": 0.3743882179260254, "6785": 0.021256839856505394, "6808": 0.1221139207482338, "6821": 0.13670019805431366, "6825": 0.014542185701429844, "6860": 0.19622190296649933, "6869": 0.672426164150238, "6871": 0.7951818704605103, "6885": 0.17759032547473907, "6947": 0.1510767638683319, "6950": 0.09761575609445572, "6952": 0.053244512528181076, "7012": 0.3012613356113434, "7017": 0.7737906575202942, "7047": 0.42735910415649414, "7080": 0.3485364317893982, "7091": 0.6674286723136902, "7099": 0.6317287683486938, "7197": 0.14602625370025635, "7198": 0.8877626657485962, "7216": 0.01934296265244484, "7226": 0.755608320236206, "7316": 0.5168620347976685, "7355": 0.5865923762321472, "7368": 0.16359257698059082, "7452": 0.01934296265244484, "7478": 0.09495500475168228, "7541": 0.03925827145576477, "7551": 0.25995752215385437, "7591": 0.7683706283569336, "7594": 0.3034266233444214, "7620": 0.06612417846918106, "7667": 0.13755162060260773, "7691": 0.13157635927200317, "7778": 0.10379679501056671, "7809": 0.7417513132095337, "7831": 0.5301685929298401, "7863": 0.3134697377681732, "7885": 0.22859740257263184, "7927": 0.37907835841178894, "8010": 0.06795065850019455, "8168": 0.45870962738990784, "8182": 0.5021947622299194, "8289": 0.4512746334075928, "8323": 0.18492233753204346, "8329": 0.3381449282169342, "8390": 0.33675122261047363, "8483": 0.495672345161438, "8554": 0.013579257763922215, "8599": 0.1332872211933136, "8704": 0.16442140936851501, "8827": 0.3615458607673645, "8937": 0.04767346754670143, "8940": 0.21293537318706512, "8984": 0.03925827145576477, "8996": 0.3870677351951599, "9022": 0.16110190749168396, "9059": 0.043007105588912964, "9147": 0.05786345899105072, "9181": 0.10291612148284912, "9289": 0.10203468054533005, "9312": 0.04207121208310127, "9349": 0.04674193635582924, "9470": 0.4679262638092041, "9544": 0.6275664567947388, "9556": 0.45623743534088135, "9560": 0.5151132941246033, "9608": 0.1011524572968483, "9619": 0.1011524572968483, "9662": 0.09938567131757736, "9750": 0.055094651877880096, "9849": 0.16690383851528168, "9871": 0.30486753582954407, "9895": 0.08871890604496002, "9896": 0.018384648486971855, "9967": 0.32764431834220886, "10174": 0.08244366943836212, "10181": 0.14686977863311768, "10309": 0.1913948506116867, "10473": 0.42608439922332764, "10502": 0.08603433519601822, "10549": 0.08064348995685577, "10599": 0.5882205963134766, "10611": 0.030771657824516296, "10744": 0.2539152204990387, "10752": 0.5433003902435303, "10753": 0.0019512200960889459, "10787": 0.2881702482700348, "10847": 0.014542185701429844, "10903": 0.4400174915790558, "10910": 0.38574060797691345, "10960": 0.4518963396549225, "11100": 0.1619328260421753, "11119": 0.2983669638633728, "11121": 0.040196798741817474, "11331": 0.04767346754670143, "11433": 0.014542185701429844, "11594": 0.13755162060260773, "11656": 0.36900100111961365, "11709": 0.10291612148284912, "11778": 0.8796916007995605, "11922": 0.5238267183303833, "11929": 0.06154331564903259, "12005": 0.5080875158309937, "12132": 0.3903779089450836, "12157": 1.2910817861557007, "12265": 0.1970241367816925, "12287": 0.7408206462860107, "12353": 0.12728634476661682, "12407": 0.0058422754518687725, "12411": 0.08603433519601822, "12435": 0.32764431834220886, "12515": 0.4041621685028076, "12596": 0.1677299439907074, "12644": 0.21765978634357452, "12654": 0.08603433519601822, "12697": 0.16524957120418549, "12735": 0.129004567861557, "12826": 0.3070250153541565, "12832": 0.043007105588912964, "13105": 0.6353566646575928, "13228": 0.11604541540145874, "13356": 0.5151132941246033, "13433": 0.1358480453491211, "13473": 0.6358738541603088, "13599": 0.40741631388664246, "13644": 0.32905077934265137, "13656": 0.08154398202896118, "13659": 0.12986256182193756, "13827": 1.0207915306091309, "14028": 0.4113073945045471, "14120": 0.659380316734314, "14155": 0.4248080551624298, "14246": 0.09495500475168228, "14358": 0.26146242022514343, "14412": 0.7182208299636841, "14639": 0.9643365740776062, "14667": 0.0606246218085289, "14817": 0.29255300760269165, "15042": 0.03831886500120163, "15074": 0.6296497583389282, "15252": 0.31489628553390503, "15306": 0.8748174905776978, "15354": 1.1070401668548584, "15396": 0.0317181795835495, "15509": 0.38441169261932373, "15844": 0.09050461649894714, "15873": 0.5232481360435486, "15901": 0.21214580535888672, "15909": 0.9650808572769165, "15982": 0.14939609169960022, "16007": 0.02316705882549286, "16134": 0.6016870141029358, "16166": 0.034552380442619324, "16227": 0.09672962874174118, "16302": 0.5629584193229675, "16330": 0.07159364968538284, "16412": 0.06154331564903259, "16463": 0.2034190446138382, "16519": 0.25694093108177185, "16822": 0.4450363218784332, "17193": 0.41065993905067444, "17208": 0.05046287178993225, "17237": 1.001607894897461, "17464": 0.6970458030700684, "17534": 0.619189441204071, "17537": 0.1332872211933136, "17573": 0.045809537172317505, "17703": 0.31845372915267944, "17847": 0.06246116757392883, "17881": 0.20102575421333313, "17908": 0.23247487843036652, "17994": 0.5347557663917542, "18075": 0.004870930220931768, "18394": 1.109619140625, "18539": 0.20739519596099854, "18759": 0.14686977863311768, "18925": 0.021256839856505394, "18949": 0.05417001247406006, "18960": 0.33675122261047363, "19233": 0.22626367211341858, "19475": 0.020300358533859253, "19692": 0.6139179468154907, "19824": 0.5104349255561829, "19960": 0.4462870955467224, "20077": 0.04207121208310127, "20080": 0.007782140281051397, "20134": 0.906871497631073, "20155": 0.15359249711036682, "20272": 0.05786345899105072, "20360": 0.17267228662967682, "20714": 0.11865071207284927, "20723": 0.7881022095680237, "20828": 0.28450319170951843, "21081": 0.014542185701429844, "21150": 0.10993985831737518, "21191": 0.12986256182193756, "21393": 0.2711893916130066, "21604": 0.2741633653640747, "21901": 0.11517547070980072, "22470": 0.5116065740585327, "22822": 0.011650617234408855, "22945": 0.045809537172317505, "22963": 0.2719337046146393, "23086": 0.42353010177612305, "23087": 0.7067264318466187, "23270": 0.058784693479537964, "23552": 0.036437395960092545, "23569": 0.5209306478500366, "23732": 0.06246116757392883, "23795": 0.08603433519601822, "24010": 0.0174254160374403, "24039": 0.32341301441192627, "24110": 0.004870930220931768, "24203": 0.33953672647476196, "24343": 1.020087480545044, "24436": 0.06612417846918106, "24757": 0.3339579105377197, "25094": 0.7463917136192322, "25352": 0.8004589080810547, "25354": 0.012615402229130268, "25409": 0.5110208988189697, "25481": 0.15359249711036682, "25613": 0.12728634476661682, "25778": 0.23710809648036957, "26179": 0.018384648486971855, "26206": 0.2317005842924118, "26243": 0.6086184978485107, "26319": 0.17431432008743286, "26462": 0.4462870955467224, "26651": 0.47036975622177124, "26846": 0.3318578004837036, "26886": 0.3297532796859741, "27144": 0.0317181795835495, "27597": 0.11778303235769272, "27615": 0.15023678541183472, "27794": 0.09672962874174118, "28170": 0.5301685929298401, "28207": 0.045809537172317505, "28321": 0.07159364968538284, "28767": 0.2881702482700348, "28794": 0.07068414986133575, "29277": 1.3580676317214966, "29353": 0.06154331564903259} | 13515165 | BACKGROUND It is commonly written that more patients wish to die at home than currently achieve this. However, the evidence for preferences for place of terminal care and death has not been systematically reviewed. AIM To carry out a systematic literature review of the preferences for place of care and death among advanced cancer patients. METHOD Studies were identified using systematic database searches of MEDLINE (1966-1999), PsychLit (1974-1999), and Bath Information Data Service (BIDS) (1981-1999). Studies were assessed and data extracted and synthesises following the NHS Centre for Reviews and Dissemination guidelines, grading studies according to design and rigor of methods. Studies of preferences in the general population and of groups including cancer patients and/or their caregivers were included. RESULTS Eighteen studies determining preferences in either the general population or groups including cancer patients were identified. Views were obtained prospectively and retrospectively from patients, the general population, families, and professionals. Respondents indicated preferences for home death (range 49%-100%), except one study of patients in the care of a continuing care team in London where only 25%-29% of patients wanted a home death, and inpatient hospice was the most favored option. However, the response rate of this study was not known. Among the general public there was a higher preference for inpatient hospice care among in people with recent experience of a close friend or relative's death or dying. Where the views of patients, families, and professionals were compared, all respondents broadly agreed although patients expressed the strongest home preferences. Only 2 of the studies provided longitudinal data, and 9 of the 18 had major deficits in design or reporting, such as poor or unknown response rate, unclear or unsystematic methods of eliciting preferences or other sample or measurement bias. However, sensitivity analysis of only the more robust and larger studies did not alter the finding of a preference for home care at the end of life in over 50% of patients. CONCLUSIONS Home care is the most common preference, with inpatient hospice care as second preference in advanced illness. Meeting these preferences could be important outcomes for services. Study designs in this area need to be improved. | Place of care in advanced cancer: a qualitative systematic literature review of patient preferences. |
{"1014": 0.1970241367816925, "1016": 0.5696102976799011, "1020": 0.40285754203796387, "1039": 0.18004031479358673, "1047": 0.4950772523880005, "1055": 0.7067264318466187, "2015": 0.2231435477733612, "2029": 0.2018241584300995, "2048": 0.129004567861557, "2057": 0.10906458646059036, "2090": 0.055094651877880096, "2116": 0.3163207769393921, "2117": 0.11604541540145874, "2119": 0.10379679501056671, "2167": 0.11168810725212097, "2179": 0.25239890813827515, "2243": 1.176850438117981, "2278": 0.6170841455459595, "2308": 0.5930894017219543, "2309": 0.8349450826644897, "2313": 0.817850649356842, "2340": 0.27934664487838745, "2408": 0.14518201351165771, "2416": 0.6415454745292664, "2426": 0.08154398202896118, "2450": 0.28743788599967957, "2458": 0.49626702070236206, "2470": 0.1685553640127182, "2475": 1.0158531665802002, "2491": 0.3850763738155365, "2509": 0.11951763927936554, "2511": 0.26146242022514343, "2512": 0.30989447236061096, "2515": 0.1905880719423294, "2523": 0.5723689198493958, "2535": 0.5767669677734375, "2555": 0.3622259199619293, "2581": 0.49864232540130615, "2590": 0.2837681770324707, "2594": 0.1693800985813141, "2642": 0.5104349255561829, "2647": 0.5461324453353882, "2691": 0.7267557382583618, "2695": 0.4248080551624298, "2817": 0.3325583338737488, "2885": 0.5313173532485962, "2912": 0.10379679501056671, "2913": 0.4518963396549225, "2918": 0.1619328260421753, "2920": 0.17922431230545044, "2931": 0.28670501708984375, "3025": 0.1602703034877777, "3132": 0.1212492436170578, "3231": 0.07431721687316895, "3251": 0.0752234235405922, "3273": 0.29036402702331543, "3278": 0.09938567131757736, "3344": 0.1889725625514984, "3378": 0.3982778787612915, "3382": 0.03360854089260101, "3426": 0.08064348995685577, "3466": 0.08961215615272522, "3484": 0.5398913025856018, "3497": 0.014542185701429844, "3517": 0.14686977863311768, "3526": 0.3547199070453644, "3540": 0.2822965085506439, "3549": 0.3163207769393921, "3572": 0.2711893916130066, "3625": 0.1358480453491211, "3670": 0.13499516248703003, "3683": 0.055094651877880096, "3747": 0.4400174915790558, "3775": 0.3346569836139679, "3801": 0.29255300760269165, "3891": 0.997294545173645, "4053": 0.15777134895324707, "4106": 0.26446542143821716, "4135": 0.22001366317272186, "4140": 0.39893341064453125, "4141": 0.15860503911972046, "4242": 0.33675122261047363, "4281": 0.9643365740776062, "4295": 0.06429435312747955, "4321": 0.058784693479537964, "4358": 0.37035053968429565, "4387": 0.306306391954422, "4395": 0.43053874373435974, "4442": 0.3353555500507355, "4453": 0.07612881064414978, "4456": 1.2985725402832031, "4467": 1.072225570678711, "4503": 0.08961215615272522, "4531": 0.06612417846918106, "4539": 0.04953393340110779, "4655": 0.35403475165367126, "4678": 0.8666408061981201, "4701": 0.9425065517425537, "4725": 0.12814582884311676, "4726": 0.42990362644195557, "4727": 0.4113073945045471, "4742": 0.6186635494232178, "4758": 0.4450363218784332, "4812": 0.5495203733444214, "4868": 0.15275461971759796, "4895": 0.29981520771980286, "4962": 1.1846466064453125, "4975": 0.3304552733898163, "5003": 0.052318159490823746, "5105": 0.13157635927200317, "5197": 0.39762192964553833, "5250": 0.030771657824516296, "5292": 0.7701805830001831, "5326": 0.255429208278656, "5345": 0.5596157908439636, "5360": 0.055094651877880096, "5387": 0.034552380442619324, "5393": 0.4926934838294983, "5402": 0.861702561378479, "5425": 0.19622190296649933, "5585": 0.18978065252304077, "5591": 0.6128603219985962, "5604": 0.01934296265244484, "5705": 0.6410312056541443, "5769": 0.3554046154022217, "6064": 0.7898768186569214, "6075": 0.8433839678764343, "6227": 0.3601844012737274, "6325": 0.4041621685028076, "6415": 0.7907629609107971, "6431": 0.11168810725212097, "6463": 0.7124901413917542, "6524": 0.03266380727291107, "6545": 0.7987030148506165, "6779": 0.5762182474136353, "6834": 0.09317722171545029, "6839": 0.450652539730072, "6976": 0.03360854089260101, "7012": 0.022212404757738113, "7017": 0.31560876965522766, "7023": 0.9123768210411072, "7080": 0.4926934838294983, "7099": 0.18978065252304077, "7127": 0.07068414986133575, "7192": 0.7934166193008423, "7327": 0.1401015669107437, "7337": 0.03266380727291107, "7382": 0.32270604372024536, "7388": 1.2605451345443726, "7403": 0.9302552938461304, "7461": 0.19622190296649933, "7551": 0.025073638185858727, "7578": 0.2969166338443756, "7645": 0.1358480453491211, "7667": 0.12470348179340363, "7691": 0.056018441915512085, "7694": 0.4709797203540802, "7711": 0.5984715819358826, "7755": 0.401551216840744, "7784": 0.2830325961112976, "7883": 0.06154331564903259, "7885": 0.0913962796330452, "7888": 0.11778303235769272, "7900": 0.2394166737794876, "7978": 0.24248650670051575, "7987": 0.41647201776504517, "8092": 0.2478361576795578, "8168": 0.25845035910606384, "8349": 0.44691193103790283, "8358": 0.45499902963638306, "8386": 0.47766464948654175, "8556": 0.03831886500120163, "8906": 0.5629584193229675, "8924": 0.4158279001712799, "8947": 0.4337083101272583, "8991": 0.6270449161529541, "9007": 0.025073638185858727, "9153": 0.053244512528181076, "9165": 1.0298984050750732, "9247": 1.1431772708892822, "9253": 0.21530038118362427, "9312": 0.36494144797325134, "9336": 0.22782009840011597, "9416": 0.09672962874174118, "9556": 0.43875885009765625, "9592": 0.07250232994556427, "9670": 0.13499516248703003, "9723": 0.05139094591140747, "10010": 0.6128603219985962, "10035": 0.5110208988189697, "10091": 0.10993985831737518, "10173": 0.6533012986183167, "10176": 0.5756692886352539, "10197": 0.3923587501049042, "10210": 0.22157983481884003, "10238": 1.185243844985962, "10315": 0.2659635543823242, "10318": 0.07793712615966797, "10381": 0.2231435477733612, "10383": 0.75193190574646, "10556": 0.0029254043474793434, "10744": 0.07612881064414978, "10831": 0.5540198087692261, "10847": 0.3963087201118469, "11363": 0.5762182474136353, "11382": 0.4938860833644867, "11538": 0.022212404757738113, "11847": 0.1905880719423294, "12115": 0.10379679501056671, "12260": 0.09406650811433792, "12407": 0.05139094591140747, "12662": 0.20580662786960602, "12682": 0.7086513638496399, "12709": 0.29619070887565613, "12987": 0.04487626627087593, "13139": 0.5151132941246033, "13191": 0.11691460013389587, "13359": 0.4891071021556854, "13458": 0.46853771805763245, "13483": 0.7352184057235718, "13642": 0.7463917136192322, "13656": 0.6000806093215942, "13671": 0.6989894509315491, "13791": 0.10203468054533005, "13874": 0.5438674688339233, "13908": 0.1889725625514984, "13912": 0.7854343056678772, "14025": 0.35745587944984436, "14067": 0.1913948506116867, "14155": 0.30558720231056213, "14163": 0.4374985992908478, "14358": 0.319873183965683, "14471": 0.4944818615913391, "14494": 0.9798521995544434, "14526": 0.29036402702331543, "14760": 0.10731173306703568, "14798": 0.06703783571720123, "14800": 0.17840765416622162, "14828": 0.19381128251552582, "14840": 0.4145384132862091, "15058": 0.5393219590187073, "15316": 0.11081436276435852, "15527": 0.6714286804199219, "15543": 0.21214580535888672, "16007": 0.3283478021621704, "16014": 0.6139179468154907, "16221": 1.1647365093231201, "16238": 0.35950297117233276, "16252": 1.029200792312622, "16275": 0.9515975713729858, "16330": 0.04394211992621422, "16371": 0.1685553640127182, "16515": 0.3963087201118469, "16578": 0.129004567861557, "16636": 0.2881702482700348, "16706": 0.25088030099868774, "17441": 0.5174443125724792, "17547": 0.5573811531066895, "17660": 0.3443928062915802, "17908": 0.021256839856505394, "18178": 1.426491141319275, "18212": 0.11256109178066254, "18228": 0.13157635927200317, "19188": 0.22392450273036957, "19314": 0.03266380727291107, "19345": 0.5855054259300232, "19539": 0.9635916948318481, "19824": 0.472198486328125, "19939": 0.0842406153678894, "20250": 0.009718249551951885, "20272": 0.11343330889940262, "20467": 0.08154398202896118, "20612": 0.07793712615966797, "20932": 0.32764431834220886, "21081": 0.4177590310573578, "21189": 0.44753631949424744, "21217": 0.42096930742263794, "21434": 0.4462870955467224, "21677": 0.4974553883075714, "21879": 0.4914994537830353, "21903": 1.452418565750122, "21919": 0.08961215615272522, "22073": 0.8715548515319824, "22096": 1.310231328010559, "22136": 0.08961215615272522, "22571": 0.7809720039367676, "22868": 0.3163207769393921, "23041": 0.1905880719423294, "23586": 0.1221139207482338, "23616": 0.3622259199619293, "23900": 0.018384648486971855, "24004": 0.02316705882549286, "24054": 0.1693800985813141, "24155": 0.19622190296649933, "24532": 0.018384648486971855, "24759": 0.7124901413917542, "25206": 0.19782574474811554, "25409": 0.9271688461303711, "25761": 0.00875066313892603, "26163": 0.2394166737794876, "26296": 0.45251765847206116, "26305": 0.987156867980957, "26520": 1.3352066278457642, "26572": 0.6492279767990112, "26601": 0.678390383720398, "26610": 0.2607102394104004, "26741": 0.4158279001712799, "26874": 0.0019512200960889459, "27144": 0.7314660549163818, "27881": 0.15526613593101501, "28196": 0.2622140049934387, "28207": 0.08782484382390976, "28436": 0.27342069149017334, "28864": 0.12384103983640671, "28873": 0.04953393340110779, "29206": 0.013579257763922215, "29347": 0.5903874635696411, "29458": 0.6022219061851501, "29477": 0.7665573358535767} | 13519661 | Background Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unknown. In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs). Methods and Findings We analyzed 14 common SNPs spanning 52 kilobases (kb) of the CHEK2 gene in 92 Swedish women. Coverage evaluation indicated that these typed SNPs would efficiently convey association signal also from untyped SNPs in the same region. Six of the 14 SNPs predicted well both the haplotypic and single SNP variations within CHEK2. We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk. The 1100delC mutation was rare in our Swedish population—0.7% in cases and 0.4% in controls— with a corresponding odds ratio for carriers versus noncarriers of 2.26 (95% confidence interval, 0.99–5.15). Estimates of the population frequency and the odds ratio of 1100delC indicate that our sample is representative of a Northern European population. | Linkage Disequilibrium Mapping of CHEK2: Common Variation and Breast Cancer Risk |
{"1011": 0.2089812457561493, "1043": 0.3526630103588104, "1996": 0.03925827145576477, "1997": 0.11343330889940262, "2006": 0.22626367211341858, "2007": 0.22782009840011597, "2011": 0.129004567861557, "2015": 0.07793712615966797, "2029": 0.17267228662967682, "2046": 0.28155985474586487, "2050": 0.33325836062431335, "2063": 0.2689530849456787, "2076": 0.0009760859538801014, "2079": 0.19541899859905243, "2094": 0.14095009863376617, "2109": 0.09672962874174118, "2110": 0.4002431631088257, "2121": 0.4831010699272156, "2128": 0.3163207769393921, "2129": 0.21214580535888672, "2135": 0.1751343309879303, "2140": 0.41840189695358276, "2155": 0.6714286804199219, "2163": 0.6107416749000549, "2169": 0.417115718126297, "2179": 0.006812678650021553, "2203": 0.3374483287334442, "2229": 0.2026219218969345, "2232": 0.10555581003427505, "2290": 0.07068414986133575, "2361": 0.029824240133166313, "2362": 0.1332872211933136, "2367": 0.2689530849456787, "2389": 0.6764062643051147, "2415": 0.9147270321846008, "2486": 0.009718249551951885, "2487": 0.5751199722290039, "2497": 0.2493593990802765, "2509": 0.5573811531066895, "2515": 0.08154398202896118, "2532": 0.803087055683136, "2535": 0.25694093108177185, "2537": 0.03360854089260101, "2546": 0.5370414853096008, "2556": 0.41001203656196594, "2592": 0.176772341132164, "2647": 0.11778303235769272, "2693": 0.3683255612850189, "2765": 0.043007105588912964, "2803": 0.46486347913742065, "2832": 0.03925827145576477, "2885": 0.1718502640724182, "2890": 0.20739519596099854, "2920": 0.4462870955467224, "2929": 0.6118015646934509, "2945": 0.47584590315818787, "3012": 0.22859740257263184, "3176": 0.12470348179340363, "3207": 0.19220098853111267, "3232": 0.0174254160374403, "3252": 0.8161250352859497, "3366": 0.07068414986133575, "3370": 0.5573811531066895, "3375": 0.8731874823570251, "3378": 0.10555581003427505, "3431": 0.151916041970253, "3449": 0.5313173532485962, "3463": 0.24171993136405945, "3508": 0.5255602598190308, "3526": 0.4891071021556854, "3563": 0.47584590315818787, "3591": 0.16690383851528168, "3625": 0.19381128251552582, "3642": 0.5238267183303833, "3775": 0.5045560002326965, "3800": 0.1889725625514984, "3828": 0.09672962874174118, "3853": 0.27044451236724854, "3858": 0.6704301834106445, "3936": 0.34300774335861206, "3940": 0.8583967685699463, "4015": 0.45994341373443604, "4019": 0.08154398202896118, "4072": 0.0174254160374403, "4094": 0.6608943343162537, "4106": 0.5640701055526733, "4111": 0.05046287178993225, "4168": 0.5168620347976685, "4195": 0.04207121208310127, "4286": 0.004870930220931768, "4294": 0.04394211992621422, "4305": 0.01934296265244484, "4402": 0.755608320236206, "4442": 0.20660123229026794, "4453": 0.022212404757738113, "4502": 0.7057625651359558, "4515": 0.15526613593101501, "4523": 0.21765978634357452, "4539": 0.06886265426874161, "4570": 0.14349138736724854, "4632": 0.11865071207284927, "4651": 0.777387797832489, "4667": 1.0437490940093994, "4796": 0.056018441915512085, "4807": 0.14433705806732178, "4853": 0.04113444685935974, "4962": 0.18329764902591705, "4972": 0.018384648486971855, "5038": 0.33953672647476196, "5050": 0.129004567861557, "5090": 0.8057082891464233, "5098": 0.058784693479537964, "5117": 0.8682814836502075, "5149": 0.8989537954330444, "5250": 1.0001721382141113, "5258": 0.02792670577764511, "5302": 0.24018502235412598, "5343": 1.0546929836273193, "5387": 1.1063944101333618, "5421": 0.495672345161438, "5449": 1.3300546407699585, "5537": 0.1384023278951645, "5549": 0.020300358533859253, "5676": 0.6608943343162537, "5732": 0.4487839937210083, "5750": 0.6522845029830933, "5829": 0.18167030811309814, "5833": 0.1401015669107437, "5836": 0.15610189735889435, "5876": 0.9170717000961304, "5886": 0.7482418417930603, "5910": 0.5551415085792542, "5942": 0.009718249551951885, "6062": 0.043007105588912964, "6064": 0.33675122261047363, "6081": 0.8100618124008179, "6149": 0.0058422754518687725, "6155": 0.08154398202896118, "6370": 0.01934296265244484, "6401": 0.7665573358535767, "6413": 0.3339579105377197, "6503": 0.1401015669107437, "6673": 0.7809720039367676, "6789": 0.24554696679115295, "6807": 0.2763880789279938, "6897": 0.27786844968795776, "7011": 0.2223619967699051, "7327": 1.076228141784668, "7336": 0.043007105588912964, "7337": 0.8264343738555908, "7366": 0.5324648022651672, "7487": 0.5718178153038025, "7645": 0.022212404757738113, "7657": 0.38041436672210693, "7677": 0.3910386264324188, "7679": 0.045809537172317505, "7689": 0.8400169610977173, "7705": 0.9576126337051392, "7711": 0.07431721687316895, "7783": 1.1425544023513794, "7790": 0.24171993136405945, "7834": 0.31489628553390503, "7843": 0.23402166366577148, "8018": 0.14686977863311768, "8031": 0.29328158497810364, "8147": 0.4734157919883728, "8171": 0.9628462791442871, "8303": 0.06429435312747955, "8321": 0.9827804565429688, "8332": 0.8780695199966431, "8360": 0.19782574474811554, "8526": 0.5483922958374023, "8649": 0.26296505331993103, "8857": 0.12556517124176025, "8878": 0.10379679501056671, "8941": 0.21214580535888672, "9007": 0.804835319519043, "9041": 0.3077431619167328, "9099": 0.52266925573349, "9211": 0.06337817758321762, "9247": 0.8764448165893555, "9285": 0.16110190749168396, "9412": 0.0174254160374403, "9413": 0.8682814836502075, "9513": 0.1064341589808464, "9537": 0.495672345161438, "9539": 0.25239890813827515, "9556": 0.12642613053321838, "9777": 0.20421554148197174, "9844": 0.176772341132164, "10148": 0.6197150945663452, "10245": 0.29981520771980286, "10266": 0.021256839856505394, "10327": 0.1212492436170578, "10335": 0.5313173532485962, "10480": 0.23556606471538544, "10595": 0.7827593088150024, "10639": 0.2637155055999756, "10640": 0.8039615154266357, "10708": 0.0058422754518687725, "10737": 0.10467668622732162, "10752": 1.1864371299743652, "10857": 0.03831886500120163, "10994": 1.02149498462677, "11022": 0.8731874823570251, "11160": 0.7067264318466187, "11211": 0.35128939151763916, "11366": 0.9317949414253235, "11403": 0.38905516266822815, "11514": 0.8349450826644897, "11649": 0.2983669638633728, "11658": 0.861702561378479, "11703": 0.6624060273170471, "11709": 0.09495500475168228, "11718": 0.29255300760269165, "11913": 0.20660123229026794, "11973": 0.15359249711036682, "11993": 0.5255602598190308, "12016": 0.2918238639831543, "12093": 0.16359257698059082, "12326": 0.820433497428894, "12335": 0.06795065850019455, "12359": 0.36086538434028625, "12527": 0.7537717819213867, "12530": 0.3750596046447754, "12596": 0.6327666640281677, "12662": 0.4500300884246826, "12719": 0.06246116757392883, "12725": 0.3170322775840759, "12732": 0.8340972661972046, "12739": 0.4425300657749176, "12748": 0.12038381397724152, "12789": 0.06977381557226181, "12987": 1.068206787109375, "13096": 0.8383291959762573, "13228": 1.0158531665802002, "13375": 0.045809537172317505, "13512": 1.2059240341186523, "13530": 0.1718502640724182, "13538": 0.3777405619621277, "13685": 0.025073638185858727, "13711": 0.010684899985790253, "13911": 0.011650617234408855, "13922": 0.05970508232712746, "14037": 0.006812678650021553, "14080": 0.22626367211341858, "14116": 0.22392450273036957, "14125": 0.5010119676589966, "14181": 1.2341761589050293, "14187": 0.021256839856505394, "14193": 0.4944818615913391, "14206": 0.1693800985813141, "14280": 0.006812678650021553, "14306": 0.28963330388069153, "14336": 0.11951763927936554, "14391": 0.20580662786960602, "14600": 0.450652539730072, "14622": 0.1718502640724182, "14774": 0.33115679025650024, "14991": 0.0797421783208847, "15210": 0.38574060797691345, "15420": 1.005902886390686, "15719": 0.8633513450622559, "15790": 0.13157635927200317, "16001": 0.004870930220931768, "16012": 0.1229778528213501, "16044": 0.27564704418182373, "16285": 0.6139179468154907, "16316": 0.16524957120418549, "16463": 0.021256839856505394, "16478": 0.3339579105377197, "16480": 0.5290185213088989, "16627": 0.052318159490823746, "16706": 0.5540198087692261, "16803": 0.7067264318466187, "16861": 0.4158279001712799, "16910": 0.7163142561912537, "16991": 0.1221139207482338, "17181": 0.35813871026039124, "17637": 0.35677260160446167, "17782": 0.12384103983640671, "17908": 0.3012613356113434, "17975": 0.08244366943836212, "18077": 0.495672345161438, "18120": 0.4158279001712799, "18136": 0.10731173306703568, "18231": 0.0354953333735466, "18260": 0.1011524572968483, "18287": 1.1406835317611694, "18345": 0.09317722171545029, "18516": 0.13414156436920166, "18953": 0.010684899985790253, "19137": 0.9922385215759277, "19293": 0.07612881064414978, "19395": 1.2499688863754272, "19563": 0.19541899859905243, "19587": 0.08961215615272522, "19601": 0.016465263441205025, "19707": 1.269914150238037, "19780": 0.17431432008743286, "19817": 0.7791815400123596, "19872": 0.0770333781838417, "20057": 0.7182208299636841, "20320": 0.8161250352859497, "20397": 0.45994341373443604, "20817": 0.10993985831737518, "20888": 0.021256839856505394, "21312": 0.5415972471237183, "21362": 0.030771657824516296, "21365": 0.2637155055999756, "21477": 0.06154331564903259, "21572": 0.08692999184131622, "21618": 0.06246116757392883, "21647": 0.1970241367816925, "21877": 0.8433839678764343, "21903": 0.1946154683828354, "21933": 1.2948341369628906, "21963": 0.034552380442619324, "22196": 0.06154331564903259, "22328": 0.013579257763922215, "22354": 0.010684899985790253, "22402": 0.2539152204990387, "22625": 0.9092346429824829, "22658": 0.6170841455459595, "22694": 0.0797421783208847, "22778": 0.5528968572616577, "22869": 0.1930064558982849, "22969": 0.10203468054533005, "23237": 0.14602625370025635, "23296": 0.053244512528181076, "23552": 0.7333439588546753, "23572": 0.7491656541824341, "23659": 0.3141832649707794, "23758": 0.9893379211425781, "23797": 0.05417001247406006, "24169": 0.23015019297599792, "24203": 0.8764448165893555, "24255": 0.5336109399795532, "24312": 0.20421554148197174, "24342": 0.6233867406845093, "24817": 0.06337817758321762, "25002": 0.0752234235405922, "25136": 0.00875066313892603, "25169": 0.0354953333735466, "25190": 0.021256839856505394, "25269": 1.0601204633712769, "25449": 0.1011524572968483, "25476": 0.4444103240966797, "26001": 0.5284429788589478, "26166": 0.07068414986133575, "26356": 1.12432062625885, "26520": 0.022212404757738113, "26524": 1.0073304176330566, "26773": 0.04674193635582924, "26874": 0.12642613053321838, "27190": 0.4419025182723999, "27233": 0.8550800085067749, "27521": 0.004870930220931768, "27642": 0.9240728616714478, "27822": 0.030771657824516296, "27854": 0.07159364968538284, "28177": 0.13071982562541962, "28691": 0.09761575609445572, "28790": 0.5893046259880066, "28848": 1.076228141784668, "28959": 0.259204238653183, "29060": 0.4728073179721832} | 13552682 | In eukaryotes, accurate protein synthesis relies on a family of translational GTPases that pair with specific decoding factors to decipher the mRNA code on ribosomes. We present structures of the mammalian ribosome engaged with decoding factor⋅GTPase complexes representing intermediates of translation elongation (aminoacyl-tRNA⋅eEF1A), termination (eRF1⋅eRF3), and ribosome rescue (Pelota⋅Hbs1l). Comparative analyses reveal that each decoding factor exploits the plasticity of the ribosomal decoding center to differentially remodel ribosomal proteins and rRNA. This leads to varying degrees of large-scale ribosome movements and implies distinct mechanisms for communicating information from the decoding center to each GTPase. Additional structural snapshots of the translation termination pathway reveal the conformational changes that choreograph the accommodation of decoding factors into the peptidyl transferase center. Our results provide a structural framework for how different states of the mammalian ribosome are selectively recognized by the appropriate decoding factor⋅GTPase complex to ensure translational fidelity. | Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes |
{"1011": 0.3883931338787079, "1016": 0.08692999184131622, "1018": 0.11778303235769272, "1039": 1.0795515775680542, "1043": 0.26146242022514343, "1056": 1.0298984050750732, "1999": 0.1011524572968483, "2002": 0.6573580503463745, "2029": 0.058784693479537964, "2044": 0.0317181795835495, "2046": 0.030771657824516296, "2075": 0.08603433519601822, "2076": 0.3381449282169342, "2079": 0.1913948506116867, "2110": 0.025073638185858727, "2135": 0.6970458030700684, "2179": 0.0770333781838417, "2188": 0.5069117546081543, "2290": 1.0158531665802002, "2302": 0.21530038118362427, "2312": 0.37707099318504333, "2339": 0.04674193635582924, "2515": 0.4425300657749176, "2529": 0.4734157919883728, "2535": 0.11691460013389587, "2549": 0.4002431631088257, "2550": 0.08692999184131622, "2575": 0.14518201351165771, "2683": 0.19541899859905243, "2695": 0.6926587820053101, "2828": 0.272677481174469, "2884": 0.08244366943836212, "2922": 0.06612417846918106, "2944": 0.5990082025527954, "2953": 0.34577593207359314, "3161": 0.08513788133859634, "3170": 0.15526613593101501, "3223": 0.36290550231933594, "3258": 0.5990082025527954, "3278": 0.5816917419433594, "3303": 0.22782009840011597, "3333": 0.5267143249511719, "3351": 0.07884006202220917, "3365": 0.5244048833847046, "3378": 0.8332487344741821, "3388": 0.1011524572968483, "3406": 0.030771657824516296, "3426": 0.4873090982437134, "3435": 0.31845372915267944, "3445": 0.26146242022514343, "3450": 0.10026945173740387, "3466": 0.17020416259765625, "3508": 0.18573370575904846, "3526": 0.1808556467294693, "3563": 0.5069117546081543, "3573": 0.4673144817352295, "3593": 0.7647408246994019, "3595": 0.7286425232887268, "3623": 0.42225050926208496, "3625": 0.6011518239974976, "3654": 0.18248429894447327, "3670": 0.04953393340110779, "3698": 0.10291612148284912, "3739": 0.13414156436920166, "3747": 0.45623743534088135, "3755": 0.15777134895324707, "3845": 0.7969439625740051, "3853": 0.17267228662967682, "3896": 0.040196798741817474, "3965": 0.04394211992621422, "3995": 0.10379679501056671, "4023": 0.5092619061470032, "4072": 0.17922431230545044, "4111": 0.5209306478500366, "4127": 0.06520967930555344, "4138": 0.29981520771980286, "4176": 0.5045560002326965, "4180": 0.4837033152580261, "4183": 0.09938567131757736, "4195": 0.1221139207482338, "4244": 0.417115718126297, "4275": 0.3388410806655884, "4286": 0.4145384132862091, "4308": 0.14095009863376617, "4355": 0.6911921501159668, "4359": 0.1485546976327896, "4361": 0.16359257698059082, "4442": 0.22626367211341858, "4453": 0.37974658608436584, "4530": 1.0305955410003662, "4568": 0.22157983481884003, "4588": 0.5415972471237183, "4598": 0.1332872211933136, "4607": 1.1363043785095215, "4653": 0.0029254043474793434, "4654": 0.46853771805763245, "4722": 0.08871890604496002, "4786": 0.021256839856505394, "4818": 0.6911921501159668, "4839": 0.1889725625514984, "4919": 0.052318159490823746, "4962": 1.1109062433242798, "4987": 0.011650617234408855, "5014": 0.036437395960092545, "5038": 0.036437395960092545, "5105": 0.151916041970253, "5139": 0.3012613356113434, "5158": 0.13499516248703003, "5178": 0.5914691090583801, "5179": 0.083342544734478, "5224": 0.1358480453491211, "5250": 0.9761797785758972, "5258": 0.11778303235769272, "5320": 0.6054253578186035, "5324": 0.4132472574710846, "5326": 0.42353010177612305, "5333": 0.3084607720375061, "5354": 0.319873183965683, "5360": 0.00875066313892603, "5387": 0.09584271162748337, "5388": 1.4046790599822998, "5423": 1.0953518152236938, "5441": 0.3339579105377197, "5478": 0.06520967930555344, "5527": 0.1510767638683319, "5531": 0.058784693479537964, "5547": 0.3191637098789215, "5620": 0.3304552733898163, "5648": 0.49982786178588867, "5685": 0.6400018334388733, "5738": 0.2837681770324707, "5741": 0.820433497428894, "5769": 0.03266380727291107, "5856": 1.3940764665603638, "5942": 0.07793712615966797, "5983": 0.05694137513637543, "5985": 0.5573811531066895, "6022": 0.7389566898345947, "6032": 0.04207121208310127, "6064": 0.3615458607673645, "6190": 0.2531573474407196, "6229": 0.3374483287334442, "6292": 0.09228714555501938, "6356": 0.25845035910606384, "6459": 0.0174254160374403, "6551": 0.2018241584300995, "6564": 0.05786345899105072, "6593": 0.2247048318386078, "6638": 0.812664806842804, "6646": 0.1734936386346817, "6693": 0.42735910415649414, "6709": 0.3485364317893982, "6812": 0.23479416966438293, "6914": 0.09672962874174118, "6937": 0.08513788133859634, "6994": 0.22937409579753876, "7070": 0.22782009840011597, "7091": 0.3134697377681732, "7137": 0.030771657824516296, "7337": 0.28082266449928284, "7356": 0.0752234235405922, "7361": 0.3416208028793335, "7366": 0.20022670924663544, "7403": 0.8195732831954956, "7446": 0.011650617234408855, "7457": 0.3519764244556427, "7461": 0.23247487843036652, "7485": 0.9900637865066528, "7510": 0.2990913391113281, "7645": 0.09317722171545029, "7694": 0.0797421783208847, "7711": 0.08064348995685577, "7784": 0.1221139207482338, "7900": 0.004870930220931768, "7954": 0.7942996621131897, "8000": 0.9386941194534302, "8039": 0.06337817758321762, "8092": 0.49030399322509766, "8114": 0.7276995778083801, "8122": 0.5450005531311035, "8153": 0.5517725944519043, "8171": 0.8592242002487183, "8184": 0.66441810131073, "8250": 0.5278670787811279, "8292": 0.10026945173740387, "8319": 0.13243216276168823, "8417": 0.19381128251552582, "8430": 0.23787821829319, "8469": 0.09672962874174118, "8496": 0.05970508232712746, "8498": 0.3499138653278351, "8521": 0.04113444685935974, "8621": 0.4824984669685364, "8642": 0.1913948506116867, "8649": 0.04487626627087593, "8699": 0.6970458030700684, "8720": 0.9029204845428467, "8761": 0.1485546976327896, "8776": 0.45499902963638306, "8878": 0.2652147710323334, "8909": 0.22704219818115234, "8991": 0.08692999184131622, "9007": 0.4437839686870575, "9010": 0.3723714053630829, "9063": 0.6872705817222595, "9096": 0.21765978634357452, "9165": 0.8748174905776978, "9289": 0.7038320899009705, "9319": 0.3982778787612915, "9350": 0.3662964701652527, "9535": 0.39433568716049194, "9572": 0.2447827309370041, "9589": 0.08064348995685577, "9821": 0.45623743534088135, "9839": 0.19541899859905243, "9885": 0.37974658608436584, "9905": 0.03360854089260101, "9987": 0.23864774405956268, "10042": 0.53589928150177, "10256": 0.4311734735965729, "10381": 0.20660123229026794, "10394": 0.5773153901100159, "10440": 0.02887592278420925, "10507": 0.10731173306703568, "10548": 0.27044451236724854, "10572": 0.4824984669685364, "10671": 0.4728073179721832, "10744": 0.1064341589808464, "10768": 0.6075552701950073, "10840": 0.28082266449928284, "10889": 0.38374659419059753, "11113": 0.11951763927936554, "11179": 0.07431721687316895, "11239": 0.26146242022514343, "11290": 0.49982786178588867, "11369": 0.9724938273429871, "11411": 0.14518201351165771, "11432": 0.49626702070236206, "11477": 0.3423145115375519, "11643": 0.2800849378108978, "12123": 0.8925741910934448, "12151": 0.4228905141353607, "12278": 0.07250232994556427, "12328": 1.1846466064453125, "12377": 0.53589928150177, "12381": 0.22937409579753876, "12554": 0.22859740257263184, "12596": 0.9987343549728394, "12737": 0.3012613356113434, "12816": 0.32341301441192627, "12859": 0.06520967930555344, "12863": 0.22548456490039825, "13012": 0.7276995778083801, "13122": 0.6482070088386536, "13153": 0.7934166193008423, "13275": 0.18573370575904846, "13416": 0.3409265875816345, "13458": 0.3177432417869568, "13461": 0.7086513638496399, "13512": 0.4349733293056488, "13791": 0.4914994537830353, "13871": 0.08871890604496002, "13922": 0.011650617234408855, "14061": 0.5438674688339233, "14067": 0.4286321699619293, "14095": 0.495672345161438, "14140": 0.4126010537147522, "14163": 0.06977381557226181, "14193": 0.015504186972975731, "14471": 0.3910386264324188, "14494": 0.9115922451019287, "14606": 0.025073638185858727, "14671": 0.6759096384048462, "14689": 0.669430673122406, "14708": 0.026976587250828743, "14800": 0.0797421783208847, "14830": 0.8074519634246826, "14841": 0.08064348995685577, "14860": 0.02887592278420925, "14956": 0.3141832649707794, "15111": 0.22157983481884003, "15306": 0.18816383183002472, "15527": 0.5612884759902954, "15543": 0.04394211992621422, "15578": 0.43623676896095276, "15663": 0.5640701055526733, "15946": 0.0797421783208847, "16221": 0.9827804565429688, "16222": 0.1401015669107437, "16238": 0.30558720231056213, "16285": 0.23633737862110138, "16326": 0.8332487344741821, "16341": 0.14939609169960022, "16389": 0.3615458607673645, "16474": 0.03925827145576477, "16480": 0.8433839678764343, "16505": 0.04394211992621422, "16530": 0.036437395960092545, "16605": 0.029824240133166313, "16627": 0.3127557039260864, "16705": 0.26446542143821716, "16706": 0.2976420819759369, "16731": 0.2674594223499298, "16748": 0.7047978043556213, "16790": 0.06520967930555344, "16844": 0.30486753582954407, "16882": 0.9170717000961304, "16888": 0.5968599319458008, "16932": 0.4500300884246826, "17119": 0.6970458030700684, "17250": 0.6471850275993347, "17427": 0.053244512528181076, "17441": 0.22626367211341858, "17627": 1.0087559223175049, "17701": 0.812664806842804, "17753": 0.022212404757738113, "17779": 0.07793712615966797, "17820": 0.014542185701429844, "17886": 0.6848117709159851, "17913": 0.4203280806541443, "17944": 0.08244366943836212, "18089": 0.8957691192626953, "18098": 0.66441810131073, "18120": 0.06246116757392883, "18133": 0.24248650670051575, "18228": 0.25995752215385437, "18260": 0.05786345899105072, "18479": 1.0782235860824585, "18647": 0.14349138736724854, "18714": 0.21687394380569458, "18720": 0.12642613053321838, "18804": 0.13414156436920166, "19009": 0.6456501483917236, "19101": 0.9650808572769165, "19126": 1.0257055759429932, "19345": 0.08692999184131622, "19357": 0.037378571927547455, "19539": 0.043007105588912964, "19577": 0.8550800085067749, "19653": 0.757441520690918, "19806": 0.25845035910606384, "20014": 1.2704625129699707, "20125": 0.28963330388069153, "20299": 1.070887804031372, "20544": 0.0317181795835495, "20752": 0.25845035910606384, "20872": 0.1221139207482338, "20915": 0.46117570996284485, "20960": 0.17759032547473907, "20998": 0.2786078155040741, "21025": 0.08871890604496002, "21083": 0.10379679501056671, "21084": 0.37907835841178894, "21453": 0.7286425232887268, "21466": 0.5816917419433594, "21709": 0.7500885725021362, "21903": 0.35950297117233276, "21967": 0.5562619566917419, "22170": 0.0354953333735466, "22330": 0.7647408246994019, "22407": 0.17020416259765625, "22511": 0.08871890604496002, "22552": 0.42735910415649414, "22694": 0.12728634476661682, "22932": 0.004870930220931768, "22975": 0.4002431631088257, "23060": 0.23787821829319, "23191": 0.05417001247406006, "23216": 0.09850110858678818, "23267": 0.036437395960092545, "23296": 0.40806588530540466, "23518": 0.6773988008499146, "23737": 0.15860503911972046, "23746": 0.04860413447022438, "23892": 0.1602703034877777, "23900": 0.14602625370025635, "23974": 0.1011524572968483, "24004": 0.0770333781838417, "24137": 0.06246116757392883, "24171": 0.2711893916130066, "24269": 0.3982778787612915, "24345": 0.1064341589808464, "24529": 0.3127557039260864, "24552": 0.8625272512435913, "24848": 0.029824240133166313, "24952": 0.9485763907432556, "24971": 0.6921701431274414, "25002": 0.6654226183891296, "25117": 0.12038381397724152, "25186": 0.08782484382390976, "25206": 0.27342069149017334, "25354": 0.3601844012737274, "25394": 0.07159364968538284, "25510": 1.20884370803833, "25643": 1.0953518152236938, "25708": 0.1994270235300064, "25711": 0.4002431631088257, "25714": 0.9470623731613159, "25761": 1.04512357711792, "26014": 0.2493593990802765, "26261": 0.87237149477005, "26305": 0.12642613053321838, "26394": 1.0695481300354004, "26402": 0.04767346754670143, "26419": 0.08871890604496002, "26524": 0.011650617234408855, "26721": 0.906871497631073, "26773": 0.08871890604496002, "26835": 0.8383291959762573, "27009": 0.1011524572968483, "27118": 0.7692760229110718, "27133": 0.022212404757738113, "27598": 0.9131608605384827, "27723": 0.08513788133859634, "27753": 0.20660123229026794, "27777": 0.129004567861557, "27814": 1.0101795196533203, "27833": 1.2599912881851196, "28041": 0.5045560002326965, "28154": 0.6654226183891296, "28156": 0.47584590315818787, "28173": 0.2749055027961731, "28517": 0.036437395960092545, "28577": 0.01934296265244484, "28691": 0.15442965924739838, "28696": 0.932563841342926, "28788": 0.7239188551902771, "28873": 0.0019512200960889459, "29090": 0.10467668622732162, "29248": 0.24325250089168549, "29290": 0.3381449282169342, "29295": 0.0038986403960734606} | 13573143 | Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes. | Intestinal Cgi-58 Deficiency Reduces Postprandial Lipid Absorption |
{"1011": 0.10818854719400406, "1016": 0.7352184057235718, "1043": 0.4831010699272156, "1056": 1.1894142627716064, "1999": 0.026025565341114998, "2003": 0.1602703034877777, "2004": 0.025073638185858727, "2008": 0.14518201351165771, "2011": 0.3339579105377197, "2029": 0.26820653676986694, "2048": 0.28597161173820496, "2063": 0.14939609169960022, "2075": 0.04487626627087593, "2076": 0.006812678650021553, "2079": 0.1229778528213501, "2109": 0.36900100111961365, "2117": 0.15860503911972046, "2121": 0.306306391954422, "2155": 0.7191727757453918, "2173": 0.33953672647476196, "2177": 0.083342544734478, "2217": 0.11256109178066254, "2266": 0.5573811531066895, "2290": 1.2053390741348267, "2372": 0.09584271162748337, "2462": 0.12384103983640671, "2465": 0.19862671196460724, "2475": 1.3128622770309448, "2483": 0.4093637466430664, "2487": 0.2667117714881897, "2509": 0.010684899985790253, "2512": 0.2539152204990387, "2515": 0.175953671336174, "2529": 0.9747070074081421, "2535": 0.5947071313858032, "2545": 0.0058422754518687725, "2590": 0.3381449282169342, "2609": 0.7333439588546753, "2692": 0.13243216276168823, "2817": 0.0038986403960734606, "2832": 0.22626367211341858, "2856": 0.4709797203540802, "2892": 0.8772575259208679, "2920": 0.3339579105377197, "2945": 0.2516399025917053, "2953": 0.7782850861549377, "2958": 0.5995445251464844, "3046": 0.817850649356842, "3161": 0.5092619061470032, "3192": 0.33675122261047363, "3248": 0.13071982562541962, "3252": 0.6155022978782654, "3273": 0.27712854743003845, "3366": 0.9576126337051392, "3370": 0.3269403576850891, "3375": 0.5127768516540527, "3378": 0.11256109178066254, "3433": 0.5197699069976807, "3445": 0.06977381557226181, "3463": 0.0019512200960889459, "3584": 0.04394211992621422, "3603": 0.10379679501056671, "3623": 0.011650617234408855, "3625": 0.20421554148197174, "3668": 0.2689530849456787, "3754": 0.29328158497810364, "3853": 0.23402166366577148, "3970": 0.40089741349220276, "3995": 0.09228714555501938, "4097": 0.04113444685935974, "4160": 0.18816383183002472, "4286": 0.5816917419433594, "4295": 0.0797421783208847, "4371": 0.2394166737794876, "4395": 0.4624064862728119, "4469": 0.6704301834106445, "4487": 0.13670019805431366, "4573": 0.7124901413917542, "4625": 0.13925230503082275, "4630": 0.4794800877571106, "4668": 0.5450005531311035, "4812": 0.175953671336174, "4819": 0.8306987881660461, "4937": 0.6075552701950073, "4957": 0.7389566898345947, "4962": 0.4431571960449219, "5022": 0.129004567861557, "5072": 0.14349138736724854, "5090": 0.35060185194015503, "5107": 0.4337083101272583, "5138": 0.9194108247756958, "5153": 0.27934664487838745, "5197": 0.07250232994556427, "5234": 1.351516842842102, "5250": 0.7182208299636841, "5267": 0.9348671436309814, "5416": 0.45437926054000854, "5449": 0.4462870955467224, "5603": 0.14349138736724854, "5620": 0.5723689198493958, "5668": 0.46363574266433716, "5799": 0.6233867406845093, "5813": 0.2852376699447632, "5939": 0.02887592278420925, "6022": 0.006812678650021553, "6064": 0.319873183965683, "6086": 0.36900100111961365, "6121": 0.8161250352859497, "6190": 0.5528968572616577, "6494": 0.2689530849456787, "6528": 1.0688776969909668, "6540": 0.25239890813827515, "6820": 0.817850649356842, "6897": 0.4512746334075928, "6914": 0.3443928062915802, "6971": 0.175953671336174, "7337": 0.25694093108177185, "7346": 0.41195443272590637, "7356": 0.40741631388664246, "7361": 0.5590575933456421, "7366": 0.8091925978660583, "7393": 0.04113444685935974, "7567": 1.029200792312622, "7630": 1.0108904838562012, "7716": 0.5051454305648804, "7783": 0.9131608605384827, "7801": 0.022212404757738113, "7821": 0.29328158497810364, "8031": 0.1677299439907074, "8077": 0.15359249711036682, "8132": 0.5197699069976807, "8153": 0.5472630262374878, "8171": 0.5450005531311035, "8185": 0.7482418417930603, "8285": 0.5984715819358826, "8332": 0.31132611632347107, "8360": 0.18492233753204346, "8516": 0.7201237678527832, "8556": 0.24171993136405945, "8583": 0.3923587501049042, "8878": 0.8022117614746094, "8915": 0.2667117714881897, "9007": 1.2704625129699707, "9096": 0.6186635494232178, "9099": 1.3645758628845215, "9211": 0.304147332906723, "9353": 0.7028654217720032, "9547": 0.18573370575904846, "9597": 0.4556184411048889, "9692": 0.2409527748823166, "9920": 0.18167030811309814, "10020": 0.07250232994556427, "10100": 0.06154331564903259, "10500": 0.0058422754518687725, "10509": 0.1718502640724182, "10564": 0.3615458607673645, "10572": 0.9842413663864136, "10631": 0.7276995778083801, "10633": 0.8187123537063599, "10708": 0.25088030099868774, "10722": 0.10291612148284912, "10737": 0.05970508232712746, "10750": 0.18167030811309814, "10847": 0.3297532796859741, "11022": 0.6573580503463745, "11163": 0.02316705882549286, "11254": 0.07884006202220917, "11383": 0.27786844968795776, "11390": 0.026976587250828743, "11393": 0.8933739066123962, "11528": 0.020300358533859253, "11538": 0.0174254160374403, "11825": 0.12728634476661682, "11867": 0.6502478122711182, "11873": 0.28670501708984375, "11937": 0.08603433519601822, "12099": 0.0058422754518687725, "12157": 0.2478361576795578, "12213": 0.14518201351165771, "12322": 0.7809720039367676, "12540": 0.10203468054533005, "12588": 0.08871890604496002, "12644": 0.12038381397724152, "12987": 0.030771657824516296, "13096": 0.06429435312747955, "13210": 1.207676887512207, "13385": 0.013579257763922215, "13463": 0.10026945173740387, "13512": 0.5220900774002075, "13767": 0.8893690705299377, "13791": 0.472198486328125, "13833": 0.11778303235769272, "13876": 0.5573811531066895, "13922": 0.319873183965683, "14031": 0.09672962874174118, "14095": 0.4574742913246155, "14120": 0.06429435312747955, "14163": 0.3070250153541565, "14181": 0.3005385100841522, "14384": 0.5421652793884277, "14438": 0.623910129070282, "14494": 0.2223619967699051, "14841": 0.2607102394104004, "15009": 0.43623676896095276, "15059": 0.23864774405956268, "15420": 0.23402166366577148, "15527": 0.736154317855835, "15946": 0.06795065850019455, "16012": 0.39893341064453125, "16122": 0.1970241367816925, "16221": 0.6639154553413391, "16285": 1.2152372598648071, "16305": 0.6202403903007507, "16627": 0.3824150264263153, "16735": 0.5347557663917542, "16771": 0.6054253578186035, "16824": 0.17267228662967682, "16882": 0.848413348197937, "16969": 0.2659635543823242, "17079": 0.22937409579753876, "17379": 0.28670501708984375, "17441": 0.06977381557226181, "17544": 0.19541899859905243, "17843": 0.22392450273036957, "18020": 1.5297857522964478, "18195": 0.151916041970253, "18260": 0.47584590315818787, "18479": 0.8332487344741821, "18720": 0.055094651877880096, "18796": 0.043007105588912964, "18900": 0.0174254160374403, "18903": 0.025073638185858727, "19009": 0.5612884759902954, "19062": 0.07341018319129944, "19317": 0.1602703034877777, "19653": 0.7124901413917542, "19696": 0.18329764902591705, "19731": 0.7898768186569214, "19780": 0.1011524572968483, "19817": 0.3615458607673645, "19839": 0.03925827145576477, "19872": 0.17840765416622162, "19882": 0.2105647772550583, "19901": 0.11081436276435852, "20017": 0.23247487843036652, "20187": 0.7220231294631958, "20205": 0.053244512528181076, "20207": 1.0519683361053467, "20467": 0.7182208299636841, "20544": 0.17020416259765625, "20620": 0.07612881064414978, "20766": 0.9915141463279724, "20807": 0.04113444685935974, "20817": 0.08782484382390976, "20958": 0.30917787551879883, "21114": 0.13243216276168823, "21252": 0.11517547070980072, "21336": 0.5685047507286072, "21477": 0.2223619967699051, "21486": 0.2689530849456787, "21508": 0.020300358533859253, "21520": 0.025073638185858727, "21600": 0.07431721687316895, "21647": 0.007782140281051397, "21685": 0.22001366317272186, "21716": 0.0317181795835495, "21733": 0.37640097737312317, "21903": 0.41001203656196594, "22008": 0.6684301495552063, "22282": 0.020300358533859253, "22311": 1.1300151348114014, "22644": 0.5947071313858032, "22731": 0.34508460760116577, "22931": 0.043007105588912964, "22977": 0.5330380201339722, "23033": 0.304147332906723, "23150": 1.0894558429718018, "23247": 0.06246116757392883, "23296": 1.2477279901504517, "23586": 0.4487839937210083, "23725": 0.6000806093215942, "23746": 0.36967599391937256, "23758": 1.094698429107666, "23797": 0.07068414986133575, "23892": 0.6684301495552063, "23943": 0.22937409579753876, "24054": 1.0409941673278809, "24169": 0.13243216276168823, "24284": 0.09850110858678818, "24529": 0.5690577030181885, "24628": 0.21214580535888672, "24848": 0.010684899985790253, "25002": 0.31845372915267944, "25117": 0.5618454217910767, "25258": 0.3464667797088623, "25394": 0.16110190749168396, "25456": 0.8340972661972046, "25643": 0.058784693479537964, "25708": 0.08782484382390976, "25761": 0.12986256182193756, "26065": 0.015504186972975731, "26117": 0.09584271162748337, "26244": 1.034073829650879, "26394": 0.9147270321846008, "26402": 0.5534584522247314, "26419": 0.20102575421333313, "26440": 0.27934664487838745, "26524": 0.026025565341114998, "26601": 0.014542185701429844, "26633": 0.2719337046146393, "26702": 0.9591107368469238, "26835": 0.8666408061981201, "27310": 1.0601204633712769, "27697": 0.7426811456680298, "27790": 1.0973093509674072, "28024": 0.4831010699272156, "28691": 0.13414156436920166, "28715": 0.4879087805747986, "28835": 0.4349733293056488, "28931": 0.46486347913742065, "29060": 0.3070250153541565, "29104": 0.5662899017333984, "29290": 0.43812891840934753} | 13578199 | Human transglutaminase 2 (TG2), a member of a large family of enzymes that catalyze protein crosslinking, plays an important role in the extracellular matrix biology of many tissues and is implicated in the gluten-induced pathogenesis of celiac sprue. Although vertebrate transglutaminases have been studied extensively, thus far all structurally characterized members of this family have been crystallized in conformations with inaccessible active sites. We have trapped human TG2 in complex with an inhibitor that mimics inflammatory gluten peptide substrates and have solved, at 2-A resolution, its x-ray crystal structure. The inhibitor stabilizes TG2 in an extended conformation that is dramatically different from earlier transglutaminase structures. The active site is exposed, revealing that catalysis takes place in a tunnel, bridged by two tryptophan residues that separate acyl-donor from acyl-acceptor and stabilize the tetrahedral reaction intermediates. Site-directed mutagenesis was used to investigate the acyl-acceptor side of the tunnel, yielding mutants with a marked increase in preference for hydrolysis over transamidation. By providing the ability to visualize this activated conformer, our results create a foundation for understanding the catalytic as well as the non-catalytic roles of TG2 in biology, and for dissecting the process by which the autoantibody response to TG2 is induced in celiac sprue patients. | Transglutaminase 2 Undergoes a Large Conformational Change upon Activation |
{"1048": 0.25088030099868774, "1049": 0.15943801403045654, "1057": 0.2976420819759369, "2001": 0.574020504951477, "2007": 0.04767346754670143, "2018": 0.22937409579753876, "2020": 0.20739519596099854, "2034": 0.3723714053630829, "2040": 0.014542185701429844, "2042": 0.2822965085506439, "2043": 0.5893046259880066, "2050": 0.14349138736724854, "2062": 0.08154398202896118, "2086": 0.1485546976327896, "2095": 0.5313173532485962, "2106": 0.5573811531066895, "2111": 0.03266380727291107, "2116": 0.5209306478500366, "2137": 0.045809537172317505, "2142": 0.48430517315864563, "2146": 0.2539152204990387, "2149": 0.43053874373435974, "2163": 0.35745587944984436, "2172": 0.1064341589808464, "2179": 0.05970508232712746, "2193": 0.22782009840011597, "2207": 0.2493593990802765, "2234": 0.129004567861557, "2272": 0.14602625370025635, "2318": 0.4203280806541443, "2363": 0.3810817003250122, "2378": 0.817850649356842, "2381": 0.175953671336174, "2397": 0.037378571927547455, "2474": 0.35334911942481995, "2504": 0.5427330136299133, "2511": 0.5370414853096008, "2540": 0.6960725784301758, "2580": 0.037378571927547455, "2637": 0.13499516248703003, "2659": 0.11430477350950241, "2668": 0.22079704701900482, "2691": 0.08961215615272522, "2707": 0.043007105588912964, "2716": 0.06795065850019455, "2721": 0.2145126610994339, "2722": 0.13157635927200317, "2727": 0.8433839678764343, "2764": 0.3409265875816345, "2771": 0.23479416966438293, "2777": 1.1738357543945312, "2786": 0.7737906575202942, "2794": 0.1905880719423294, "2795": 0.2837681770324707, "2800": 0.012615402229130268, "2807": 0.06337817758321762, "2833": 0.0842406153678894, "2846": 0.23710809648036957, "2966": 0.10203468054533005, "2976": 0.05139094591140747, "2988": 0.5914691090583801, "2999": 0.07341018319129944, "3047": 0.12384103983640671, "3058": 0.3297532796859741, "3107": 0.8813109993934631, "3115": 0.012615402229130268, "3170": 0.14518201351165771, "3189": 0.5393219590187073, "3197": 0.04394211992621422, "3231": 0.28450319170951843, "3273": 0.19782574474811554, "3303": 0.0913962796330452, "3378": 0.17267228662967682, "3426": 0.37102460861206055, "3445": 0.10291612148284912, "3446": 0.07884006202220917, "3447": 0.38041436672210693, "3461": 0.34370049834251404, "3466": 0.2409527748823166, "3559": 0.567951500415802, "3572": 0.2447827309370041, "3603": 0.5387523174285889, "3643": 0.2034190446138382, "3647": 0.013579257763922215, "3671": 0.21293537318706512, "3798": 0.5116065740585327, "3808": 0.04207121208310127, "3818": 0.04113444685935974, "3867": 0.21687394380569458, "3891": 0.5478278398513794, "3893": 0.20739519596099854, "3896": 0.1384023278951645, "3915": 0.3485364317893982, "3949": 0.2954642176628113, "3978": 0.10026945173740387, "4034": 0.4673144817352295, "4143": 0.1913948506116867, "4158": 0.1332872211933136, "4200": 0.037378571927547455, "4233": 0.28082266449928284, "4295": 0.5707147121429443, "4311": 0.5838727951049805, "4319": 0.4531385898590088, "4340": 0.04953393340110779, "4371": 0.0797421783208847, "4453": 0.014542185701429844, "4484": 0.6759096384048462, "4588": 0.7872136831283569, "4700": 0.06703783571720123, "4747": 0.083342544734478, "4795": 0.021256839856505394, "4841": 0.11168810725212097, "4844": 0.2763880789279938, "4928": 0.06795065850019455, "4945": 0.7791815400123596, "4955": 0.21372433006763458, "5022": 0.7124901413917542, "5300": 0.3499138653278351, "5320": 0.05786345899105072, "5360": 0.0752234235405922, "5387": 0.10818854719400406, "5456": 0.05046287178993225, "5604": 0.026976587250828743, "5648": 1.202409029006958, "5699": 0.010684899985790253, "5776": 0.5849615335464478, "5845": 0.5033760666847229, "5850": 0.4002431631088257, "5852": 0.06429435312747955, "5876": 0.2852376699447632, "6011": 0.04113444685935974, "6190": 0.04767346754670143, "6226": 0.25845035910606384, "6501": 0.03360854089260101, "6612": 0.19782574474811554, "6657": 0.043007105588912964, "6693": 0.176772341132164, "6747": 0.026976587250828743, "6887": 0.07431721687316895, "7011": 0.14264501631259918, "7017": 0.2689530849456787, "7076": 0.40089741349220276, "7316": 0.24401791393756866, "7383": 0.14686977863311768, "7438": 0.3318578004837036, "7528": 0.1913948506116867, "7609": 0.02887592278420925, "7629": 0.255429208278656, "7630": 0.35060185194015503, "7645": 0.055094651877880096, "7718": 0.1930064558982849, "7870": 0.38041436672210693, "7917": 0.1212492436170578, "7989": 0.022212404757738113, "8124": 0.07159364968538284, "8246": 0.12556517124176025, "8319": 0.1358480453491211, "8343": 0.030771657824516296, "8368": 0.02792670577764511, "8564": 0.10203468054533005, "8715": 0.20660123229026794, "8826": 0.5500838756561279, "8832": 0.2607102394104004, "8944": 0.27044451236724854, "8970": 0.46363574266433716, "9181": 0.6430866718292236, "9556": 0.06977381557226181, "10003": 0.1221139207482338, "10086": 0.034552380442619324, "10195": 0.5957841277122498, "10230": 0.08603433519601822, "10381": 0.0913962796330452, "10431": 0.029824240133166313, "10449": 0.036437395960092545, "10738": 0.1358480453491211, "10831": 0.27564704418182373, "10847": 0.04953393340110779, "11047": 0.04487626627087593, "11156": 0.34023189544677734, "11207": 0.12986256182193756, "11441": 0.5936289429664612, "11487": 0.07431721687316895, "11616": 0.7220231294631958, "11748": 0.09761575609445572, "11825": 0.014542185701429844, "12030": 0.04674193635582924, "12210": 0.4318077862262726, "12259": 0.9029204845428467, "12391": 0.020300358533859253, "12650": 1.0001721382141113, "12737": 0.6123310327529907, "12763": 0.01934296265244484, "13070": 0.015504186972975731, "13341": 0.0752234235405922, "13441": 0.06154331564903259, "13859": 0.1734936386346817, "13964": 0.22001366317272186, "14192": 1.390192985534668, "14606": 0.14349138736724854, "14667": 0.3870677351951599, "14671": 0.5421652793884277, "14971": 0.004870930220931768, "15050": 0.5607312321662903, "15345": 0.0019512200960889459, "16250": 0.14095009863376617, "16311": 0.15023678541183472, "16474": 0.21214580535888672, "16748": 0.2160874605178833, "16812": 0.43812891840934753, "17473": 1.1198691129684448, "17577": 0.1751343309879303, "17722": 0.31560876965522766, "18423": 0.08603433519601822, "18639": 0.23710809648036957, "18749": 1.4339678287506104, "18949": 0.3134697377681732, "19229": 0.24554696679115295, "19230": 0.013579257763922215, "19362": 0.33953672647476196, "19722": 0.04860413447022438, "19875": 0.3005385100841522, "19960": 0.05970508232712746, "20119": 0.1602703034877777, "20162": 0.04394211992621422, "20194": 0.0019512200960889459, "20214": 0.3381449282169342, "20272": 0.12728634476661682, "20992": 0.17020416259765625, "21202": 0.07068414986133575, "21469": 0.06795065850019455, "22458": 0.630689799785614, "22597": 0.5393219590187073, "22694": 0.5466978549957275, "22935": 0.23864774405956268, "22939": 0.22157983481884003, "23238": 0.28963330388069153, "23283": 0.31845372915267944, "23675": 0.848413348197937, "24171": 0.8748174905776978, "24576": 0.17922431230545044, "24797": 0.09228714555501938, "25783": 0.06337817758321762, "26478": 0.5104349255561829, "26745": 0.5811457633972168, "26773": 0.06520967930555344, "28263": 0.2145126610994339, "28613": 0.1685553640127182, "29021": 0.6400018334388733, "29215": 0.020300358533859253, "29234": 0.07431721687316895, "29491": 0.05046287178993225} | 13580614 | To the Editor: From May 1995, when metformin was introduced in the United States, through June 30, 1996, the Food and Drug Administration (FDA) received reports of lactic acidosis in 66 patients treated with metformin. In 47 patients, the diagnosis was confirmed on the basis of circulating lactate values (>5 mmol per liter), in accordance with established criteria for the diagnosis of lactic acidosis (Table 1).1,2 Of the 47 patients with confirmed diagnoses, 43 had one or more risk factors for lactic acidosis. Thirty (64 percent) had preexisting cardiac disease, of whom 18 had histories of congestive heart failure. . . . | Lactic acidosis in patients with diabetes treated with metformin. |
{"1011": 0.43875885009765625, "1015": 0.2674594223499298, "1017": 0.43244171142578125, "1023": 1.1530905961990356, "1052": 0.7482418417930603, "1996": 0.04953393340110779, "1997": 0.1221139207482338, "1999": 0.39893341064453125, "2004": 0.757441520690918, "2007": 0.3683255612850189, "2008": 0.09317722171545029, "2011": 0.3864043951034546, "2012": 0.347847044467926, "2029": 0.3777405619621277, "2034": 0.32199856638908386, "2043": 0.06977381557226181, "2063": 0.4764525294303894, "2071": 0.014542185701429844, "2073": 0.05970508232712746, "2075": 0.22392450273036957, "2076": 0.6286086440086365, "2079": 0.010684899985790253, "2083": 0.19782574474811554, "2089": 0.00875066313892603, "2093": 0.23633737862110138, "2098": 0.08692999184131622, "2109": 0.06520967930555344, "2121": 0.5756692886352539, "2129": 0.25995752215385437, "2206": 0.1685553640127182, "2229": 0.3409265875816345, "2235": 0.175953671336174, "2306": 0.35060185194015503, "2361": 0.24325250089168549, "2379": 0.4568560719490051, "2389": 0.10291612148284912, "2429": 0.1970241367816925, "2433": 0.7210738658905029, "2485": 0.07341018319129944, "2487": 0.2493593990802765, "2509": 0.26446542143821716, "2515": 0.0606246218085289, "2535": 0.06703783571720123, "2545": 0.6270449161529541, "2550": 0.0038986403960734606, "2571": 0.16524957120418549, "2583": 0.04767346754670143, "2609": 0.6343214511871338, "2612": 0.08154398202896118, "2618": 0.23402166366577148, "2620": 0.043007105588912964, "2683": 1.034073829650879, "2719": 0.45499902963638306, "2765": 0.15860503911972046, "2863": 0.3027053773403168, "2865": 0.8374842405319214, "2886": 0.06612417846918106, "2892": 0.8885661959648132, "2895": 0.05694137513637543, "2913": 0.176772341132164, "2920": 0.2881702482700348, "2947": 0.24171993136405945, "2953": 0.1994270235300064, "3012": 0.11168810725212097, "3081": 0.23556606471538544, "3117": 0.3824150264263153, "3157": 0.9139442443847656, "3161": 0.5021947622299194, "3252": 0.2763880789279938, "3283": 0.19541899859905243, "3350": 0.6327666640281677, "3366": 0.052318159490823746, "3370": 0.4248080551624298, "3375": 0.6400018334388733, "3378": 0.574020504951477, "3406": 0.08513788133859634, "3431": 0.25239890813827515, "3445": 0.21687394380569458, "3450": 0.3325583338737488, "3452": 0.46363574266433716, "3463": 0.11256109178066254, "3466": 0.09938567131757736, "3486": 0.0019512200960889459, "3490": 0.7028654217720032, "3495": 0.21765978634357452, "3540": 0.5827828645706177, "3563": 0.6265231370925903, "3596": 0.5651806592941284, "3622": 0.25239890813827515, "3623": 0.2576959431171417, "3674": 0.045809537172317505, "3718": 0.5860490798950195, "3754": 0.45251765847206116, "3853": 0.6476961374282837, "3899": 0.8022117614746094, "3921": 0.3084607720375061, "3989": 0.11081436276435852, "4013": 0.9333322048187256, "4023": 0.6389714479446411, "4195": 0.7863243818283081, "4254": 0.28890204429626465, "4263": 0.7737906575202942, "4371": 0.2954642176628113, "4403": 0.11951763927936554, "4502": 0.7333439588546753, "4523": 0.1332872211933136, "4525": 0.2800849378108978, "4539": 0.1685553640127182, "4570": 0.4764525294303894, "4573": 0.5816917419433594, "4625": 0.1905880719423294, "4668": 0.2983669638633728, "4796": 0.26820653676986694, "4852": 0.07612881064414978, "4957": 0.9951307773590088, "4962": 0.3883931338787079, "4972": 0.3930181860923767, "4987": 0.0009760859538801014, "5072": 0.417115718126297, "5153": 0.2749055027961731, "5158": 0.2026219218969345, "5201": 0.16524957120418549, "5214": 0.0606246218085289, "5250": 0.4248080551624298, "5258": 0.25845035910606384, "5302": 0.2830325961112976, "5360": 0.12986256182193756, "5387": 0.25694093108177185, "5416": 0.31132611632347107, "5422": 0.06795065850019455, "5449": 0.46670228242874146, "5461": 0.3325583338737488, "5516": 0.1685553640127182, "5537": 0.14433705806732178, "5556": 0.10026945173740387, "5641": 0.07793712615966797, "5716": 0.27044451236724854, "5799": 0.6170841455459595, "5854": 0.45499902963638306, "5857": 0.08513788133859634, "5884": 0.8143964409828186, "6022": 0.18492233753204346, "6028": 0.5903874635696411, "6064": 0.6734226942062378, "6077": 0.20022670924663544, "6169": 0.2026219218969345, "6280": 0.5668440461158752, "6342": 0.5805994272232056, "6366": 0.2990913391113281, "6370": 0.2741633653640747, "6576": 0.06703783571720123, "6578": 0.1602703034877777, "6591": 0.6038249135017395, "6619": 0.5618454217910767, "6691": 0.2478361576795578, "6822": 0.562402069568634, "6897": 0.18004031479358673, "6970": 0.7701805830001831, "6971": 0.5590575933456421, "7011": 0.1718502640724182, "7077": 0.012615402229130268, "7192": 0.09495500475168228, "7293": 1.0546929836273193, "7337": 0.520350456237793, "7361": 0.9717550277709961, "7366": 0.3084607720375061, "7405": 0.05417001247406006, "7453": 0.0354953333735466, "7457": 0.3084607720375061, "7461": 0.17267228662967682, "7512": 0.5098485946655273, "7531": 0.10993985831737518, "7570": 0.6563454270362854, "7645": 0.012615402229130268, "7704": 0.18654440343379974, "7711": 0.04394211992621422, "7783": 0.10731173306703568, "7821": 0.30917787551879883, "8020": 0.020300358533859253, "8031": 0.7201237678527832, "8107": 0.4926934838294983, "8114": 0.44691193103790283, "8122": 0.09672962874174118, "8171": 0.20580662786960602, "8185": 0.16690383851528168, "8208": 0.34577593207359314, "8290": 0.17922431230545044, "8332": 0.004870930220931768, "8360": 0.37907835841178894, "8462": 0.9591107368469238, "8524": 0.12038381397724152, "8569": 0.8004589080810547, "8878": 1.1076855659484863, "8883": 0.009718249551951885, "9002": 0.4980490207672119, "9007": 0.8666408061981201, "9096": 0.11517547070980072, "9165": 0.0038986403960734606, "9239": 0.42353010177612305, "9268": 0.09406650811433792, "9276": 0.6512666940689087, "9397": 0.00875066313892603, "9495": 0.20501139760017395, "9547": 0.08782484382390976, "9597": 0.19541899859905243, "9706": 1.0257055759429932, "9884": 0.2711893916130066, "10039": 1.0567318201065063, "10057": 0.1064341589808464, "10210": 0.05694137513637543, "10266": 0.1889725625514984, "10354": 1.1959327459335327, "10479": 0.07159364968538284, "10509": 0.2247048318386078, "10521": 0.06520967930555344, "10572": 0.8989537954330444, "10595": 0.1751343309879303, "10624": 0.41840189695358276, "10696": 0.13157635927200317, "10698": 0.010684899985790253, "10708": 0.09672962874174118, "10737": 0.010684899985790253, "10752": 0.0913962796330452, "10769": 0.021256839856505394, "10790": 0.8349450826644897, "11022": 0.2983669638633728, "11124": 0.45499902963638306, "11211": 0.3170322775840759, "11254": 0.7009293437004089, "11383": 0.5151132941246033, "11598": 0.11430477350950241, "11835": 0.21687394380569458, "11923": 0.3963087201118469, "12130": 0.06886265426874161, "12247": 1.3362338542938232, "12521": 0.6629094481468201, "12649": 0.3304552733898163, "12719": 0.029824240133166313, "12732": 0.08692999184131622, "12987": 0.5180262327194214, "13100": 0.7258110046386719, "13122": 0.7210738658905029, "13228": 0.812664806842804, "13330": 0.32553088665008545, "13490": 0.016465263441205025, "13595": 0.1229778528213501, "13671": 0.2539152204990387, "13767": 0.9240728616714478, "13791": 0.8492490649223328, "13833": 0.1710275560617447, "13922": 0.2539152204990387, "14031": 0.0354953333735466, "14187": 0.8039615154266357, "14191": 0.6086184978485107, "14193": 0.025073638185858727, "14210": 0.8383291959762573, "14670": 0.11168810725212097, "14949": 0.13755162060260773, "15115": 0.02887592278420925, "15420": 0.4158279001712799, "15431": 0.9333322048187256, "15543": 0.08603433519601822, "15663": 0.3034266233444214, "15671": 1.1192315816879272, "15869": 0.6533012986183167, "15946": 0.29400965571403503, "16012": 0.6011518239974976, "16029": 0.029824240133166313, "16134": 0.10731173306703568, "16285": 0.4914994537830353, "16305": 0.2881702482700348, "16389": 0.025073638185858727, "16487": 0.08782484382390976, "16605": 0.3409265875816345, "16706": 0.33115679025650024, "16771": 0.16276304423809052, "16884": 0.21687394380569458, "16910": 0.1212492436170578, "17344": 0.09406650811433792, "17379": 0.32270604372024536, "17441": 0.609149694442749, "17666": 0.0752234235405922, "17820": 0.2470736801624298, "17890": 0.09761575609445572, "18120": 0.05046287178993225, "18136": 0.24325250089168549, "18228": 0.36086538434028625, "18260": 0.14686977863311768, "18568": 0.8323994874954224, "18639": 0.04860413447022438, "18804": 0.045809537172317505, "18903": 0.04394211992621422, "19137": 0.17431432008743286, "19209": 0.630689799785614, "19362": 0.16607704758644104, "19481": 1.1076855659484863, "19601": 0.27712854743003845, "19653": 0.7408206462860107, "19707": 1.4321038722991943, "19780": 0.1229778528213501, "19839": 0.0009760859538801014, "19872": 0.4158279001712799, "19882": 0.2447827309370041, "19992": 0.0752234235405922, "20353": 0.014542185701429844, "20362": 0.1994270235300064, "20544": 0.8748174905776978, "20766": 0.2018241584300995, "20817": 0.7755908370018005, "21466": 0.22937409579753876, "21572": 0.17759032547473907, "21770": 0.9302552938461304, "21903": 0.6980181336402893, "21967": 0.24018502235412598, "22022": 0.22157983481884003, "22172": 1.2158164978027344, "22419": 0.034552380442619324, "22476": 0.07612881064414978, "22644": 0.04487626627087593, "22694": 0.12038381397724152, "22904": 0.8161250352859497, "23079": 0.11343330889940262, "23216": 0.29255300760269165, "23586": 0.6729245185852051, "23737": 0.1710275560617447, "23758": 0.9115922451019287, "24004": 1.102510929107666, "24054": 0.6471850275993347, "24137": 0.18978065252304077, "24203": 0.016465263441205025, "24312": 0.8550800085067749, "24396": 0.26446542143821716, "25002": 0.3269403576850891, "25194": 0.3084607720375061, "25219": 0.7791815400123596, "25222": 1.3049486875534058, "25456": 0.4500300884246826, "25761": 0.21687394380569458, "25897": 0.20739519596099854, "25950": 1.2012346982955933, "26243": 0.06886265426874161, "26244": 0.1970241367816925, "26394": 0.3723714053630829, "26402": 0.987156867980957, "26435": 0.026976587250828743, "26601": 0.00875066313892603, "26642": 0.11865071207284927, "26721": 0.7638313174247742, "26846": 1.0628231763839722, "27099": 0.21135559678077698, "27211": 0.0354953333735466, "27854": 0.5618454217910767, "28424": 0.022212404757738113, "28691": 1.4478377103805542, "28727": 0.1734936386346817, "28873": 0.016465263441205025, "29050": 1.0298984050750732, "29290": 0.7276995778083801, "29295": 0.10291612148284912} | 13583521 | According to dogma, initiator caspases are activated through proximity-induced homodimerization, but some studies infer that during apoptosis caspase-9 may instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical approaches, including a novel site-specific crosslinking technique, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, markedly increasing its avidity for the complex and inducing selective intramolecular cleavage at Asp-315. Remarkably, however, procaspase-9 could also bind via its small subunit to the NOD domain in Apaf-1, resulting in the formation of a heterodimer that more efficiently activated procaspase-3. Following cleavage, the intersubunit linker (and associated conformational changes) in caspase-9-p35/p12 inhibited its ability to form homo- and heterodimers, but feedback cleavage by caspase-3 at Asp-330 removed the linker entirely and partially restored activity to caspase-9-p35/p10. Thus, the apoptosome mediates the formation of caspase-9 homo- and heterodimers, both of which are impacted by cleavage and contribute to its overall function. | The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities |
{"1011": 0.2830325961112976, "1015": 0.41001203656196594, "1038": 0.5104349255561829, "1045": 0.6332852244377136, "1996": 0.10379679501056671, "1997": 0.16442140936851501, "2008": 0.07250232994556427, "2011": 0.38441169261932373, "2012": 0.19220098853111267, "2015": 0.1619328260421753, "2019": 0.4734157919883728, "2028": 0.03831886500120163, "2029": 0.35403475165367126, "2031": 0.07612881064414978, "2038": 0.026976587250828743, "2043": 0.2918238639831543, "2048": 0.04674193635582924, "2058": 0.22392450273036957, "2076": 0.6492279767990112, "2094": 0.02792670577764511, "2100": 0.1602703034877777, "2129": 0.151916041970253, "2170": 0.02316705882549286, "2179": 0.20977331697940826, "2220": 0.16690383851528168, "2229": 0.2852376699447632, "2362": 0.13670019805431366, "2407": 0.4248080551624298, "2427": 0.4437839686870575, "2487": 0.3423145115375519, "2515": 0.056018441915512085, "2529": 0.22157983481884003, "2550": 0.009718249551951885, "2567": 0.29473719000816345, "2587": 0.2822965085506439, "2618": 0.13499516248703003, "2696": 0.5104349255561829, "2716": 0.15023678541183472, "2719": 0.1212492436170578, "2754": 0.3683255612850189, "2765": 0.3170322775840759, "2818": 0.5244048833847046, "2828": 0.09228714555501938, "2832": 0.21765978634357452, "2863": 0.19782574474811554, "2890": 0.46670228242874146, "2905": 1.2267581224441528, "2906": 0.5051454305648804, "2920": 0.11865071207284927, "3022": 1.0492360591888428, "3141": 0.30989447236061096, "3232": 0.25088030099868774, "3252": 0.15777134895324707, "3276": 0.036437395960092545, "3288": 0.25694093108177185, "3320": 1.024303913116455, "3341": 0.906871497631073, "3344": 0.29036402702331543, "3366": 0.5267143249511719, "3370": 0.0174254160374403, "3378": 0.11691460013389587, "3449": 0.5607312321662903, "3463": 0.25467249751091003, "3464": 0.03360854089260101, "3468": 0.5668440461158752, "3491": 0.13414156436920166, "3526": 0.16524957120418549, "3550": 0.026025565341114998, "3560": 0.46914875507354736, "3603": 0.055094651877880096, "3653": 0.06154331564903259, "3674": 0.02316705882549286, "3693": 0.1212492436170578, "3714": 0.09406650811433792, "3775": 0.034552380442619324, "3853": 0.04953393340110779, "3891": 0.5427330136299133, "3905": 0.1212492436170578, "3940": 0.6254787445068359, "4013": 0.13157635927200317, "4078": 0.8143964409828186, "4117": 0.06520967930555344, "4127": 0.007782140281051397, "4195": 0.24325250089168549, "4198": 0.6212902665138245, "4286": 0.4794800877571106, "4287": 0.3374483287334442, "4403": 0.6016870141029358, "4434": 0.272677481174469, "4442": 0.07159364968538284, "4453": 0.05786345899105072, "4517": 0.03831886500120163, "4525": 0.083342544734478, "4570": 0.1212492436170578, "4593": 0.23015019297599792, "4678": 0.05139094591140747, "4719": 0.3170322775840759, "4755": 0.11081436276435852, "4895": 0.9131608605384827, "4957": 0.18573370575904846, "4962": 0.3297532796859741, "4987": 0.8039615154266357, "4991": 0.6466736793518066, "5026": 0.12986256182193756, "5090": 0.052318159490823746, "5098": 0.09050461649894714, "5104": 0.3346569836139679, "5158": 0.3409265875816345, "5159": 0.13243216276168823, "5208": 0.8796916007995605, "5258": 0.3883931338787079, "5314": 0.18816383183002472, "5320": 0.15610189735889435, "5391": 0.05786345899105072, "5402": 0.319873183965683, "5412": 0.1718502640724182, "5428": 0.32553088665008545, "5519": 0.1946154683828354, "5681": 0.347847044467926, "5684": 0.8433839678764343, "5711": 0.14179791510105133, "5799": 0.15943801403045654, "6058": 0.6533012986183167, "6062": 0.11081436276435852, "6064": 0.5080875158309937, "6072": 0.8861536383628845, "6151": 0.6016870141029358, "6162": 0.29328158497810364, "6296": 0.0317181795835495, "6433": 0.014542185701429844, "6438": 0.5495203733444214, "6459": 0.08692999184131622, "6540": 0.20022670924663544, "6632": 0.030771657824516296, "6714": 0.7163142561912537, "6775": 0.05046287178993225, "6844": 0.29981520771980286, "6897": 0.24401791393756866, "6970": 0.0770333781838417, "6971": 0.2918238639831543, "7068": 0.11604541540145874, "7264": 0.151916041970253, "7337": 0.42225050926208496, "7356": 0.1889725625514984, "7366": 0.5278670787811279, "7403": 0.3325583338737488, "7444": 0.21530038118362427, "7507": 0.24018502235412598, "7532": 0.38441169261932373, "7545": 0.3554046154022217, "7584": 0.32129061222076416, "7645": 0.151916041970253, "7689": 0.5461324453353882, "7783": 0.03925827145576477, "7794": 0.12728634476661682, "7883": 0.48430517315864563, "7895": 0.7755908370018005, "7926": 0.678390383720398, "7927": 0.5336109399795532, "7976": 0.7889899015426636, "8031": 0.34370049834251404, "8048": 0.4337083101272583, "8133": 0.32553088665008545, "8138": 0.09406650811433792, "8178": 0.1510767638683319, "8281": 0.006812678650021553, "8288": 0.0842406153678894, "8376": 0.09406650811433792, "8462": 0.006812678650021553, "8524": 0.8247235417366028, "8539": 0.31132611632347107, "8553": 0.10467668622732162, "8590": 0.083342544734478, "8753": 0.00875066313892603, "8885": 0.1677299439907074, "8890": 0.06154331564903259, "8915": 0.6244332790374756, "9007": 0.3283478021621704, "9165": 0.1221139207482338, "9211": 0.5220900774002075, "9232": 0.04860413447022438, "9240": 0.2478361576795578, "9307": 0.6882523894309998, "9314": 0.8400169610977173, "9319": 0.030771657824516296, "9331": 0.6902132034301758, "9335": 0.02887592278420925, "9413": 0.06703783571720123, "9488": 0.04394211992621422, "9504": 0.6823468804359436, "9513": 0.11604541540145874, "9527": 0.6739205718040466, "9563": 0.8212929964065552, "9610": 1.108330488204956, "9617": 0.5816917419433594, "9905": 1.141931176185608, "9958": 0.3019835948944092, "9962": 0.29619070887565613, "10077": 0.9553611874580383, "10210": 0.38308101892471313, "10288": 0.020300358533859253, "10296": 0.17759032547473907, "10362": 0.6764062643051147, "10381": 0.6754127144813538, "10450": 0.983511209487915, "10463": 0.255429208278656, "10572": 0.07612881064414978, "10595": 0.12470348179340363, "10610": 0.11168810725212097, "10624": 0.0019512200960889459, "10744": 0.0842406153678894, "10788": 0.08244366943836212, "10831": 0.2105647772550583, "11119": 0.05417001247406006, "11156": 0.5723689198493958, "11211": 0.37707099318504333, "11444": 0.9005423784255981, "11487": 0.38174858689308167, "11506": 0.38308101892471313, "11566": 0.21922965347766876, "11650": 0.1873544454574585, "11714": 0.07431721687316895, "11767": 0.26296505331993103, "11865": 0.6107416749000549, "12170": 0.9886114001274109, "12260": 0.45994341373443604, "12287": 0.18978065252304077, "12399": 1.0748957395553589, "12516": 0.9929623603820801, "12631": 1.2677175998687744, "12650": 1.1089750528335571, "12702": 0.6970458030700684, "12739": 0.7009293437004089, "12754": 0.04767346754670143, "12928": 0.861702561378479, "13158": 1.3123366832733154, "13585": 0.18816383183002472, "13590": 0.4673144817352295, "13595": 0.23092569410800934, "13759": 0.1913948506116867, "13765": 0.9409833550453186, "13811": 0.04113444685935974, "14045": 0.15023678541183472, "14187": 0.04113444685935974, "14194": 0.8973627090454102, "14366": 0.5925496220588684, "14442": 0.13243216276168823, "14449": 1.2204381227493286, "14454": 0.7809720039367676, "14471": 0.05786345899105072, "14494": 0.10026945173740387, "14516": 0.0019512200960889459, "14570": 0.0842406153678894, "14627": 0.5629584193229675, "14774": 0.13414156436920166, "14800": 0.20739519596099854, "14949": 0.5069117546081543, "14991": 0.34508460760116577, "15100": 0.17840765416622162, "15289": 0.2105647772550583, "15527": 0.2089812457561493, "15908": 0.16442140936851501, "15923": 0.15693697333335876, "16012": 0.9515975713729858, "16026": 0.06154331564903259, "16136": 1.1255888938903809, "16221": 0.41001203656196594, "16308": 0.469759464263916, "16480": 0.3850763738155365, "16505": 0.10026945173740387, "16706": 1.1647365093231201, "16865": 1.0229004621505737, "16924": 0.15023678541183472, "17079": 0.22548456490039825, "17086": 0.4349733293056488, "17143": 0.10026945173740387, "17288": 0.22157983481884003, "17629": 0.8550800085067749, "17720": 0.25088030099868774, "18120": 0.08692999184131622, "18155": 0.9470623731613159, "18231": 0.13670019805431366, "18413": 1.035461664199829, "18414": 0.6497380137443542, "18606": 0.176772341132164, "18804": 0.20818853378295898, "18847": 0.8109301924705505, "18900": 0.29473719000816345, "18903": 1.1798561811447144, "19009": 0.11256109178066254, "19234": 0.27934664487838745, "19470": 0.4624064862728119, "19539": 0.09406650811433792, "19587": 0.09495500475168228, "19653": 0.29619070887565613, "19660": 1.2250384092330933, "19734": 1.293763518333435, "19780": 0.3084607720375061, "19882": 0.15275461971759796, "19884": 0.3318578004837036, "19976": 0.9531047344207764, "20214": 0.401551216840744, "20353": 0.09938567131757736, "20363": 0.004870930220931768, "20377": 0.025073638185858727, "20546": 0.7047978043556213, "20624": 0.009718249551951885, "20760": 0.10026945173740387, "20793": 1.0485517978668213, "20817": 0.17020416259765625, "20875": 0.08782484382390976, "20877": 0.6107416749000549, "20939": 0.07884006202220917, "21001": 0.021256839856505394, "21022": 1.2273306846618652, "21053": 0.053244512528181076, "21114": 0.037378571927547455, "21191": 0.49030399322509766, "21197": 0.822151780128479, "21365": 0.7314660549163818, "21376": 0.11517547070980072, "21471": 0.4337083101272583, "21579": 0.1358480453491211, "21647": 0.3388410806655884, "21716": 1.0312920808792114, "21770": 0.058784693479537964, "21890": 0.7728893756866455, "21957": 1.104454517364502, "22153": 0.04674193635582924, "22354": 0.5947071313858032, "22476": 0.9147270321846008, "22717": 0.14602625370025635, "22731": 0.20421554148197174, "22776": 0.4556184411048889, "22778": 0.436867892742157, "22869": 0.16607704758644104, "22941": 0.6254787445068359, "23144": 1.3740122318267822, "23169": 0.10731173306703568, "23316": 0.4837033152580261, "23737": 0.029824240133166313, "23892": 0.04767346754670143, "23924": 0.0029254043474793434, "24004": 1.0628231763839722, "24759": 0.7701805830001831, "24768": 0.7755908370018005, "24854": 0.10203468054533005, "24879": 1.2677175998687744, "25705": 0.11517547070980072, "26083": 0.1510767638683319, "26305": 0.37974658608436584, "26399": 0.7352184057235718, "26520": 1.0519683361053467, "26874": 1.20884370803833, "26928": 0.10203468054533005, "27169": 0.043007105588912964, "27310": 0.05417001247406006, "27465": 0.2561853528022766, "27521": 0.9842413663864136, "27559": 0.10993985831737518, "27642": 0.4450363218784332, "27697": 0.9455460906028748, "27710": 0.3070250153541565, "27711": 0.23633737862110138, "27790": 1.0641717910766602, "27822": 0.44753631949424744, "27965": 0.015504186972975731, "28024": 0.15610189735889435, "28184": 0.5795059204101562, "28251": 1.1363043785095215, "28297": 0.22392450273036957, "28691": 0.13670019805431366, "28715": 1.1744394302368164, "28795": 0.08603433519601822, "28828": 0.25088030099868774, "29129": 0.06886265426874161, "29290": 0.026976587250828743, "29486": 0.4337083101272583, "29489": 0.7565253376960754} | 13583615 | During meiosis I, kinetochores of sister chromatids are juxtaposed or fused and mono-orient, while homologous chromosomes that are paired by chiasmata (bivalents) have to biorient. In the absence of chiasmata, biorientation of sister chromatids (univalents), which carries a risk of aneuploidy, has been occasionally detected in several species, including humans. We show in fission yeast that biorientation of fused sister kinetochores predominates during early prometaphase I. Without chiasmata, this undesirable biorientation of univalents persists and eventually evades the spindle assembly checkpoint, provoking abnormal anaphase. When univalents are connected by chiasmata or by an artificial tether, this erroneous attachment is converted to monopolar attachment and stabilized. This stabilization is apparently achieved by a chromosome configuration that brings kinetochores to the outer edge of the bivalent, while bringing Aurora B, a destabilizer of kinetochore-microtubule attachment, inward. Our results elucidate how chiasmata favor biorientation of bivalents over that of univalents at meiosis I. | Repositioning of aurora B promoted by chiasmata ensures sister chromatid mono-orientation in meiosis I. |
{"1011": 0.12038381397724152, "1043": 0.4196864068508148, "2000": 0.14518201351165771, "2003": 0.03831886500120163, "2011": 0.2018241584300995, "2029": 0.18004031479358673, "2064": 0.14179791510105133, "2075": 0.020300358533859253, "2084": 0.27934664487838745, "2090": 0.3723714053630829, "2116": 0.01934296265244484, "2119": 0.20818853378295898, "2152": 0.13670019805431366, "2169": 0.16690383851528168, "2172": 0.020300358533859253, "2200": 0.0174254160374403, "2367": 0.1485546976327896, "2382": 0.0174254160374403, "2389": 0.4196864068508148, "2504": 0.5069117546081543, "2515": 0.0842406153678894, "2522": 0.009718249551951885, "2555": 0.417115718126297, "2609": 0.4437839686870575, "2695": 0.49030399322509766, "2714": 0.0019512200960889459, "2752": 0.007782140281051397, "2802": 0.11430477350950241, "2828": 0.036437395960092545, "2846": 0.5925496220588684, "2878": 0.18654440343379974, "2897": 0.5057345628738403, "2920": 0.10379679501056671, "2944": 0.30917787551879883, "2972": 0.6833335757255554, "3020": 0.5295937061309814, "3252": 0.5495203733444214, "3267": 0.11430477350950241, "3284": 0.12384103983640671, "3366": 0.7528522610664368, "3372": 0.7565253376960754, "3395": 0.03831886500120163, "3433": 0.018384648486971855, "3445": 0.08603433519601822, "3463": 0.15275461971759796, "3466": 0.7408206462860107, "3563": 0.0058422754518687725, "3565": 1.0802149772644043, "3597": 0.979118824005127, "3605": 0.5156965255737305, "3618": 0.5495203733444214, "3623": 0.2539152204990387, "3670": 1.3128622770309448, "3730": 0.2531573474407196, "3747": 0.15860503911972046, "3798": 0.6573580503463745, "3811": 0.7134475708007812, "3867": 0.09228714555501938, "3896": 0.8004589080810547, "3949": 0.4419025182723999, "3973": 0.1229778528213501, "4014": 0.6603899002075195, "4044": 0.0842406153678894, "4102": 0.29255300760269165, "4106": 0.04953393340110779, "4127": 0.2493593990802765, "4168": 0.055094651877880096, "4254": 0.20818853378295898, "4275": 0.20977331697940826, "4278": 0.2881702482700348, "4489": 0.23710809648036957, "4539": 0.04767346754670143, "4541": 0.10555581003427505, "4573": 0.6989894509315491, "4602": 0.23556606471538544, "4655": 0.6744182109832764, "4671": 0.5860490798950195, "4726": 0.012615402229130268, "4765": 0.04953393340110779, "4863": 0.29619070887565613, "4921": 0.04113444685935974, "4962": 1.3474642038345337, "5054": 0.7124901413917542, "5056": 0.6165571808815002, "5090": 0.3615458607673645, "5105": 0.06154331564903259, "5144": 0.11430477350950241, "5186": 0.06886265426874161, "5228": 0.6160298585891724, "5301": 0.3248254358768463, "5335": 0.5057345628738403, "5360": 0.4537591338157654, "5412": 0.5860490798950195, "5449": 0.15023678541183472, "5512": 1.0855059623718262, "5537": 0.36290550231933594, "5604": 0.022212404757738113, "5789": 0.08871890604496002, "5845": 0.06246116757392883, "5876": 0.026025565341114998, "5966": 0.45994341373443604, "6022": 0.12986256182193756, "6028": 0.07250232994556427, "6064": 1.0172666311264038, "6123": 1.3248759508132935, "6125": 0.6022219061851501, "6129": 0.8500841856002808, "6388": 0.29400965571403503, "6431": 0.10203468054533005, "6459": 0.2576959431171417, "6512": 0.7951818704605103, "6540": 0.5838727951049805, "6551": 0.0038986403960734606, "6698": 0.04860413447022438, "6872": 0.020300358533859253, "6914": 0.5139457583427429, "6942": 0.9936857223510742, "6970": 1.0151457786560059, "7017": 0.37640097737312317, "7183": 0.30558720231056213, "7237": 0.3283478021621704, "7337": 0.0797421783208847, "7366": 0.2976420819759369, "7403": 1.0101795196533203, "7438": 0.20580662786960602, "7457": 0.014542185701429844, "7461": 0.7038320899009705, "7551": 0.3141832649707794, "7565": 0.5751199722290039, "7578": 0.1384023278951645, "7591": 1.109619140625, "7607": 0.09850110858678818, "7620": 0.03831886500120163, "7711": 0.06886265426874161, "7730": 0.6471850275993347, "7783": 0.08154398202896118, "7790": 0.034552380442619324, "7816": 0.083342544734478, "7831": 0.45251765847206116, "7885": 0.40871503949165344, "7976": 0.15442965924739838, "8031": 0.8022117614746094, "8048": 0.906871497631073, "8092": 0.25088030099868774, "8211": 0.08782484382390976, "8332": 0.23247487843036652, "8363": 0.029824240133166313, "8377": 0.009718249551951885, "8483": 0.18329764902591705, "8674": 0.0038986403960734606, "8790": 0.8534175157546997, "8878": 0.026976587250828743, "8893": 0.15275461971759796, "8898": 0.31845372915267944, "8991": 0.6793810129165649, "9007": 0.04487626627087593, "9099": 0.06703783571720123, "9165": 1.254435658454895, "9211": 0.8600510358810425, "9229": 0.11604541540145874, "9253": 0.25239890813827515, "9260": 0.022212404757738113, "9265": 0.2763880789279938, "9398": 0.472198486328125, "9412": 0.3499138653278351, "9463": 0.15777134895324707, "9483": 0.6502478122711182, "9530": 0.13071982562541962, "9869": 0.7038320899009705, "10071": 0.42608439922332764, "10266": 0.01934296265244484, "10288": 0.07793712615966797, "10296": 1.2499688863754272, "10335": 0.07250232994556427, "10572": 1.1846466064453125, "10738": 0.1677299439907074, "10744": 0.75193190574646, "10750": 0.13414156436920166, "10752": 0.3297532796859741, "10788": 0.7701805830001831, "10906": 0.175953671336174, "10924": 0.3012613356113434, "10949": 0.28082266449928284, "11087": 0.5865923762321472, "11099": 0.9076598286628723, "11113": 0.3339579105377197, "11156": 0.45499902963638306, "11207": 1.0458102226257324, "11234": 0.28450319170951843, "11423": 0.854249119758606, "11461": 0.8517522215843201, "11487": 0.4831010699272156, "11521": 0.018384648486971855, "11598": 0.2689530849456787, "11643": 0.5278670787811279, "11991": 0.5404602885246277, "12139": 0.03925827145576477, "12403": 0.8152611255645752, "12411": 0.1905880719423294, "12435": 0.2918238639831543, "12473": 0.22626367211341858, "12477": 0.006812678650021553, "12504": 0.0842406153678894, "12553": 1.4615178108215332, "12596": 0.13499516248703003, "12637": 0.30558720231056213, "12644": 0.0317181795835495, "12789": 0.12384103983640671, "12826": 0.5197699069976807, "12987": 0.33675122261047363, "12997": 0.04113444685935974, "13070": 0.11604541540145874, "13113": 0.16110190749168396, "13441": 0.25995752215385437, "13458": 0.4248080551624298, "13494": 0.02792670577764511, "13531": 0.6317287683486938, "13589": 1.1381834745407104, "13599": 0.34508460760116577, "13671": 0.010684899985790253, "13791": 0.175953671336174, "13819": 0.26820653676986694, "13833": 0.09228714555501938, "14026": 0.46608972549438477, "14048": 0.23247487843036652, "14061": 0.08154398202896118, "14187": 0.0842406153678894, "14192": 0.09406650811433792, "14193": 0.9546096324920654, "14386": 0.03360854089260101, "14413": 0.06977381557226181, "14442": 0.025073638185858727, "14471": 0.6769026517868042, "14480": 0.07612881064414978, "14591": 0.1734936386346817, "14639": 0.9485763907432556, "14670": 0.11778303235769272, "15053": 0.06977381557226181, "15115": 0.6583697199821472, "15305": 0.02412080205976963, "15316": 0.029824240133166313, "15502": 0.03925827145576477, "15543": 1.0375399589538574, "15924": 0.953857421875, "15929": 0.2667117714881897, "15946": 1.0546929836273193, "16012": 0.28670501708984375, "16026": 0.055094651877880096, "16221": 0.11778303235769272, "16281": 1.340332269668579, "16406": 0.006812678650021553, "16463": 0.09495500475168228, "16505": 1.0802149772644043, "16515": 0.22782009840011597, "16530": 0.19782574474811554, "16690": 0.04767346754670143, "16706": 0.12986256182193756, "16761": 0.020300358533859253, "16861": 0.5347557663917542, "16865": 0.2689530849456787, "16991": 0.08871890604496002, "17544": 0.4190443754196167, "17856": 1.0264055728912354, "17905": 0.14518201351165771, "18002": 0.06337817758321762, "18046": 0.6430866718292236, "18077": 0.11865071207284927, "18130": 0.03266380727291107, "18231": 0.9576126337051392, "18450": 0.3676496744155884, "18539": 0.1677299439907074, "18549": 0.3519764244556427, "18612": 0.5651806592941284, "18804": 0.39367714524269104, "18969": 0.38574060797691345, "19034": 0.3982778787612915, "19064": 0.03360854089260101, "19137": 0.5232481360435486, "19143": 0.9680526852607727, "19199": 0.1358480453491211, "19293": 0.30917787551879883, "19345": 0.319873183965683, "19395": 0.7352184057235718, "19518": 0.04394211992621422, "19539": 0.2837681770324707, "19563": 1.0116009712219238, "19613": 0.3485364317893982, "19653": 0.935633659362793, "19680": 0.0752234235405922, "19872": 0.7827593088150024, "20567": 0.08244366943836212, "20817": 0.17759032547473907, "21230": 0.10467668622732162, "21688": 0.3241194784641266, "21770": 0.2607102394104004, "21799": 0.3526630103588104, "22026": 0.31845372915267944, "22415": 0.021256839856505394, "22422": 0.06703783571720123, "22570": 0.040196798741817474, "22694": 0.03925827145576477, "22963": 0.3930181860923767, "23370": 0.940220832824707, "23572": 0.29255300760269165, "23691": 0.0029254043474793434, "23737": 0.41389304399490356, "23900": 0.03266380727291107, "23924": 0.5882205963134766, "24051": 0.2516399025917053, "24203": 0.5045560002326965, "24269": 0.2719337046146393, "24278": 0.48430517315864563, "24324": 0.23556606471538544, "24679": 1.4274288415908813, "24710": 0.21372433006763458, "24840": 0.14939609169960022, "24854": 0.02792670577764511, "24989": 0.5104349255561829, "25175": 0.012615402229130268, "25194": 0.08244366943836212, "25206": 0.0606246218085289, "25524": 0.33953672647476196, "25705": 0.055094651877880096, "25714": 0.9425065517425537, "25952": 0.14602625370025635, "25971": 0.42225050926208496, "26402": 0.10731173306703568, "26512": 0.8674615025520325, "26534": 0.09050461649894714, "26565": 0.8893690705299377, "26651": 0.3325583338737488, "26721": 1.0621482133865356, "26775": 0.10379679501056671, "27354": 0.2145126610994339, "27575": 0.06795065850019455, "27642": 0.22704219818115234, "27790": 0.10467668622732162, "28032": 0.5822374224662781, "28314": 1.3274686336517334, "28436": 0.016465263441205025, "28637": 0.07612881064414978, "29206": 0.4818955361843109, "29290": 0.6583697199821472} | 13592721 | Synthetic gene expression is highly sensitive to intragenic compositional context (promoter structure, spacing regions between promoter and coding sequences, and ribosome binding sites). However, much less is known about the effects of intergenic compositional context (spatial arrangement and orientation of entire genes on DNA) on expression levels in synthetic gene networks. We compare expression of induced genes arranged in convergent, divergent, or tandem orientations. Induction of convergent genes yielded up to 400% higher expression, greater ultrasensitivity, and dynamic range than divergent- or tandem-oriented genes. Orientation affects gene expression whether one or both genes are induced. We postulate that transcriptional interference in divergent and tandem genes, mediated by supercoiling, can explain differences in expression and validate this hypothesis through modeling and in vitro supercoiling relaxation experiments. Treatment with gyrase abrogated intergenic context effects, bringing expression levels within 30% of each other. We rebuilt the toggle switch with convergent genes, taking advantage of supercoiling effects to improve threshold detection and switch stability. | Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks. |
{"1043": 0.5318912267684937, "1054": 0.3325583338737488, "1055": 0.40871503949165344, "1997": 0.22782009840011597, "2005": 0.10993985831737518, "2006": 0.05139094591140747, "2011": 0.1693800985813141, "2029": 0.03360854089260101, "2054": 0.1064341589808464, "2064": 0.07068414986133575, "2076": 0.12038381397724152, "2078": 0.6734226942062378, "2079": 0.32341301441192627, "2109": 0.11778303235769272, "2179": 0.021256839856505394, "2224": 0.09761575609445572, "2339": 0.1619328260421753, "2364": 0.04860413447022438, "2389": 0.0317181795835495, "2475": 0.40806588530540466, "2482": 0.3416208028793335, "2487": 0.4158279001712799, "2491": 0.14179791510105133, "2509": 0.18004031479358673, "2511": 0.055094651877880096, "2515": 0.34577593207359314, "2522": 0.06977381557226181, "2535": 0.46363574266433716, "2546": 0.4794800877571106, "2550": 0.15860503911972046, "2556": 0.18492233753204346, "2590": 0.045809537172317505, "2695": 0.48430517315864563, "2832": 0.05694137513637543, "2833": 0.07431721687316895, "2846": 0.1011524572968483, "2850": 0.052318159490823746, "2890": 0.1677299439907074, "2898": 0.1011524572968483, "2920": 0.6102113127708435, "2943": 0.9621002674102783, "3078": 0.7809720039367676, "3120": 0.7827593088150024, "3161": 0.04113444685935974, "3319": 0.151916041970253, "3433": 0.013579257763922215, "3450": 0.6714286804199219, "3466": 0.7201237678527832, "3526": 0.6254787445068359, "3619": 0.12038381397724152, "3625": 0.13755162060260773, "3640": 0.09406650811433792, "3701": 0.2990913391113281, "3739": 0.7201237678527832, "3747": 0.1064341589808464, "3798": 0.17759032547473907, "3800": 0.05139094591140747, "3806": 0.30917787551879883, "3853": 0.45870962738990784, "3893": 0.009718249551951885, "3896": 0.7239188551902771, "3952": 0.1889725625514984, "4023": 0.6754127144813538, "4054": 0.026025565341114998, "4216": 0.5551415085792542, "4219": 0.09406650811433792, "4254": 0.05694137513637543, "4335": 0.15023678541183472, "4395": 0.28450319170951843, "4442": 0.7267557382583618, "4522": 0.3127557039260864, "4598": 0.03831886500120163, "4621": 0.4487839937210083, "4667": 0.8682814836502075, "4679": 0.42544642090797424, "4742": 0.4311734735965729, "4758": 0.40546512603759766, "4762": 0.39433568716049194, "4962": 0.0606246218085289, "4972": 0.17020416259765625, "5012": 0.15860503911972046, "5069": 0.18248429894447327, "5072": 0.08154398202896118, "5092": 0.06795065850019455, "5144": 0.056018441915512085, "5158": 0.12470348179340363, "5250": 0.14433705806732178, "5258": 0.1064341589808464, "5323": 0.04487626627087593, "5360": 0.2719337046146393, "5449": 0.6664261221885681, "5577": 0.08603433519601822, "5589": 0.014542185701429844, "5699": 1.240975022315979, "5910": 0.04674193635582924, "5991": 0.0797421783208847, "6038": 0.15359249711036682, "6194": 0.04674193635582924, "6243": 0.1930064558982849, "6351": 1.1929750442504883, "6459": 0.07159364968538284, "6464": 0.0038986403960734606, "6585": 0.6522845029830933, "6914": 0.17922431230545044, "7137": 0.055094651877880096, "7336": 0.07612881064414978, "7337": 0.29619070887565613, "7366": 0.3070250153541565, "7444": 0.8289952278137207, "7461": 0.5483922958374023, "7507": 0.4770587682723999, "7630": 0.7352184057235718, "7692": 0.04953393340110779, "7711": 0.3777405619621277, "7755": 0.26296505331993103, "7775": 0.14095009863376617, "7790": 0.11951763927936554, "7816": 0.4041621685028076, "8092": 0.12470348179340363, "8290": 0.5232481360435486, "8292": 0.48850810527801514, "8303": 0.5232481360435486, "8360": 0.014542185701429844, "8382": 0.45437926054000854, "8663": 0.6548244953155518, "8670": 0.052318159490823746, "8780": 0.7096124291419983, "8878": 0.010684899985790253, "8918": 0.016465263441205025, "9007": 0.4412745535373688, "9096": 0.3499138653278351, "9099": 0.2837681770324707, "9125": 0.13243216276168823, "9197": 0.1718502640724182, "9232": 0.3019835948944092, "9358": 0.20818853378295898, "9507": 0.13670019805431366, "9597": 0.013579257763922215, "9756": 0.129004567861557, "10210": 0.40220460295677185, "10266": 0.7565253376960754, "10327": 0.17020416259765625, "10572": 0.21530038118362427, "10595": 0.0038986403960734606, "10737": 0.14349138736724854, "10738": 0.10818854719400406, "10867": 0.4770587682723999, "11160": 0.0009760859538801014, "11365": 0.9100211262702942, "11767": 0.14686977863311768, "11835": 0.3883931338787079, "12016": 0.5495203733444214, "12093": 0.16524957120418549, "12222": 0.47036975622177124, "12353": 0.22782009840011597, "12473": 0.0038986403960734606, "12550": 0.38574060797691345, "12562": 0.0913962796330452, "12649": 0.2830325961112976, "12702": 0.15023678541183472, "12732": 0.6107416749000549, "13007": 1.187628984451294, "13228": 0.13670019805431366, "13375": 0.1212492436170578, "13494": 0.0038986403960734606, "13512": 0.8893690705299377, "13530": 0.36426326632499695, "13531": 0.3723714053630829, "13592": 0.04767346754670143, "13617": 0.16276304423809052, "13712": 0.6338034868240356, "13791": 0.04860413447022438, "13811": 0.33953672647476196, "13833": 0.15777134895324707, "13851": 0.46486347913742065, "13922": 0.1930064558982849, "13978": 0.0752234235405922, "14193": 1.0236024856567383, "14206": 0.736154317855835, "14670": 0.020300358533859253, "14671": 0.40285754203796387, "14774": 0.026976587250828743, "14828": 0.6233867406845093, "14956": 0.37102460861206055, "15122": 0.004870930220931768, "15176": 0.5718178153038025, "15289": 0.2659635543823242, "15543": 0.13414156436920166, "15923": 0.14602625370025635, "16012": 0.15275461971759796, "16081": 1.094698429107666, "16119": 0.35813871026039124, "16216": 0.055094651877880096, "16256": 0.7105726003646851, "16285": 0.22782009840011597, "16305": 0.15359249711036682, "16341": 0.8764448165893555, "16360": 0.3850763738155365, "16462": 0.5882205963134766, "16622": 0.25088030099868774, "16781": 0.822151780128479, "16840": 0.3012613356113434, "16910": 0.4831010699272156, "16911": 0.33953672647476196, "16952": 0.083342544734478, "17147": 0.12986256182193756, "17266": 0.9363996982574463, "17341": 0.1064341589808464, "17666": 0.04860413447022438, "17710": 0.026976587250828743, "17822": 0.07250232994556427, "18089": 1.0512858629226685, "18114": 0.03266380727291107, "18282": 0.08961215615272522, "18423": 1.5144401788711548, "18428": 0.08154398202896118, "18672": 0.020300358533859253, "18714": 0.4248080551624298, "18804": 0.1751343309879303, "18908": 0.06429435312747955, "19001": 0.8383291959762573, "19220": 0.020300358533859253, "19304": 0.6286086440086365, "19355": 0.32764431834220886, "19653": 0.29328158497810364, "19723": 0.0752234235405922, "19795": 0.2990913391113281, "19811": 0.272677481174469, "19872": 0.01934296265244484, "20007": 0.08782484382390976, "20145": 0.26296505331993103, "20435": 0.12470348179340363, "20544": 0.020300358533859253, "20647": 0.1677299439907074, "20752": 0.2749055027961731, "20915": 0.16276304423809052, "21047": 0.04953393340110779, "21150": 0.07793712615966797, "21252": 0.20501139760017395, "21453": 0.7201237678527832, "21466": 0.04674193635582924, "21573": 0.07431721687316895, "21575": 0.28450319170951843, "21618": 0.2576959431171417, "21716": 0.40546512603759766, "21852": 0.4132472574710846, "21919": 0.33953672647476196, "21957": 1.7265262603759766, "22282": 0.524982750415802, "22422": 1.1524739265441895, "22597": 0.26446542143821716, "23184": 0.056018441915512085, "23216": 0.2223619967699051, "23586": 0.6144463419914246, "23737": 0.7220231294631958, "24054": 0.35745587944984436, "24203": 0.036437395960092545, "24501": 0.5174443125724792, "25194": 0.23556606471538544, "25456": 0.13925230503082275, "25761": 0.07159364968538284, "25932": 0.6754127144813538, "26190": 0.06520967930555344, "26243": 0.036437395960092545, "26402": 0.6461620330810547, "26427": 0.06520967930555344, "26534": 0.25995752215385437, "26734": 0.6543170213699341, "26773": 0.5914691090583801, "26775": 0.026025565341114998, "26780": 0.22937409579753876, "27142": 0.036437395960092545, "27467": 0.3903779089450836, "27790": 0.13157635927200317, "27891": 0.08871890604496002, "28079": 0.4093637466430664, "28467": 0.02316705882549286, "28901": 0.013579257763922215, "29297": 1.1616848707199097, "29516": 0.2637155055999756} | 13613916 | Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression. | Glucose repression in Saccharomyces cerevisiae |
{"1011": 0.319873183965683, "1015": 0.19541899859905243, "1016": 0.23092569410800934, "1037": 0.23633737862110138, "1039": 0.31132611632347107, "1040": 0.4624064862728119, "1041": 0.29473719000816345, "1043": 0.26820653676986694, "1047": 0.7047978043556213, "1052": 0.18329764902591705, "1055": 0.33953672647476196, "1056": 0.1510767638683319, "1999": 0.10993985831737518, "2007": 0.48430517315864563, "2008": 0.2026219218969345, "2011": 0.28963330388069153, "2029": 0.4938860833644867, "2048": 0.37640097737312317, "2076": 0.3163207769393921, "2094": 0.24325250089168549, "2179": 0.4764525294303894, "2243": 1.1444218158721924, "2291": 0.11430477350950241, "2361": 0.7163142561912537, "2378": 0.7546905279159546, "2426": 0.04953393340110779, "2475": 0.8349450826644897, "2487": 0.823009729385376, "2491": 0.8649974465370178, "2529": 0.5186077356338501, "2535": 0.23247487843036652, "2538": 0.4974553883075714, "2549": 0.53589928150177, "2556": 0.016465263441205025, "2890": 0.2749055027961731, "2891": 0.37907835841178894, "2920": 0.4568560719490051, "2981": 0.02887592278420925, "3001": 0.08782484382390976, "3117": 0.1229778528213501, "3161": 0.08244366943836212, "3231": 0.0038986403960734606, "3283": 0.1477125883102417, "3375": 0.6202403903007507, "3378": 0.5151132941246033, "3433": 0.08782484382390976, "3457": 0.05417001247406006, "3526": 0.7067264318466187, "3563": 0.04674193635582924, "3595": 0.08064348995685577, "3597": 0.17020416259765625, "3625": 0.1619328260421753, "3642": 0.11604541540145874, "3670": 0.22782009840011597, "3729": 1.2273306846618652, "3853": 0.401551216840744, "4022": 0.75193190574646, "4176": 0.1229778528213501, "4286": 0.4374985992908478, "4372": 0.12814582884311676, "4389": 0.25088030099868774, "4403": 0.906871497631073, "4442": 0.45994341373443604, "4453": 0.469759464263916, "4523": 0.848413348197937, "4539": 0.2539152204990387, "4758": 0.8004589080810547, "4962": 0.87237149477005, "4972": 0.18978065252304077, "5072": 0.06337817758321762, "5082": 0.13071982562541962, "5228": 0.0038986403960734606, "5250": 0.7647408246994019, "5301": 0.34577593207359314, "5387": 0.07793712615966797, "5393": 0.13670019805431366, "5402": 0.9576126337051392, "5449": 0.1477125883102417, "5450": 0.011650617234408855, "5482": 0.53589928150177, "5521": 0.5936289429664612, "5705": 0.7978238463401794, "5769": 0.25239890813827515, "5799": 0.08244366943836212, "6064": 0.3012613356113434, "6591": 0.040196798741817474, "6653": 0.8699195384979248, "6709": 0.417115718126297, "6887": 0.21687394380569458, "6895": 0.9783848524093628, "6897": 0.13499516248703003, "7076": 0.3903779089450836, "7077": 0.0009760859538801014, "7127": 0.04487626627087593, "7275": 0.6931471824645996, "7337": 0.36494144797325134, "7361": 0.11168810725212097, "7366": 0.22626367211341858, "7371": 0.06337817758321762, "7403": 0.5562619566917419, "7453": 0.28890204429626465, "7551": 0.07068414986133575, "7591": 0.10379679501056671, "7645": 0.11256109178066254, "7711": 0.8608771562576294, "7783": 0.0174254160374403, "7790": 1.1337933540344238, "7816": 0.674915611743927, "7883": 0.16110190749168396, "7885": 0.38041436672210693, "7889": 0.07884006202220917, "8031": 0.47463157773017883, "8171": 0.791648268699646, "8278": 0.004870930220931768, "8290": 0.5255602598190308, "8292": 0.3141832649707794, "8360": 0.03360854089260101, "8458": 0.22392450273036957, "8878": 0.2607102394104004, "8893": 0.9256220459938049, "9007": 0.7863243818283081, "9096": 0.052318159490823746, "9165": 0.8989537954330444, "9228": 0.6233867406845093, "9280": 0.09672962874174118, "9358": 0.10818854719400406, "9412": 0.19782574474811554, "9416": 0.10379679501056671, "9537": 0.06520967930555344, "9670": 0.24018502235412598, "9756": 0.5191890001296997, "10047": 0.29473719000816345, "10210": 0.025073638185858727, "10253": 0.7018978595733643, "10266": 0.5838727951049805, "10381": 0.28450319170951843, "10572": 0.020300358533859253, "10595": 0.06977381557226181, "10737": 0.14518201351165771, "10738": 0.6709295511245728, "11163": 0.1384023278951645, "11211": 0.2622140049934387, "11486": 0.3304552733898163, "11598": 0.0354953333735466, "11835": 0.3283478021621704, "11993": 0.6181373596191406, "12016": 0.05139094591140747, "12115": 0.053244512528181076, "12151": 0.022212404757738113, "12222": 0.7220231294631958, "12328": 0.1930064558982849, "12335": 0.630689799785614, "12359": 0.5483922958374023, "12477": 0.6744182109832764, "12530": 0.3982778787612915, "12562": 0.13071982562541962, "12709": 0.4356052577495575, "12732": 0.02412080205976963, "12740": 0.6674286723136902, "13100": 0.0913962796330452, "13490": 0.6181373596191406, "13791": 0.1477125883102417, "13808": 0.19220098853111267, "13833": 0.20421554148197174, "13922": 0.2637155055999756, "14031": 0.0354953333735466, "14187": 0.0842406153678894, "14193": 0.46424978971481323, "14340": 0.3339579105377197, "14471": 0.06246116757392883, "14494": 0.06886265426874161, "14828": 0.26146242022514343, "14847": 0.1332872211933136, "14967": 0.6853039860725403, "15113": 0.1602703034877777, "15115": 0.06612417846918106, "15176": 0.6317287683486938, "15420": 0.861702561378479, "15459": 0.006812678650021553, "15527": 0.40806588530540466, "15543": 0.4041621685028076, "15663": 0.272677481174469, "15924": 0.1401015669107437, "16044": 0.37640097737312317, "16081": 0.10203468054533005, "16221": 0.2822965085506439, "16285": 0.450652539730072, "16305": 0.21922965347766876, "16463": 0.011650617234408855, "16706": 0.06612417846918106, "16834": 0.6102113127708435, "17181": 0.6754127144813538, "17379": 0.8949713706970215, "17459": 0.5712664127349854, "17465": 0.6000806093215942, "17917": 0.7067264318466187, "18120": 0.3381449282169342, "18231": 0.0606246218085289, "18491": 0.6410312056541443, "18642": 0.026025565341114998, "18714": 0.16690383851528168, "18715": 0.056018441915512085, "18856": 0.23092569410800934, "19653": 0.40285754203796387, "19872": 0.04767346754670143, "20199": 0.06246116757392883, "20271": 0.7258110046386719, "20350": 0.3916989266872406, "20464": 1.1287524700164795, "20467": 0.6410312056541443, "20544": 0.24631060659885406, "20752": 0.21372433006763458, "20817": 0.25239890813827515, "21144": 0.2637155055999756, "21257": 0.0913962796330452, "21575": 0.4624064862728119, "21618": 1.1031591892242432, "21677": 0.15359249711036682, "21903": 1.4812493324279785, "21935": 0.7436100244522095, "22166": 0.5685047507286072, "22248": 0.18329764902591705, "22330": 1.0960047245025635, "22402": 0.012615402229130268, "22747": 0.6400018334388733, "22930": 0.02316705882549286, "22931": 0.14179791510105133, "23041": 0.6573580503463745, "23150": 0.052318159490823746, "23216": 0.12642613053321838, "23237": 0.47463157773017883, "23270": 0.6502478122711182, "23376": 0.6286086440086365, "23586": 0.6254787445068359, "23616": 0.319873183965683, "23750": 0.0354953333735466, "23892": 0.0770333781838417, "24054": 1.039613962173462, "24324": 0.12038381397724152, "24394": 0.2976420819759369, "24848": 0.16690383851528168, "25022": 1.2985725402832031, "25456": 0.8022117614746094, "25476": 0.29400965571403503, "25644": 1.057410478591919, "25778": 0.17922431230545044, "26046": 1.0116009712219238, "26305": 0.01934296265244484, "26402": 0.9591107368469238, "26512": 0.2447827309370041, "26520": 0.44753631949424744, "26524": 0.6624060273170471, "26534": 0.12814582884311676, "26773": 0.7445381283760071, "27099": 0.021256839856505394, "27152": 0.8973627090454102, "27781": 0.04487626627087593, "27854": 0.40481385588645935, "28309": 0.1221139207482338, "28873": 0.7426811456680298} | 13614794 | The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals. To identify potential Cdk2 regulators, we have employed an improved two-hybrid system to isolate human genes encoding Cdk-interacting proteins (Cips). CIP1 encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E, and Cdk2 immunoprecipitates. p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. Cotransfection experiments indicate that CIP1 and SV40 T antigen function in a mutually antagonistic manner to control cell cycle progression. | The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. |
{"1011": 0.3283478021621704, "1051": 0.8796916007995605, "1997": 0.034552380442619324, "2000": 0.040196798741817474, "2003": 0.15610189735889435, "2012": 0.3027053773403168, "2021": 0.10555581003427505, "2023": 0.02887592278420925, "2033": 0.319873183965683, "2034": 0.053244512528181076, "2051": 1.0008903741836548, "2064": 0.4196864068508148, "2071": 0.05694137513637543, "2075": 0.11604541540145874, "2076": 0.08154398202896118, "2077": 0.11517547070980072, "2079": 0.15359249711036682, "2080": 0.6139179468154907, "2083": 0.22079704701900482, "2086": 0.32764431834220886, "2090": 0.40351006388664246, "2109": 0.7182208299636841, "2124": 0.09495500475168228, "2129": 0.2394166737794876, "2146": 0.13243216276168823, "2155": 0.052318159490823746, "2169": 0.12384103983640671, "2170": 0.07159364968538284, "2182": 0.10467668622732162, "2224": 0.46853771805763245, "2241": 0.04207121208310127, "2275": 0.6218147873878479, "2290": 0.10731173306703568, "2335": 0.6911921501159668, "2339": 0.21214580535888672, "2367": 0.5822374224662781, "2391": 0.26296505331993103, "2393": 0.1734936386346817, "2411": 0.04113444685935974, "2470": 0.15693697333335876, "2478": 0.49626702070236206, "2492": 0.3325583338737488, "2515": 0.16110190749168396, "2523": 0.36358460783958435, "2532": 0.007782140281051397, "2536": 0.18167030811309814, "2565": 0.20818853378295898, "2592": 0.15693697333335876, "2641": 0.04860413447022438, "2685": 0.2976420819759369, "2689": 0.23247487843036652, "2691": 0.2470736801624298, "2706": 0.4914994537830353, "2817": 0.01934296265244484, "2818": 1.0257055759429932, "2850": 0.014542185701429844, "2891": 0.3241194784641266, "2892": 0.7124901413917542, "2944": 0.5495203733444214, "2951": 0.9878844022750854, "3019": 0.46363574266433716, "3058": 0.7038320899009705, "3070": 0.15526613593101501, "3107": 0.16690383851528168, "3130": 0.036437395960092545, "3160": 0.29400965571403503, "3188": 0.4920966327190399, "3200": 0.5364705324172974, "3204": 0.44691193103790283, "3217": 0.25467249751091003, "3231": 0.08513788133859634, "3251": 0.06520967930555344, "3274": 0.14095009863376617, "3291": 0.43244171142578125, "3314": 0.06154331564903259, "3351": 0.11778303235769272, "3372": 0.040196798741817474, "3378": 0.026976587250828743, "3392": 0.07793712615966797, "3406": 0.09050461649894714, "3431": 0.12728634476661682, "3471": 0.5301685929298401, "3508": 0.6270449161529541, "3560": 0.5973974466323853, "3594": 0.36086538434028625, "3630": 0.004870930220931768, "3674": 0.15943801403045654, "3695": 0.04674193635582924, "3697": 0.04674193635582924, "3737": 0.5057345628738403, "3800": 0.2516399025917053, "3839": 0.5139457583427429, "3853": 0.01934296265244484, "3921": 0.38174858689308167, "3973": 0.03360854089260101, "3980": 0.053244512528181076, "3989": 0.22392450273036957, "3995": 0.35060185194015503, "4007": 0.9194108247756958, "4094": 0.15693697333335876, "4106": 0.9092346429824829, "4118": 0.0842406153678894, "4130": 1.0567318201065063, "4132": 0.7674643993377686, "4245": 0.4450363218784332, "4249": 0.38574060797691345, "4275": 0.40806588530540466, "4281": 0.007782140281051397, "4297": 0.4437839686870575, "4328": 0.5461324453353882, "4340": 0.02316705882549286, "4453": 0.4337083101272583, "4520": 0.7144040465354919, "4638": 0.2576959431171417, "4677": 0.006812678650021553, "4710": 0.1477125883102417, "4725": 0.14179791510105133, "4742": 0.6461620330810547, "4765": 0.48068851232528687, "4948": 0.8682814836502075, "4958": 0.5751199722290039, "4962": 1.0403043031692505, "5063": 0.9650808572769165, "5072": 0.32553088665008545, "5107": 0.53589928150177, "5119": 1.261651873588562, "5144": 0.4770587682723999, "5178": 0.6719275116920471, "5198": 0.10203468054533005, "5246": 0.791648268699646, "5278": 0.029824240133166313, "5289": 0.15860503911972046, "5292": 0.006812678650021553, "5306": 0.3916989266872406, "5358": 0.32129061222076416, "5428": 0.004870930220931768, "5461": 0.02412080205976963, "5468": 0.18167030811309814, "5521": 0.014542185701429844, "5537": 1.134421706199646, "5546": 0.0913962796330452, "5579": 0.02792670577764511, "5603": 0.23479416966438293, "5604": 0.24631060659885406, "5646": 0.31204116344451904, "5754": 0.7845434546470642, "5769": 0.012615402229130268, "5863": 0.13071982562541962, "5884": 0.04487626627087593, "5901": 0.4909018874168396, "5906": 0.6160298585891724, "5911": 0.10203468054533005, "5915": 0.040196798741817474, "6028": 0.14179791510105133, "6052": 0.18329764902591705, "6064": 0.7951818704605103, "6075": 0.06703783571720123, "6123": 0.08603433519601822, "6179": 0.4500300884246826, "6370": 0.3269403576850891, "6499": 0.0842406153678894, "6622": 0.5816917419433594, "6709": 0.6223390698432922, "6721": 0.1685553640127182, "6747": 0.18492233753204346, "6769": 0.03360854089260101, "6777": 0.007782140281051397, "6779": 0.5882205963134766, "6806": 0.026025565341114998, "6820": 0.5762182474136353, "6841": 1.0815403461456299, "6845": 0.026025565341114998, "6873": 0.030771657824516296, "6887": 0.7067264318466187, "6897": 0.6989894509315491, "6903": 0.08244366943836212, "6914": 0.7683706283569336, "6994": 0.7845434546470642, "7058": 0.11517547070980072, "7099": 0.8813109993934631, "7182": 0.1905880719423294, "7248": 0.5640701055526733, "7292": 0.4374985992908478, "7366": 0.8893690705299377, "7375": 0.24631060659885406, "7403": 1.0478670597076416, "7446": 0.06977381557226181, "7512": 0.8238670229911804, "7528": 0.40220460295677185, "7561": 0.9553611874580383, "7594": 0.1685553640127182, "7667": 0.32058215141296387, "7749": 0.30989447236061096, "7755": 0.42353010177612305, "7809": 0.5398913025856018, "7860": 0.13925230503082275, "7865": 0.7047978043556213, "8059": 0.012615402229130268, "8094": 0.11517547070980072, "8107": 0.1913948506116867, "8168": 0.77198725938797, "8190": 0.129004567861557, "8202": 0.15943801403045654, "8321": 0.15777134895324707, "8361": 0.23556606471538544, "8376": 0.32058215141296387, "8382": 1.1102628707885742, "8450": 0.26446542143821716, "8516": 1.0229004621505737, "8609": 0.03360854089260101, "8621": 0.14518201351165771, "8674": 0.1889725625514984, "8720": 0.3027053773403168, "8780": 0.18329764902591705, "8849": 0.22157983481884003, "8913": 0.0842406153678894, "8920": 0.2531573474407196, "8924": 0.2034190446138382, "8970": 0.15943801403045654, "8979": 0.4512746334075928, "8991": 1.1935672760009766, "9123": 0.7370892763137817, "9165": 0.8893690705299377, "9285": 0.25467249751091003, "9289": 0.6619023680686951, "9312": 0.02316705882549286, "9361": 0.056018441915512085, "9367": 0.13925230503082275, "9447": 0.04207121208310127, "9572": 0.1358480453491211, "9601": 0.26820653676986694, "9651": 0.007782140281051397, "9710": 0.1994270235300064, "9798": 0.09495500475168228, "9896": 0.2822965085506439, "9905": 0.09938567131757736, "10071": 1.0172666311264038, "10408": 0.22704219818115234, "10425": 0.319873183965683, "10535": 0.0842406153678894, "10569": 0.036437395960092545, "10609": 0.045809537172317505, "10624": 0.6719275116920471, "10640": 0.49864232540130615, "10697": 0.8691008687019348, "10737": 0.4337083101272583, "10788": 0.02412080205976963, "10838": 0.5393219590187073, "10903": 0.05139094591140747, "10984": 0.15610189735889435, "11031": 0.0354953333735466, "11046": 0.08154398202896118, "11131": 0.011650617234408855, "11156": 0.06429435312747955, "11234": 0.1602703034877777, "11326": 0.04860413447022438, "11375": 0.20102575421333313, "11421": 0.083342544734478, "11487": 0.3077431619167328, "11543": 0.0174254160374403, "11628": 0.4228905141353607, "11643": 0.42416930198669434, "11709": 0.058784693479537964, "11718": 0.04674193635582924, "11775": 0.013579257763922215, "11852": 0.0009760859538801014, "12061": 0.3283478021621704, "12139": 0.8893690705299377, "12151": 0.3283478021621704, "12503": 0.04674193635582924, "12504": 0.1332872211933136, "12515": 0.06337817758321762, "12637": 0.0038986403960734606, "12702": 0.07341018319129944, "12732": 0.42353010177612305, "12761": 0.7028654217720032, "12789": 0.03831886500120163, "12800": 0.151916041970253, "12832": 0.10467668622732162, "12835": 0.08961215615272522, "12843": 0.1477125883102417, "12850": 0.12814582884311676, "12876": 0.11256109178066254, "12898": 0.04113444685935974, "12941": 0.347847044467926, "12987": 0.19782574474811554, "13103": 0.10467668622732162, "13115": 0.22392450273036957, "13159": 0.24325250089168549, "13181": 0.20102575421333313, "13369": 0.19862671196460724, "13434": 0.35745587944984436, "13453": 0.0009760859538801014, "13458": 0.6882523894309998, "13462": 0.46608972549438477, "13483": 0.006812678650021553, "13589": 0.0317181795835495, "13595": 0.638455867767334, "13701": 0.19381128251552582, "13765": 0.11604541540145874, "13792": 0.1619328260421753, "13827": 0.15777134895324707, "13922": 0.45251765847206116, "14031": 0.13670019805431366, "14080": 0.00875066313892603, "14148": 0.06886265426874161, "14155": 0.29109421372413635, "14193": 0.16524957120418549, "14358": 0.5947071313858032, "14386": 0.07612881064414978, "14408": 0.0770333781838417, "14471": 0.7647408246994019, "14554": 0.05417001247406006, "14828": 0.08603433519601822, "14847": 0.2674594223499298, "15007": 0.07612881064414978, "15109": 0.6244332790374756, "15113": 0.33675122261047363, "15359": 0.20739519596099854, "15396": 0.045809537172317505, "15643": 0.5027855634689331, "15776": 0.13071982562541962, "15850": 1.1211429834365845, "16012": 0.6389714479446411, "16014": 0.1212492436170578, "16126": 0.2976420819759369, "16134": 0.14349138736724854, "16216": 0.12556517124176025, "16221": 0.13243216276168823, "16227": 1.2375813722610474, "16281": 0.11517547070980072, "16335": 0.1064341589808464, "16381": 0.11168810725212097, "16478": 0.304147332906723, "16505": 0.07341018319129944, "16523": 0.21372433006763458, "16578": 0.2501201331615448, "16706": 0.1477125883102417, "16755": 0.08961215615272522, "16765": 0.1064341589808464, "16910": 0.1710275560617447, "16924": 0.025073638185858727, "17060": 0.34370049834251404, "17287": 1.0326838493347168, "17547": 0.037378571927547455, "17592": 0.5116065740585327, "17598": 0.12038381397724152, "17698": 0.11430477350950241, "17701": 0.1221139207482338, "17826": 0.3019835948944092, "17830": 0.11430477350950241, "17856": 1.0748957395553589, "17881": 0.0752234235405922, "17905": 0.7445381283760071, "17908": 0.7701805830001831, "18150": 0.27786844968795776, "18191": 0.8366385698318481, "18207": 0.12814582884311676, "18288": 0.1212492436170578, "18612": 0.7258110046386719, "18700": 0.04113444685935974, "18701": 1.0920805931091309, "18750": 0.04394211992621422, "18804": 0.05417001247406006, "18856": 0.2478361576795578, "18866": 0.2516399025917053, "18925": 1.2732000350952148, "19143": 0.036437395960092545, "19293": 0.03925827145576477, "19314": 0.13243216276168823, "19345": 0.45499902963638306, "19450": 0.5027855634689331, "19518": 0.11256109178066254, "19539": 0.13925230503082275, "19852": 0.38308101892471313, "19901": 0.009718249551951885, "20077": 0.1913948506116867, "20155": 0.10467668622732162, "20253": 0.43812891840934753, "20302": 0.3381449282169342, "20307": 0.3723714053630829, "20353": 0.5232481360435486, "20470": 0.3877306580543518, "20600": 0.02792670577764511, "20607": 0.732405424118042, "20793": 0.09495500475168228, "20794": 0.09317722171545029, "20940": 0.9425065517425537, "21113": 0.6016870141029358, "21114": 1.0172666311264038, "21197": 0.2034190446138382, "21230": 0.12986256182193756, "21477": 0.6048921346664429, "21647": 0.11256109178066254, "21685": 0.5080875158309937, "21697": 0.42735910415649414, "21708": 0.06612417846918106, "21770": 1.0030416250228882, "22026": 0.21687394380569458, "22107": 0.06337817758321762, "22313": 0.11081436276435852, "22419": 0.11343330889940262, "22553": 1.9158880710601807, "22609": 0.4824984669685364, "22844": 0.0038986403960734606, "22974": 0.0058422754518687725, "23192": 1.0881409645080566, "23274": 0.22548456490039825, "23350": 0.12986256182193756, "23521": 0.10906458646059036, "23579": 0.045809537172317505, "23737": 0.0752234235405922, "23767": 0.07159364968538284, "23777": 0.0174254160374403, "23924": 0.848413348197937, "23943": 0.4337083101272583, "24004": 0.12814582884311676, "24051": 0.30486753582954407, "24166": 0.04674193635582924, "24203": 0.02412080205976963, "24278": 0.1685553640127182, "24318": 0.06977381557226181, "24353": 0.21687394380569458, "24396": 0.46302130818367004, "24490": 0.011650617234408855, "24558": 0.8641747236251831, "24710": 0.20977331697940826, "24848": 0.0009760859538801014, "24854": 0.10379679501056671, "24949": 0.09850110858678818, "25077": 0.025073638185858727, "25095": 0.3810817003250122, "25369": 0.02412080205976963, "25524": 0.5393219590187073, "25582": 0.0009760859538801014, "25705": 0.4556184411048889, "26163": 0.013579257763922215, "26237": 0.9092346429824829, "26282": 0.11256109178066254, "26305": 0.036437395960092545, "26319": 0.08064348995685577, "26515": 0.011650617234408855, "26601": 0.13499516248703003, "26702": 0.07250232994556427, "26835": 0.17759032547473907, "27354": 0.06520967930555344, "27425": 0.11430477350950241, "27642": 0.08154398202896118, "27691": 0.31132611632347107, "28024": 0.018384648486971855, "28212": 0.11343330889940262, "28314": 0.26446542143821716, "28329": 0.8699195384979248, "28436": 0.24171993136405945, "28561": 0.04207121208310127, "28667": 0.6563454270362854, "28937": 0.037378571927547455, "29107": 0.04953393340110779, "29129": 0.500420093536377, "29206": 0.12038381397724152, "29336": 0.11256109178066254, "29458": 0.15777134895324707} | 13618987 | Gene sequences sampled at different points in time can be used to infer molecular phylogenies on a natural timescale of months or years, provided that the sequences in question undergo measurable amounts of evolutionary change between sampling times. Data sets with this property are termed heterochronous and have become increasingly common in several fields of biology, most notably the molecular epidemiology of rapidly evolving viruses. Here we introduce the cross-platform software tool, TempEst (formerly known as Path-O-Gen), for the visualization and analysis of temporally sampled sequence data. Given a molecular phylogeny and the dates of sampling for each sequence, TempEst uses an interactive regression approach to explore the association between genetic divergence through time and sampling dates. TempEst can be used to (1) assess whether there is sufficient temporal signal in the data to proceed with phylogenetic molecular clock analysis, and (2) identify sequences whose genetic divergence and sampling date are incongruent. Examination of the latter can help identify data quality problems, including errors in data annotation, sample contamination, sequence recombination, or alignment error. We recommend that all users of the molecular clock models implemented in BEAST first check their data using TempEst prior to analysis. | Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen) |
{"1014": 0.25694093108177185, "1016": 0.6833335757255554, "1020": 0.17922431230545044, "1043": 0.8366385698318481, "1044": 0.2478361576795578, "1053": 0.7163142561912537, "2005": 0.04207121208310127, "2006": 0.11778303235769272, "2007": 0.29619070887565613, "2015": 0.07793712615966797, "2029": 0.053244512528181076, "2039": 0.011650617234408855, "2048": 0.19541899859905243, "2060": 0.14686977863311768, "2064": 0.151916041970253, "2076": 0.23633737862110138, "2084": 0.09406650811433792, "2086": 0.22937409579753876, "2093": 0.00875066313892603, "2109": 0.12556517124176025, "2111": 0.10203468054533005, "2116": 0.151916041970253, "2135": 0.5186077356338501, "2146": 0.018384648486971855, "2152": 0.13071982562541962, "2166": 0.22001366317272186, "2179": 0.11081436276435852, "2184": 0.20102575421333313, "2193": 0.3949938118457794, "2206": 0.1221139207482338, "2217": 0.25467249751091003, "2287": 0.4248080551624298, "2289": 0.48670899868011475, "2290": 0.05046287178993225, "2297": 0.015504186972975731, "2313": 0.09584271162748337, "2325": 0.678885817527771, "2330": 0.4944818615913391, "2331": 0.1946154683828354, "2362": 0.009718249551951885, "2363": 0.02792670577764511, "2364": 0.27934664487838745, "2378": 0.7528522610664368, "2401": 0.37640097737312317, "2414": 0.01934296265244484, "2423": 0.16442140936851501, "2426": 0.12728634476661682, "2443": 0.14686977863311768, "2470": 0.03925827145576477, "2475": 0.46914875507354736, "2501": 0.2667117714881897, "2509": 0.5979346632957458, "2512": 0.24554696679115295, "2515": 0.03831886500120163, "2522": 0.38441169261932373, "2527": 0.0009760859538801014, "2538": 0.31845372915267944, "2563": 0.47463157773017883, "2593": 0.14095009863376617, "2595": 0.06977381557226181, "2628": 0.30989447236061096, "2636": 0.33115679025650024, "2640": 0.5968599319458008, "2659": 0.1913948506116867, "2668": 0.08064348995685577, "2680": 0.45251765847206116, "2714": 0.013579257763922215, "2721": 0.13755162060260773, "2729": 0.41065993905067444, "2765": 0.23710809648036957, "2771": 0.09761575609445572, "2777": 0.9857001900672913, "2817": 0.5336109399795532, "2818": 0.18816383183002472, "2828": 0.4412745535373688, "2846": 0.14602625370025635, "2866": 0.6128603219985962, "2881": 0.07068414986133575, "2885": 0.13414156436920166, "2890": 0.20501139760017395, "2894": 0.45251765847206116, "2896": 0.2749055027961731, "2902": 0.5427330136299133, "2906": 0.0354953333735466, "2913": 0.43875885009765625, "2920": 0.09317722171545029, "2944": 0.5506471395492554, "2951": 0.520350456237793, "2988": 0.16524957120418549, "3022": 0.5162794589996338, "3078": 0.9225212931632996, "3112": 0.05786345899105072, "3218": 0.1677299439907074, "3239": 0.05046287178993225, "3258": 0.4831010699272156, "3273": 0.32058215141296387, "3278": 0.35745587944984436, "3313": 0.04487626627087593, "3378": 0.8374842405319214, "3426": 0.009718249551951885, "3429": 0.0038986403960734606, "3445": 0.47827014327049255, "3446": 0.5925496220588684, "3463": 0.39762192964553833, "3466": 0.1808556467294693, "3478": 0.23092569410800934, "3491": 0.058784693479537964, "3515": 0.1401015669107437, "3517": 0.20660123229026794, "3540": 0.7220231294631958, "3582": 0.5947071313858032, "3590": 0.19541899859905243, "3616": 0.35334911942481995, "3623": 0.14433705806732178, "3647": 0.4794800877571106, "3674": 0.04394211992621422, "3725": 0.13755162060260773, "3770": 0.10026945173740387, "3807": 0.3297532796859741, "3808": 0.25239890813827515, "3891": 1.0655186176300049, "3896": 0.35950297117233276, "3905": 0.11951763927936554, "3949": 0.4654768109321594, "3979": 0.3810817003250122, "4005": 0.6533012986183167, "4022": 0.77198725938797, "4102": 0.7845434546470642, "4117": 0.3662964701652527, "4127": 0.0038986403960734606, "4143": 0.20739519596099854, "4200": 0.11865071207284927, "4275": 0.46363574266433716, "4292": 0.3683255612850189, "4295": 0.19381128251552582, "4319": 0.35813871026039124, "4358": 0.6011518239974976, "4359": 0.021256839856505394, "4432": 0.37707099318504333, "4456": 0.07884006202220917, "4583": 0.04113444685935974, "4659": 0.4400174915790558, "4793": 0.14518201351165771, "4795": 0.49923527240753174, "4945": 0.9440274834632874, "5012": 0.026976587250828743, "5022": 0.6517757177352905, "5187": 0.19541899859905243, "5257": 0.7389566898345947, "5292": 0.08782484382390976, "5345": 0.7258110046386719, "5397": 0.6709295511245728, "5400": 0.0842406153678894, "5423": 0.23092569410800934, "5468": 0.23247487843036652, "5473": 0.05046287178993225, "5617": 0.16607704758644104, "5643": 0.24171993136405945, "5699": 0.3177432417869568, "5729": 0.7389566898345947, "5761": 0.3588210940361023, "5776": 0.5968599319458008, "5786": 0.19782574474811554, "5790": 0.0019512200960889459, "5802": 0.1358480453491211, "5812": 0.10906458646059036, "5816": 0.004870930220931768, "5845": 0.23402166366577148, "5850": 0.5762182474136353, "5859": 0.045809537172317505, "5986": 0.26296505331993103, "5994": 0.16607704758644104, "6022": 0.9178520441055298, "6030": 0.052318159490823746, "6072": 0.7153595685958862, "6074": 0.7872136831283569, "6078": 0.26820653676986694, "6086": 0.6170841455459595, "6165": 0.4537591338157654, "6255": 0.0019512200960889459, "6273": 0.06429435312747955, "6390": 0.13157635927200317, "6391": 0.013579257763922215, "6397": 0.9100211262702942, "6420": 0.9287132620811462, "6431": 0.036437395960092545, "6463": 1.0087559223175049, "6540": 0.20102575421333313, "6551": 0.056018441915512085, "6564": 0.12986256182193756, "6612": 0.17431432008743286, "6632": 0.09228714555501938, "6691": 0.16442140936851501, "6818": 0.3784096837043762, "6844": 0.8408597707748413, "6939": 0.08782484382390976, "7011": 0.053244512528181076, "7012": 0.4709797203540802, "7017": 0.3381449282169342, "7023": 1.130645751953125, "7037": 0.839173436164856, "7076": 0.5381823778152466, "7146": 0.2145126610994339, "7242": 0.7889899015426636, "7438": 0.32129061222076416, "7457": 0.045809537172317505, "7507": 0.053244512528181076, "7524": 0.9092346429824829, "7594": 0.010684899985790253, "7629": 0.9583619832992554, "7630": 0.3163207769393921, "7646": 0.04113444685935974, "7667": 0.5557019114494324, "7691": 0.06429435312747955, "7790": 0.2034190446138382, "7809": 0.5789587497711182, "7831": 0.7124901413917542, "7863": 0.9994535446166992, "7989": 0.1693800985813141, "8020": 0.2881702482700348, "8178": 0.11691460013389587, "8189": 0.23324857652187347, "8193": 0.12814582884311676, "8246": 0.41065993905067444, "8319": 0.18492233753204346, "8323": 0.1994270235300064, "8516": 0.7124901413917542, "8564": 0.052318159490823746, "8599": 0.12470348179340363, "8649": 0.817850649356842, "8718": 0.05139094591140747, "8832": 0.07068414986133575, "8949": 0.11951763927936554, "9002": 0.0797421783208847, "9280": 0.259204238653183, "9312": 0.09672962874174118, "9336": 0.026025565341114998, "9367": 0.21530038118362427, "9453": 0.06429435312747955, "9530": 0.3560888469219208, "9560": 0.6603899002075195, "9574": 0.9279413223266602, "9657": 0.04860413447022438, "9750": 0.04953393340110779, "9839": 0.09317722171545029, "9885": 0.04953393340110779, "10035": 0.09317722171545029, "10092": 0.3381449282169342, "10197": 0.09050461649894714, "10426": 0.7942996621131897, "10509": 0.26820653676986694, "10548": 0.3304552733898163, "10611": 0.18248429894447327, "10672": 0.036437395960092545, "10831": 0.9084475636482239, "10847": 0.0009760859538801014, "10947": 0.4770587682723999, "11100": 0.7028654217720032, "11146": 0.056018441915512085, "11290": 0.05786345899105072, "11441": 0.04953393340110779, "11514": 0.17922431230545044, "11566": 0.20421554148197174, "11597": 0.24859806895256042, "11616": 0.1718502640724182, "11643": 0.3163207769393921, "11704": 0.4132472574710846, "11721": 0.04767346754670143, "11835": 0.2184450328350067, "11896": 0.151916041970253, "12044": 0.25239890813827515, "12184": 0.07884006202220917, "12248": 0.10379679501056671, "12353": 0.12470348179340363, "12381": 0.12384103983640671, "12435": 0.47584590315818787, "12596": 0.12470348179340363, "12763": 0.29473719000816345, "12765": 0.010684899985790253, "12826": 0.42608439922332764, "13004": 0.03266380727291107, "13046": 0.23247487843036652, "13070": 0.2607102394104004, "13091": 0.0058422754518687725, "13105": 0.6833335757255554, "13153": 0.21687394380569458, "13180": 0.016465263441205025, "13210": 0.472198486328125, "13356": 0.6989894509315491, "13412": 0.14264501631259918, "13441": 0.27934664487838745, "13483": 1.0137293338775635, "13523": 0.013579257763922215, "13599": 0.574020504951477, "13770": 0.1602703034877777, "13938": 0.04860413447022438, "13944": 0.040196798741817474, "14025": 0.5773153901100159, "14031": 0.0038986403960734606, "14155": 0.6244332790374756, "14171": 0.347847044467926, "14192": 1.1555536985397339, "14234": 1.1444218158721924, "14358": 0.680370569229126, "14451": 0.14095009863376617, "14455": 0.22392450273036957, "14480": 0.006812678650021553, "14621": 0.09672962874174118, "14639": 0.16690383851528168, "14644": 0.9147270321846008, "14667": 0.5483922958374023, "14671": 1.276475191116333, "14751": 0.0009760859538801014, "14863": 0.176772341132164, "14876": 0.678390383720398, "14900": 0.3883931338787079, "14930": 0.3443928062915802, "14971": 0.2954642176628113, "15000": 1.1109062433242798, "15316": 0.38441169261932373, "15354": 0.11343330889940262, "15428": 0.15693697333335876, "15459": 0.22548456490039825, "15559": 1.070887804031372, "15596": 0.11256109178066254, "15660": 0.1384023278951645, "15725": 0.01934296265244484, "15877": 0.05046287178993225, "15909": 0.15359249711036682, "15975": 1.0848461389541626, "16122": 0.14433705806732178, "16149": 0.2696990668773651, "16183": 0.04487626627087593, "16215": 0.5573811531066895, "16216": 0.029824240133166313, "16250": 0.757441520690918, "16330": 0.21687394380569458, "16483": 0.08244366943836212, "16515": 0.19220098853111267, "16670": 0.055094651877880096, "16748": 0.10906458646059036, "16796": 0.11081436276435852, "17237": 0.07068414986133575, "17261": 0.3870677351951599, "17350": 0.02792670577764511, "17473": 0.18248429894447327, "17577": 0.9139442443847656, "17631": 0.3012613356113434, "17663": 0.04674193635582924, "17760": 0.47827014327049255, "17864": 0.6118015646934509, "17920": 0.020300358533859253, "18231": 0.32905077934265137, "18423": 0.46670228242874146, "18512": 0.015504186972975731, "18539": 0.2954642176628113, "18595": 0.09584271162748337, "18609": 0.05970508232712746, "18639": 0.3615458607673645, "18684": 0.09050461649894714, "18714": 0.07068414986133575, "18743": 0.12384103983640671, "18847": 1.1708117723464966, "18949": 0.28155985474586487, "18976": 0.4132472574710846, "19037": 0.5092619061470032, "19064": 0.1734936386346817, "19158": 0.45623743534088135, "19188": 0.5410289764404297, "19362": 0.24631060659885406, "19518": 0.02412080205976963, "19739": 0.11430477350950241, "19915": 0.06703783571720123, "20077": 0.3615458607673645, "20162": 0.40741631388664246, "20422": 0.5336109399795532, "20576": 0.026976587250828743, "20641": 0.29328158497810364, "20647": 0.03925827145576477, "20694": 0.083342544734478, "20752": 0.0019512200960889459, "20794": 0.15526613593101501, "20824": 0.8298473954200745, "20828": 0.15943801403045654, "20846": 0.920189380645752, "20900": 1.0464962720870972, "20915": 1.1462857723236084, "20960": 0.28963330388069153, "20992": 0.35128939151763916, "21150": 0.31845372915267944, "21273": 0.9209672808647156, "21280": 0.5767669677734375, "21396": 0.9155091643333435, "21539": 0.025073638185858727, "21557": 0.04767346754670143, "21879": 0.8780695199966431, "21903": 0.07341018319129944, "22010": 0.6389714479446411, "22060": 0.1808556467294693, "22068": 0.02887592278420925, "22214": 0.010684899985790253, "22254": 0.3339579105377197, "22423": 0.3883931338787079, "22571": 0.7818660736083984, "22597": 1.207676887512207, "22643": 0.11081436276435852, "22686": 0.12814582884311676, "22694": 0.49982786178588867, "22939": 0.35745587944984436, "22963": 0.3870677351951599, "22989": 0.13243216276168823, "23238": 0.4909018874168396, "23260": 0.11256109178066254, "23713": 0.9621002674102783, "23722": 0.20739519596099854, "23760": 0.7491656541824341, "23900": 0.14518201351165771, "23943": 0.13499516248703003, "24054": 0.10555581003427505, "24081": 0.20660123229026794, "24124": 0.10026945173740387, "24198": 0.17267228662967682, "24232": 0.7638313174247742, "24284": 0.20580662786960602, "24576": 0.3191637098789215, "24622": 0.08064348995685577, "24710": 0.10379679501056671, "24755": 0.02316705882549286, "24759": 0.20580662786960602, "24848": 0.1064341589808464, "25025": 0.2223619967699051, "25121": 0.026025565341114998, "25125": 0.6389714479446411, "25135": 0.053244512528181076, "25226": 0.07341018319129944, "25456": 0.026025565341114998, "25643": 1.068206787109375, "25690": 0.24325250089168549, "25708": 0.10203468054533005, "26117": 0.9857001900672913, "26290": 1.179255723953247, "26462": 0.24018502235412598, "26601": 0.15860503911972046, "26745": 0.5244048833847046, "26754": 0.21214580535888672, "27144": 0.19381128251552582, "27204": 0.02316705882549286, "27385": 0.3339579105377197, "27606": 1.1166772842407227, "27794": 1.013020396232605, "28177": 0.25088030099868774, "28225": 0.27044451236724854, "28436": 0.06612417846918106, "28689": 0.058784693479537964, "29021": 0.29981520771980286, "29166": 0.0770333781838417, "29234": 0.3743882179260254, "29295": 0.08692999184131622, "29336": 0.1212492436170578, "29361": 0.18329764902591705} | 13619127 | OBJECTIVE To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones). DESIGN Open cohort study in primary care. SETTING 1243 practices contributing data to the QResearch database in England. PARTICIPANTS 469,688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. EXPOSURES Hypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination. MAIN OUTCOME MEASURES First recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders. RESULTS 21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94). CONCLUSIONS We have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs. | Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care |
{"1006": 0.3012613356113434, "1007": 0.03831886500120163, "1009": 0.7701805830001831, "1011": 0.23092569410800934, "1016": 0.4286321699619293, "1039": 0.19622190296649933, "1045": 0.4950772523880005, "1047": 1.0030416250228882, "1996": 0.007782140281051397, "1997": 0.1889725625514984, "1999": 0.18411032855510712, "2006": 0.03360854089260101, "2011": 0.15526613593101501, "2012": 0.06246116757392883, "2029": 0.304147332906723, "2048": 0.1229778528213501, "2049": 0.11604541540145874, "2050": 0.7191727757453918, "2075": 0.4950772523880005, "2076": 0.026976587250828743, "2078": 0.0174254160374403, "2079": 0.0038986403960734606, "2102": 0.3034266233444214, "2109": 0.20501139760017395, "2129": 0.022212404757738113, "2135": 0.1946154683828354, "2147": 0.021256839856505394, "2213": 0.20580662786960602, "2235": 0.13414156436920166, "2304": 0.16110190749168396, "2312": 0.3676496744155884, "2332": 0.06429435312747955, "2439": 0.4349733293056488, "2464": 0.21135559678077698, "2475": 0.5080875158309937, "2478": 0.09228714555501938, "2487": 0.5618454217910767, "2503": 0.11256109178066254, "2504": 0.25239890813827515, "2509": 0.4617912769317627, "2515": 0.1677299439907074, "2531": 0.8143964409828186, "2549": 0.5947071313858032, "2550": 0.04860413447022438, "2555": 0.4531385898590088, "2556": 0.052318159490823746, "2561": 0.42161011695861816, "2583": 0.010684899985790253, "2595": 0.6911921501159668, "2601": 0.9194108247756958, "2662": 0.11430477350950241, "2717": 0.5191890001296997, "2783": 1.035461664199829, "2828": 0.23864774405956268, "2844": 0.6048921346664429, "2890": 0.6543170213699341, "2895": 0.12728634476661682, "2920": 0.022212404757738113, "2922": 0.17267228662967682, "2953": 0.812664806842804, "2981": 0.3134697377681732, "3024": 0.1602703034877777, "3073": 0.1677299439907074, "3149": 1.0478670597076416, "3161": 0.34715715050697327, "3231": 0.1685553640127182, "3252": 0.04207121208310127, "3279": 0.2447827309370041, "3283": 0.0009760859538801014, "3401": 0.5278670787811279, "3424": 0.9005423784255981, "3449": 0.7426811456680298, "3452": 0.01934296265244484, "3466": 0.7463917136192322, "3491": 0.3777405619621277, "3593": 0.7333439588546753, "3625": 0.7182208299636841, "3634": 0.2160874605178833, "3640": 0.30558720231056213, "3670": 0.16690383851528168, "3671": 0.3269403576850891, "3715": 0.29109421372413635, "3751": 0.2976420819759369, "3798": 0.18248429894447327, "3853": 0.29109421372413635, "3869": 0.10026945173740387, "3896": 0.495672345161438, "3898": 0.009718249551951885, "3921": 0.5523349046707153, "3997": 0.3353555500507355, "4005": 0.0174254160374403, "4022": 1.1481462717056274, "4029": 0.43053874373435974, "4039": 0.37907835841178894, "4063": 0.8550800085067749, "4081": 0.018384648486971855, "4111": 0.011650617234408855, "4117": 0.06337817758321762, "4118": 0.02316705882549286, "4127": 0.055094651877880096, "4140": 0.36967599391937256, "4146": 0.3897167444229126, "4162": 0.7067264318466187, "4176": 0.0009760859538801014, "4263": 0.0842406153678894, "4359": 0.5607312321662903, "4403": 0.020300358533859253, "4415": 0.2539152204990387, "4489": 0.02887592278420925, "4558": 0.2034190446138382, "4600": 0.48068851232528687, "4606": 0.14602625370025635, "4621": 0.75193190574646, "4646": 0.38374659419059753, "4655": 0.4431571960449219, "4668": 0.3318578004837036, "4671": 0.4145384132862091, "4698": 0.1510767638683319, "4725": 0.02412080205976963, "4742": 0.3547199070453644, "4758": 0.03360854089260101, "4768": 0.3883931338787079, "4796": 0.4132472574710846, "4937": 0.1229778528213501, "4942": 0.4914994537830353, "4984": 0.28890204429626465, "5012": 0.37640097737312317, "5072": 0.5267143249511719, "5097": 0.0797421783208847, "5110": 0.7201237678527832, "5228": 0.40089741349220276, "5248": 0.6502478122711182, "5257": 0.4203280806541443, "5285": 0.32341301441192627, "5320": 0.012615402229130268, "5338": 0.04860413447022438, "5360": 0.1332872211933136, "5393": 0.1619328260421753, "5416": 0.3588210940361023, "5452": 0.07250232994556427, "5468": 0.13157635927200317, "5474": 0.17840765416622162, "5547": 0.417115718126297, "5571": 0.09406650811433792, "5658": 0.6011518239974976, "5668": 0.7969439625740051, "5675": 0.2184450328350067, "5735": 0.03831886500120163, "5748": 0.030771657824516296, "5753": 1.0485517978668213, "5769": 0.29400965571403503, "5855": 0.25239890813827515, "5992": 0.4770587682723999, "6028": 0.12986256182193756, "6072": 0.14602625370025635, "6075": 0.21214580535888672, "6083": 0.21765978634357452, "6118": 0.2719337046146393, "6187": 0.9857001900672913, "6191": 0.28155985474586487, "6204": 1.299638032913208, "6302": 0.9084475636482239, "6370": 0.34715715050697327, "6388": 0.3910386264324188, "6409": 0.12038381397724152, "6428": 0.27786844968795776, "6448": 0.26446542143821716, "6451": 0.371698260307312, "6459": 0.20580662786960602, "6464": 0.3622259199619293, "6499": 0.987156867980957, "6592": 0.15943801403045654, "6611": 0.10291612148284912, "6651": 0.8433839678764343, "6693": 0.09495500475168228, "6711": 0.23556606471538544, "6833": 0.9115922451019287, "6887": 0.23247487843036652, "6903": 0.6583697199821472, "6958": 0.11604541540145874, "7017": 0.06337817758321762, "7077": 0.2184450328350067, "7127": 0.15359249711036682, "7198": 0.960606575012207, "7312": 0.09850110858678818, "7337": 0.43434104323387146, "7366": 0.25467249751091003, "7461": 0.4938860833644867, "7488": 0.272677481174469, "7551": 0.6296497583389282, "7568": 0.04394211992621422, "7589": 0.5855054259300232, "7591": 0.17840765416622162, "7645": 0.3601844012737274, "7646": 0.1212492436170578, "7711": 0.0913962796330452, "7730": 0.3374483287334442, "7760": 0.5186077356338501, "7783": 0.8925741910934448, "7790": 1.0416836738586426, "7885": 0.6441128253936768, "8031": 0.00875066313892603, "8060": 0.26296505331993103, "8077": 0.022212404757738113, "8088": 0.12986256182193756, "8107": 0.6202403903007507, "8114": 0.14095009863376617, "8127": 0.034552380442619324, "8161": 0.11256109178066254, "8281": 0.15610189735889435, "8290": 0.27786844968795776, "8292": 0.1751343309879303, "8335": 0.2659635543823242, "8345": 0.940220832824707, "8360": 0.9045027494430542, "8473": 1.1906025409698486, "8522": 0.1873544454574585, "8878": 1.0973093509674072, "9007": 0.3547199070453644, "9036": 0.04953393340110779, "9113": 0.23015019297599792, "9138": 0.11951763927936554, "9164": 0.2852376699447632, "9179": 0.1064341589808464, "9214": 0.6332852244377136, "9283": 0.6296497583389282, "9308": 0.0019512200960889459, "9447": 0.11691460013389587, "9507": 0.1212492436170578, "9597": 0.12470348179340363, "9702": 0.9628462791442871, "9706": 0.472198486328125, "9821": 0.3499138653278351, "9885": 0.07159364968538284, "9890": 0.848413348197937, "9904": 0.3070250153541565, "9966": 0.37907835841178894, "9982": 0.20421554148197174, "9997": 0.22548456490039825, "10004": 1.0808777809143066, "10047": 0.4770587682723999, "10163": 0.4944818615913391, "10177": 0.026976587250828743, "10250": 0.4158279001712799, "10266": 0.07431721687316895, "10473": 0.5784112811088562, "10479": 0.07431721687316895, "10507": 0.04394211992621422, "10509": 0.1994270235300064, "10548": 0.18573370575904846, "10556": 0.4512746334075928, "10572": 0.3547199070453644, "10631": 1.072893738746643, "10729": 0.5789587497711182, "10744": 0.10203468054533005, "10769": 0.4190443754196167, "10804": 0.979118824005127, "10862": 0.29109421372413635, "10936": 0.7115318179130554, "11085": 0.1913948506116867, "11099": 0.06977381557226181, "11124": 0.7389566898345947, "11211": 0.14686977863311768, "11243": 0.04767346754670143, "11307": 0.06795065850019455, "11382": 0.44753631949424744, "11439": 0.679875910282135, "11487": 0.19622190296649933, "11508": 0.45499902963638306, "11566": 0.0842406153678894, "11598": 0.029824240133166313, "11631": 0.6064908504486084, "11835": 0.02792670577764511, "12033": 0.06429435312747955, "12247": 0.2493593990802765, "12353": 0.5696102976799011, "12386": 0.06612417846918106, "12416": 0.08154398202896118, "12530": 0.3656192123889923, "12599": 0.08961215615272522, "12638": 0.06154331564903259, "12702": 0.5139457583427429, "12849": 0.09317722171545029, "12971": 0.2145126610994339, "13003": 0.14264501631259918, "13221": 0.7665573358535767, "13308": 0.07793712615966797, "13330": 0.10731173306703568, "13375": 0.6149744987487793, "13416": 0.36967599391937256, "13531": 0.25995752215385437, "13532": 0.10203468054533005, "13720": 0.151916041970253, "13791": 0.8057082891464233, "13833": 0.5069117546081543, "13853": 0.7314660549163818, "13874": 0.3318578004837036, "13876": 0.6719275116920471, "13922": 0.06154331564903259, "14127": 0.2478361576795578, "14161": 0.06429435312747955, "14260": 0.020300358533859253, "14731": 1.0478670597076416, "14828": 0.02316705882549286, "15000": 0.8450632095336914, "15113": 0.347847044467926, "15115": 0.03360854089260101, "15286": 0.05694137513637543, "15315": 1.0979610681533813, "15450": 0.1477125883102417, "15527": 0.07341018319129944, "15592": 0.12556517124176025, "15599": 0.43244171142578125, "15660": 0.04487626627087593, "15663": 0.24325250089168549, "15869": 0.8796916007995605, "15956": 0.2561853528022766, "16175": 0.8281423449516296, "16183": 1.0960047245025635, "16221": 0.08154398202896118, "16582": 0.3012613356113434, "16610": 0.16607704758644104, "16613": 1.2900071144104004, "16626": 0.12384103983640671, "16771": 0.05046287178993225, "16880": 0.026976587250828743, "17063": 0.1946154683828354, "17379": 0.17267228662967682, "17441": 0.5080875158309937, "17582": 0.5033760666847229, "17698": 0.1734936386346817, "17710": 0.06886265426874161, "17727": 0.2145126610994339, "17913": 0.129004567861557, "17976": 0.4938860833644867, "18044": 1.1858406066894531, "18053": 0.010684899985790253, "18155": 0.17840765416622162, "18554": 0.45870962738990784, "18586": 0.40546512603759766, "18642": 0.05046287178993225, "18856": 1.004473328590393, "19034": 0.05786345899105072, "19057": 0.24554696679115295, "19220": 0.16359257698059082, "19485": 1.2460440397262573, "19515": 0.00875066313892603, "19653": 0.2089812457561493, "19692": 0.680370569229126, "19696": 0.1946154683828354, "19780": 0.0038986403960734606, "19872": 0.05970508232712746, "19934": 0.27934664487838745, "20026": 0.8877626657485962, "20030": 0.33605360984802246, "20286": 0.036437395960092545, "20303": 0.8057082891464233, "20350": 0.08961215615272522, "20483": 0.9680526852607727, "20544": 0.6931471824645996, "20681": 0.009718249551951885, "20694": 0.006812678650021553, "20763": 0.8332487344741821, "20828": 0.28670501708984375, "20858": 0.083342544734478, "20912": 1.1756457090377808, "20936": 0.1602703034877777, "21017": 0.1384023278951645, "21083": 0.02887592278420925, "21101": 0.9576126337051392, "21117": 1.1337933540344238, "21150": 0.3995884954929352, "21162": 0.15526613593101501, "21281": 0.38308101892471313, "21307": 1.0094679594039917, "21344": 0.40285754203796387, "21618": 0.04113444685935974, "21677": 0.33675122261047363, "21903": 0.4002431631088257, "21967": 0.18004031479358673, "22015": 0.15943801403045654, "22100": 0.06703783571720123, "22154": 0.010684899985790253, "22184": 0.14939609169960022, "22208": 0.011650617234408855, "22423": 0.03831886500120163, "22543": 0.14264501631259918, "22618": 0.16524957120418549, "22684": 0.8247235417366028, "22694": 0.055094651877880096, "22930": 0.045809537172317505, "22931": 1.0802149772644043, "22974": 0.16607704758644104, "23036": 0.46608972549438477, "23041": 0.6902132034301758, "23093": 1.3433949947357178, "23180": 0.12728634476661682, "23216": 0.06977381557226181, "23316": 0.04767346754670143, "23389": 0.07793712615966797, "23396": 0.42735910415649414, "23586": 0.3560888469219208, "23616": 0.13157635927200317, "23713": 0.5584990978240967, "23799": 0.34508460760116577, "23923": 1.180456280708313, "24053": 0.23247487843036652, "24054": 0.1808556467294693, "24229": 0.14686977863311768, "24614": 0.15442965924739838, "24635": 0.058784693479537964, "24720": 0.6170841455459595, "24774": 0.1401015669107437, "24794": 0.1710275560617447, "24810": 0.034552380442619324, "24888": 0.07793712615966797, "24972": 0.6808650493621826, "25167": 1.1121915578842163, "25194": 0.3339579105377197, "25377": 0.3077431619167328, "25458": 0.21530038118362427, "25597": 0.7482418417930603, "25761": 0.14939609169960022, "26058": 0.259204238653183, "26089": 0.1485546976327896, "26243": 0.16690383851528168, "26244": 0.20977331697940826, "26288": 0.014542185701429844, "26376": 0.5762182474136353, "26402": 0.23710809648036957, "26755": 0.04394211992621422, "26897": 0.1221139207482338, "27094": 0.5483922958374023, "27292": 0.757441520690918, "27381": 0.016465263441205025, "27781": 1.0001721382141113, "27854": 0.46302130818367004, "28242": 0.09584271162748337, "28282": 0.20102575421333313, "28432": 0.009718249551951885, "28688": 0.4002431631088257, "28873": 0.18248429894447327, "29090": 0.5601736903190613, "29111": 0.2954642176628113, "29490": 0.15023678541183472, "29535": 0.043007105588912964} | 13621186 | In salamander rods, Ca(2+)-activated K(+) current (I(KCa)) provides an effective "clamp" of the dark membrane potential to its normal resting level. By a combination of electrophysiological, pharmacological, and immunohistochemical approaches, we show that salamander rods functionally express large-conductance Ca(2+)- and voltage-dependent potassium (BK) channel and intermediate-conductance Ca(2+)-dependent potassium (IK) channel, but not small-conductance Ca(2+)-dependent potassium channel (SK) subtypes. Application of 100 nM iberiotoxin and 100 nM clotrimazole reduced net I(KCa) to 36% and 63%, respectively, whereas the current was unaffected by application of 1 microM apamin. Consistently, anti- SK1, -SK2, and -SK3 antibodies were unable to stain rod photoreceptors, whereas both anti-BK and -SK4/ IK1 antibodies heavily stained the ellipsoid region of the inner segments of the rods. Moreover, by using current-clamp experiments, it was clearly seen that the strong clamping effect of the total I(KCa) was lost when IbTx, but not CLTZ, was applied to the bath. This behavior strongly suggests that of BK and IK channels, only the former are responsible for the clamping effect on the photoreceptor membrane potential. | Vertebrate rod photoreceptors express both BK and IK calcium-activated potassium channels, but only BK channels are involved in receptor potential regulation. |
{"1014": 0.2637155055999756, "1018": 0.14179791510105133, "1052": 0.4145384132862091, "2005": 0.12642613053321838, "2006": 1.0802149772644043, "2011": 0.6054253578186035, "2028": 0.21372433006763458, "2034": 0.22548456490039825, "2044": 0.10467668622732162, "2051": 0.6254787445068359, "2053": 0.2918238639831543, "2075": 0.1485546976327896, "2078": 0.6181373596191406, "2086": 0.32270604372024536, "2095": 0.020300358533859253, "2109": 0.21135559678077698, "2116": 0.3554046154022217, "2128": 0.5478278398513794, "2146": 0.5936289429664612, "2166": 0.04207121208310127, "2172": 0.637939989566803, "2173": 0.7220231294631958, "2184": 0.029824240133166313, "2193": 0.27044451236724854, "2214": 0.0174254160374403, "2217": 0.306306391954422, "2260": 0.2983669638633728, "2275": 0.33325836062431335, "2287": 0.681853175163269, "2302": 0.33325836062431335, "2309": 0.7951818704605103, "2313": 0.058784693479537964, "2319": 0.11430477350950241, "2320": 0.0058422754518687725, "2335": 0.33675122261047363, "2336": 0.8433839678764343, "2368": 0.07341018319129944, "2378": 0.14264501631259918, "2445": 0.28155985474586487, "2470": 0.15610189735889435, "2491": 0.3810817003250122, "2504": 0.11256109178066254, "2527": 0.16359257698059082, "2549": 0.34508460760116577, "2588": 0.20739519596099854, "2615": 0.40351006388664246, "2638": 0.16359257698059082, "2695": 0.39893341064453125, "2696": 0.1685553640127182, "2721": 0.006812678650021553, "2775": 0.7389566898345947, "2779": 0.5404602885246277, "2781": 0.5010119676589966, "2792": 0.6441128253936768, "2817": 0.5483922958374023, "2846": 0.28670501708984375, "2850": 0.40285754203796387, "2902": 0.009718249551951885, "2913": 0.43053874373435974, "3031": 0.11604541540145874, "3091": 0.05694137513637543, "3112": 0.3241194784641266, "3115": 0.012615402229130268, "3144": 0.18654440343379974, "3223": 0.0797421783208847, "3231": 0.021256839856505394, "3273": 0.3656192123889923, "3278": 0.1718502640724182, "3284": 0.09850110858678818, "3313": 0.6228629946708679, "3325": 0.35334911942481995, "3336": 0.2696990668773651, "3366": 0.06246116757392883, "3371": 0.30558720231056213, "3429": 0.1734936386346817, "3433": 0.025073638185858727, "3435": 0.04113444685935974, "3446": 0.4203280806541443, "3452": 0.5347557663917542, "3463": 0.06795065850019455, "3465": 0.08154398202896118, "3466": 0.3170322775840759, "3527": 0.11604541540145874, "3550": 0.1332872211933136, "3556": 0.2317005842924118, "3560": 0.3443928062915802, "3619": 0.12556517124176025, "3635": 0.3127557039260864, "3643": 0.11865071207284927, "3647": 0.7057625651359558, "3671": 0.11951763927936554, "3674": 0.0009760859538801014, "3718": 0.06703783571720123, "3808": 0.7647408246994019, "3815": 0.4196864068508148, "3817": 0.0019512200960889459, "3867": 0.05694137513637543, "3896": 0.4818955361843109, "3949": 0.5450005531311035, "3979": 0.906871497631073, "3988": 0.015504186972975731, "4022": 0.259204238653183, "4090": 0.08692999184131622, "4094": 0.11430477350950241, "4098": 0.5635144114494324, "4102": 0.07250232994556427, "4106": 0.05786345899105072, "4115": 0.19782574474811554, "4143": 0.31132611632347107, "4178": 0.7352184057235718, "4215": 0.030771657824516296, "4219": 0.6613984704017639, "4254": 0.18654440343379974, "4268": 0.4002431631088257, "4270": 0.25088030099868774, "4305": 0.06977381557226181, "4308": 0.32129061222076416, "4359": 0.42735910415649414, "4413": 0.17759032547473907, "4555": 0.8845420479774475, "4621": 0.6410312056541443, "4705": 0.7445381283760071, "4724": 0.1332872211933136, "4758": 0.7389566898345947, "4788": 0.004870930220931768, "4793": 0.10731173306703568, "4795": 0.15526613593101501, "4800": 0.4974553883075714, "4907": 0.03266380727291107, "4921": 0.4932899475097656, "4948": 0.8715548515319824, "4971": 0.4412745535373688, "5022": 0.39696553349494934, "5054": 0.040196798741817474, "5092": 0.7601850032806396, "5162": 0.04394211992621422, "5171": 0.20977331697940826, "5280": 0.04394211992621422, "5281": 0.37640097737312317, "5289": 0.13414156436920166, "5343": 0.6573580503463745, "5443": 0.34508460760116577, "5466": 0.680370569229126, "5521": 0.3464667797088623, "5547": 0.3949938118457794, "5575": 0.05046287178993225, "5593": 0.3777405619621277, "5604": 0.00875066313892603, "5643": 0.35677260160446167, "5729": 0.2969166338443756, "5776": 0.45932671427726746, "5787": 0.20818853378295898, "5790": 0.29109421372413635, "5794": 0.49864232540130615, "5845": 0.4487839937210083, "5970": 0.4330752193927765, "6022": 0.7683706283569336, "6075": 0.1994270235300064, "6133": 0.14264501631259918, "6165": 0.13925230503082275, "6197": 1.1573970317840576, "6388": 0.11256109178066254, "6397": 0.9232974052429199, "6431": 0.12384103983640671, "6444": 0.41065993905067444, "6463": 0.11691460013389587, "6551": 0.1693800985813141, "6583": 0.48670899868011475, "6593": 0.04207121208310127, "6605": 0.05417001247406006, "6612": 0.2837681770324707, "6657": 0.2741633653640747, "6693": 0.2447827309370041, "6721": 0.7028654217720032, "6758": 0.14686977863311768, "6810": 0.2247048318386078, "6821": 0.40806588530540466, "6844": 0.2830325961112976, "6886": 0.5729197263717651, "6927": 0.32129061222076416, "7012": 0.8885661959648132, "7017": 0.2969166338443756, "7068": 0.11343330889940262, "7242": 0.03360854089260101, "7312": 0.14939609169960022, "7352": 0.0354953333735466, "7438": 0.3177432417869568, "7551": 0.2089812457561493, "7630": 0.0058422754518687725, "7667": 0.3177432417869568, "7691": 0.20580662786960602, "7692": 0.791648268699646, "7711": 0.22079704701900482, "7820": 0.1401015669107437, "7831": 0.15860503911972046, "7847": 1.0828639268875122, "7856": 0.053244512528181076, "7861": 0.8764448165893555, "7885": 0.030771657824516296, "8015": 0.38441169261932373, "8030": 0.23556606471538544, "8082": 0.44691193103790283, "8117": 0.1485546976327896, "8159": 0.8349450826644897, "8161": 0.0317181795835495, "8193": 0.05970508232712746, "8208": 0.006812678650021553, "8329": 0.8212929964065552, "8465": 0.2689530849456787, "8557": 0.11865071207284927, "8564": 0.2741633653640747, "8599": 0.10906458646059036, "8718": 0.02792670577764511, "8830": 0.7314660549163818, "8943": 0.2719337046146393, "8977": 0.06154331564903259, "9126": 0.11430477350950241, "9153": 0.1401015669107437, "9155": 0.04953393340110779, "9305": 0.011650617234408855, "9312": 0.2622140049934387, "9314": 0.6689305305480957, "9351": 0.09228714555501938, "9367": 0.5751199722290039, "9560": 0.25694093108177185, "9601": 0.16442140936851501, "9633": 0.14686977863311768, "9689": 0.06795065850019455, "9839": 0.09317722171545029, "9998": 1.1005635261535645, "10111": 0.011650617234408855, "10148": 0.7701805830001831, "10228": 0.3963087201118469, "10286": 0.083342544734478, "10484": 0.7791815400123596, "10527": 0.3141832649707794, "10534": 0.35745587944984436, "10577": 0.00875066313892603, "10609": 0.08603433519601822, "10632": 0.29400965571403503, "10649": 0.9217445850372314, "10715": 0.10906458646059036, "10834": 0.3381449282169342, "10936": 0.2231435477733612, "10994": 0.10291612148284912, "11207": 0.10993985831737518, "11460": 0.7389566898345947, "11500": 0.4556184411048889, "11502": 0.3374483287334442, "11704": 0.11343330889940262, "11707": 0.0797421783208847, "11788": 0.05417001247406006, "11806": 0.06154331564903259, "12171": 0.14264501631259918, "12248": 0.1693800985813141, "12269": 0.14602625370025635, "12353": 0.7473171949386597, "12380": 0.1873544454574585, "12526": 0.10555581003427505, "12638": 0.006812678650021553, "12693": 0.14264501631259918, "12765": 0.00875066313892603, "12928": 0.16690383851528168, "13004": 1.1141164302825928, "13013": 0.7314660549163818, "13029": 0.5579402446746826, "13070": 0.045809537172317505, "13105": 0.1693800985813141, "13153": 0.05970508232712746, "13183": 0.08513788133859634, "13341": 0.28963330388069153, "13377": 0.05046287178993225, "13390": 0.011650617234408855, "13416": 0.18167030811309814, "13433": 0.6709295511245728, "13441": 0.07612881064414978, "13453": 0.2976420819759369, "13462": 1.0601204633712769, "13471": 0.3027053773403168, "13494": 1.0580886602401733, "13595": 0.22548456490039825, "13701": 0.13499516248703003, "13716": 0.06703783571720123, "13749": 0.010684899985790253, "14155": 0.6369074583053589, "14358": 0.31560876965522766, "14447": 0.09850110858678818, "14621": 0.08961215615272522, "14667": 0.3995884954929352, "14697": 0.13670019805431366, "14971": 0.07341018319129944, "14996": 0.26146242022514343, "15170": 0.020300358533859253, "15316": 0.24325250089168549, "15459": 0.06795065850019455, "15464": 0.0174254160374403, "15556": 0.2531573474407196, "15853": 0.052318159490823746, "15872": 0.037378571927547455, "15928": 0.38174858689308167, "16102": 0.1685553640127182, "16150": 0.1946154683828354, "16231": 0.015504186972975731, "16298": 0.9037119746208191, "16330": 0.3304552733898163, "16530": 0.7426811456680298, "16670": 0.11604541540145874, "16725": 0.45437926054000854, "16834": 0.1905880719423294, "16940": 0.6420594453811646, "17042": 0.1011524572968483, "17062": 0.11168810725212097, "17086": 0.49626702070236206, "17168": 0.14349138736724854, "17190": 0.030771657824516296, "17191": 0.12384103983640671, "17473": 0.15442965924739838, "17503": 0.2160874605178833, "17635": 0.058784693479537964, "17686": 0.06520967930555344, "17713": 0.11256109178066254, "17768": 0.18248429894447327, "17819": 0.030771657824516296, "18164": 0.27712854743003845, "18178": 0.010684899985790253, "18417": 0.1229778528213501, "18595": 0.23324857652187347, "18634": 0.4349733293056488, "18639": 0.10993985831737518, "18847": 0.0009760859538801014, "18857": 0.31132611632347107, "18861": 0.21687394380569458, "18891": 0.31132611632347107, "18949": 0.040196798741817474, "18976": 0.7791815400123596, "19009": 0.997294545173645, "19029": 1.2599912881851196, "19132": 0.16524957120418549, "19235": 0.28743788599967957, "19388": 0.36086538434028625, "19440": 0.10555581003427505, "19761": 0.05417001247406006, "19883": 0.05694137513637543, "20047": 0.0752234235405922, "20363": 0.0009760859538801014, "20389": 0.28082266449928284, "20409": 0.14264501631259918, "20523": 0.4437839686870575, "20584": 0.4500300884246826, "20624": 0.23324857652187347, "20641": 0.02792670577764511, "20662": 0.12642613053321838, "20738": 0.20102575421333313, "20793": 0.5191890001296997, "20828": 0.35128939151763916, "20936": 0.026025565341114998, "20992": 0.018384648486971855, "21046": 0.0913962796330452, "21150": 1.0051883459091187, "21254": 0.0058422754518687725, "21604": 0.0913962796330452, "21656": 0.9271688461303711, "21678": 0.1685553640127182, "21748": 0.09406650811433792, "21779": 0.0752234235405922, "22423": 0.14939609169960022, "22436": 0.12556517124176025, "22471": 0.5438674688339233, "22648": 0.1710275560617447, "22834": 0.034552380442619324, "22903": 0.16110190749168396, "22930": 0.06703783571720123, "22943": 0.1401015669107437, "23251": 0.6563454270362854, "23274": 0.3374483287334442, "23597": 0.3388410806655884, "23614": 0.5827828645706177, "23659": 0.19622190296649933, "23805": 0.083342544734478, "24393": 0.1602703034877777, "24479": 0.1229778528213501, "24714": 0.0019512200960889459, "24735": 0.018384648486971855, "24755": 0.09761575609445572, "24780": 1.1102628707885742, "24798": 0.010684899985790253, "24901": 0.0797421783208847, "24979": 0.11081436276435852, "25323": 0.45499902963638306, "25344": 0.2501201331615448, "25604": 0.5267143249511719, "25750": 0.12384103983640671, "25775": 0.07068414986133575, "25918": 0.8869584798812866, "26001": 0.23710809648036957, "26243": 0.06246116757392883, "26290": 0.22782009840011597, "26370": 0.0174254160374403, "26462": 0.06612417846918106, "26721": 0.8332487344741821, "26788": 0.19541899859905243, "27144": 0.1930064558982849, "27166": 0.012615402229130268, "27441": 0.16110190749168396, "28345": 0.21922965347766876, "28472": 0.016465263441205025, "28716": 0.08961215615272522, "28741": 0.052318159490823746, "29031": 0.15023678541183472, "29160": 0.083342544734478, "29212": 0.004870930220931768, "29234": 0.055094651877880096, "29336": 0.2317005842924118, "29361": 0.03925827145576477, "29533": 0.17840765416622162, "29610": 0.05786345899105072} | 13624704 | The efficacy, safety and resource implications of a single intravenous dose of ondansetron (0.1 mg.kg-1, maximum 4 mg) were assessed in a multinational, multicentre, randomized, double-blind, placebo-controlled trial of 427 children aged 1-12 years, undergoing tonsillectomy with/without adenoidectomy. Emesis (retching and/or vomiting) and nausea were analysed separately. Significantly more ondansetron-treated children had no episodes of emesis (127/212 (60%) vs 100/215 (47%); P = 0.004) and experienced no postoperative nausea (135/211 (64%) vs 108/213 (51%); P = 0.004) in the first 24 h. Ondansetron also reduced the number of emetic episodes (P < 0.001), the time to the first emetic episode (P < 0.001) and overall nausea severity (P = 0.003). Significantly fewer ondansetron-treated children were rescued or withdrawn from the study (5% vs 10%; P = 0.042). Fewer ondansetron-treated patients required nursing intervention (34% vs 45%; P = 0.007) and the average intervention time was significantly shorter (4.6 vs 8.1 minutes; P = 0.001). Resources used to manage PONV were significantly reduced by ondansetron (43% vs 57%; P = 0.014). | Ondansetron reduces nausea and vomiting after paediatric adenotonsillectomy. |
{"1039": 0.8161250352859497, "1043": 0.6400018334388733, "1053": 0.966567873954773, "2015": 0.11778303235769272, "2044": 0.18004031479358673, "2051": 0.11517547070980072, "2077": 0.2184450328350067, "2086": 0.5127768516540527, "2095": 0.07341018319129944, "2102": 0.0058422754518687725, "2109": 0.12470348179340363, "2116": 0.030771657824516296, "2120": 0.4794800877571106, "2121": 0.3723714053630829, "2146": 0.34577593207359314, "2154": 0.46363574266433716, "2166": 0.7047978043556213, "2169": 0.0029254043474793434, "2172": 0.3409265875816345, "2184": 0.1751343309879303, "2199": 0.36290550231933594, "2235": 0.06612417846918106, "2241": 0.38308101892471313, "2302": 0.440646231174469, "2313": 0.39367714524269104, "2322": 0.06246116757392883, "2326": 0.44691193103790283, "2344": 0.3127557039260864, "2382": 0.06703783571720123, "2420": 0.3084607720375061, "2478": 0.48008447885513306, "2504": 0.35950297117233276, "2531": 0.5267143249511719, "2540": 0.6249561905860901, "2545": 0.5139457583427429, "2566": 0.7134475708007812, "2578": 0.016465263441205025, "2582": 0.12038381397724152, "2592": 0.4873090982437134, "2605": 0.10731173306703568, "2640": 0.791648268699646, "2647": 0.27342069149017334, "2692": 0.05417001247406006, "2710": 0.6882523894309998, "2724": 0.6517757177352905, "2740": 0.5069117546081543, "2747": 0.2852376699447632, "2765": 0.32129061222076416, "2779": 0.1212492436170578, "2783": 0.2493593990802765, "2804": 0.16276304423809052, "2812": 0.010684899985790253, "2824": 0.7737906575202942, "2832": 0.3416208028793335, "2836": 0.02412080205976963, "2854": 0.16359257698059082, "2862": 0.11168810725212097, "2864": 0.3084607720375061, "2866": 0.05786345899105072, "2881": 0.35334911942481995, "2885": 0.48670899868011475, "2896": 0.32199856638908386, "2902": 0.15693697333335876, "2944": 0.7629209756851196, "2951": 0.4400174915790558, "3010": 0.39433568716049194, "3020": 0.0029254043474793434, "3025": 0.14264501631259918, "3112": 0.034552380442619324, "3117": 0.6327666640281677, "3130": 0.09672962874174118, "3144": 0.1685553640127182, "3161": 0.007782140281051397, "3176": 0.630689799785614, "3188": 1.0641717910766602, "3189": 0.08154398202896118, "3195": 0.2231435477733612, "3231": 0.11604541540145874, "3247": 0.8247235417366028, "3265": 0.21372433006763458, "3370": 0.5341835021972656, "3378": 0.6970458030700684, "3403": 0.841701865196228, "3436": 0.2689530849456787, "3446": 0.6902132034301758, "3452": 0.1221139207482338, "3463": 0.6415454745292664, "3465": 1.2347444295883179, "3466": 0.4337083101272583, "3524": 0.678390383720398, "3540": 0.00875066313892603, "3556": 0.8877626657485962, "3641": 0.040196798741817474, "3643": 0.040196798741817474, "3653": 0.5500838756561279, "3679": 0.11168810725212097, "3695": 0.4002431631088257, "3722": 0.3615458607673645, "3737": 0.6212902665138245, "3798": 0.1930064558982849, "3891": 0.9724938273429871, "3896": 0.5450005531311035, "3938": 0.6086184978485107, "3976": 0.7009293437004089, "3981": 0.6573580503463745, "4003": 0.4556184411048889, "4013": 0.5800528526306152, "4094": 0.026025565341114998, "4102": 0.6950984001159668, "4106": 0.6867793202400208, "4160": 0.2247048318386078, "4236": 0.3615458607673645, "4254": 0.6759096384048462, "4275": 0.40741631388664246, "4340": 0.4879087805747986, "4358": 0.7898768186569214, "4361": 0.4067663550376892, "4467": 1.0030416250228882, "4488": 0.11343330889940262, "4561": 1.0023250579833984, "4577": 0.40806588530540466, "4621": 0.9747070074081421, "4632": 0.043007105588912964, "4685": 0.18654440343379974, "4701": 0.8715548515319824, "4710": 0.0317181795835495, "4741": 0.07159364968538284, "4795": 0.02887592278420925, "4921": 0.1751343309879303, "5022": 0.45437926054000854, "5043": 0.1710275560617447, "5046": 0.1384023278951645, "5067": 0.1384023278951645, "5068": 0.07612881064414978, "5083": 0.043007105588912964, "5134": 0.129004567861557, "5159": 0.3269403576850891, "5250": 0.9842413663864136, "5337": 0.7426811456680298, "5366": 0.6960725784301758, "5387": 0.08692999184131622, "5400": 0.4500300884246826, "5468": 0.2539152204990387, "5531": 0.21922965347766876, "5548": 0.09938567131757736, "5585": 0.5903874635696411, "5617": 0.2659635543823242, "5646": 0.34300774335861206, "5656": 0.8957691192626953, "5695": 0.1677299439907074, "5761": 0.0913962796330452, "5776": 0.637939989566803, "5790": 0.3262358605861664, "5816": 0.6118015646934509, "5859": 0.18004031479358673, "5970": 0.7647408246994019, "5986": 0.0038986403960734606, "6032": 0.009718249551951885, "6053": 0.7665573358535767, "6064": 0.043007105588912964, "6165": 0.37371641397476196, "6258": 0.23556606471538544, "6364": 0.14518201351165771, "6450": 0.3269403576850891, "6464": 0.31489628553390503, "6470": 0.16359257698059082, "6480": 0.7124901413917542, "6540": 0.969535231590271, "6567": 0.2822965085506439, "6612": 0.7436100244522095, "6648": 0.23710809648036957, "6694": 0.053244512528181076, "7038": 0.7163142561912537, "7091": 0.6563454270362854, "7092": 0.07250232994556427, "7096": 0.6583697199821472, "7192": 0.0354953333735466, "7315": 0.036437395960092545, "7327": 0.0913962796330452, "7375": 0.5197699069976807, "7461": 0.14264501631259918, "7528": 0.17020416259765625, "7594": 0.5827828645706177, "7597": 0.08064348995685577, "7644": 0.5756692886352539, "7649": 0.20102575421333313, "7667": 0.45623743534088135, "7709": 0.6075552701950073, "7831": 0.6502478122711182, "7863": 1.0464962720870972, "7934": 0.7286425232887268, "8015": 0.06977381557226181, "8114": 0.17840765416622162, "8122": 0.33675122261047363, "8156": 0.7710843086242676, "8166": 0.37102460861206055, "8171": 0.678390383720398, "8197": 0.026976587250828743, "8321": 0.07250232994556427, "8394": 0.27044451236724854, "8458": 0.29255300760269165, "8536": 0.1011524572968483, "8599": 0.17759032547473907, "8819": 0.21372433006763458, "8830": 0.053244512528181076, "8853": 0.38905516266822815, "8947": 0.6128603219985962, "9044": 1.1319060325622559, "9128": 0.07793712615966797, "9211": 0.6902132034301758, "9250": 0.23864774405956268, "9312": 0.4462870955467224, "9363": 0.018384648486971855, "9367": 0.2247048318386078, "9431": 0.05139094591140747, "9556": 0.2223619967699051, "9560": 0.12986256182193756, "9582": 0.18167030811309814, "9765": 0.19381128251552582, "9871": 0.009718249551951885, "9942": 0.7009293437004089, "9944": 0.8195732831954956, "10035": 0.2852376699447632, "10068": 0.05970508232712746, "10074": 0.5489565134048462, "10174": 0.2561853528022766, "10197": 0.5398913025856018, "10216": 0.007782140281051397, "10381": 0.043007105588912964, "10408": 0.32270604372024536, "10426": 0.5640701055526733, "10464": 0.04207121208310127, "10507": 0.16359257698059082, "10509": 0.48068851232528687, "10640": 0.22626367211341858, "10665": 0.9900637865066528, "10831": 0.630689799785614, "10882": 0.4794800877571106, "10903": 0.2516399025917053, "10927": 0.02792670577764511, "11069": 0.1970241367816925, "11100": 0.7863243818283081, "11162": 0.12556517124176025, "11207": 1.061472773551941, "11236": 0.151916041970253, "11307": 0.27934664487838745, "11326": 0.08692999184131622, "11387": 0.3930181860923767, "11436": 0.16690383851528168, "11441": 0.1384023278951645, "11616": 0.3353555500507355, "11643": 0.5330380201339722, "11707": 0.3127557039260864, "11826": 1.2129170894622803, "12044": 0.5838727951049805, "12058": 0.058784693479537964, "12353": 1.068206787109375, "12367": 0.2561853528022766, "12435": 0.22782009840011597, "12504": 0.2881702482700348, "12515": 0.015504186972975731, "12596": 0.2607102394104004, "12654": 0.07793712615966797, "12697": 0.36697331070899963, "12826": 0.37707099318504333, "12941": 0.13414156436920166, "12942": 0.0009760859538801014, "12943": 0.18004031479358673, "13105": 0.021256839856505394, "13113": 0.3304552733898163, "13153": 0.052318159490823746, "13320": 0.2516399025917053, "13485": 0.02412080205976963, "13599": 0.5914691090583801, "13649": 0.0009760859538801014, "13661": 0.47584590315818787, "13706": 0.9256220459938049, "13887": 0.03925827145576477, "14040": 0.004870930220931768, "14083": 0.4624064862728119, "14142": 0.5517725944519043, "14155": 0.6773988008499146, "14171": 0.021256839856505394, "14223": 0.24171993136405945, "14234": 0.4794800877571106, "14358": 0.5139457583427429, "14480": 0.1751343309879303, "14670": 0.09317722171545029, "14971": 0.13499516248703003, "14972": 0.5127768516540527, "15050": 0.6897233724594116, "15186": 0.6664261221885681, "15306": 0.5762182474136353, "15316": 0.0174254160374403, "15497": 0.848413348197937, "15584": 0.9621002674102783, "15725": 0.006812678650021553, "15727": 0.14602625370025635, "16012": 0.848413348197937, "16134": 0.259204238653183, "16157": 0.1734936386346817, "16185": 0.75193190574646, "16259": 0.14349138736724854, "16268": 0.06246116757392883, "16330": 0.2881702482700348, "16474": 0.15442965924739838, "16478": 0.3070250153541565, "16519": 0.20977331697940826, "16731": 0.1401015669107437, "16749": 1.0087559223175049, "16771": 0.16607704758644104, "16882": 0.011650617234408855, "16940": 0.0842406153678894, "17042": 0.15777134895324707, "17047": 0.1930064558982849, "17076": 0.9591107368469238, "17080": 0.09672962874174118, "17208": 0.32129061222076416, "17237": 0.3409265875816345, "17298": 0.02792670577764511, "17345": 0.029824240133166313, "17463": 0.2493593990802765, "17660": 0.1946154683828354, "17695": 0.018384648486971855, "17736": 0.04860413447022438, "17826": 0.7809720039367676, "17839": 0.0009760859538801014, "17908": 0.49626702070236206, "18133": 0.4400174915790558, "18422": 0.22626367211341858, "18539": 0.2145126610994339, "18804": 0.6160298585891724, "18816": 0.24325250089168549, "19037": 0.2184450328350067, "19064": 0.1889725625514984, "19188": 0.3325583338737488, "19199": 0.14349138736724854, "19209": 0.0174254160374403, "19317": 0.6872705817222595, "19329": 0.6107416749000549, "19353": 0.9621002674102783, "19481": 0.9084475636482239, "19518": 0.27934664487838745, "19620": 0.07431721687316895, "19681": 0.29619070887565613, "19723": 0.14179791510105133, "19961": 0.014542185701429844, "19974": 0.5027855634689331, "20077": 0.22548456490039825, "20116": 0.09495500475168228, "20118": 0.14179791510105133, "20162": 0.34370049834251404, "20177": 0.06886265426874161, "20353": 0.19220098853111267, "20469": 0.1229778528213501, "20569": 0.34508460760116577, "20588": 0.12556517124176025, "20612": 0.08244366943836212, "20694": 0.10291612148284912, "20702": 0.28890204429626465, "20704": 0.036437395960092545, "20766": 1.3149620294570923, "20906": 0.1229778528213501, "20960": 0.175953671336174, "21011": 0.17922431230545044, "21074": 0.08961215615272522, "21150": 0.7454653382301331, "21297": 1.034073829650879, "21449": 0.4974553883075714, "21486": 0.15610189735889435, "21557": 0.0019512200960889459, "21716": 0.15693697333335876, "21887": 1.004473328590393, "22022": 0.03266380727291107, "22049": 0.3346569836139679, "22160": 1.0655186176300049, "22173": 0.22859740257263184, "22291": 0.7647408246994019, "22394": 0.7105726003646851, "22458": 0.7528522610664368, "22643": 1.3186259269714355, "22835": 0.18004031479358673, "22836": 0.47827014327049255, "22935": 0.9379299283027649, "22963": 0.28597161173820496, "23208": 0.3877306580543518, "23521": 0.3615458607673645, "23632": 0.5455666780471802, "23643": 0.11691460013389587, "24010": 0.2622140049934387, "24023": 0.02887592278420925, "24155": 0.3547199070453644, "24360": 0.2034190446138382, "24411": 0.2674594223499298, "24710": 0.13071982562541962, "24714": 0.04394211992621422, "24755": 0.10291612148284912, "24759": 0.39762192964553833, "24847": 0.02887592278420925, "24848": 0.022212404757738113, "24978": 0.27934664487838745, "25070": 0.1808556467294693, "25090": 0.1384023278951645, "25095": 0.24554696679115295, "25117": 0.14939609169960022, "25121": 0.06520967930555344, "25125": 0.11951763927936554, "25196": 0.30989447236061096, "25543": 0.503966212272644, "25608": 0.034552380442619324, "25708": 0.23324857652187347, "26089": 0.40546512603759766, "26226": 0.401551216840744, "26244": 0.21530038118362427, "26261": 0.23864774405956268, "26462": 0.3824150264263153, "26535": 0.7295845746994019, "26745": 0.7096124291419983, "26751": 0.2247048318386078, "27011": 0.10906458646059036, "27065": 0.32058215141296387, "27159": 0.22859740257263184, "27373": 0.5685047507286072, "27528": 0.15442965924739838, "27539": 0.2830325961112976, "27615": 0.020300358533859253, "27697": 0.24631060659885406, "27790": 0.3012613356113434, "27794": 0.8829278349876404, "28134": 0.10026945173740387, "28353": 0.41840189695358276, "28406": 0.2800849378108978, "28674": 0.14686977863311768, "28727": 0.0606246218085289, "28849": 0.2576959431171417, "28915": 0.7201237678527832, "29003": 0.16442140936851501, "29248": 0.037378571927547455, "29458": 0.06337817758321762} | 13625993 | OBJECTIVE To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. DESIGN Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. DATA SOURCES Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. RESULTS The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of pound20,000- pound30,000 (euro22,000-euro33,000; $32,000-$48,000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was < pound410 compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100,000 patients at an additional cost of pound 245,000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. CONCLUSION Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches. | Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery |
{"1009": 0.4531385898590088, "1011": 0.12986256182193756, "1021": 0.41195443272590637, "1022": 0.6482070088386536, "1039": 0.026025565341114998, "1056": 1.0775588750839233, "1157": 0.5936289429664612, "1996": 0.14179791510105133, "1999": 0.1685553640127182, "2008": 0.053244512528181076, "2012": 0.2394166737794876, "2029": 0.37907835841178894, "2031": 0.04113444685935974, "2038": 0.015504186972975731, "2043": 0.03360854089260101, "2064": 0.04207121208310127, "2076": 0.3283478021621704, "2078": 0.08244366943836212, "2079": 0.26296505331993103, "2109": 0.0019512200960889459, "2147": 0.010684899985790253, "2155": 0.8805016279220581, "2169": 0.176772341132164, "2177": 0.1510767638683319, "2182": 0.13414156436920166, "2206": 0.1889725625514984, "2266": 0.3743882179260254, "2278": 0.6583697199821472, "2321": 0.5607312321662903, "2372": 0.3163207769393921, "2407": 0.2637155055999756, "2515": 0.15860503911972046, "2535": 0.8796916007995605, "2550": 0.058784693479537964, "2552": 0.46117570996284485, "2571": 0.30486753582954407, "2581": 0.6714286804199219, "2590": 0.1602703034877777, "2620": 1.1375575065612793, "2628": 0.025073638185858727, "2629": 0.0019512200960889459, "2691": 0.47463157773017883, "2698": 0.24325250089168549, "2754": 0.5057345628738403, "2809": 0.42608439922332764, "2828": 0.1011524572968483, "2832": 0.004870930220931768, "2895": 0.18004031479358673, "2920": 0.40481385588645935, "2945": 0.5104349255561829, "2973": 0.1930064558982849, "3161": 0.007782140281051397, "3170": 0.5215105414390564, "3248": 0.07341018319129944, "3322": 0.29036402702331543, "3327": 0.14179791510105133, "3342": 0.6950984001159668, "3350": 0.7791815400123596, "3378": 0.2026219218969345, "3433": 0.6773988008499146, "3526": 1.0361549854278564, "3582": 0.1913948506116867, "3625": 0.2667117714881897, "3638": 1.304418921470642, "3659": 0.1808556467294693, "3729": 0.9842413663864136, "3772": 0.08871890604496002, "3800": 0.21135559678077698, "3853": 0.3930181860923767, "3893": 0.20818853378295898, "3930": 0.0752234235405922, "3937": 0.04953393340110779, "3961": 0.06429435312747955, "3988": 0.678390383720398, "4047": 0.34023189544677734, "4072": 0.04113444685935974, "4076": 0.02887592278420925, "4127": 0.02792670577764511, "4141": 0.04674193635582924, "4167": 0.4537591338157654, "4195": 0.176772341132164, "4245": 0.755608320236206, "4340": 0.5080875158309937, "4395": 0.7144040465354919, "4403": 0.34300774335861206, "4442": 1.1375575065612793, "4456": 0.009718249551951885, "4490": 0.30558720231056213, "4622": 0.2231435477733612, "4677": 0.8633513450622559, "4770": 0.4311734735965729, "4919": 0.0797421783208847, "4935": 0.04487626627087593, "4962": 0.09850110858678818, "4972": 0.25088030099868774, "4982": 0.15943801403045654, "5158": 0.04953393340110779, "5182": 0.011650617234408855, "5224": 0.5618454217910767, "5250": 0.12642613053321838, "5258": 0.08064348995685577, "5267": 0.05786345899105072, "5326": 0.48670899868011475, "5387": 0.11430477350950241, "5393": 0.20421554148197174, "5402": 0.03831886500120163, "5417": 0.026976587250828743, "5441": 0.5844172835350037, "5452": 0.07159364968538284, "5589": 0.04674193635582924, "5646": 0.5461324453353882, "5676": 0.0317181795835495, "5711": 0.4248080551624298, "5758": 0.9131608605384827, "5769": 0.23402166366577148, "5788": 0.30989447236061096, "5964": 0.23710809648036957, "6032": 0.19541899859905243, "6335": 0.9256220459938049, "6540": 0.7028654217720032, "6580": 1.0382318496704102, "6622": 0.22079704701900482, "6827": 0.2145126610994339, "6869": 0.14518201351165771, "6970": 0.7426811456680298, "7013": 0.022212404757738113, "7127": 0.0770333781838417, "7337": 0.259204238653183, "7366": 0.1064341589808464, "7461": 0.05417001247406006, "7578": 0.0354953333735466, "7645": 0.02412080205976963, "7691": 0.6149744987487793, "7694": 0.21765978634357452, "7711": 0.129004567861557, "7772": 0.08244366943836212, "7883": 0.11604541540145874, "8050": 0.8780695199966431, "8153": 0.07884006202220917, "8171": 0.3077431619167328, "8213": 0.5596157908439636, "8223": 0.21687394380569458, "8449": 0.10993985831737518, "8498": 0.30917787551879883, "8859": 0.4855078160762787, "8878": 0.6714286804199219, "8991": 0.06154331564903259, "9002": 0.0058422754518687725, "9007": 0.28670501708984375, "9031": 0.045809537172317505, "9128": 0.17267228662967682, "9165": 0.05139094591140747, "9211": 0.3588210940361023, "9279": 0.10026945173740387, "9319": 0.5795059204101562, "9359": 0.1221139207482338, "9474": 0.347847044467926, "9699": 0.18978065252304077, "10210": 0.004870930220931768, "10232": 0.01934296265244484, "10397": 0.16359257698059082, "10461": 0.3070250153541565, "10586": 0.7951818704605103, "10737": 0.21135559678077698, "10744": 0.20421554148197174, "10769": 0.8357921838760376, "10960": 0.23479416966438293, "11311": 0.9994535446166992, "11717": 0.17759032547473907, "12005": 0.040196798741817474, "12115": 0.11081436276435852, "12210": 0.03360854089260101, "12335": 0.13243216276168823, "12515": 0.17431432008743286, "12562": 0.055094651877880096, "12679": 0.22782009840011597, "12732": 0.11168810725212097, "13007": 0.10026945173740387, "13091": 0.6348392367362976, "13595": 0.0797421783208847, "13791": 0.7818660736083984, "13833": 0.8845420479774475, "13922": 0.14095009863376617, "14031": 0.021256839856505394, "14067": 0.3325583338737488, "14120": 0.23402166366577148, "14228": 1.1798561811447144, "14828": 0.30989447236061096, "15370": 0.11604541540145874, "15403": 0.5941681861877441, "15663": 0.05046287178993225, "15698": 0.025073638185858727, "15770": 0.014542185701429844, "15900": 0.176772341132164, "16014": 0.24859806895256042, "16026": 0.10818854719400406, "16036": 0.3883931338787079, "16068": 0.3723714053630829, "16098": 0.8433839678764343, "16221": 0.08782484382390976, "16249": 0.14602625370025635, "16285": 0.151916041970253, "16387": 0.11778303235769272, "16463": 0.7182208299636841, "16745": 0.05417001247406006, "16762": 0.018384648486971855, "17379": 0.12728634476661682, "17441": 0.33605360984802246, "17678": 0.20580662786960602, "17749": 0.53589928150177, "17820": 0.06977381557226181, "17914": 0.2719337046146393, "18120": 0.0058422754518687725, "18227": 0.27342069149017334, "18714": 0.37035053968429565, "18715": 1.504077434539795, "18969": 0.09672962874174118, "19653": 0.1011524572968483, "19852": 0.30917787551879883, "19872": 0.1229778528213501, "20250": 0.8135309815406799, "20467": 0.012615402229130268, "20544": 0.6327666640281677, "20582": 1.061472773551941, "20594": 0.6456501483917236, "20752": 0.3982778787612915, "20852": 0.0038986403960734606, "21032": 0.6573580503463745, "21312": 0.045809537172317505, "21466": 0.020300358533859253, "21471": 0.03266380727291107, "21890": 0.10555581003427505, "21901": 0.43244171142578125, "21903": 0.3743882179260254, "21967": 0.08603433519601822, "22137": 0.0058422754518687725, "22153": 0.06246116757392883, "22170": 0.1751343309879303, "22330": 1.1425544023513794, "22930": 0.14686977863311768, "22931": 0.16276304423809052, "22975": 0.05694137513637543, "23041": 0.678390383720398, "23216": 0.1229778528213501, "23692": 0.3916989266872406, "23737": 0.20977331697940826, "23807": 0.06337817758321762, "24169": 0.37371641397476196, "24335": 0.15359249711036682, "24374": 0.5696102976799011, "24529": 0.08692999184131622, "24670": 0.06703783571720123, "25194": 0.2674594223499298, "25605": 0.10993985831737518, "25761": 0.12038381397724152, "26288": 0.08782484382390976, "26417": 0.40546512603759766, "26520": 1.1312761306762695, "26773": 0.07068414986133575, "27321": 0.28963330388069153, "27343": 0.22704219818115234, "27790": 0.12470348179340363, "27854": 0.2667117714881897, "28170": 0.12470348179340363, "28264": 0.18167030811309814, "28767": 0.24631060659885406, "28788": 0.4518963396549225, "28873": 0.28597161173820496, "29222": 0.1718502640724182, "29458": 0.013579257763922215, "29610": 0.04860413447022438} | 13636631 | Evidence has accumulated that cytokines have a fundamental role in the differentiation of memory T cells. Here, we follow the CD8+ T cell from initial activation to memory-cell generation, indicating the checkpoints at which cytokines determine the fate of the T cell. Members of the common cytokine-receptor γ-chain (γc)-cytokine family — in particular, interleukin-7 (IL-7) and IL-15 — act at each stage of the immune response to promote proliferation and survival. In this manner, a stable and protective, long-lived memory CD8+ T-cell pool can be propagated and maintained. | Cytokine control of memory T-cell development and survival |
{"1011": 0.06703783571720123, "1015": 0.03266380727291107, "1048": 0.6548244953155518, "2000": 0.05694137513637543, "2002": 0.04674193635582924, "2005": 0.18816383183002472, "2010": 0.9922385215759277, "2011": 0.2539152204990387, "2049": 0.1229778528213501, "2076": 0.01934296265244484, "2079": 0.20580662786960602, "2100": 0.08782484382390976, "2102": 0.7047978043556213, "2109": 0.34577593207359314, "2129": 0.034552380442619324, "2135": 0.20022670924663544, "2182": 0.03266380727291107, "2236": 0.3683255612850189, "2241": 0.2034190446138382, "2339": 0.1751343309879303, "2342": 0.02412080205976963, "2389": 0.38574060797691345, "2442": 0.10379679501056671, "2465": 0.27564704418182373, "2487": 0.5393219590187073, "2515": 0.22937409579753876, "2522": 0.15610189735889435, "2535": 0.272677481174469, "2560": 0.06337817758321762, "2689": 0.3325583338737488, "2724": 0.15526613593101501, "2734": 0.3070250153541565, "2777": 0.24859806895256042, "2819": 0.41389304399490356, "2824": 0.3381449282169342, "2904": 0.0009760859538801014, "2920": 0.16359257698059082, "2941": 0.24631060659885406, "2953": 0.5822374224662781, "2981": 0.0913962796330452, "3141": 0.06703783571720123, "3161": 0.05139094591140747, "3215": 1.0094679594039917, "3223": 0.6823468804359436, "3251": 0.17759032547473907, "3283": 0.029824240133166313, "3366": 0.3588210940361023, "3370": 0.6699305176734924, "3419": 0.00875066313892603, "3426": 0.15610189735889435, "3431": 0.5370414853096008, "3466": 0.08064348995685577, "3563": 0.8264343738555908, "3619": 0.31489628553390503, "3642": 0.4400174915790558, "3670": 0.7692760229110718, "3747": 0.10818854719400406, "3796": 0.0842406153678894, "3800": 0.16276304423809052, "3853": 0.6075552701950073, "3863": 0.6096806526184082, "4047": 0.11691460013389587, "4072": 0.33675122261047363, "4130": 0.7144040465354919, "4160": 0.04767346754670143, "4242": 0.33115679025650024, "4263": 0.35060185194015503, "4280": 0.1994270235300064, "4473": 0.055094651877880096, "4517": 1.4037197828292847, "4527": 0.13755162060260773, "4539": 0.7408206462860107, "4563": 0.8666408061981201, "4652": 0.6000806093215942, "4742": 0.7889899015426636, "4758": 0.46486347913742065, "4786": 0.06612417846918106, "4796": 0.9531047344207764, "4895": 0.2531573474407196, "4919": 0.0354953333735466, "4957": 0.4286321699619293, "4958": 0.6989894509315491, "4962": 1.1262223720550537, "4972": 0.48670899868011475, "5025": 0.5197699069976807, "5158": 0.04394211992621422, "5228": 0.08692999184131622, "5258": 0.058784693479537964, "5278": 0.0354953333735466, "5320": 0.28082266449928284, "5387": 0.6064908504486084, "5449": 0.24554696679115295, "5478": 0.5033760666847229, "5524": 0.8195732831954956, "5656": 1.0298984050750732, "5668": 0.3923587501049042, "5799": 0.3346569836139679, "5834": 0.2516399025917053, "5876": 0.7067264318466187, "5918": 0.6096806526184082, "5942": 0.5151132941246033, "5991": 0.09672962874174118, "6024": 0.7389566898345947, "6028": 0.08603433519601822, "6064": 0.4879087805747986, "6143": 0.2034190446138382, "6177": 0.19220098853111267, "6245": 0.17759032547473907, "6438": 0.32905077934265137, "6494": 0.6502478122711182, "6591": 0.2881702482700348, "6593": 0.20421554148197174, "6635": 0.08064348995685577, "6733": 0.4487839937210083, "6779": 0.22937409579753876, "6897": 0.22157983481884003, "6922": 0.4177590310573578, "6939": 0.04767346754670143, "6971": 0.18816383183002472, "7096": 0.0797421783208847, "7220": 0.7182208299636841, "7337": 0.5393219590187073, "7366": 0.1677299439907074, "7403": 0.8039615154266357, "7591": 0.0174254160374403, "7670": 0.0029254043474793434, "7711": 0.06154331564903259, "7755": 0.5816917419433594, "7790": 1.1994705200195312, "7816": 0.7153595685958862, "7889": 0.5914691090583801, "7906": 0.030771657824516296, "7936": 0.15442965924739838, "8018": 0.012615402229130268, "8031": 0.8731874823570251, "8092": 0.1477125883102417, "8290": 0.0354953333735466, "8303": 0.13755162060260773, "8360": 0.2089812457561493, "8401": 0.011650617234408855, "8525": 0.6634125709533691, "8583": 0.10818854719400406, "8637": 0.5990082025527954, "8729": 0.371698260307312, "8776": 0.06246116757392883, "8878": 0.7951818704605103, "8989": 0.083342544734478, "8991": 0.11168810725212097, "9007": 0.4914994537830353, "9034": 0.23324857652187347, "9041": 0.28890204429626465, "9095": 0.6400018334388733, "9099": 0.39696553349494934, "9146": 0.6497380137443542, "9165": 1.0001721382141113, "9223": 0.7267557382583618, "9416": 0.3297532796859741, "9530": 0.4450363218784332, "9537": 0.24554696679115295, "9593": 0.3027053773403168, "9601": 0.32199856638908386, "9675": 0.0038986403960734606, "9694": 0.02412080205976963, "9770": 0.6608943343162537, "9887": 0.040196798741817474, "9942": 0.9240728616714478, "9962": 0.053244512528181076, "10091": 0.4412745535373688, "10266": 0.012615402229130268, "10572": 0.9147270321846008, "10573": 0.21293537318706512, "10595": 0.2881702482700348, "10684": 0.5662899017333984, "10708": 0.2018241584300995, "10723": 0.304147332906723, "10738": 0.6553317308425903, "10769": 1.2364475727081299, "10859": 0.3910386264324188, "10915": 0.13414156436920166, "10956": 0.08782484382390976, "11031": 0.947819709777832, "11115": 0.5010119676589966, "11160": 0.4431571960449219, "11211": 0.08961215615272522, "11341": 0.053244512528181076, "11423": 0.20739519596099854, "11444": 0.5729197263717651, "11890": 0.757441520690918, "11909": 0.029824240133166313, "12115": 0.23864774405956268, "12222": 1.1211429834365845, "12247": 0.04113444685935974, "12530": 0.9194108247756958, "12719": 0.23864774405956268, "12732": 0.3012613356113434, "12789": 0.012615402229130268, "12987": 0.09850110858678818, "13070": 0.08603433519601822, "13106": 1.1211429834365845, "13221": 0.2711893916130066, "13308": 0.11604541540145874, "13502": 0.5528968572616577, "13538": 0.2018241584300995, "13595": 0.7665573358535767, "13644": 0.3743882179260254, "13791": 1.1481462717056274, "13833": 1.3367470502853394, "14080": 0.12814582884311676, "14126": 0.22001366317272186, "14187": 0.5701626539230347, "14193": 1.207676887512207, "14245": 0.40806588530540466, "14471": 0.45994341373443604, "14621": 0.17840765416622162, "14679": 0.05417001247406006, "14715": 0.8022117614746094, "14800": 0.11081436276435852, "14828": 0.6430866718292236, "14996": 0.18492233753204346, "15115": 0.1994270235300064, "15176": 0.5979346632957458, "15266": 0.5957841277122498, "15338": 0.6011518239974976, "15445": 0.39433568716049194, "15543": 0.8731874823570251, "15680": 0.11517547070980072, "15800": 0.27786844968795776, "15946": 1.2129170894622803, "16026": 0.1212492436170578, "16044": 0.0606246218085289, "16127": 0.3134697377681732, "16150": 1.274838924407959, "16209": 0.7934166193008423, "16263": 0.6054253578186035, "16285": 0.22782009840011597, "16344": 0.018384648486971855, "16371": 0.3485364317893982, "16530": 0.5341835021972656, "16570": 0.04113444685935974, "16625": 0.9123768210411072, "16643": 0.7881022095680237, "16705": 0.1970241367816925, "16730": 0.045809537172317505, "16771": 0.21214580535888672, "16803": 0.3070250153541565, "16861": 0.15943801403045654, "16910": 0.058784693479537964, "17183": 0.9842413663864136, "17212": 0.2696990668773651, "17215": 0.0752234235405922, "17241": 0.04113444685935974, "17303": 0.010684899985790253, "17379": 0.3622259199619293, "17441": 0.75193190574646, "17607": 1.1012130975723267, "17669": 0.37907835841178894, "17785": 0.034552380442619324, "17820": 0.1693800985813141, "17890": 0.3777405619621277, "17975": 0.34300774335861206, "18260": 0.009718249551951885, "18321": 0.3241194784641266, "18345": 0.2493593990802765, "18642": 0.8315495252609253, "18699": 0.02792670577764511, "19037": 0.15860503911972046, "19389": 0.7692760229110718, "19653": 1.0073304176330566, "19717": 0.26146242022514343, "19872": 0.17267228662967682, "20110": 0.8666408061981201, "20287": 1.5263959169387817, "20544": 0.8715548515319824, "20766": 0.32764431834220886, "20817": 0.5685047507286072, "20858": 0.04767346754670143, "21114": 0.06886265426874161, "21446": 0.20739519596099854, "21466": 0.3027053773403168, "21575": 0.4568560719490051, "21618": 0.30989447236061096, "21903": 0.38041436672210693, "21919": 0.3910386264324188, "21967": 0.1930064558982849, "22422": 0.24401791393756866, "22930": 0.1358480453491211, "23216": 0.1477125883102417, "23586": 0.5947071313858032, "23758": 1.0641717910766602, "23767": 0.09050461649894714, "23943": 0.8500841856002808, "24051": 0.012615402229130268, "24054": 1.1786550283432007, "24081": 0.04113444685935974, "24278": 0.030771657824516296, "24394": 1.1537069082260132, "24523": 0.04674193635582924, "24524": 0.026976587250828743, "24764": 0.7009293437004089, "24871": 0.18329764902591705, "25003": 1.1236859560012817, "25022": 0.2501201331615448, "25175": 0.011650617234408855, "25194": 0.17840765416622162, "25456": 0.8534175157546997, "25499": 0.33115679025650024, "25644": 0.05694137513637543, "25761": 0.29400965571403503, "25848": 0.9463045597076416, "26243": 0.040196798741817474, "26244": 0.07793712615966797, "26402": 0.5795059204101562, "26512": 0.8813109993934631, "26520": 0.015504186972975731, "26534": 0.14179791510105133, "26703": 0.055094651877880096, "26721": 0.18329764902591705, "26773": 0.6734226942062378, "26775": 0.5584990978240967, "26942": 0.030771657824516296, "27142": 0.17840765416622162, "27295": 0.6102113127708435, "27709": 0.966567873954773, "27794": 1.0051883459091187, "27854": 1.3555532693862915, "28155": 0.7827593088150024, "29129": 0.5751199722290039, "29206": 0.8989537954330444, "29290": 0.6897233724594116, "29431": 0.0606246218085289} | 13639330 | Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT-dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal-dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors. | Histone Methylation-Dependent Mechanisms Impose Ligand Dependency for Gene Activation by Nuclear Receptors |
{"1041": 0.09050461649894714, "1043": 0.48430517315864563, "1054": 0.0038986403960734606, "2003": 0.1221139207482338, "2005": 0.0174254160374403, "2011": 0.33953672647476196, "2026": 0.7782850861549377, "2029": 0.2145126610994339, "2058": 0.3269403576850891, "2063": 0.1332872211933136, "2076": 0.08782484382390976, "2079": 0.04487626627087593, "2094": 0.0058422754518687725, "2114": 0.5707147121429443, "2236": 0.2231435477733612, "2290": 0.6916812658309937, "2331": 0.8065804839134216, "2378": 0.33605360984802246, "2491": 0.6139179468154907, "2515": 0.22392450273036957, "2529": 0.5903874635696411, "2535": 0.2478361576795578, "2540": 0.1064341589808464, "2757": 0.1485546976327896, "2886": 0.12814582884311676, "2895": 0.7163142561912537, "2954": 0.29400965571403503, "2966": 0.11430477350950241, "2970": 0.11168810725212097, "2981": 0.8039615154266357, "3102": 0.11168810725212097, "3141": 0.33325836062431335, "3161": 0.022212404757738113, "3231": 0.06246116757392883, "3258": 0.3930181860923767, "3280": 0.16607704758644104, "3303": 0.29255300760269165, "3351": 0.4728073179721832, "3378": 0.2145126610994339, "3424": 0.21135559678077698, "3426": 0.20739519596099854, "3433": 0.3750596046447754, "3466": 0.4617912769317627, "3491": 0.06977381557226181, "3526": 0.8264343738555908, "3554": 0.13414156436920166, "3593": 0.6461620330810547, "3595": 0.01934296265244484, "3597": 0.49982786178588867, "3603": 0.05694137513637543, "3625": 0.03925827145576477, "3639": 0.8264343738555908, "3640": 0.0019512200960889459, "3654": 0.29036402702331543, "3662": 0.02887592278420925, "3676": 0.3601844012737274, "3747": 0.33675122261047363, "3772": 0.28670501708984375, "3795": 0.03831886500120163, "3853": 0.20977331697940826, "3860": 0.6512666940689087, "3896": 0.38174858689308167, "3989": 0.4349733293056488, "4003": 0.7352184057235718, "4005": 0.07793712615966797, "4047": 0.6181373596191406, "4053": 0.12642613053321838, "4072": 0.5551415085792542, "4135": 0.38174858689308167, "4242": 0.7105726003646851, "4286": 0.4891071021556854, "4288": 0.17267228662967682, "4295": 0.5168620347976685, "4313": 0.18329764902591705, "4360": 0.32553088665008545, "4403": 0.2231435477733612, "4442": 0.6160298585891724, "4490": 0.09850110858678818, "4502": 0.5590575933456421, "4506": 0.3850763738155365, "4517": 0.10203468054533005, "4539": 0.14095009863376617, "4621": 0.02887592278420925, "4652": 0.18492233753204346, "4721": 0.8649974465370178, "4758": 0.5209306478500366, "4921": 0.0842406153678894, "4962": 0.1619328260421753, "5012": 0.2983669638633728, "5041": 0.03925827145576477, "5105": 0.37707099318504333, "5123": 0.22937409579753876, "5250": 0.2763880789279938, "5320": 0.34508460760116577, "5360": 0.5278670787811279, "5387": 0.1510767638683319, "5423": 1.013020396232605, "5549": 0.6059582233428955, "5600": 0.24859806895256042, "5603": 0.28890204429626465, "5714": 0.0752234235405922, "5850": 0.0174254160374403, "5866": 0.06246116757392883, "5996": 0.07884006202220917, "6064": 0.03360854089260101, "6074": 0.08871890604496002, "6099": 0.3662964701652527, "6127": 0.18167030811309814, "6292": 0.762009859085083, "6444": 0.18573370575904846, "6882": 0.36358460783958435, "6897": 0.08871890604496002, "6958": 0.025073638185858727, "6970": 0.12470348179340363, "6984": 0.02316705882549286, "6985": 0.5290185213088989, "7242": 0.15860503911972046, "7337": 0.8091925978660583, "7366": 0.23710809648036957, "7461": 0.4349733293056488, "7512": 0.3353555500507355, "7591": 0.1332872211933136, "7645": 0.6400018334388733, "7691": 0.10203468054533005, "7711": 0.5838727951049805, "7712": 0.07341018319129944, "7790": 0.7009293437004089, "7870": 0.39893341064453125, "8031": 0.1064341589808464, "8047": 0.08244366943836212, "8092": 0.255429208278656, "8171": 0.22626367211341858, "8285": 1.0841858386993408, "8486": 0.15943801403045654, "8670": 0.5729197263717651, "8803": 0.24171993136405945, "8878": 0.1946154683828354, "8883": 0.04113444685935974, "9007": 0.5860490798950195, "9099": 0.6999598741531372, "9174": 0.14264501631259918, "9223": 0.7809720039367676, "9252": 0.10906458646059036, "9276": 0.3339579105377197, "9413": 0.6654226183891296, "9474": 0.4932899475097656, "9530": 0.1693800985813141, "9590": 0.036437395960092545, "9756": 0.37974658608436584, "9821": 0.30486753582954407, "10047": 0.18573370575904846, "10163": 0.004870930220931768, "10210": 1.0236024856567383, "10288": 0.495672345161438, "10327": 0.680370569229126, "10440": 0.1889725625514984, "10572": 0.7537717819213867, "10580": 0.0606246218085289, "10595": 0.6107416749000549, "10611": 0.1930064558982849, "10719": 0.6075552701950073, "10737": 0.08064348995685577, "10744": 0.07884006202220917, "10804": 0.6317287683486938, "11163": 0.043007105588912964, "11311": 0.9425065517425537, "11341": 0.026976587250828743, "11486": 0.11430477350950241, "11508": 0.8877626657485962, "11514": 0.8143964409828186, "11522": 0.083342544734478, "11528": 0.2447827309370041, "11583": 0.32129061222076416, "11631": 0.5707147121429443, "11658": 0.9929623603820801, "11663": 0.6543170213699341, "11721": 0.01934296265244484, "11767": 0.03831886500120163, "12098": 0.3353555500507355, "12442": 0.22157983481884003, "12456": 0.05417001247406006, "12530": 0.10993985831737518, "12562": 0.35677260160446167, "12649": 0.0913962796330452, "12702": 0.36426326632499695, "12765": 0.27044451236724854, "12863": 0.8298473954200745, "12921": 0.8195732831954956, "12987": 0.12642613053321838, "13070": 0.3485364317893982, "13091": 0.014542185701429844, "13231": 0.4673144817352295, "13250": 0.3106105625629425, "13345": 0.6410312056541443, "13434": 0.055094651877880096, "13531": 0.2470736801624298, "13675": 0.42990362644195557, "13791": 0.13157635927200317, "13833": 0.18329764902591705, "13871": 0.6921701431274414, "13922": 0.2493593990802765, "13938": 0.2852376699447632, "13986": 0.15693697333335876, "14074": 0.07068414986133575, "14181": 1.0485517978668213, "14611": 0.5701626539230347, "14621": 0.14179791510105133, "14639": 0.31845372915267944, "14774": 0.38441169261932373, "14949": 0.3601844012737274, "14956": 0.021256839856505394, "15011": 0.2622140049934387, "15050": 0.2231435477733612, "15186": 0.43938836455345154, "15403": 1.068206787109375, "15422": 0.8492490649223328, "15527": 0.05139094591140747, "15544": 0.010684899985790253, "15663": 0.10731173306703568, "15877": 0.969535231590271, "15916": 0.1485546976327896, "15923": 0.11256109178066254, "15946": 0.2837681770324707, "16081": 0.1401015669107437, "16221": 0.15526613593101501, "16285": 0.22704219818115234, "16341": 0.052318159490823746, "16360": 0.1221139207482338, "16523": 0.22157983481884003, "16529": 0.5685047507286072, "16691": 0.04207121208310127, "16706": 0.036437395960092545, "16730": 1.2318994998931885, "16828": 0.41840189695358276, "16834": 0.04113444685935974, "16882": 1.0382318496704102, "17341": 0.2954642176628113, "17379": 0.3077431619167328, "17404": 0.38174858689308167, "17631": 0.07612881064414978, "17701": 0.32129061222076416, "18089": 0.18329764902591705, "18155": 0.5506471395492554, "18191": 0.28963330388069153, "18227": 0.48670899868011475, "18714": 0.24631060659885406, "18715": 0.06520967930555344, "18960": 0.21922965347766876, "19132": 0.07341018319129944, "19293": 0.1734936386346817, "19469": 0.22079704701900482, "19653": 0.5893046259880066, "19696": 0.07431721687316895, "19707": 1.3595733642578125, "19872": 0.24018502235412598, "20014": 0.012615402229130268, "20110": 0.6867793202400208, "20142": 0.29109421372413635, "20187": 0.6634125709533691, "20282": 0.7934166193008423, "20350": 0.1913948506116867, "20817": 0.1994270235300064, "20868": 1.475906491279602, "20960": 0.052318159490823746, "21102": 0.01934296265244484, "21150": 0.021256839856505394, "21162": 0.7755908370018005, "21252": 0.021256839856505394, "21314": 0.34508460760116577, "21446": 0.22782009840011597, "21600": 0.0058422754518687725, "21685": 0.12556517124176025, "21693": 1.6678541898727417, "21733": 0.7314660549163818, "21759": 0.1994270235300064, "21890": 1.0257055759429932, "21903": 0.38041436672210693, "22694": 0.2830325961112976, "22834": 0.29619070887565613, "22869": 0.46670228242874146, "22931": 0.5718178153038025, "23041": 0.7067264318466187, "23079": 1.2878543138504028, "23296": 0.6400018334388733, "23446": 0.0019512200960889459, "23586": 0.12986256182193756, "24054": 0.3963087201118469, "24093": 0.053244512528181076, "24278": 0.17020416259765625, "24396": 0.5795059204101562, "24964": 0.21530038118362427, "24972": 0.3423145115375519, "25002": 0.052318159490823746, "25194": 0.11951763927936554, "25407": 0.05139094591140747, "25456": 0.06429435312747955, "25605": 0.14939609169960022, "25708": 0.45251765847206116, "25714": 0.08154398202896118, "25778": 0.034552380442619324, "25950": 0.2696990668773651, "26282": 0.3381449282169342, "26402": 0.25995752215385437, "26419": 0.6833335757255554, "26520": 0.09761575609445572, "26524": 0.09406650811433792, "26591": 0.151916041970253, "26646": 0.15442965924739838, "26721": 0.9680526852607727, "26773": 0.026976587250828743, "26835": 1.0464962720870972, "27521": 1.2041680812835693, "27781": 0.4855078160762787, "27854": 0.1677299439907074, "28548": 0.011650617234408855, "28691": 0.2018241584300995, "28873": 0.2822965085506439, "28896": 0.32270604372024536, "29090": 0.25995752215385437, "29290": 0.3141832649707794} | 13651792 | IRGM, a human immunity-related GTPase, confers autophagic defence against intracellular pathogens by an unknown mechanism. Here, we report an unexpected mode of IRGM action. IRGM demonstrated differential affinity for the mitochondrial lipid cardiolipin, translocated to mitochondria, affected mitochondrial fission and induced autophagy. Mitochondrial fission was necessary for autophagic control of intracellular mycobacteria by IRGM. IRGM influenced mitochondrial membrane polarization and cell death. Overexpression of IRGMd, but not IRGMb splice isoforms, caused mitochondrial depolarization and autophagy-independent, but Bax/Bak-dependent, cell death. By acting on mitochondria, IRGM confers autophagic protection or cell death, explaining IRGM action both in defence against tuberculosis and in the damaging inflammation caused by Crohn's disease. | Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria |
{"1009": 0.24171993136405945, "1011": 0.3750596046447754, "1051": 0.44753631949424744, "1053": 0.04674193635582924, "1999": 0.016465263441205025, "2000": 0.05417001247406006, "2005": 0.21214580535888672, "2011": 0.05786345899105072, "2015": 0.25467249751091003, "2024": 0.15526613593101501, "2034": 0.2516399025917053, "2042": 0.083342544734478, "2046": 0.37371641397476196, "2047": 0.3683255612850189, "2048": 0.259204238653183, "2050": 0.35060185194015503, "2051": 0.2018241584300995, "2054": 0.0029254043474793434, "2057": 0.12986256182193756, "2061": 0.6704301834106445, "2063": 0.4158279001712799, "2072": 0.3757305145263672, "2076": 0.3027053773403168, "2079": 0.04113444685935974, "2094": 0.15442965924739838, "2106": 0.05139094591140747, "2109": 0.4831010699272156, "2116": 0.2719337046146393, "2129": 0.07612881064414978, "2135": 0.06337817758321762, "2179": 0.016465263441205025, "2193": 0.4093637466430664, "2203": 0.5376120805740356, "2220": 0.32341301441192627, "2224": 0.23710809648036957, "2226": 0.1994270235300064, "2229": 0.5778634548187256, "2235": 0.6482070088386536, "2239": 0.5404602885246277, "2241": 0.44753631949424744, "2284": 0.45870962738990784, "2339": 0.10555581003427505, "2391": 0.15943801403045654, "2458": 0.7592713832855225, "2470": 0.1619328260421753, "2478": 0.24325250089168549, "2491": 0.9425065517425537, "2515": 0.040196798741817474, "2529": 0.7665573358535767, "2532": 0.3588210940361023, "2555": 0.4734157919883728, "2581": 0.1229778528213501, "2590": 0.38441169261932373, "2592": 0.2607102394104004, "2666": 0.0606246218085289, "2668": 0.319873183965683, "2685": 0.3777405619621277, "2764": 0.3897167444229126, "2802": 0.6000806093215942, "2918": 0.2689530849456787, "2920": 0.056018441915512085, "2931": 0.41065993905067444, "2951": 0.6613984704017639, "3037": 0.4419025182723999, "3064": 0.5051454305648804, "3073": 0.04487626627087593, "3078": 0.6202403903007507, "3111": 0.4349733293056488, "3117": 1.0179725885391235, "3120": 0.06612417846918106, "3193": 0.22782009840011597, "3207": 0.7426811456680298, "3231": 0.6482070088386536, "3252": 0.0029254043474793434, "3287": 0.4849066734313965, "3295": 0.11865071207284927, "3330": 0.10993985831737518, "3348": 0.7172679901123047, "3366": 0.5930894017219543, "3433": 0.4431571960449219, "3463": 0.27342069149017334, "3497": 0.4855078160762787, "3540": 0.06795065850019455, "3560": 0.16359257698059082, "3563": 0.4624064862728119, "3594": 0.151916041970253, "3603": 0.1970241367816925, "3616": 0.036437395960092545, "3623": 0.026976587250828743, "3670": 0.9515975713729858, "3716": 0.09584271162748337, "3745": 0.26446542143821716, "3756": 0.8433839678764343, "3760": 0.16359257698059082, "3767": 0.22157983481884003, "3800": 0.08871890604496002, "3801": 0.25845035910606384, "3968": 0.18573370575904846, "4022": 0.7086513638496399, "4048": 0.11951763927936554, "4106": 0.1221139207482338, "4111": 0.5914691090583801, "4160": 1.0688776969909668, "4176": 0.5444341897964478, "4179": 0.43244171142578125, "4207": 0.4950772523880005, "4286": 0.7144040465354919, "4287": 0.016465263441205025, "4295": 0.7528522610664368, "4313": 0.02792670577764511, "4340": 0.4311734735965729, "4397": 0.06703783571720123, "4424": 0.08513788133859634, "4453": 0.6096806526184082, "4503": 0.469759464263916, "4525": 0.029824240133166313, "4539": 0.12470348179340363, "4573": 0.10731173306703568, "4639": 0.7333439588546753, "4654": 0.44753631949424744, "4655": 0.8039615154266357, "4667": 0.03831886500120163, "4671": 0.3499138653278351, "4714": 0.083342544734478, "4758": 0.638455867767334, "4824": 0.4311734735965729, "4919": 0.4624064862728119, "4957": 0.15943801403045654, "4962": 1.1720224618911743, "4975": 0.5220900774002075, "5100": 0.6430866718292236, "5104": 0.2018241584300995, "5197": 0.16110190749168396, "5228": 0.7610978484153748, "5250": 0.0842406153678894, "5269": 0.0317181795835495, "5328": 0.09850110858678818, "5354": 0.0913962796330452, "5379": 0.5696102976799011, "5418": 0.3084607720375061, "5421": 0.14686977863311768, "5426": 0.022212404757738113, "5449": 0.45437926054000854, "5456": 0.14602625370025635, "5537": 0.23402166366577148, "5604": 0.018384648486971855, "5644": 0.7482418417930603, "5646": 0.045809537172317505, "5656": 0.8057082891464233, "5657": 0.4950772523880005, "5700": 0.21687394380569458, "5754": 0.4654768109321594, "5799": 0.10203468054533005, "5813": 0.7333439588546753, "5852": 0.21372433006763458, "5884": 0.15023678541183472, "5906": 0.043007105588912964, "5907": 0.3423145115375519, "6001": 0.6212902665138245, "6002": 0.10291612148284912, "6028": 0.020300358533859253, "6064": 0.8247235417366028, "6137": 0.1064341589808464, "6143": 0.09317722171545029, "6155": 1.1506214141845703, "6292": 0.7426811456680298, "6337": 0.7295845746994019, "6377": 0.19782574474811554, "6415": 0.022212404757738113, "6529": 0.2837681770324707, "6661": 0.0009760859538801014, "6709": 0.6233867406845093, "6786": 0.029824240133166313, "6851": 0.05139094591140747, "6870": 0.045809537172317505, "6895": 0.5925496220588684, "6897": 0.5307431221008301, "6914": 0.8272887468338013, "6971": 0.3283478021621704, "7060": 0.4400174915790558, "7155": 0.09850110858678818, "7356": 0.4512746334075928, "7366": 0.8433839678764343, "7367": 1.0506030321121216, "7403": 0.9783848524093628, "7479": 0.26296505331993103, "7556": 0.12470348179340363, "7645": 0.07431721687316895, "7711": 0.6405166387557983, "7809": 0.18978065252304077, "7865": 0.0913962796330452, "7870": 0.7370892763137817, "7882": 0.3381449282169342, "7883": 0.016465263441205025, "7885": 0.09406650811433792, "7888": 0.15860503911972046, "7908": 0.0019512200960889459, "7978": 0.22782009840011597, "8153": 0.66441810131073, "8171": 0.10555581003427505, "8290": 0.2622140049934387, "8462": 0.8366385698318481, "8521": 0.3923587501049042, "8525": 0.07793712615966797, "8569": 0.12556517124176025, "8695": 0.0770333781838417, "8720": 0.5827828645706177, "8740": 0.08871890604496002, "8773": 0.040196798741817474, "8840": 0.5517725944519043, "8883": 0.27934664487838745, "8917": 0.25239890813827515, "8991": 0.6664261221885681, "9007": 0.3519764244556427, "9016": 0.8707374930381775, "9099": 0.7978238463401794, "9148": 0.8383291959762573, "9165": 1.1598494052886963, "9207": 1.2985725402832031, "9416": 0.15359249711036682, "9699": 0.00875066313892603, "9722": 0.08154398202896118, "9728": 0.603290855884552, "9756": 0.5968599319458008, "9797": 0.1734936386346817, "9867": 0.04767346754670143, "9896": 0.022212404757738113, "9942": 0.9209672808647156, "10015": 0.053244512528181076, "10029": 0.4580921530723572, "10071": 0.10379679501056671, "10179": 0.06703783571720123, "10250": 0.36494144797325134, "10266": 0.4093637466430664, "10362": 0.04674193635582924, "10371": 0.960606575012207, "10479": 0.2501201331615448, "10521": 0.22157983481884003, "10654": 0.04207121208310127, "10737": 0.09317722171545029, "10738": 0.15275461971759796, "10755": 0.8674615025520325, "10861": 0.007782140281051397, "10867": 0.5404602885246277, "10956": 0.469759464263916, "11022": 0.4248080551624298, "11099": 0.4158279001712799, "11156": 0.04113444685935974, "11157": 0.2918238639831543, "11163": 0.6634125709533691, "11423": 0.5133614540100098, "11486": 0.18167030811309814, "11487": 0.04487626627087593, "11548": 0.4248080551624298, "11649": 0.8829278349876404, "11658": 0.8837352395057678, "11767": 0.10555581003427505, "11791": 0.12728634476661682, "11829": 0.41195443272590637, "11860": 0.004870930220931768, "12151": 0.3870677351951599, "12359": 0.4770587682723999, "12374": 0.28890204429626465, "12477": 0.009718249551951885, "12581": 0.0174254160374403, "12644": 0.5701626539230347, "12667": 0.00875066313892603, "12702": 0.151916041970253, "12789": 0.6410312056541443, "12883": 0.08692999184131622, "12884": 0.6296497583389282, "12987": 1.551543951034546, "13070": 0.07431721687316895, "13100": 0.026976587250828743, "13103": 0.02792670577764511, "13265": 0.37907835841178894, "13369": 0.014542185701429844, "13458": 1.0788878202438354, "13543": 0.22079704701900482, "13876": 0.848413348197937, "13908": 0.6808650493621826, "13922": 0.2478361576795578, "14026": 0.2763880789279938, "14080": 0.11604541540145874, "14085": 0.043007105588912964, "14095": 0.619189441204071, "14120": 0.04487626627087593, "14151": 0.09672962874174118, "14192": 0.45251765847206116, "14193": 0.8764448165893555, "14211": 0.7701805830001831, "14255": 0.77198725938797, "14471": 0.5573811531066895, "14494": 0.0038986403960734606, "14627": 0.13670019805431366, "14693": 0.02316705882549286, "14719": 0.9348671436309814, "14774": 0.29981520771980286, "14800": 0.09495500475168228, "14847": 0.4126010537147522, "15007": 0.8022117614746094, "15023": 0.09584271162748337, "15053": 0.1477125883102417, "15058": 0.7295845746994019, "15113": 0.1212492436170578, "15115": 0.53589928150177, "15543": 0.11343330889940262, "15596": 0.18004031479358673, "15826": 0.14095009863376617, "15900": 0.16110190749168396, "15923": 0.2160874605178833, "16012": 0.48068851232528687, "16030": 0.4132472574710846, "16216": 0.4974553883075714, "16221": 0.23864774405956268, "16285": 0.2034190446138382, "16463": 0.21293537318706512, "16505": 0.45251765847206116, "16515": 0.36697331070899963, "16602": 0.5450005531311035, "16706": 0.0317181795835495, "16783": 0.036437395960092545, "16935": 0.37371641397476196, "17181": 0.0038986403960734606, "17287": 0.8845420479774475, "17503": 0.11081436276435852, "17592": 0.09228714555501938, "17701": 0.055094651877880096, "17879": 0.8989537954330444, "18047": 0.037378571927547455, "18191": 0.29255300760269165, "18715": 0.016465263441205025, "18853": 0.2719337046146393, "19019": 1.1381834745407104, "19132": 0.7537717819213867, "19345": 0.20818853378295898, "19411": 0.0797421783208847, "19601": 0.22782009840011597, "19761": 0.013579257763922215, "19852": 0.0038986403960734606, "20353": 0.30558720231056213, "20582": 0.007782140281051397, "21198": 0.04394211992621422, "21230": 0.3374483287334442, "21257": 0.0317181795835495, "21376": 0.010684899985790253, "21477": 0.43875885009765625, "21508": 0.47463157773017883, "21639": 0.5461324453353882, "21663": 0.15777134895324707, "21685": 0.20977331697940826, "21752": 0.053244512528181076, "21935": 0.32553088665008545, "22026": 0.4728073179721832, "22529": 1.6432353258132935, "22694": 0.8674615025520325, "23191": 0.2409527748823166, "23572": 0.03360854089260101, "23737": 0.20102575421333313, "23924": 0.757441520690918, "23996": 0.02316705882549286, "24019": 0.43875885009765625, "24051": 1.076228141784668, "24278": 0.3170322775840759, "24290": 0.04487626627087593, "24324": 0.6291293501853943, "24558": 0.3963087201118469, "25022": 0.33325836062431335, "25269": 0.1358480453491211, "25524": 0.4431571960449219, "25700": 0.0019512200960889459, "26083": 0.28743788599967957, "26223": 0.6897233724594116, "26305": 0.39433568716049194, "26572": 0.6744182109832764, "26601": 0.06246116757392883, "26741": 0.022212404757738113, "26775": 0.1913948506116867, "26835": 0.3547199070453644, "26953": 0.45499902963638306, "26957": 1.1481462717056274, "26986": 0.07159364968538284, "27173": 0.4177590310573578, "27226": 0.056018441915512085, "27642": 0.11343330889940262, "27777": 0.09672962874174118, "28024": 0.018384648486971855, "28086": 1.0101795196533203, "28283": 0.0009760859538801014, "28687": 0.04394211992621422, "28739": 0.04674193635582924, "28848": 1.039613962173462, "29206": 0.2026219218969345, "29347": 1.187628984451294, "29458": 0.01934296265244484} | 13702924 | Mosquitoes are vectors of a number of important human and animal diseases. The development of novel vector control strategies requires a thorough understanding of mosquito biology. To facilitate this, we used RNA-seq to identify novel genes and provide the first high-resolution view of the transcriptome throughout development and in response to blood feeding in a mosquito vector of human disease, Aedes aegypti, the primary vector for Dengue and yellow fever. We characterized mRNA expression at 34 distinct time points throughout Aedes development, including adult somatic and germline tissues, by using polyA+ RNA-seq. We identify a total of 14,238 novel new transcribed regions corresponding to 12,597 new loci, as well as many novel transcript isoforms of previously annotated genes. Altogether these results increase the annotated fraction of the transcribed genome into long polyA+ RNAs by more than twofold. We also identified a number of patterns of shared gene expression, as well as genes and/or exons expressed sex-specifically or sex-differentially. Expression profiles of small RNAs in ovaries, early embryos, testes, and adult male and female somatic tissues also were determined, resulting in the identification of 38 new Aedes-specific miRNAs, and ~291,000 small RNA new transcribed regions, many of which are likely to be endogenous small-interfering RNAs and Piwi-interacting RNAs. Genes of potential interest for transgene-based vector control strategies also are highlighted. Our data have been incorporated into a user-friendly genome browser located at www. Aedes.caltech.edu, with relevant links to Vectorbase (www.vectorbase.org). | The Developmental Transcriptome of the Mosquito Aedes aegypti, an Invasive Species and Major Arbovirus Vector |
{"1003": 0.010684899985790253, "1014": 0.04860413447022438, "1039": 0.11430477350950241, "1052": 0.9739698171615601, "1059": 0.08244366943836212, "2007": 0.11081436276435852, "2011": 0.1229778528213501, "2044": 0.4093637466430664, "2075": 0.24171993136405945, "2089": 0.13071982562541962, "2090": 0.26446542143821716, "2135": 0.22704219818115234, "2140": 0.12470348179340363, "2155": 0.5751199722290039, "2179": 0.1718502640724182, "2235": 0.19862671196460724, "2287": 0.6734226942062378, "2303": 0.13925230503082275, "2308": 0.7737906575202942, "2339": 0.03266380727291107, "2368": 0.47766464948654175, "2423": 0.13157635927200317, "2450": 0.5324648022651672, "2470": 0.0174254160374403, "2482": 0.6118015646934509, "2504": 0.11168810725212097, "2515": 0.2089812457561493, "2522": 0.4196864068508148, "2523": 0.503966212272644, "2529": 0.5074998140335083, "2561": 0.5220900774002075, "2571": 0.5478278398513794, "2615": 0.9643365740776062, "2690": 0.5838727951049805, "2714": 0.012615402229130268, "2765": 0.1602703034877777, "2791": 0.5833279490470886, "2817": 0.13157635927200317, "2836": 0.036437395960092545, "2860": 1.094698429107666, "2865": 0.23710809648036957, "2913": 0.03360854089260101, "2920": 0.037378571927547455, "2931": 0.5232481360435486, "2944": 0.14179791510105133, "2945": 0.23556606471538544, "2951": 0.4673144817352295, "3080": 0.06703783571720123, "3131": 0.3019835948944092, "3141": 0.13414156436920166, "3151": 0.35128939151763916, "3169": 0.2719337046146393, "3177": 0.5278670787811279, "3197": 0.43938836455345154, "3226": 0.06795065850019455, "3231": 0.4512746334075928, "3251": 0.17020416259765625, "3273": 0.2478361576795578, "3276": 0.3870677351951599, "3278": 0.6902132034301758, "3289": 0.05417001247406006, "3350": 0.0038986403960734606, "3375": 0.034552380442619324, "3378": 0.8925741910934448, "3401": 0.4487839937210083, "3445": 0.03266380727291107, "3446": 0.06795065850019455, "3452": 0.28450319170951843, "3463": 0.4938860833644867, "3466": 0.7295845746994019, "3491": 0.05046287178993225, "3562": 0.10555581003427505, "3593": 0.7047978043556213, "3597": 0.5903874635696411, "3603": 0.03360854089260101, "3605": 0.7417513132095337, "3623": 0.22937409579753876, "3674": 0.3353555500507355, "3676": 0.1384023278951645, "3723": 0.4926934838294983, "3730": 0.11951763927936554, "3742": 0.371698260307312, "3747": 0.7276995778083801, "3778": 0.6476961374282837, "3787": 0.08961215615272522, "3798": 0.37907835841178894, "3801": 0.472198486328125, "3867": 0.20977331697940826, "3891": 0.7182208299636841, "3893": 0.04207121208310127, "3896": 0.6270449161529541, "3936": 0.13925230503082275, "3949": 0.18167030811309814, "4081": 0.319873183965683, "4094": 0.22548456490039825, "4106": 0.6931471824645996, "4117": 0.5404602885246277, "4118": 0.255429208278656, "4140": 0.6291293501853943, "4146": 0.0009760859538801014, "4168": 0.8332487344741821, "4180": 0.2223619967699051, "4221": 0.3241194784641266, "4254": 0.06246116757392883, "4286": 0.49626702070236206, "4308": 0.2741633653640747, "4400": 1.12432062625885, "4453": 0.33115679025650024, "4492": 0.010684899985790253, "4531": 0.03266380727291107, "4539": 0.5925496220588684, "4541": 0.5255602598190308, "4725": 0.42735910415649414, "4783": 0.5865923762321472, "4793": 0.3374483287334442, "4863": 0.41065993905067444, "4903": 0.2447827309370041, "4957": 0.45499902963638306, "4997": 0.2470736801624298, "5012": 0.8989537954330444, "5105": 0.45499902963638306, "5159": 0.13157635927200317, "5173": 0.7537717819213867, "5213": 0.0058422754518687725, "5250": 0.4770587682723999, "5337": 0.28670501708984375, "5345": 0.8091925978660583, "5360": 0.23092569410800934, "5387": 0.6573580503463745, "5468": 0.6553317308425903, "5482": 0.043007105588912964, "5512": 1.248288631439209, "5519": 0.6461620330810547, "5531": 0.27564704418182373, "5579": 0.3269403576850891, "5604": 0.5156965255737305, "5740": 0.8509185314178467, "5761": 0.46363574266433716, "5769": 0.09761575609445572, "5789": 0.12642613053321838, "5799": 0.512191891670227, "5845": 0.07431721687316895, "5852": 0.2837681770324707, "5876": 0.7764897346496582, "5950": 0.6709295511245728, "5975": 0.9754437208175659, "6022": 0.29473719000816345, "6079": 0.23710809648036957, "6083": 0.5573811531066895, "6132": 0.06337817758321762, "6383": 0.020300358533859253, "6388": 0.052318159490823746, "6459": 0.1710275560617447, "6463": 0.0770333781838417, "6515": 0.7018978595733643, "6529": 0.058784693479537964, "6541": 0.2976420819759369, "6592": 0.49030399322509766, "6614": 0.512191891670227, "6638": 0.512191891670227, "6691": 0.08692999184131622, "6789": 0.0842406153678894, "6812": 0.3519764244556427, "6887": 0.6848117709159851, "6897": 0.3777405619621277, "6968": 0.6950984001159668, "6980": 0.14433705806732178, "7017": 0.45994341373443604, "7023": 0.9531047344207764, "7091": 0.15526613593101501, "7108": 0.13670019805431366, "7242": 0.20580662786960602, "7337": 0.07250232994556427, "7356": 0.029824240133166313, "7366": 0.1685553640127182, "7367": 0.2749055027961731, "7399": 1.094698429107666, "7438": 0.4831010699272156, "7453": 0.014542185701429844, "7457": 0.11691460013389587, "7461": 0.44753631949424744, "7495": 0.09672962874174118, "7551": 0.18329764902591705, "7578": 0.7755908370018005, "7594": 0.4196864068508148, "7607": 0.029824240133166313, "7616": 0.6286086440086365, "7645": 0.18492233753204346, "7657": 0.011650617234408855, "7667": 0.04113444685935974, "7711": 0.14179791510105133, "7718": 0.35745587944984436, "7784": 0.3526630103588104, "7823": 0.24859806895256042, "7834": 0.401551216840744, "7863": 0.2394166737794876, "7865": 0.23247487843036652, "7885": 0.13499516248703003, "7889": 0.5778634548187256, "8023": 0.6674286723136902, "8089": 0.7201237678527832, "8092": 0.820433497428894, "8150": 0.15442965924739838, "8171": 0.3601844012737274, "8178": 0.9092346429824829, "8187": 1.180456280708313, "8247": 0.1677299439907074, "8290": 0.1332872211933136, "8332": 0.12038381397724152, "8335": 0.014542185701429844, "8386": 0.2184450328350067, "8556": 0.004870930220931768, "8578": 0.22937409579753876, "8636": 0.13414156436920166, "8704": 0.5528968572616577, "8715": 0.7370892763137817, "8790": 0.011650617234408855, "8906": 1.057410478591919, "8920": 0.175953671336174, "8924": 0.6286086440086365, "9002": 0.0174254160374403, "9007": 0.1332872211933136, "9071": 0.5773153901100159, "9104": 0.18329764902591705, "9265": 0.5261374711990356, "9312": 0.053244512528181076, "9333": 0.23787821829319, "9416": 0.5098485946655273, "9420": 0.5540198087692261, "9507": 0.14602625370025635, "9535": 1.4339678287506104, "9556": 0.3170322775840759, "9574": 0.034552380442619324, "9718": 0.07159364968538284, "9750": 0.15777134895324707, "9821": 0.2741633653640747, "9990": 0.09938567131757736, "9996": 0.02316705882549286, "10088": 0.2822965085506439, "10124": 0.5324648022651672, "10128": 0.45499902963638306, "10146": 1.0648454427719116, "10174": 0.0174254160374403, "10266": 0.15275461971759796, "10327": 0.7969439625740051, "10426": 0.6603899002075195, "10502": 0.11081436276435852, "10509": 0.013579257763922215, "10551": 1.3848284482955933, "10744": 0.32905077934265137, "10755": 0.8298473954200745, "10768": 0.6369074583053589, "10817": 0.9621002674102783, "10831": 0.32129061222076416, "10847": 0.10731173306703568, "10857": 0.7546905279159546, "10867": 0.0058422754518687725, "10881": 0.7445381283760071, "10898": 0.14179791510105133, "10903": 0.40806588530540466, "10949": 0.259204238653183, "11031": 0.8567397594451904, "11071": 0.18492233753204346, "11100": 0.20580662786960602, "11211": 0.09406650811433792, "11233": 0.812664806842804, "11383": 0.5104349255561829, "11387": 0.011650617234408855, "11424": 0.987156867980957, "11619": 0.1685553640127182, "11628": 0.28743788599967957, "11709": 0.3304552733898163, "11767": 0.3883931338787079, "11835": 0.013579257763922215, "11841": 0.5220900774002075, "11983": 0.022212404757738113, "12241": 0.8973627090454102, "12328": 0.1718502640724182, "12403": 0.018384648486971855, "12435": 0.1718502640724182, "12490": 0.034552380442619324, "12520": 0.29400965571403503, "12556": 0.7728893756866455, "12681": 0.5618454217910767, "12702": 1.0775588750839233, "12868": 0.1994270235300064, "12990": 0.42990362644195557, "13070": 0.66441810131073, "13143": 0.8349450826644897, "13181": 0.04394211992621422, "13210": 0.8289952278137207, "13336": 0.0038986403960734606, "13483": 0.9287132620811462, "13531": 0.2317005842924118, "13659": 0.23556606471538544, "13806": 0.1332872211933136, "14025": 0.5410289764404297, "14080": 0.22157983481884003, "14126": 0.6634125709533691, "14155": 0.32553088665008545, "14171": 0.6170841455459595, "14267": 0.7086513638496399, "14343": 0.4770587682723999, "14358": 0.04207121208310127, "14396": 0.026976587250828743, "14402": 0.15777134895324707, "14531": 0.8091925978660583, "14639": 0.06337817758321762, "14670": 0.0058422754518687725, "14719": 0.15023678541183472, "14956": 0.846739649772644, "15050": 0.20977331697940826, "15070": 0.13414156436920166, "15088": 0.2493593990802765, "15189": 0.09584271162748337, "15253": 1.1641268730163574, "15306": 0.5098485946655273, "15403": 0.04767346754670143, "15442": 0.10379679501056671, "15485": 0.01934296265244484, "15536": 0.083342544734478, "15772": 1.102510929107666, "15923": 0.2976420819759369, "16012": 0.7934166193008423, "16014": 0.2763880789279938, "16090": 0.01934296265244484, "16134": 0.33115679025650024, "16185": 0.5751199722290039, "16211": 0.08692999184131622, "16264": 0.2689530849456787, "16285": 0.11951763927936554, "16330": 0.006812678650021553, "16381": 0.1477125883102417, "16478": 0.22079704701900482, "16483": 0.7295845746994019, "16535": 0.6754127144813538, "16578": 0.03360854089260101, "16605": 0.09761575609445572, "16665": 0.8004589080810547, "16705": 0.056018441915512085, "16749": 0.7809720039367676, "16844": 0.29109421372413635, "16902": 1.09404456615448, "16913": 0.7067264318466187, "16924": 0.16690383851528168, "17194": 0.6054253578186035, "17202": 0.05786345899105072, "17221": 0.010684899985790253, "17245": 0.1677299439907074, "17261": 0.6186635494232178, "17341": 0.5517725944519043, "17826": 0.06337817758321762, "17880": 0.1064341589808464, "17886": 0.5718178153038025, "17908": 0.39762192964553833, "17959": 0.2830325961112976, "18089": 0.75193190574646, "18330": 0.17759032547473907, "18452": 0.014542185701429844, "18453": 0.6664261221885681, "18547": 0.15023678541183472, "18583": 0.030771657824516296, "18647": 0.1970241367816925, "18804": 0.7610978484153748, "19037": 1.0116009712219238, "19064": 0.4145384132862091, "19126": 0.6684301495552063, "19158": 0.4794800877571106, "19173": 0.3106105625629425, "19210": 0.9317949414253235, "19230": 0.011650617234408855, "19262": 0.9754437208175659, "19293": 0.06703783571720123, "19357": 0.7951818704605103, "19379": 1.0841858386993408, "19539": 0.0606246218085289, "19653": 0.1212492436170578, "19762": 0.42225050926208496, "19872": 0.9178520441055298, "20014": 0.06429435312747955, "20155": 0.19541899859905243, "20187": 0.7352184057235718, "20194": 0.49982786178588867, "20228": 0.0058422754518687725, "20253": 0.026976587250828743, "20353": 0.21530038118362427, "21025": 0.06246116757392883, "21102": 0.7473171949386597, "21150": 0.10818854719400406, "21162": 0.42096930742263794, "21281": 0.010684899985790253, "21325": 0.1477125883102417, "21374": 0.056018441915512085, "21424": 0.11168810725212097, "21449": 0.2447827309370041, "21453": 1.06619131565094, "21485": 0.04113444685935974, "21572": 0.6926587820053101, "21639": 0.19782574474811554, "21663": 0.12038381397724152, "21685": 0.6704301834106445, "21697": 0.0058422754518687725, "21733": 0.803087055683136, "21759": 0.43875885009765625, "21770": 0.13670019805431366, "21778": 0.11951763927936554, "21781": 0.21372433006763458, "22026": 0.33325836062431335, "22049": 1.156782865524292, "22071": 0.8534175157546997, "22597": 0.8559102416038513, "22643": 0.8550800085067749, "22935": 0.7105726003646851, "23139": 0.4938860833644867, "23192": 0.42416930198669434, "23260": 0.004870930220931768, "23284": 1.02149498462677, "23296": 0.8973627090454102, "23350": 0.07250232994556427, "23894": 0.7647408246994019, "23900": 1.1153976917266846, "23943": 0.8340972661972046, "23951": 0.1685553640127182, "24012": 0.07612881064414978, "24054": 0.026025565341114998, "24081": 0.7201237678527832, "24107": 0.2607102394104004, "24269": 0.06520967930555344, "24278": 0.030771657824516296, "24353": 0.2493593990802765, "24552": 0.1710275560617447, "24848": 0.11430477350950241, "24872": 0.058784693479537964, "24952": 0.09938567131757736, "25274": 0.53589928150177, "25292": 0.638455867767334, "25502": 0.1889725625514984, "25524": 0.8091925978660583, "25543": 1.178053855895996, "25714": 0.22392450273036957, "25870": 0.2160874605178833, "26282": 1.0907690525054932, "26396": 0.026976587250828743, "26404": 0.2539152204990387, "26435": 1.0312920808792114, "26591": 0.6603899002075195, "26651": 0.18004031479358673, "26677": 0.18329764902591705, "26786": 0.2659635543823242, "26835": 0.5551415085792542, "26906": 0.012615402229130268, "27400": 0.45499902963638306, "27651": 0.12642613053321838, "27691": 0.8074519634246826, "27794": 0.6857960224151611, "27920": 0.472198486328125, "28141": 0.05970508232712746, "28309": 0.22626367211341858, "28436": 0.5092619061470032, "28739": 0.043007105588912964, "28751": 0.36358460783958435, "28915": 0.46117570996284485, "29299": 0.42735910415649414, "29458": 0.1384023278951645} | 13714201 | Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness. Methods and results We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 × 10-4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing-two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3-12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing. | Gut microbial diversity is associated with lower arterial stiffness in women |
{"1011": 0.2763880789279938, "1020": 0.23633737862110138, "1043": 0.21765978634357452, "1047": 0.4944818615913391, "1048": 0.16607704758644104, "1052": 0.7144040465354919, "1055": 0.03360854089260101, "1057": 0.2637155055999756, "1061": 0.3656192123889923, "2007": 0.06612417846918106, "2012": 0.029824240133166313, "2015": 1.0423725843429565, "2020": 0.06246116757392883, "2042": 0.12814582884311676, "2063": 0.13499516248703003, "2066": 0.31204116344451904, "2075": 0.13157635927200317, "2090": 0.18248429894447327, "2092": 0.23402166366577148, "2106": 0.1332872211933136, "2112": 0.037378571927547455, "2119": 0.3269403576850891, "2124": 0.05046287178993225, "2140": 0.42735910415649414, "2164": 0.08782484382390976, "2179": 0.29036402702331543, "2200": 0.18654440343379974, "2229": 0.09406650811433792, "2265": 0.30558720231056213, "2339": 0.06337817758321762, "2348": 0.0058422754518687725, "2361": 0.6296497583389282, "2389": 0.272677481174469, "2416": 0.2516399025917053, "2421": 0.3170322775840759, "2443": 0.20022670924663544, "2470": 0.176772341132164, "2475": 0.5404602885246277, "2509": 0.07612881064414978, "2515": 0.31560876965522766, "2522": 0.20818853378295898, "2549": 0.5151132941246033, "2553": 0.619189441204071, "2560": 0.3930181860923767, "2570": 0.06154331564903259, "2575": 0.8057082891464233, "2594": 0.09938567131757736, "2595": 0.41840189695358276, "2618": 0.07612881064414978, "2629": 0.5295937061309814, "2649": 0.7047978043556213, "2682": 0.06337817758321762, "2692": 0.48850810527801514, "2750": 0.13670019805431366, "2765": 0.31560876965522766, "2812": 0.004870930220931768, "2817": 0.6212902665138245, "2825": 0.31489628553390503, "2828": 0.3923587501049042, "2838": 0.7978238463401794, "2896": 0.39433568716049194, "2913": 0.5506471395492554, "2920": 0.23787821829319, "3065": 0.22626367211341858, "3107": 0.006812678650021553, "3141": 0.026976587250828743, "3154": 0.09850110858678818, "3231": 0.12986256182193756, "3273": 0.35745587944984436, "3278": 0.6212902665138245, "3303": 0.29981520771980286, "3356": 0.8756314516067505, "3378": 0.6233867406845093, "3426": 0.562402069568634, "3444": 0.6754127144813538, "3463": 0.500420093536377, "3491": 0.5707147121429443, "3522": 0.09850110858678818, "3544": 0.12384103983640671, "3572": 0.6086184978485107, "3603": 0.7134475708007812, "3662": 0.42608439922332764, "3670": 0.006812678650021553, "3701": 0.06703783571720123, "3711": 0.38441169261932373, "3728": 0.23556606471538544, "3800": 0.3743882179260254, "3858": 0.08154398202896118, "3893": 0.7701805830001831, "3917": 0.8039615154266357, "3936": 0.6043586730957031, "4048": 0.09938567131757736, "4081": 0.3134697377681732, "4127": 0.1384023278951645, "4130": 0.9754437208175659, "4140": 0.5517725944519043, "4167": 0.7067264318466187, "4295": 0.7067264318466187, "4304": 0.8152611255645752, "4310": 0.1734936386346817, "4326": 0.04487626627087593, "4413": 0.029824240133166313, "4453": 0.14939609169960022, "4456": 0.07431721687316895, "4484": 0.3170322775840759, "4523": 0.1808556467294693, "4531": 0.13243216276168823, "4541": 0.055094651877880096, "4570": 0.40806588530540466, "4609": 0.6773988008499146, "4654": 0.10291612148284912, "4659": 0.5033760666847229, "4678": 0.8764448165893555, "4720": 0.469759464263916, "4724": 0.8383291959762573, "4757": 0.2749055027961731, "4760": 0.1332872211933136, "4877": 0.07250232994556427, "4906": 0.0029254043474793434, "4928": 0.11081436276435852, "4955": 0.732405424118042, "4962": 1.151856780052185, "4997": 0.6629094481468201, "5013": 1.0137293338775635, "5022": 0.16359257698059082, "5038": 0.06337817758321762, "5082": 0.1994270235300064, "5250": 0.6389714479446411, "5320": 0.6128603219985962, "5360": 0.04953393340110779, "5418": 0.6149744987487793, "5456": 0.3656192123889923, "5531": 0.0019512200960889459, "5577": 0.14433705806732178, "5638": 0.2983669638633728, "5644": 0.02316705882549286, "5666": 0.2800849378108978, "5769": 0.16359257698059082, "5799": 0.1718502640724182, "5860": 0.5381823778152466, "5866": 0.7836518287658691, "5875": 0.15610189735889435, "6022": 0.28450319170951843, "6064": 0.5069117546081543, "6075": 0.672426164150238, "6083": 0.24018502235412598, "6091": 0.19782574474811554, "6235": 0.3297532796859741, "6337": 0.7934166193008423, "6377": 0.08782484382390976, "6388": 0.1212492436170578, "6459": 0.09406650811433792, "6483": 0.025073638185858727, "6592": 0.4267219603061676, "6612": 0.8780695199966431, "6632": 0.6054253578186035, "6689": 0.6833335757255554, "6740": 0.15275461971759796, "6779": 0.679875910282135, "6806": 0.0842406153678894, "6825": 0.006812678650021553, "6835": 0.13157635927200317, "6864": 1.004473328590393, "6887": 0.4914994537830353, "6936": 0.16359257698059082, "6937": 0.01934296265244484, "6961": 0.08871890604496002, "7060": 0.3662964701652527, "7082": 0.00875066313892603, "7091": 0.08692999184131622, "7092": 0.08961215615272522, "7127": 0.04767346754670143, "7146": 0.11951763927936554, "7297": 0.11430477350950241, "7336": 0.3297532796859741, "7356": 0.09406650811433792, "7361": 0.4831010699272156, "7403": 0.9417452812194824, "7487": 0.4938860833644867, "7523": 0.14602625370025635, "7551": 0.05417001247406006, "7614": 0.012615402229130268, "7629": 0.6823468804359436, "7645": 0.4311734735965729, "7657": 0.5472630262374878, "7784": 0.2026219218969345, "7809": 0.175953671336174, "7843": 0.7845434546470642, "7870": 0.4831010699272156, "7872": 0.083342544734478, "7885": 0.1212492436170578, "7900": 0.39367714524269104, "8031": 0.9294845461845398, "8040": 0.5849615335464478, "8171": 0.41065993905067444, "8560": 0.39696553349494934, "8583": 0.0174254160374403, "8715": 0.5415972471237183, "8740": 0.029824240133166313, "8761": 0.20102575421333313, "8832": 0.638455867767334, "8902": 0.0029254043474793434, "8920": 0.4286321699619293, "8991": 0.36900100111961365, "9113": 0.6456501483917236, "9125": 0.2822965085506439, "9165": 0.9732321500778198, "9223": 0.1718502640724182, "9289": 0.678390383720398, "9426": 0.34715715050697327, "9496": 0.6338034868240356, "9556": 0.29328158497810364, "9693": 0.31132611632347107, "9702": 0.40806588530540466, "9739": 0.6441128253936768, "9742": 0.3810817003250122, "9839": 0.007782140281051397, "10003": 0.0354953333735466, "10091": 0.7463917136192322, "10115": 0.10291612148284912, "10358": 0.5278670787811279, "10502": 1.2889312505722046, "10627": 0.30558720231056213, "10719": 0.29109421372413635, "10744": 0.055094651877880096, "10788": 0.32058215141296387, "10840": 0.06337817758321762, "10847": 0.1685553640127182, "10976": 0.8323994874954224, "11089": 0.5051454305648804, "11156": 0.6517757177352905, "11157": 0.27712854743003845, "11265": 0.6139179468154907, "11323": 0.025073638185858727, "11457": 1.1005635261535645, "11487": 0.4412745535373688, "11601": 1.0158531665802002, "11628": 0.020300358533859253, "11865": 1.531476378440857, "12210": 0.4462870955467224, "12328": 0.030771657824516296, "12650": 0.7473171949386597, "12732": 0.23092569410800934, "12759": 0.03360854089260101, "12839": 0.15442965924739838, "12889": 0.036437395960092545, "12890": 0.05417001247406006, "12898": 0.4914994537830353, "12921": 0.20977331697940826, "12955": 0.21922965347766876, "13139": 0.22626367211341858, "13191": 0.24171993136405945, "13458": 0.4002431631088257, "13472": 0.07159364968538284, "13656": 0.13499516248703003, "13806": 0.6358738541603088, "13874": 0.5990082025527954, "13924": 0.2447827309370041, "13993": 0.1332872211933136, "14080": 0.10291612148284912, "14163": 0.6223390698432922, "14187": 0.08154398202896118, "14332": 0.08064348995685577, "14343": 0.6980181336402893, "14413": 0.12470348179340363, "14471": 0.6754127144813538, "14494": 1.2660669088363647, "14595": 0.7342816591262817, "14800": 0.48430517315864563, "14967": 0.6699305176734924, "14981": 0.3027053773403168, "15069": 1.039613962173462, "15306": 0.3588210940361023, "15396": 0.08154398202896118, "15527": 0.966567873954773, "15549": 0.7096124291419983, "15596": 0.03360854089260101, "15698": 0.8633513450622559, "15756": 0.48068851232528687, "15945": 0.15359249711036682, "15981": 0.36967599391937256, "16007": 0.0058422754518687725, "16066": 0.5069117546081543, "16086": 0.0317181795835495, "16096": 0.04207121208310127, "16150": 0.03925827145576477, "16221": 1.387270450592041, "16238": 0.8143964409828186, "16280": 0.0038986403960734606, "16364": 0.1677299439907074, "16492": 0.8442239761352539, "16505": 0.1064341589808464, "16515": 0.8013357520103455, "16691": 0.14518201351165771, "16703": 0.045809537172317505, "16706": 0.41389304399490356, "16902": 0.9279413223266602, "16962": 0.15359249711036682, "16985": 0.9900637865066528, "17160": 0.08064348995685577, "17174": 0.20818853378295898, "17614": 0.31560876965522766, "17864": 0.016465263441205025, "17879": 0.5517725944519043, "18252": 0.7276995778083801, "18275": 0.08513788133859634, "18349": 0.20022670924663544, "18419": 0.18978065252304077, "18439": 0.07250232994556427, "18678": 0.2763880789279938, "18809": 0.05970508232712746, "18896": 0.0038986403960734606, "18939": 1.2215901613235474, "18981": 0.8649974465370178, "19021": 0.8383291959762573, "19184": 0.06886265426874161, "19195": 0.04394211992621422, "19251": 0.07250232994556427, "19274": 0.056018441915512085, "19314": 0.9417452812194824, "19345": 0.5455666780471802, "19389": 0.08513788133859634, "19466": 0.9005423784255981, "19470": 0.14518201351165771, "19476": 0.08961215615272522, "19539": 0.2018241584300995, "19611": 0.055094651877880096, "19680": 0.0606246218085289, "19817": 0.42608439922332764, "19961": 0.06429435312747955, "19962": 0.11865071207284927, "19976": 0.0606246218085289, "20166": 0.5701626539230347, "20214": 0.06337817758321762, "20310": 0.46363574266433716, "20467": 0.07341018319129944, "20569": 0.15693697333335876, "20792": 0.2231435477733612, "20817": 0.2607102394104004, "20952": 0.0019512200960889459, "21017": 0.9531047344207764, "21101": 0.7565253376960754, "21262": 0.15359249711036682, "21396": 0.36697331070899963, "21486": 0.14686977863311768, "21901": 0.24248650670051575, "21903": 0.20102575421333313, "22025": 0.06429435312747955, "22203": 0.9886114001274109, "22248": 0.22937409579753876, "22260": 0.11604541540145874, "22275": 0.37102460861206055, "22747": 0.034552380442619324, "23079": 0.00875066313892603, "23130": 0.39762192964553833, "23150": 0.08244366943836212, "23283": 0.5021947622299194, "23683": 0.08782484382390976, "23777": 0.6451379656791687, "23824": 0.7601850032806396, "23892": 0.39762192964553833, "23900": 0.7482418417930603, "24012": 0.05139094591140747, "24279": 0.04207121208310127, "24434": 0.8332487344741821, "24551": 0.5767669677734375, "25206": 0.0913962796330452, "25284": 0.04767346754670143, "25520": 1.417065978050232, "25746": 1.020087480545044, "25940": 0.2470736801624298, "26287": 0.24248650670051575, "26305": 0.3910386264324188, "26452": 0.21293537318706512, "26601": 0.33605360984802246, "26745": 0.14179791510105133, "26786": 0.28963330388069153, "27009": 0.34370049834251404, "27094": 0.2852376699447632, "27673": 0.018384648486971855, "28046": 0.020300358533859253, "28154": 0.083342544734478, "28228": 0.6327666640281677, "28290": 0.15442965924739838, "28685": 0.16524957120418549, "28774": 0.36290550231933594, "28828": 0.14349138736724854, "29295": 0.37102460861206055} | 13717103 | INTRODUCTION Mutations in the FUS gene have been shown to be a rare cause of amyotrophic lateral sclerosis (ALS-FUS) and whilst well documented clinically and genetically there have been relatively few neuropathological studies. Recent work suggested a possible correlation between pathological features such as frequency of basophilic inclusions in neurons and rate of clinical decline, other studies have revealed a discrepancy between the upper motor neuron features detected clinically and the associated pathology. The purpose of this study was to describe the pathological features associated with more recently discovered FUS mutations and reinvestigate those with well recognised mutations in an attempt to correlate the pathology with mutation and/or clinical phenotype. The brains and spinal cords of seven cases of ALS-FUS were examined neuropathologically, including cases with the newly described p. K510E mutation and a case with both a known p. P525L mutation in the FUS gene and a truncating p. Y374X mutation in the TARDBP gene. RESULTS The neuropathology in all cases revealed basophilic and FUS inclusions in the cord. The density and type of inclusions varied markedly between cases, but did not allow a clear correlation with clinical progression. Only one case showed significant motor cortical pathology despite the upper motor neuron clinical features being evident in 4 patients. The case with both a FUS and TARDBP mutation revealed FUS positive inclusions but no TDP-43 pathology. Instead there were unusual p62 positive, FUS negative neuronal and glial inclusions as well as dot-like neurites. CONCLUSIONS The study confirms cases of ALS-FUS to be mainly a lower motor neuron disease and to have pathology that does not appear to neatly correlate with clinical features or genetics. Furthermore, the case with both a FUS and TARDBP mutation reveals an intriguing pathological profile which at least in part involves a very unusual staining pattern for the ubiquitin-binding protein p62. | ALS-FUS pathology revisited: singleton FUS mutations and an unusual case with both a FUS and TARDBP mutation |
{"1044": 0.2026219218969345, "2013": 0.5255602598190308, "2015": 0.12470348179340363, "2025": 0.058784693479537964, "2031": 0.013579257763922215, "2038": 0.08603433519601822, "2039": 0.09672962874174118, "2042": 0.06429435312747955, "2072": 0.012615402229130268, "2073": 0.3141832649707794, "2088": 0.42990362644195557, "2094": 0.5573811531066895, "2111": 0.48008447885513306, "2140": 0.27934664487838745, "2148": 1.0464962720870972, "2152": 0.7647408246994019, "2177": 0.2689530849456787, "2179": 0.43875885009765625, "2205": 0.09672962874174118, "2272": 0.19862671196460724, "2331": 0.11081436276435852, "2339": 0.42735910415649414, "2367": 0.3547199070453644, "2406": 0.19541899859905243, "2426": 0.06703783571720123, "2464": 0.00875066313892603, "2504": 0.0797421783208847, "2512": 0.3134697377681732, "2540": 1.3038887977600098, "2555": 0.11604541540145874, "2634": 1.0409941673278809, "2653": 0.14349138736724854, "2659": 0.4228905141353607, "2660": 0.04394211992621422, "2668": 0.3027053773403168, "2670": 0.469759464263916, "2691": 0.6980181336402893, "2711": 0.056018441915512085, "2740": 0.40806588530540466, "2761": 0.043007105588912964, "2789": 0.14939609169960022, "2796": 1.059443712234497, "2822": 0.0174254160374403, "2854": 0.53589928150177, "2896": 0.13414156436920166, "2913": 0.14433705806732178, "2966": 0.1718502640724182, "2967": 0.27712854743003845, "2988": 0.3930181860923767, "3020": 0.43623676896095276, "3032": 0.4196864068508148, "3060": 0.0913962796330452, "3088": 0.11256109178066254, "3108": 0.0842406153678894, "3189": 0.1619328260421753, "3226": 0.015504186972975731, "3284": 0.47463157773017883, "3291": 0.0606246218085289, "3305": 0.21687394380569458, "3314": 0.08961215615272522, "3378": 0.20421554148197174, "3391": 0.09850110858678818, "3412": 0.2018241584300995, "3426": 0.272677481174469, "3445": 0.4425300657749176, "3446": 0.6212902665138245, "3451": 0.1485546976327896, "3471": 0.4944818615913391, "3497": 0.11951763927936554, "3544": 0.17267228662967682, "3618": 0.1905880719423294, "3623": 0.1905880719423294, "3695": 0.13755162060260773, "3701": 0.02412080205976963, "3711": 0.40871503949165344, "3778": 0.1693800985813141, "3798": 0.3883931338787079, "3811": 0.1401015669107437, "3849": 0.1477125883102417, "3891": 0.5074998140335083, "3896": 0.1619328260421753, "3978": 0.3662964701652527, "3981": 0.06795065850019455, "4003": 0.5506471395492554, "4004": 1.202409029006958, "4021": 0.9178520441055298, "4025": 0.0842406153678894, "4119": 0.45499902963638306, "4125": 0.2247048318386078, "4141": 0.25239890813827515, "4155": 0.1889725625514984, "4244": 0.5080875158309937, "4286": 0.022212404757738113, "4295": 1.0257055759429932, "4311": 0.09495500475168228, "4501": 0.4500300884246826, "4541": 0.49982786178588867, "4643": 0.08603433519601822, "4650": 0.2018241584300995, "4652": 0.23479416966438293, "4655": 0.10203468054533005, "4676": 0.47463157773017883, "4678": 0.04394211992621422, "4703": 0.11951763927936554, "4761": 0.6358738541603088, "4795": 0.0354953333735466, "4824": 0.34508460760116577, "4852": 0.06337817758321762, "4863": 0.4950772523880005, "4942": 0.0038986403960734606, "4943": 0.14602625370025635, "4945": 0.34300774335861206, "5012": 0.7854343056678772, "5134": 0.05139094591140747, "5152": 0.3601844012737274, "5178": 0.22157983481884003, "5185": 0.1677299439907074, "5186": 0.040196798741817474, "5258": 0.11778303235769272, "5264": 0.15359249711036682, "5292": 0.013579257763922215, "5320": 0.38174858689308167, "5333": 0.3588210940361023, "5360": 0.151916041970253, "5423": 0.42225050926208496, "5610": 0.41001203656196594, "5636": 0.5784112811088562, "5699": 0.10993985831737518, "5769": 0.02316705882549286, "5866": 0.39893341064453125, "5876": 0.2447827309370041, "6008": 0.24401791393756866, "6165": 0.603290855884552, "6447": 0.15693697333335876, "6505": 0.8109301924705505, "6558": 0.2983669638633728, "6592": 0.04207121208310127, "6678": 0.27342069149017334, "6768": 0.11604541540145874, "6917": 0.011650617234408855, "6931": 0.45251765847206116, "6976": 0.14264501631259918, "7252": 0.04113444685935974, "7269": 0.09672962874174118, "7273": 0.06520967930555344, "7320": 0.08692999184131622, "7321": 0.2223619967699051, "7355": 0.2160874605178833, "7457": 0.23092569410800934, "7461": 0.1913948506116867, "7486": 0.38308101892471313, "7526": 0.11865071207284927, "7560": 0.4944818615913391, "7607": 0.3084607720375061, "7790": 0.7295845746994019, "7842": 0.7314660549163818, "7860": 0.6430866718292236, "7870": 0.9687942266464233, "7911": 0.27044451236724854, "7940": 0.5290185213088989, "8030": 0.11081436276435852, "8040": 0.14264501631259918, "8072": 0.2969166338443756, "8187": 0.18492233753204346, "8191": 0.09672962874174118, "8222": 0.0029254043474793434, "8315": 0.259204238653183, "8319": 0.6813592314720154, "8335": 0.07431721687316895, "8578": 0.026976587250828743, "8621": 0.29036402702331543, "8649": 0.06520967930555344, "8715": 0.07159364968538284, "8729": 0.19220098853111267, "8761": 0.03925827145576477, "8791": 0.02412080205976963, "8872": 0.0038986403960734606, "8935": 0.1751343309879303, "8939": 0.21372433006763458, "8995": 0.17267228662967682, "9002": 0.015504186972975731, "9028": 0.0009760859538801014, "9098": 0.05970508232712746, "9141": 0.28670501708984375, "9183": 0.3464667797088623, "9213": 0.16607704758644104, "9269": 0.32129061222076416, "9422": 0.659380316734314, "9740": 0.31845372915267944, "9889": 0.07068414986133575, "9983": 0.4818955361843109, "9990": 0.014542185701429844, "10056": 0.5990082025527954, "10318": 0.053244512528181076, "10368": 0.34577593207359314, "10381": 0.7258110046386719, "10505": 0.2763880789279938, "10548": 0.04207121208310127, "10662": 0.16524957120418549, "10751": 0.9546096324920654, "10831": 0.07884006202220917, "10862": 0.010684899985790253, "11424": 0.5151132941246033, "11481": 0.129004567861557, "11522": 0.30558720231056213, "11822": 0.32129061222076416, "11826": 0.06612417846918106, "11890": 0.037378571927547455, "11952": 0.09406650811433792, "12044": 0.27934664487838745, "12058": 0.04394211992621422, "12123": 0.9271688461303711, "12251": 0.46608972549438477, "12763": 0.1064341589808464, "12878": 0.06246116757392883, "12890": 0.401551216840744, "13012": 0.3464667797088623, "13070": 0.5590575933456421, "13153": 0.2223619967699051, "13191": 0.07884006202220917, "13275": 0.05970508232712746, "13356": 0.08961215615272522, "13531": 0.03925827145576477, "14040": 0.11951763927936554, "14065": 0.058784693479537964, "14542": 0.21372433006763458, "14671": 1.0655186176300049, "14802": 0.5461324453353882, "14971": 0.3423145115375519, "15001": 0.3318578004837036, "15050": 0.9194108247756958, "15157": 0.40741631388664246, "15396": 0.09938567131757736, "16185": 0.176772341132164, "16311": 0.2089812457561493, "16480": 0.5427330136299133, "16749": 0.38308101892471313, "16896": 0.30558720231056213, "16915": 0.45499902963638306, "17076": 0.31845372915267944, "17077": 0.1332872211933136, "17080": 0.36426326632499695, "17119": 0.5421652793884277, "17151": 0.0606246218085289, "17289": 0.10993985831737518, "17355": 0.03266380727291107, "17531": 0.0606246218085289, "17681": 0.08513788133859634, "17707": 0.0058422754518687725, "17917": 0.18004031479358673, "17959": 0.27712854743003845, "18089": 0.16110190749168396, "18166": 0.151916041970253, "18221": 0.25995752215385437, "18239": 0.004870930220931768, "18240": 0.30558720231056213, "18423": 0.18978065252304077, "18949": 0.33115679025650024, "19470": 0.040196798741817474, "20166": 0.2576959431171417, "20194": 0.6280876994132996, "20272": 0.7172679901123047, "20282": 0.08692999184131622, "20482": 0.0842406153678894, "20569": 0.567397952079773, "20915": 0.9123768210411072, "20969": 0.25995752215385437, "21106": 0.1332872211933136, "21453": 0.5568217039108276, "21709": 0.022212404757738113, "21754": 0.7182208299636841, "21887": 1.2627575397491455, "22190": 0.31560876965522766, "22254": 0.25845035910606384, "22420": 0.2018241584300995, "22571": 0.009718249551951885, "22597": 0.9769153594970703, "22935": 0.7995813488960266, "23760": 0.6176109313964844, "23969": 0.32199856638908386, "23983": 0.21765978634357452, "24180": 0.05417001247406006, "24535": 0.31132611632347107, "24552": 0.05139094591140747, "24755": 0.21214580535888672, "24757": 0.29328158497810364, "24904": 0.06246116757392883, "25032": 0.17267228662967682, "25070": 0.24325250089168549, "25430": 0.3443928062915802, "25510": 0.012615402229130268, "25632": 0.10467668622732162, "25643": 0.8357921838760376, "25808": 0.11951763927936554, "25883": 0.07793712615966797, "26030": 0.22626367211341858, "26125": 1.176850438117981, "26226": 0.6160298585891724, "26236": 0.18573370575904846, "26836": 0.17267228662967682, "26837": 0.20739519596099854, "27746": 0.33953672647476196, "27833": 1.1192315816879272, "27974": 0.2822965085506439, "28093": 0.16442140936851501, "28353": 0.6471850275993347, "28466": 0.19782574474811554, "28915": 0.4158279001712799, "29048": 0.8022117614746094, "29166": 0.34715715050697327} | 13726379 | Coronary heart disease rates have been reported in several parts of the world to be unusually high in people originating from the Indian subcontinent. High coronary disease rates appear to be common to South Asian groups of different geographical origin, religion, and language. This presents a challenge to the understanding of coronary heart disease: the high rates in South Asians are not explained on the basis of elevated serum cholesterol, smoking or hypertension. Low plasma HDL cholesterol, high plasma triglyceride levels and high prevalence of non-insulin-dependent diabetes have been consistently found in South Asians overseas: this probably reflects an underlying state of insulin resistance. Further studies are needed to determine whether this metabolic disturbance can account for the high rates of coronary heart disease in South Asians, and to identify possibilities for prevention. | Coronary heart disease in south Asians overseas: a review. |
{"1052": 0.20022670924663544, "1999": 0.4311734735965729, "2000": 0.2622140049934387, "2001": 0.05046287178993225, "2005": 0.21530038118362427, "2015": 0.011650617234408855, "2020": 0.11517547070980072, "2025": 0.259204238653183, "2043": 0.2852376699447632, "2052": 0.39762192964553833, "2053": 0.26146242022514343, "2055": 0.21765978634357452, "2058": 0.7701805830001831, "2064": 0.18978065252304077, "2071": 0.21372433006763458, "2072": 0.151916041970253, "2074": 0.9348671436309814, "2098": 0.4818955361843109, "2106": 0.15359249711036682, "2109": 0.3353555500507355, "2116": 0.1677299439907074, "2129": 0.24018502235412598, "2154": 0.1384023278951645, "2155": 0.31132611632347107, "2215": 0.23633737862110138, "2220": 0.04674193635582924, "2241": 0.06886265426874161, "2287": 0.0606246218085289, "2302": 0.053244512528181076, "2306": 0.5562619566917419, "2321": 0.1710275560617447, "2323": 0.20977331697940826, "2336": 1.004473328590393, "2339": 0.417115718126297, "2342": 0.18329764902591705, "2358": 0.09761575609445572, "2371": 0.1970241367816925, "2401": 0.31132611632347107, "2421": 0.42608439922332764, "2443": 0.31204116344451904, "2460": 0.609149694442749, "2470": 0.5914691090583801, "2478": 0.08961215615272522, "2514": 0.13414156436920166, "2553": 0.9531047344207764, "2554": 0.0038986403960734606, "2561": 0.46608972549438477, "2591": 0.7987030148506165, "2640": 0.053244512528181076, "2641": 0.14939609169960022, "2660": 0.0317181795835495, "2682": 0.15693697333335876, "2729": 0.8583967685699463, "2734": 0.07612881064414978, "2747": 0.14686977863311768, "2765": 0.4374985992908478, "2775": 1.0409941673278809, "2777": 0.3547199070453644, "2783": 0.6389714479446411, "2787": 0.3656192123889923, "2817": 0.8383291959762573, "2825": 0.052318159490823746, "2827": 0.07612881064414978, "2902": 0.3485364317893982, "2913": 0.9115922451019287, "2920": 0.016465263441205025, "2937": 0.7163142561912537, "2944": 0.13755162060260773, "2945": 0.2696990668773651, "2951": 0.5523349046707153, "2966": 0.41065993905067444, "2988": 0.39893341064453125, "3008": 1.029200792312622, "3024": 0.03266380727291107, "3056": 0.10731173306703568, "3073": 0.19220098853111267, "3078": 1.223315715789795, "3089": 0.440646231174469, "3112": 0.014542185701429844, "3113": 0.6043586730957031, "3116": 0.43244171142578125, "3188": 0.04207121208310127, "3189": 0.25088030099868774, "3193": 0.6006163358688354, "3231": 0.037378571927547455, "3247": 0.8901712894439697, "3273": 0.4248080551624298, "3289": 0.2089812457561493, "3319": 0.8893690705299377, "3336": 0.15275461971759796, "3343": 0.10731173306703568, "3350": 0.27342069149017334, "3424": 0.8600510358810425, "3452": 0.2493593990802765, "3460": 0.11951763927936554, "3463": 0.6497380137443542, "3466": 0.10026945173740387, "3497": 0.4831010699272156, "3512": 0.3127557039260864, "3572": 0.5618454217910767, "3576": 0.2470736801624298, "3601": 0.1602703034877777, "3653": 0.9240728616714478, "3680": 0.12642613053321838, "3778": 0.77198725938797, "3791": 0.39433568716049194, "3800": 0.176772341132164, "3802": 0.7276995778083801, "3818": 0.058784693479537964, "3896": 0.1619328260421753, "3905": 0.23710809648036957, "3906": 0.8949713706970215, "3921": 0.1677299439907074, "3949": 0.07068414986133575, "3979": 0.3662964701652527, "4009": 0.15023678541183472, "4081": 0.4093637466430664, "4106": 0.6813592314720154, "4118": 0.7239188551902771, "4146": 0.23402166366577148, "4200": 0.3339579105377197, "4268": 0.5495203733444214, "4295": 0.0029254043474793434, "4299": 0.21135559678077698, "4319": 0.3547199070453644, "4359": 0.08603433519601822, "4391": 0.43875885009765625, "4431": 0.018384648486971855, "4468": 0.8400169610977173, "4498": 0.15610189735889435, "4504": 0.01934296265244484, "4531": 0.38441169261932373, "4567": 0.5381823778152466, "4652": 0.18248429894447327, "4668": 0.1710275560617447, "4725": 0.804835319519043, "4737": 0.0606246218085289, "4766": 0.20739519596099854, "4812": 0.4849066734313965, "4845": 0.2622140049934387, "4874": 0.06886265426874161, "4912": 0.31560876965522766, "4953": 0.3499138653278351, "4986": 0.6118015646934509, "5002": 0.14686977863311768, "5009": 0.16607704758644104, "5012": 0.8861536383628845, "5022": 0.030771657824516296, "5059": 0.22782009840011597, "5105": 0.22001366317272186, "5142": 0.6502478122711182, "5157": 0.319873183965683, "5191": 0.13755162060260773, "5219": 0.17431432008743286, "5301": 0.09317722171545029, "5328": 0.8247235417366028, "5335": 0.4330752193927765, "5393": 0.6348392367362976, "5448": 0.19220098853111267, "5461": 0.21372433006763458, "5531": 0.24171993136405945, "5547": 0.5427330136299133, "5561": 0.20580662786960602, "5593": 1.1141164302825928, "5604": 0.14349138736724854, "5630": 0.34508460760116577, "5656": 0.7305257320404053, "5769": 0.13670019805431366, "5776": 0.09584271162748337, "5845": 0.04860413447022438, "5850": 0.28082266449928284, "5852": 0.02792670577764511, "5918": 0.11430477350950241, "5936": 0.7201237678527832, "6010": 0.5162794589996338, "6028": 0.2881702482700348, "6083": 0.4891071021556854, "6098": 0.15023678541183472, "6143": 0.15359249711036682, "6148": 0.42225050926208496, "6195": 0.08154398202896118, "6224": 0.05046287178993225, "6226": 0.0842406153678894, "6388": 0.10906458646059036, "6439": 0.034552380442619324, "6521": 0.052318159490823746, "6523": 0.025073638185858727, "6567": 0.8109301924705505, "6592": 0.732405424118042, "6594": 0.07068414986133575, "6600": 0.0606246218085289, "6612": 0.9209672808647156, "6614": 0.10993985831737518, "6643": 0.8281423449516296, "6687": 0.9531047344207764, "6727": 0.055094651877880096, "6749": 0.10203468054533005, "6817": 0.8264343738555908, "6848": 0.1994270235300064, "6871": 0.684319257736206, "6927": 0.5483922958374023, "6936": 0.1358480453491211, "7012": 0.4974553883075714, "7023": 0.040196798741817474, "7066": 0.8666408061981201, "7091": 0.6684301495552063, "7099": 0.24171993136405945, "7175": 0.2539152204990387, "7242": 0.09050461649894714, "7288": 0.15359249711036682, "7295": 0.6882523894309998, "7312": 0.034552380442619324, "7315": 0.02316705882549286, "7316": 0.022212404757738113, "7339": 0.11256109178066254, "7355": 0.1358480453491211, "7435": 0.151916041970253, "7461": 0.05970508232712746, "7473": 0.22626367211341858, "7551": 0.23710809648036957, "7613": 0.43875885009765625, "7620": 0.25995752215385437, "7667": 0.34370049834251404, "7863": 1.0815403461456299, "7870": 0.13243216276168823, "7885": 0.35677260160446167, "7941": 0.04953393340110779, "8030": 0.12470348179340363, "8082": 0.15777134895324707, "8089": 0.11081436276435852, "8161": 0.23247487843036652, "8182": 0.5562619566917419, "8411": 0.014542185701429844, "8510": 0.7163142561912537, "8556": 0.7009293437004089, "8584": 0.27044451236724854, "8670": 0.13157635927200317, "8690": 0.5186077356338501, "8729": 0.1751343309879303, "8775": 0.07884006202220917, "8778": 0.026976587250828743, "8800": 0.10818854719400406, "8822": 0.018384648486971855, "8830": 0.8195732831954956, "8930": 0.44566190242767334, "8985": 0.9463045597076416, "9016": 0.12986256182193756, "9104": 0.3757305145263672, "9128": 0.16690383851528168, "9181": 0.8715548515319824, "9229": 0.06337817758321762, "9312": 0.8861536383628845, "9349": 0.9287132620811462, "9410": 0.036437395960092545, "9420": 0.037378571927547455, "9469": 0.2652147710323334, "9507": 0.29981520771980286, "9511": 0.5838727951049805, "9517": 0.09761575609445572, "9544": 0.29473719000816345, "9556": 0.8567397594451904, "9560": 0.8349450826644897, "9597": 0.22001366317272186, "9662": 0.8869584798812866, "9720": 0.14349138736724854, "9740": 0.129004567861557, "9751": 0.10467668622732162, "9820": 0.13499516248703003, "9871": 0.20421554148197174, "9888": 0.38441169261932373, "9942": 0.7845434546470642, "9967": 0.49864232540130615, "9992": 0.6492279767990112, "10327": 0.40546512603759766, "10372": 0.14264501631259918, "10462": 0.7755908370018005, "10472": 0.5618454217910767, "10502": 1.0207915306091309, "10521": 0.23556606471538544, "10527": 0.23864774405956268, "10552": 0.5640701055526733, "10561": 0.2516399025917053, "10599": 0.05970508232712746, "10617": 0.052318159490823746, "10740": 0.2786078155040741, "10744": 0.3923587501049042, "10802": 0.5156965255737305, "10834": 0.2852376699447632, "10847": 0.4855078160762787, "10975": 0.0038986403960734606, "11014": 0.00875066313892603, "11020": 0.613389253616333, "11100": 1.0285027027130127, "11194": 0.45870962738990784, "11325": 0.8821197748184204, "11326": 0.20818853378295898, "11433": 0.16359257698059082, "11475": 0.5045560002326965, "11498": 0.1693800985813141, "11538": 0.3005385100841522, "11594": 0.1332872211933136, "11616": 0.0842406153678894, "11628": 0.18978065252304077, "11670": 0.3963087201118469, "11709": 0.029824240133166313, "11778": 0.8459017872810364, "11799": 0.08154398202896118, "12157": 0.2447827309370041, "12353": 0.12814582884311676, "12375": 0.20501139760017395, "12407": 0.3519764244556427, "12412": 0.6674286723136902, "12421": 0.21922965347766876, "12422": 0.151916041970253, "12433": 0.49626702070236206, "12503": 0.9568626880645752, "12654": 0.0009760859538801014, "12702": 0.21214580535888672, "12832": 0.26146242022514343, "12941": 0.12814582884311676, "13070": 0.7389566898345947, "13105": 0.9348671436309814, "13225": 0.11604541540145874, "13416": 0.0797421783208847, "13553": 0.0770333781838417, "13640": 0.1212492436170578, "13705": 0.6322478652000427, "13706": 0.3464667797088623, "13882": 0.2822965085506439, "13908": 0.1332872211933136, "14037": 0.03360854089260101, "14155": 0.33953672647476196, "14246": 0.25088030099868774, "14286": 0.34300774335861206, "14358": 0.28450319170951843, "14396": 0.03925827145576477, "14651": 0.1510767638683319, "14667": 0.7863243818283081, "14693": 0.2667117714881897, "14773": 0.15442965924739838, "14995": 0.08871890604496002, "15055": 0.3956514894962311, "15069": 0.11691460013389587, "15245": 0.9348671436309814, "15251": 0.11343330889940262, "15252": 0.5092619061470032, "15306": 0.8925741910934448, "15316": 1.024303913116455, "15354": 0.2409527748823166, "15399": 0.14602625370025635, "15459": 0.2741633653640747, "15549": 0.08244366943836212, "15596": 0.07612881064414978, "15644": 0.08154398202896118, "15727": 0.06337817758321762, "15804": 0.4950772523880005, "15849": 0.41001203656196594, "15877": 0.2160874605178833, "15945": 0.34370049834251404, "16053": 1.039613962173462, "16134": 0.6734226942062378, "16157": 0.3810817003250122, "16250": 0.7881022095680237, "16302": 0.960606575012207, "16330": 0.5116065740585327, "16474": 0.10291612148284912, "16478": 0.06703783571720123, "16514": 0.5903874635696411, "16519": 0.05046287178993225, "16599": 0.09761575609445572, "16646": 0.14433705806732178, "16725": 0.3070250153541565, "16755": 0.18492233753204346, "16852": 0.013579257763922215, "17145": 0.10026945173740387, "17261": 0.026025565341114998, "17341": 0.20421554148197174, "17404": 0.255429208278656, "17463": 0.34508460760116577, "17464": 0.18411032855510712, "17535": 0.11865071207284927, "17537": 0.02316705882549286, "17841": 0.8649974465370178, "17865": 0.2830325961112976, "17908": 0.417115718126297, "18012": 0.053244512528181076, "18100": 0.1212492436170578, "18382": 0.010684899985790253, "18583": 0.32058215141296387, "18643": 0.7710843086242676, "18678": 0.39893341064453125, "18793": 0.319873183965683, "18804": 0.8699195384979248, "19229": 0.4196864068508148, "19388": 0.8625272512435913, "19465": 0.05139094591140747, "19670": 0.026025565341114998, "19960": 0.3916989266872406, "20026": 0.2622140049934387, "20077": 0.06977381557226181, "20080": 0.04487626627087593, "20155": 0.5805994272232056, "20233": 0.1905880719423294, "20246": 0.18248429894447327, "20274": 0.15860503911972046, "20302": 0.15777134895324707, "20422": 0.8633513450622559, "20464": 0.129004567861557, "20589": 0.014542185701429844, "20662": 0.1930064558982849, "20794": 0.045809537172317505, "20992": 0.3870677351951599, "21150": 0.3005385100841522, "21162": 0.1011524572968483, "21202": 0.6054253578186035, "21371": 0.1930064558982849, "21386": 0.17922431230545044, "21393": 0.09317722171545029, "21685": 0.2822965085506439, "21759": 0.004870930220931768, "21877": 0.12470348179340363, "21888": 0.17840765416622162, "21893": 0.040196798741817474, "22283": 0.17020416259765625, "22329": 0.07068414986133575, "22585": 0.04767346754670143, "22865": 0.045809537172317505, "23041": 0.004870930220931768, "23087": 0.5010119676589966, "23208": 0.2501201331615448, "23329": 0.26146242022514343, "23363": 0.823009729385376, "23614": 0.8459017872810364, "23655": 0.38574060797691345, "24010": 0.18492233753204346, "24039": 0.083342544734478, "24209": 0.554580807685852, "24251": 0.05046287178993225, "24479": 1.2284748554229736, "24685": 0.4831010699272156, "25044": 0.045809537172317505, "25095": 0.03360854089260101, "25227": 0.9900637865066528, "25455": 0.4462870955467224, "25947": 0.0038986403960734606, "25969": 0.3723714053630829, "26282": 0.03925827145576477, "26563": 0.1873544454574585, "26591": 1.1153976917266846, "26655": 0.026025565341114998, "26777": 0.4041621685028076, "27152": 0.010684899985790253, "27292": 0.1064341589808464, "27453": 0.6989894509315491, "27631": 0.1384023278951645, "27637": 0.09495500475168228, "27794": 0.06520967930555344, "27815": 0.15275461971759796, "27918": 0.2561853528022766, "28581": 0.2493593990802765, "28586": 0.3949938118457794, "28775": 0.09584271162748337, "28804": 0.3656192123889923, "29234": 0.8550800085067749, "29392": 0.1946154683828354, "29598": 0.3070250153541565} | 13732033 | OBJECTIVES To investigate the views of parents, clinicians, and children pertaining to prescribing decisions for acute childhood infection in primary care. METHODS A systematic review of qualitative studies. Meta-ethnographic methods were used, with data drawn from the primary studies in an interpretive analysis. RESULTS A total of 15 studies met the inclusion criteria. The literature was dominated by concerns about antibiotic over-prescription. Children's views were not reported. Clinicians prescribed antibiotics when they felt pressured by parents or others (e.g. employers) to do so, when they believed there was a clear clinical indication, but also when they felt uncertain of clinical or social outcomes they prescribed "just in case". Parents wanted antibiotics when they felt they would improve the current illness, and when they felt pressure from daycare providers or employers. Clinicians avoided antibiotics when they were concerned about adverse reactions or drug resistance, when certain they were not indicated, and when there was no perceived pressure from parents. Parents also wished to avoid adverse effects of antibiotics, and did not want antibiotics when they would not relieve current symptoms. Some parents preferred to avoid medication altogether. Within paediatric consultations, parents sought a medical evaluation and decision. Primary care clinicians want satisfied parents and short consultations. CONCLUSIONS Antibiotic prescriptions for childhood infections in primary care often result from "just in case" prescribing. These findings suggest that interventions which reduce clinician uncertainty regarding social or clinical outcomes and provide strategies to meet parents' needs within a short consultation are most likely to reduce antibiotic prescribing. | A systematic review of parent and clinician views and perceptions that influence prescribing decisions in relation to acute childhood infections in primary care |
{"1003": 0.02887592278420925, "1052": 0.06703783571720123, "2001": 0.18573370575904846, "2007": 0.3897167444229126, "2012": 0.22859740257263184, "2013": 0.20580662786960602, "2019": 0.31489628553390503, "2020": 0.2394166737794876, "2043": 0.21293537318706512, "2044": 0.06612417846918106, "2090": 0.06154331564903259, "2094": 0.27342069149017334, "2095": 0.2018241584300995, "2106": 0.04394211992621422, "2111": 0.2763880789279938, "2116": 0.32553088665008545, "2119": 0.13670019805431366, "2141": 0.9287132620811462, "2152": 0.5756692886352539, "2179": 0.3930181860923767, "2193": 0.38905516266822815, "2199": 0.1873544454574585, "2239": 0.822151780128479, "2271": 0.36086538434028625, "2275": 0.22859740257263184, "2287": 0.12470348179340363, "2312": 0.31132611632347107, "2313": 1.0742288827896118, "2329": 0.009718249551951885, "2361": 0.8400169610977173, "2367": 0.21687394380569458, "2378": 0.5707147121429443, "2408": 0.5186077356338501, "2414": 0.2026219218969345, "2454": 0.8143964409828186, "2470": 0.36086538434028625, "2487": 0.0354953333735466, "2488": 0.06429435312747955, "2504": 0.5347557663917542, "2509": 0.7782850861549377, "2511": 0.07341018319129944, "2522": 0.2034190446138382, "2529": 0.03360854089260101, "2533": 0.22157983481884003, "2553": 0.3547199070453644, "2556": 0.304147332906723, "2563": 0.417115718126297, "2566": 0.8349450826644897, "2575": 0.5596157908439636, "2582": 0.17267228662967682, "2590": 0.09761575609445572, "2594": 0.1619328260421753, "2620": 0.3443928062915802, "2638": 0.5551415085792542, "2640": 0.47463157773017883, "2660": 0.0009760859538801014, "2668": 0.6522845029830933, "2683": 0.015504186972975731, "2691": 0.3897167444229126, "2714": 0.7067264318466187, "2752": 0.10291612148284912, "2765": 0.44753631949424744, "2777": 0.5370414853096008, "2817": 0.7647408246994019, "2846": 0.41647201776504517, "2866": 0.7898768186569214, "2881": 0.0752234235405922, "2885": 0.04953393340110779, "2890": 0.19220098853111267, "2896": 0.011650617234408855, "2902": 0.5232481360435486, "2913": 0.6502478122711182, "2951": 0.2447827309370041, "2968": 0.4500300884246826, "2983": 0.0797421783208847, "3020": 0.12038381397724152, "3025": 0.40351006388664246, "3041": 0.18167030811309814, "3058": 0.28450319170951843, "3069": 0.14939609169960022, "3106": 0.7665573358535767, "3118": 0.23015019297599792, "3130": 0.0058422754518687725, "3170": 0.5127768516540527, "3172": 0.0019512200960889459, "3189": 0.009718249551951885, "3231": 0.5925496220588684, "3266": 0.11691460013389587, "3273": 0.47827014327049255, "3278": 0.13670019805431366, "3284": 0.34508460760116577, "3287": 0.1212492436170578, "3305": 0.22079704701900482, "3344": 0.3012613356113434, "3348": 0.08871890604496002, "3350": 0.03925827145576477, "3378": 0.2689530849456787, "3385": 0.2026219218969345, "3401": 0.5186077356338501, "3438": 0.17759032547473907, "3445": 0.25694093108177185, "3446": 0.304147332906723, "3452": 0.6833335757255554, "3463": 0.6512666940689087, "3491": 0.06246116757392883, "3501": 0.9769153594970703, "3517": 0.05139094591140747, "3556": 0.10555581003427505, "3563": 0.0038986403960734606, "3570": 0.8315495252609253, "3572": 0.6709295511245728, "3590": 0.5979346632957458, "3603": 0.17840765416622162, "3616": 0.10818854719400406, "3618": 0.018384648486971855, "3624": 0.3409265875816345, "3653": 0.09406650811433792, "3671": 0.562402069568634, "3688": 0.4518963396549225, "3699": 0.11517547070980072, "3705": 0.09050461649894714, "3725": 0.41840189695358276, "3734": 0.10731173306703568, "3739": 0.7144040465354919, "3767": 0.14264501631259918, "3770": 0.5784112811088562, "3777": 0.5404602885246277, "3798": 0.6086184978485107, "3801": 0.09672962874174118, "3811": 0.12642613053321838, "3851": 0.026025565341114998, "3867": 0.3262358605861664, "3874": 0.6857960224151611, "3878": 0.10026945173740387, "3885": 0.18816383183002472, "3891": 0.0317181795835495, "3893": 0.9287132620811462, "3912": 0.1734936386346817, "3936": 0.40220460295677185, "3943": 0.02412080205976963, "3979": 0.020300358533859253, "3995": 0.7028654217720032, "4008": 0.21922965347766876, "4013": 0.16690383851528168, "4031": 0.24554696679115295, "4048": 0.6512666940689087, "4081": 0.2711893916130066, "4094": 0.7610978484153748, "4102": 0.6228629946708679, "4106": 0.19220098853111267, "4130": 0.2830325961112976, "4135": 0.19782574474811554, "4146": 0.3127557039260864, "4167": 0.045809537172317505, "4182": 0.8550800085067749, "4194": 0.13670019805431366, "4292": 0.6149744987487793, "4293": 0.4248080551624298, "4295": 0.4500300884246826, "4304": 0.08244366943836212, "4340": 0.043007105588912964, "4358": 0.4818955361843109, "4372": 0.5893046259880066, "4453": 0.17020416259765625, "4456": 0.11604541540145874, "4464": 0.0770333781838417, "4484": 0.6451379656791687, "4489": 0.022212404757738113, "4493": 0.32129061222076416, "4523": 0.17759032547473907, "4531": 0.37102460861206055, "4595": 0.22782009840011597, "4601": 0.2830325961112976, "4632": 0.0317181795835495, "4663": 0.09850110858678818, "4673": 0.05694137513637543, "4678": 0.16110190749168396, "4749": 0.5450005531311035, "4812": 0.0029254043474793434, "4942": 0.757441520690918, "4957": 0.6327666640281677, "4958": 0.6669275164604187, "4962": 0.6096806526184082, "4964": 0.36494144797325134, "5002": 0.981317400932312, "5041": 0.31845372915267944, "5063": 0.7863243818283081, "5067": 0.06977381557226181, "5159": 0.04113444685935974, "5246": 0.05046287178993225, "5250": 0.8682814836502075, "5292": 0.02412080205976963, "5306": 0.009718249551951885, "5331": 0.004870930220931768, "5337": 0.8796916007995605, "5345": 0.8559102416038513, "5360": 0.5936289429664612, "5393": 0.3318578004837036, "5468": 0.013579257763922215, "5498": 0.5069117546081543, "5531": 0.37304413318634033, "5589": 0.24859806895256042, "5604": 0.6877616047859192, "5617": 0.09761575609445572, "5643": 0.2493593990802765, "5644": 0.8917738795280457, "5646": 0.05970508232712746, "5688": 0.13670019805431366, "5693": 0.7201237678527832, "5761": 0.053244512528181076, "5769": 0.3141832649707794, "5799": 0.33115679025650024, "5852": 0.4512746334075928, "5866": 0.2539152204990387, "5907": 0.3269403576850891, "5966": 0.3019835948944092, "5970": 0.2830325961112976, "6022": 0.8039615154266357, "6064": 0.4158279001712799, "6075": 0.8281423449516296, "6083": 0.44753631949424744, "6165": 0.10026945173740387, "6388": 0.1401015669107437, "6421": 0.7086513638496399, "6459": 0.06520967930555344, "6463": 0.09761575609445572, "6535": 0.36697331070899963, "6551": 0.12814582884311676, "6560": 0.26146242022514343, "6577": 0.757441520690918, "6592": 0.3982778787612915, "6602": 0.5579402446746826, "6605": 0.021256839856505394, "6612": 0.6926587820053101, "6640": 0.12384103983640671, "6694": 0.056018441915512085, "6721": 0.16690383851528168, "6747": 0.32553088665008545, "6779": 0.5415972471237183, "6818": 0.1677299439907074, "6839": 0.854249119758606, "6873": 0.04860413447022438, "6923": 0.2018241584300995, "6971": 0.32129061222076416, "6976": 0.03266380727291107, "6982": 0.0913962796330452, "7012": 0.28082266449928284, "7017": 0.6233867406845093, "7023": 1.0655186176300049, "7065": 0.016465263441205025, "7076": 0.12986256182193756, "7080": 0.6848117709159851, "7091": 0.47463157773017883, "7099": 0.9333322048187256, "7125": 0.18654440343379974, "7127": 0.12986256182193756, "7275": 0.21293537318706512, "7320": 0.23864774405956268, "7403": 0.9878844022750854, "7461": 0.31204116344451904, "7487": 0.05139094591140747, "7505": 0.08244366943836212, "7551": 0.29619070887565613, "7594": 0.1734936386346817, "7640": 0.2145126610994339, "7645": 0.2674594223499298, "7657": 0.09495500475168228, "7675": 0.1485546976327896, "7718": 0.6374238729476929, "7778": 0.14095009863376617, "7784": 0.1510767638683319, "7809": 0.013579257763922215, "7831": 0.5461324453353882, "7863": 0.6714286804199219, "7865": 0.15693697333335876, "7870": 0.3283478021621704, "7885": 0.30558720231056213, "7900": 0.1751343309879303, "7975": 0.29328158497810364, "8019": 0.22079704701900482, "8042": 0.09584271162748337, "8131": 0.2607102394104004, "8137": 0.04394211992621422, "8168": 1.0298984050750732, "8171": 0.6538092494010925, "8264": 0.9115922451019287, "8304": 0.8973627090454102, "8319": 0.3297532796859741, "8323": 0.4950772523880005, "8347": 0.4132472574710846, "8357": 0.07250232994556427, "8411": 0.09050461649894714, "8465": 0.0019512200960889459, "8554": 0.1889725625514984, "8715": 0.4330752193927765, "8756": 0.8247235417366028, "8761": 0.00875066313892603, "8776": 0.04860413447022438, "8817": 0.25845035910606384, "8832": 0.0797421783208847, "8945": 0.7144040465354919, "8971": 0.2954642176628113, "8985": 0.9417452812194824, "8991": 0.5882205963134766, "9007": 0.11778303235769272, "9096": 0.7755908370018005, "9104": 0.19782574474811554, "9165": 0.45499902963638306, "9183": 0.5021947622299194, "9227": 0.35334911942481995, "9289": 0.6882523894309998, "9398": 0.12986256182193756, "9431": 0.014542185701429844, "9532": 0.06977381557226181, "9539": 0.3106105625629425, "9556": 0.817850649356842, "9560": 0.09938567131757736, "9626": 0.07159364968538284, "9657": 0.07431721687316895, "9723": 0.04860413447022438, "9749": 1.246605634689331, "9762": 0.7445381283760071, "9800": 0.12038381397724152, "9839": 0.30558720231056213, "9908": 0.4450363218784332, "10003": 0.1332872211933136, "10035": 0.6573580503463745, "10056": 0.7201237678527832, "10091": 0.3297532796859741, "10174": 0.018384648486971855, "10197": 0.5979346632957458, "10327": 0.3982778787612915, "10372": 0.43244171142578125, "10439": 0.6275664567947388, "10497": 0.9209672808647156, "10505": 0.24325250089168549, "10640": 0.055094651877880096, "10698": 0.8433839678764343, "10744": 0.10731173306703568, "10758": 0.06520967930555344, "10817": 0.9310253858566284, "10847": 0.175953671336174, "10928": 0.02316705882549286, "10975": 1.105748176574707, "10993": 0.7951818704605103, "11100": 0.7201237678527832, "11119": 0.025073638185858727, "11156": 0.401551216840744, "11157": 0.7889899015426636, "11190": 0.043007105588912964, "11234": 0.7370892763137817, "11268": 0.004870930220931768, "11326": 0.255429208278656, "11331": 0.03360854089260101, "11363": 0.6096806526184082, "11375": 0.5098485946655273, "11383": 0.2160874605178833, "11498": 0.7592713832855225, "11518": 0.10291612148284912, "11629": 0.056018441915512085, "11707": 0.6451379656791687, "11748": 0.7463917136192322, "11767": 0.05417001247406006, "11860": 0.1734936386346817, "11867": 0.6075552701950073, "11899": 0.14602625370025635, "12115": 0.007782140281051397, "12210": 0.3339579105377197, "12265": 0.861702561378479, "12319": 0.42353010177612305, "12333": 0.030771657824516296, "12368": 0.3241194784641266, "12381": 0.15275461971759796, "12407": 0.02316705882549286, "12435": 0.3777405619621277, "12477": 0.0842406153678894, "12596": 0.1905880719423294, "12697": 0.009718249551951885, "12702": 0.29255300760269165, "12821": 1.0312920808792114, "12826": 0.255429208278656, "12876": 0.3127557039260864, "12898": 0.1229778528213501, "12980": 0.0029254043474793434, "13014": 0.07341018319129944, "13029": 0.08244366943836212, "13070": 0.09317722171545029, "13105": 0.06429435312747955, "13139": 0.4126010537147522, "13180": 0.2918238639831543, "13285": 0.06977381557226181, "13369": 0.02412080205976963, "13458": 0.2822965085506439, "13464": 0.1602703034877777, "13483": 1.020087480545044, "13494": 0.953857421875, "13599": 0.45994341373443604, "13767": 0.7898768186569214, "13874": 0.35677260160446167, "13964": 0.0317181795835495, "14025": 0.6833335757255554, "14028": 0.5438674688339233, "14155": 0.020300358533859253, "14168": 0.02792670577764511, "14267": 0.23710809648036957, "14378": 1.2375813722610474, "14402": 0.5925496220588684, "14405": 0.14518201351165771, "14471": 0.6296497583389282, "14494": 0.05970508232712746, "14506": 0.04207121208310127, "14592": 0.02412080205976963, "14639": 0.05786345899105072, "14800": 0.45251765847206116, "14817": 0.09584271162748337, "14906": 0.01934296265244484, "14949": 0.13071982562541962, "15069": 0.21687394380569458, "15113": 0.04767346754670143, "15157": 0.7934166193008423, "15170": 0.4318077862262726, "15245": 0.7370892763137817, "15258": 0.07793712615966797, "15306": 0.7220231294631958, "15356": 0.0797421783208847, "15379": 1.0768938064575195, "15396": 0.1677299439907074, "15543": 0.02887592278420925, "15596": 0.03266380727291107, "15725": 0.00875066313892603, "15877": 0.2447827309370041, "15900": 0.08782484382390976, "15923": 0.2607102394104004, "15982": 0.1485546976327896, "16014": 0.05970508232712746, "16015": 0.23402166366577148, "16211": 0.0058422754518687725, "16221": 0.4462870955467224, "16227": 0.7105726003646851, "16275": 1.0492360591888428, "16285": 0.02887592278420925, "16505": 0.034552380442619324, "16514": 0.6833335757255554, "16515": 0.3864043951034546, "16519": 0.026025565341114998, "16585": 0.7076893448829651, "16706": 0.2089812457561493, "16734": 0.07341018319129944, "16813": 0.08782484382390976, "16902": 0.0842406153678894, "16965": 0.13414156436920166, "17188": 0.13925230503082275, "17191": 0.14349138736724854, "17206": 0.7934166193008423, "17237": 0.22392450273036957, "17245": 0.022212404757738113, "17296": 0.6286086440086365, "17332": 0.00875066313892603, "17403": 0.1994270235300064, "17422": 0.0029254043474793434, "17503": 0.05139094591140747, "17599": 0.12986256182193756, "17696": 0.6202403903007507, "17867": 0.129004567861557, "17943": 0.3388410806655884, "18118": 0.755608320236206, "18191": 0.129004567861557, "18250": 0.020300358533859253, "18253": 0.17267228662967682, "18260": 0.14349138736724854, "18315": 0.8805016279220581, "18419": 0.09584271162748337, "18512": 0.2741633653640747, "18539": 0.2223619967699051, "18701": 0.1619328260421753, "18914": 0.8764448165893555, "18925": 0.9317949414253235, "18933": 0.7229714393615723, "18949": 0.34922540187835693, "19064": 0.151916041970253, "19106": 0.11343330889940262, "19173": 0.5092619061470032, "19195": 0.11951763927936554, "19314": 0.6989894509315491, "19345": 0.5267143249511719, "19429": 1.0409941673278809, "19470": 0.9739698171615601, "19476": 0.007782140281051397, "19539": 0.0058422754518687725, "19541": 0.3005385100841522, "19654": 0.36426326632499695, "19701": 0.1011524572968483, "20003": 0.3963087201118469, "20119": 0.08871890604496002, "20155": 0.15359249711036682, "20166": 0.8332487344741821, "20272": 1.276475191116333, "20311": 0.06886265426874161, "20464": 0.6759096384048462, "20534": 1.094698429107666, "20576": 0.04113444685935974, "20662": 0.25088030099868774, "20905": 0.2470736801624298, "20969": 0.2719337046146393, "21024": 0.5151132941246033, "21162": 0.08064348995685577, "21262": 0.08782484382390976, "21472": 0.10026945173740387, "21486": 0.05417001247406006, "21685": 0.040196798741817474, "21709": 0.0752234235405922, "21770": 0.3353555500507355, "21879": 0.10818854719400406, "21890": 0.762009859085083, "22107": 0.06886265426874161, "22199": 0.010684899985790253, "22203": 0.020300358533859253, "22524": 1.4311705827713013, "22571": 0.00875066313892603, "22578": 0.2018241584300995, "22631": 1.0907690525054932, "22796": 0.3084607720375061, "22835": 0.3241194784641266, "22865": 0.20977331697940826, "22931": 0.06154331564903259, "22963": 0.32270604372024536, "22993": 0.13157635927200317, "23041": 0.06977381557226181, "23150": 0.040196798741817474, "23169": 0.010684899985790253, "23283": 0.1221139207482338, "23350": 0.058784693479537964, "23368": 0.07159364968538284, "23522": 0.15943801403045654, "23900": 0.2719337046146393, "24004": 0.9900637865066528, "24155": 0.4412745535373688, "24269": 0.06703783571720123, "24558": 0.06703783571720123, "24624": 0.026025565341114998, "24854": 0.255429208278656, "24921": 0.22859740257263184, "25117": 0.018384648486971855, "25169": 0.08244366943836212, "25206": 0.08692999184131622, "25269": 0.007782140281051397, "25323": 0.4950772523880005, "25494": 0.04767346754670143, "25504": 0.08961215615272522, "25625": 0.14518201351165771, "25714": 0.0770333781838417, "25717": 0.8500841856002808, "25755": 0.055094651877880096, "25873": 0.8715548515319824, "25969": 0.565735399723053, "26013": 0.18492233753204346, "26267": 0.5957841277122498, "26305": 0.981317400932312, "26319": 0.0058422754518687725, "26591": 0.09050461649894714, "26728": 0.11343330889940262, "26741": 0.03360854089260101, "26835": 0.5168620347976685, "26847": 0.17020416259765625, "26874": 0.10993985831737518, "26927": 1.20182204246521, "26953": 0.30558720231056213, "27152": 0.0606246218085289, "27391": 0.18654440343379974, "27480": 0.026976587250828743, "27528": 0.036437395960092545, "27794": 0.9643365740776062, "28015": 0.1685553640127182, "28086": 0.13755162060260773, "28297": 0.23864774405956268, "28321": 0.0317181795835495, "28389": 0.5979346632957458, "28436": 0.24325250089168549, "28489": 0.15943801403045654, "28498": 0.32764431834220886, "28685": 0.4158279001712799, "28732": 0.8674615025520325, "28775": 0.3560888469219208, "28828": 0.5973974466323853, "28873": 0.1913948506116867, "28977": 0.25995752215385437, "29107": 0.09584271162748337, "29295": 0.12556517124176025} | 13734012 | OBJECTIVES To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments. DESIGN Irreversibly unlinked and anonymised large scale survey of archived appendix samples. SETTING Archived appendix samples from the pathology departments of 41 UK hospitals participating in the earlier survey, and additional hospitals in regions with lower levels of participation in that survey. SAMPLE 32,441 archived appendix samples fixed in formalin and embedded in paraffin and tested for the presence of abnormal prion protein (PrP). RESULTS Of the 32,441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million). The prevalence in those born in 1941-60 (733 per million, 269 to 1596 per million) did not differ significantly from those born between 1961 and 1985 (412 per million, 198 to 758 per million) and was similar in both sexes and across the three broad geographical areas sampled. Genetic testing of the positive specimens for the genotype at PRNP codon 129 revealed a high proportion that were valine homozygous compared with the frequency in the normal population, and in stark contrast with confirmed clinical cases of vCJD, all of which were methionine homozygous at PRNP codon 129. CONCLUSIONS This study corroborates previous studies and suggests a high prevalence of infection with abnormal PrP, indicating vCJD carrier status in the population compared with the 177 vCJD cases to date. These findings have important implications for the management of blood and blood products and for the handling of surgical instruments. | Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey |
{"1011": 0.2394166737794876, "1045": 0.11081436276435852, "1052": 0.6096806526184082, "1058": 0.3409265875816345, "1996": 0.06795065850019455, "1999": 0.5168620347976685, "2003": 0.016465263441205025, "2007": 0.2969166338443756, "2015": 0.25694093108177185, "2024": 0.1685553640127182, "2029": 0.15860503911972046, "2072": 0.6265231370925903, "2075": 0.00875066313892603, "2079": 0.04767346754670143, "2109": 0.12642613053321838, "2121": 0.4145384132862091, "2229": 0.15693697333335876, "2236": 0.013579257763922215, "2239": 0.762009859085083, "2378": 0.1751343309879303, "2458": 0.4855078160762787, "2470": 0.21372433006763458, "2483": 0.21135559678077698, "2515": 0.04860413447022438, "2522": 0.29400965571403503, "2529": 0.22626367211341858, "2535": 0.24325250089168549, "2590": 0.40089741349220276, "2666": 0.2539152204990387, "2764": 0.24401791393756866, "2817": 0.015504186972975731, "2820": 0.25845035910606384, "2828": 0.4093637466430664, "2897": 0.8264343738555908, "2913": 0.09317722171545029, "2920": 0.6522845029830933, "2944": 0.3388410806655884, "2951": 0.06429435312747955, "2953": 0.026976587250828743, "2966": 0.09850110858678818, "3070": 0.5244048833847046, "3141": 0.045809537172317505, "3161": 0.05417001247406006, "3273": 0.08513788133859634, "3319": 0.15275461971759796, "3370": 0.11081436276435852, "3378": 0.7314660549163818, "3426": 0.151916041970253, "3433": 0.025073638185858727, "3435": 0.6664261221885681, "3457": 0.06429435312747955, "3466": 0.05694137513637543, "3526": 0.8366385698318481, "3563": 0.2711893916130066, "3625": 0.1384023278951645, "3676": 0.8264343738555908, "3751": 0.004870930220931768, "3853": 0.6054253578186035, "3893": 0.8255793452262878, "3896": 0.11256109178066254, "3949": 0.35403475165367126, "4022": 0.27712854743003845, "4108": 0.007782140281051397, "4111": 0.5092619061470032, "4127": 0.371698260307312, "4167": 0.791648268699646, "4176": 0.5301685929298401, "4195": 0.07250232994556427, "4198": 0.26446542143821716, "4275": 0.3027053773403168, "4286": 0.4500300884246826, "4295": 0.30558720231056213, "4372": 0.006812678650021553, "4400": 0.14095009863376617, "4402": 0.19782574474811554, "4434": 0.3381449282169342, "4442": 1.001607894897461, "4454": 0.1889725625514984, "4503": 0.3381449282169342, "4588": 0.10818854719400406, "4654": 0.3870677351951599, "4722": 0.02792670577764511, "4742": 0.7028654217720032, "4796": 0.03831886500120163, "4903": 0.03360854089260101, "4942": 0.6950984001159668, "4957": 0.129004567861557, "4958": 0.9155091643333435, "4962": 0.3662964701652527, "4972": 0.34300774335861206, "4975": 0.32341301441192627, "4984": 0.08603433519601822, "5013": 0.28155985474586487, "5197": 0.09228714555501938, "5285": 0.21765978634357452, "5320": 0.15359249711036682, "5387": 0.23015019297599792, "5408": 0.11517547070980072, "5514": 0.10906458646059036, "5644": 0.8592242002487183, "5799": 0.3963087201118469, "5833": 0.2026219218969345, "5901": 0.10731173306703568, "5915": 0.28963330388069153, "5943": 0.5805994272232056, "5975": 0.1685553640127182, "5992": 0.11604541540145874, "6091": 0.5584990978240967, "6125": 0.574020504951477, "6137": 0.3956514894962311, "6204": 0.2026219218969345, "6364": 0.5618454217910767, "6377": 0.026025565341114998, "6388": 0.5876781344413757, "6473": 0.28082266449928284, "6591": 0.05694137513637543, "6825": 0.1064341589808464, "6895": 0.38374659419059753, "6970": 0.4481603503227234, "7012": 0.020300358533859253, "7076": 0.1994270235300064, "7077": 0.4132472574710846, "7242": 0.41195443272590637, "7297": 0.056018441915512085, "7336": 0.02412080205976963, "7337": 0.26446542143821716, "7356": 0.052318159490823746, "7368": 0.5778634548187256, "7403": 0.7191727757453918, "7438": 0.2954642176628113, "7461": 0.0606246218085289, "7484": 0.11951763927936554, "7532": 0.12038381397724152, "7551": 0.31132611632347107, "7568": 0.24018502235412598, "7591": 0.06429435312747955, "7645": 0.06612417846918106, "7711": 0.18329764902591705, "7755": 0.5438674688339233, "7768": 0.38574060797691345, "7816": 0.6006163358688354, "7870": 0.23479416966438293, "7885": 0.4425300657749176, "7900": 0.055094651877880096, "7915": 0.2493593990802765, "8010": 0.5151132941246033, "8062": 0.1677299439907074, "8092": 0.026976587250828743, "8109": 0.23247487843036652, "8153": 0.06612417846918106, "8360": 0.3547199070453644, "8569": 0.9417452812194824, "8571": 0.11778303235769272, "8715": 0.06246116757392883, "8761": 0.43623676896095276, "8776": 0.2637155055999756, "8878": 0.053244512528181076, "9007": 0.02792670577764511, "9094": 0.0317181795835495, "9113": 0.6558387279510498, "9125": 0.21687394380569458, "9165": 0.32764431834220886, "9230": 0.0606246218085289, "9289": 0.7220231294631958, "9331": 0.6139179468154907, "9412": 0.27712854743003845, "9463": 1.1413075923919678, "9808": 0.637939989566803, "10004": 0.4196864068508148, "10020": 0.7463917136192322, "10163": 0.034552380442619324, "10175": 1.173231601715088, "10285": 0.18411032855510712, "10502": 0.026976587250828743, "10572": 0.12384103983640671, "10595": 0.011650617234408855, "10699": 0.6075552701950073, "10708": 0.03925827145576477, "10738": 0.5318912267684937, "10744": 0.020300358533859253, "10769": 0.14095009863376617, "10810": 1.4293015003204346, "10840": 0.47158926725387573, "10976": 0.24018502235412598, "11211": 0.08961215615272522, "11236": 1.0485517978668213, "11265": 0.3283478021621704, "11383": 0.3084607720375061, "11486": 0.02887592278420925, "11498": 0.045809537172317505, "11721": 1.0695481300354004, "11791": 0.1384023278951645, "11835": 0.052318159490823746, "11867": 0.6764062643051147, "11968": 0.9710156321525574, "12123": 0.23247487843036652, "12222": 0.5646255612373352, "12247": 0.33115679025650024, "12285": 0.2539152204990387, "12328": 0.03925827145576477, "12432": 0.07884006202220917, "12436": 0.26446542143821716, "12644": 0.05786345899105072, "12732": 0.02316705882549286, "12827": 0.03360854089260101, "12863": 0.9052929878234863, "12997": 0.02792670577764511, "13026": 0.2918238639831543, "13091": 1.0298984050750732, "13228": 0.025073638185858727, "13441": 0.05786345899105072, "13617": 0.010684899985790253, "13782": 0.16359257698059082, "13791": 0.08871890604496002, "13833": 0.4330752193927765, "13866": 0.2317005842924118, "13874": 0.6999598741531372, "13907": 0.06977381557226181, "13908": 0.32129061222076416, "13995": 0.2105647772550583, "14048": 0.554580807685852, "14353": 0.4654768109321594, "14397": 0.3409265875816345, "14471": 0.2763880789279938, "14800": 0.26446542143821716, "14828": 0.13670019805431366, "14955": 0.3177432417869568, "14982": 0.24018502235412598, "14988": 0.9432673454284668, "15074": 0.004870930220931768, "15115": 0.19381128251552582, "15176": 0.4837033152580261, "15185": 0.39762192964553833, "15527": 0.052318159490823746, "15543": 0.16524957120418549, "15660": 0.2674594223499298, "15698": 0.7295845746994019, "15756": 0.21687394380569458, "15850": 0.011650617234408855, "15918": 0.12728634476661682, "15965": 0.5197699069976807, "16021": 1.4450790882110596, "16175": 0.04767346754670143, "16221": 0.24631060659885406, "16910": 0.0354953333735466, "16915": 0.010684899985790253, "17132": 0.02792670577764511, "17261": 0.3141832649707794, "17379": 0.07431721687316895, "17471": 0.9485763907432556, "17727": 0.13499516248703003, "17880": 0.053244512528181076, "18075": 1.0030416250228882, "18163": 0.06612417846918106, "18234": 1.02149498462677, "18419": 0.045809537172317505, "18439": 0.022212404757738113, "18509": 0.18329764902591705, "18609": 0.9186317324638367, "18634": 1.0271050930023193, "18719": 0.17840765416622162, "18809": 0.33115679025650024, "18922": 0.0019512200960889459, "18924": 0.03360854089260101, "19087": 0.1905880719423294, "19184": 0.034552380442619324, "19220": 0.15860503911972046, "19345": 0.27786844968795776, "19470": 0.06337817758321762, "19565": 0.0009760859538801014, "19601": 0.11691460013389587, "19872": 0.02412080205976963, "19962": 0.5370414853096008, "20011": 0.4794800877571106, "20014": 0.07793712615966797, "20064": 0.04394211992621422, "20310": 0.07612881064414978, "20350": 0.6833335757255554, "20382": 1.0158531665802002, "20467": 0.151916041970253, "20746": 0.512191891670227, "20770": 0.02316705882549286, "20831": 0.7295845746994019, "20858": 0.6338034868240356, "20868": 0.4067663550376892, "21017": 0.6823468804359436, "21210": 0.49982786178588867, "21371": 0.09938567131757736, "21449": 0.39696553349494934, "21541": 0.14433705806732178, "21575": 0.4318077862262726, "21618": 1.0312920808792114, "21738": 0.20739519596099854, "21821": 0.1485546976327896, "21877": 0.2394166737794876, "21903": 0.006812678650021553, "22261": 0.20421554148197174, "22291": 0.42096930742263794, "22676": 0.09672962874174118, "22834": 0.4500300884246826, "22930": 0.5472630262374878, "23041": 0.08154398202896118, "23068": 0.05046287178993225, "23150": 0.10555581003427505, "23200": 0.02412080205976963, "23216": 0.3757305145263672, "23900": 0.18411032855510712, "23993": 0.013579257763922215, "24054": 0.3963087201118469, "24312": 0.1064341589808464, "24582": 0.14433705806732178, "25172": 0.8212929964065552, "25194": 0.40481385588645935, "25204": 1.229617714881897, "25212": 0.1734936386346817, "25456": 0.12556517124176025, "25644": 1.0257055759429932, "25710": 0.8161250352859497, "25750": 1.0775588750839233, "25946": 0.9747070074081421, "26189": 1.6371746063232422, "26243": 0.906871497631073, "26288": 0.03266380727291107, "26305": 0.17431432008743286, "26476": 0.06520967930555344, "26497": 0.567397952079773, "26512": 0.06795065850019455, "26572": 0.500420093536377, "26744": 0.0770333781838417, "26773": 0.5887627601623535, "27169": 0.4494072198867798, "27287": 0.25995752215385437, "27295": 0.24554696679115295, "27427": 0.40546512603759766, "27969": 0.08871890604496002, "27989": 0.12728634476661682, "28173": 0.43244171142578125, "28210": 0.11604541540145874, "28228": 0.8853482007980347, "28466": 0.823009729385376, "28688": 0.08782484382390976, "28767": 0.0606246218085289, "28788": 0.35334911942481995, "28828": 0.15275461971759796, "28879": 0.025073638185858727, "28927": 0.12470348179340363, "29398": 0.19622190296649933, "29536": 0.22079704701900482, "29577": 0.05417001247406006} | 13757347 | GABAergic interneurons of the parvalbumin-positive fast-spiking basket cells subtype (PV INs) are important regulators of cortical network excitability and of gamma oscillations, involved in signal processing and cognition. Impaired development or function of PV INs has been associated with epilepsy in various animal models of epilepsy, as well as in some genetic forms of epilepsy in humans. In this review, we provide an overview of some of the experimental data linking PV INs dysfunction with epilepsy, focusing on disorders of the specification, migration, maturation, synaptic function, or connectivity of PV INs. Furthermore, we reflect on the potential therapeutic use of cell-type specific stimulation of PV INs within active networks and on the transplantation of PV INs precursors in the treatment of epilepsy and its comorbidities. | Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy. |
{"1011": 0.2531573474407196, "1019": 0.08603433519601822, "1044": 0.7710843086242676, "2000": 0.08603433519601822, "2005": 0.04953393340110779, "2011": 0.1808556467294693, "2013": 0.11343330889940262, "2026": 0.8517522215843201, "2029": 0.30558720231056213, "2033": 0.0752234235405922, "2046": 0.40741631388664246, "2051": 0.5784112811088562, "2064": 0.31132611632347107, "2076": 0.02316705882549286, "2083": 0.43434104323387146, "2090": 0.27342069149017334, "2101": 0.11604541540145874, "2109": 0.13414156436920166, "2110": 0.37640097737312317, "2129": 0.2667117714881897, "2140": 0.5381823778152466, "2146": 0.6139179468154907, "2152": 0.1930064558982849, "2154": 0.037378571927547455, "2163": 0.09938567131757736, "2182": 0.22782009840011597, "2186": 0.7009293437004089, "2203": 0.6476961374282837, "2241": 0.5789587497711182, "2278": 0.48430517315864563, "2335": 0.15943801403045654, "2362": 0.036437395960092545, "2367": 0.5255602598190308, "2389": 0.1930064558982849, "2407": 0.25088030099868774, "2411": 0.09761575609445572, "2420": 0.4067663550376892, "2424": 0.040196798741817474, "2478": 0.1685553640127182, "2491": 0.151916041970253, "2529": 0.6312094330787659, "2535": 0.03360854089260101, "2575": 0.20580662786960602, "2582": 0.3297532796859741, "2592": 0.15777134895324707, "2618": 0.3106105625629425, "2668": 0.2145126610994339, "2685": 0.08961215615272522, "2689": 0.0009760859538801014, "2692": 0.026025565341114998, "2750": 0.07431721687316895, "2771": 0.037378571927547455, "2784": 0.2763880789279938, "2828": 0.10906458646059036, "2832": 0.04207121208310127, "2855": 0.043007105588912964, "2897": 1.0695481300354004, "2920": 0.007782140281051397, "2944": 0.2034190446138382, "2951": 0.9333322048187256, "3145": 0.36426326632499695, "3227": 0.472198486328125, "3231": 0.056018441915512085, "3351": 0.47463157773017883, "3366": 0.17020416259765625, "3431": 0.32553088665008545, "3433": 0.674915611743927, "3435": 0.016465263441205025, "3438": 1.0423725843429565, "3526": 0.9317949414253235, "3584": 0.12470348179340363, "3593": 0.6244332790374756, "3670": 0.8989537954330444, "3697": 0.2830325961112976, "3921": 0.39762192964553833, "4009": 0.21135559678077698, "4050": 0.03360854089260101, "4081": 0.08154398202896118, "4106": 0.20580662786960602, "4117": 0.2539152204990387, "4118": 0.037378571927547455, "4119": 0.47463157773017883, "4127": 0.26296505331993103, "4130": 0.47402387857437134, "4135": 0.7144040465354919, "4160": 0.8893690705299377, "4286": 0.5215105414390564, "4442": 0.9287132620811462, "4515": 0.29255300760269165, "4539": 0.5957841277122498, "4566": 0.13499516248703003, "4663": 0.03360854089260101, "4668": 0.14349138736724854, "4671": 0.13670019805431366, "4719": 0.4337083101272583, "4725": 0.09406650811433792, "4758": 0.4286321699619293, "4904": 0.672426164150238, "4962": 1.207676887512207, "5158": 0.1384023278951645, "5159": 0.04394211992621422, "5173": 0.9115922451019287, "5182": 0.18978065252304077, "5228": 0.2539152204990387, "5257": 0.18816383183002472, "5258": 0.2652147710323334, "5292": 0.03925827145576477, "5387": 0.5707147121429443, "5402": 0.016465263441205025, "5449": 0.007782140281051397, "5461": 0.02412080205976963, "5537": 0.791648268699646, "5604": 0.012615402229130268, "5666": 1.0158531665802002, "5769": 0.036437395960092545, "5876": 0.6543170213699341, "5901": 0.36086538434028625, "5915": 0.6435998678207397, "5957": 0.6538092494010925, "5966": 0.38574060797691345, "5967": 0.004870930220931768, "5995": 0.7258110046386719, "6028": 0.1930064558982849, "6064": 0.6461620330810547, "6083": 0.19862671196460724, "6125": 1.0735615491867065, "6162": 0.6181373596191406, "6337": 0.6482070088386536, "6459": 0.04953393340110779, "6502": 0.18167030811309814, "6529": 0.026025565341114998, "6592": 0.2659635543823242, "6672": 1.06619131565094, "6869": 0.4286321699619293, "6914": 0.08244366943836212, "6939": 0.08064348995685577, "6968": 0.0058422754518687725, "7012": 0.09850110858678818, "7040": 0.42096930742263794, "7077": 0.1064341589808464, "7096": 0.02412080205976963, "7264": 0.1212492436170578, "7274": 0.1751343309879303, "7337": 0.2447827309370041, "7356": 0.016465263441205025, "7366": 0.34508460760116577, "7367": 0.9302552938461304, "7403": 1.0073304176330566, "7512": 0.7153595685958862, "7578": 0.3810817003250122, "7642": 0.06703783571720123, "7645": 0.1011524572968483, "7711": 0.46608972549438477, "7755": 0.011650617234408855, "7801": 0.33675122261047363, "7809": 0.33953672647476196, "7816": 0.9827804565429688, "7860": 0.6139179468154907, "7872": 0.0770333781838417, "7885": 0.10291612148284912, "7889": 0.678390383720398, "7908": 0.06154331564903259, "7915": 0.013579257763922215, "8107": 0.2990913391113281, "8114": 0.22079704701900482, "8122": 0.015504186972975731, "8153": 0.14686977863311768, "8315": 0.12470348179340363, "8442": 0.2231435477733612, "8449": 0.8989537954330444, "8516": 0.036437395960092545, "8581": 0.2184450328350067, "8735": 1.0151457786560059, "8790": 1.1005635261535645, "8885": 0.02887592278420925, "8991": 0.5438674688339233, "9007": 0.2105647772550583, "9031": 0.06977381557226181, "9099": 0.1808556467294693, "9165": 1.117316484451294, "9367": 0.1358480453491211, "9416": 0.2852376699447632, "9420": 0.02412080205976963, "9597": 0.15275461971759796, "9756": 0.011650617234408855, "9821": 0.4537591338157654, "9896": 0.22548456490039825, "10071": 0.5162794589996338, "10318": 0.7610978484153748, "10368": 0.4617912769317627, "10381": 0.5662899017333984, "10448": 0.1718502640724182, "10483": 0.04674193635582924, "10509": 0.20022670924663544, "10595": 0.1332872211933136, "10610": 0.08513788133859634, "10738": 1.2671676874160767, "10744": 0.13499516248703003, "10769": 0.3374483287334442, "10782": 0.034552380442619324, "10910": 0.3897167444229126, "10949": 0.7827593088150024, "10960": 0.34300774335861206, "11143": 0.30989447236061096, "11163": 0.12470348179340363, "11211": 0.10555581003427505, "11234": 0.23324857652187347, "11265": 0.638455867767334, "11423": 0.4067663550376892, "11506": 0.13499516248703003, "11566": 0.6064908504486084, "11619": 0.07250232994556427, "11643": 0.09050461649894714, "11658": 0.036437395960092545, "11767": 0.010684899985790253, "11949": 0.22782009840011597, "12115": 0.6441128253936768, "12153": 0.24554696679115295, "12222": 0.9147270321846008, "12477": 0.08782484382390976, "12562": 0.4462870955467224, "12732": 0.2954642176628113, "12740": 0.13755162060260773, "12789": 0.014542185701429844, "12793": 0.09938567131757736, "12987": 1.034073829650879, "13045": 0.006812678650021553, "13100": 0.07159364968538284, "13248": 0.255429208278656, "13321": 0.7352184057235718, "13330": 0.00875066313892603, "13458": 0.43053874373435974, "13585": 0.04394211992621422, "13791": 0.1401015669107437, "13792": 0.08603433519601822, "13819": 0.053244512528181076, "13833": 0.4537591338157654, "14026": 0.052318159490823746, "14048": 0.7934166193008423, "14120": 0.41195443272590637, "14126": 0.0842406153678894, "14164": 0.1384023278951645, "14193": 1.0526502132415771, "14386": 0.13925230503082275, "14443": 0.030771657824516296, "14471": 0.6430866718292236, "14570": 0.1212492436170578, "14613": 0.08603433519601822, "14800": 0.3077431619167328, "14828": 0.40089741349220276, "14858": 0.3777405619621277, "14949": 0.15526613593101501, "14988": 0.02792670577764511, "15059": 0.39367714524269104, "15070": 0.03266380727291107, "15113": 0.2674594223499298, "15176": 0.8772575259208679, "15370": 0.9194108247756958, "15543": 0.2674594223499298, "15643": 0.0029254043474793434, "16001": 0.09938567131757736, "16012": 0.04674193635582924, "16014": 0.14518201351165771, "16026": 0.04953393340110779, "16086": 0.7528522610664368, "16134": 0.018384648486971855, "16221": 0.04394211992621422, "16285": 0.037378571927547455, "16387": 0.8057082891464233, "16412": 0.12986256182193756, "16463": 0.012615402229130268, "16599": 0.02792670577764511, "16706": 0.2231435477733612, "16745": 0.8004589080810547, "16840": 0.30989447236061096, "16910": 0.22157983481884003, "17183": 0.19381128251552582, "17250": 0.38374659419059753, "17409": 0.009718249551951885, "17441": 0.04674193635582924, "17879": 0.7047978043556213, "18228": 0.3923587501049042, "18349": 1.2381477355957031, "18547": 0.7389566898345947, "18780": 1.035461664199829, "18847": 0.9568626880645752, "18963": 0.14264501631259918, "18981": 0.6674286723136902, "19220": 0.9178520441055298, "19293": 0.5027855634689331, "19345": 0.5074998140335083, "19466": 0.969535231590271, "19653": 0.07250232994556427, "19723": 0.255429208278656, "19780": 0.030771657824516296, "20155": 0.030771657824516296, "20287": 0.20501139760017395, "20341": 0.06246116757392883, "20350": 0.1602703034877777, "20363": 0.8949713706970215, "20576": 0.1693800985813141, "20582": 1.3433949947357178, "20752": 0.0019512200960889459, "20852": 0.33675122261047363, "20858": 0.129004567861557, "20877": 1.0001721382141113, "21032": 0.7755908370018005, "21095": 0.175953671336174, "21179": 0.0058422754518687725, "21575": 0.7163142561912537, "21618": 0.6451379656791687, "21647": 0.6921701431274414, "21716": 0.940220832824707, "21738": 0.053244512528181076, "21890": 0.8965662121772766, "21903": 0.20022670924663544, "21919": 0.1510767638683319, "22239": 0.6218147873878479, "22248": 0.33953672647476196, "22330": 0.2470736801624298, "22422": 0.05786345899105072, "23147": 0.11778303235769272, "23216": 0.10291612148284912, "23661": 0.4938860833644867, "23758": 0.13670019805431366, "23924": 0.20421554148197174, "24051": 0.272677481174469, "24319": 1.197703242301941, "24374": 0.8433839678764343, "24396": 0.2659635543823242, "24558": 1.072225570678711, "24629": 0.619189441204071, "24848": 0.23864774405956268, "24873": 0.18167030811309814, "24908": 0.011650617234408855, "25194": 0.2034190446138382, "25468": 0.4248080551624298, "25524": 0.05970508232712746, "25644": 0.4914994537830353, "26236": 0.3070250153541565, "26268": 0.045809537172317505, "26520": 0.2493593990802765, "26524": 0.03925827145576477, "26534": 0.18573370575904846, "26632": 0.9687942266464233, "26651": 0.2501201331615448, "26702": 0.014542185701429844, "26713": 0.06795065850019455, "26773": 0.8592242002487183, "26775": 0.42096930742263794, "27152": 0.22548456490039825, "27321": 0.979118824005127, "27343": 0.23402166366577148, "27572": 0.022212404757738113, "27642": 0.03831886500120163, "28024": 0.7791815400123596, "28086": 0.07612881064414978, "28404": 0.12384103983640671, "28436": 0.14095009863376617, "28788": 0.5244048833847046, "28848": 0.29981520771980286, "29206": 0.01934296265244484, "29458": 0.11343330889940262, "29533": 1.1487655639648438} | 13759726 | The reconstruction of gene regulatory networks underlying cell differentiation from high-throughput gene expression and chromatin data remains a challenge. Here, we derive dynamic gene regulatory networks for human myeloid differentiation using a 5-day time series of RNA-seq and ATAC-seq data. We profile HL-60 promyelocytes differentiating into macrophages, neutrophils, monocytes, and monocyte-derived macrophages. We find a rapid response in the expression of key transcription factors and lineage markers that only regulate a subset of their targets at a given time, which is followed by chromatin accessibility changes that occur later along with further gene expression changes. We observe differences between promyelocyte- and monocyte-derived macrophages at both the transcriptional and chromatin landscape level, despite using the same differentiation stimulus, which suggest that the path taken by cells in the differentiation landscape defines their end cell state. More generally, our approach of combining neighboring time points and replicates to achieve greater sequencing depth can efficiently infer footprint-based regulatory networks from long series data. | Dynamic Gene Regulatory Networks of Human Myeloid Differentiation. |
{"1006": 0.10291612148284912, "1009": 0.6709295511245728, "1011": 0.15526613593101501, "1016": 0.5174443125724792, "1019": 0.0038986403960734606, "1997": 0.04674193635582924, "1999": 0.09317722171545029, "2004": 0.6149744987487793, "2005": 0.06337817758321762, "2007": 0.27934664487838745, "2011": 0.4734157919883728, "2029": 0.3560888469219208, "2030": 0.9037119746208191, "2036": 0.3883931338787079, "2043": 0.00875066313892603, "2048": 0.3910386264324188, "2058": 0.5957841277122498, "2075": 0.1734936386346817, "2076": 0.17840765416622162, "2091": 0.41065993905067444, "2117": 0.02887592278420925, "2119": 0.25995752215385437, "2124": 0.2478361576795578, "2129": 0.0842406153678894, "2139": 0.9115922451019287, "2140": 0.5376120805740356, "2169": 0.09672962874174118, "2207": 0.6420594453811646, "2232": 0.2918238639831543, "2240": 0.2034190446138382, "2339": 0.1229778528213501, "2358": 0.5336109399795532, "2378": 0.46608972549438477, "2475": 0.4679262638092041, "2487": 0.6471850275993347, "2490": 0.2447827309370041, "2509": 0.5893046259880066, "2515": 0.05970508232712746, "2535": 0.10467668622732162, "2550": 0.0354953333735466, "2556": 0.23092569410800934, "2566": 0.6420594453811646, "2629": 0.7647408246994019, "2662": 0.21687394380569458, "2713": 0.8821197748184204, "2804": 0.371698260307312, "2832": 0.043007105588912964, "2895": 0.19782574474811554, "2920": 0.25239890813827515, "2981": 0.020300358533859253, "3039": 0.2969166338443756, "3085": 0.6332852244377136, "3133": 0.08064348995685577, "3149": 1.1102628707885742, "3161": 0.32129061222076416, "3169": 0.4709797203540802, "3210": 0.06977381557226181, "3258": 0.7629209756851196, "3283": 0.11343330889940262, "3370": 0.06612417846918106, "3378": 0.34300774335861206, "3426": 0.0058422754518687725, "3433": 0.7978238463401794, "3491": 0.1946154683828354, "3497": 0.034552380442619324, "3498": 0.8022117614746094, "3499": 0.5324648022651672, "3525": 0.2501201331615448, "3526": 0.8247235417366028, "3569": 0.08154398202896118, "3573": 0.7987030148506165, "3605": 0.09938567131757736, "3615": 0.5092619061470032, "3625": 0.2184450328350067, "3686": 0.14095009863376617, "3739": 0.4818955361843109, "3853": 0.19622190296649933, "4005": 0.7144040465354919, "4022": 0.6181373596191406, "4048": 0.4400174915790558, "4064": 0.8641747236251831, "4072": 0.13071982562541962, "4078": 0.319873183965683, "4081": 0.009718249551951885, "4168": 0.7144040465354919, "4211": 0.5822374224662781, "4352": 0.18167030811309814, "4442": 0.8780695199966431, "4443": 0.9915141463279724, "4473": 0.5433003902435303, "4496": 0.0752234235405922, "4523": 0.6054253578186035, "4525": 0.016465263441205025, "4607": 0.6704301834106445, "4668": 0.4437839686870575, "4742": 0.7601850032806396, "4745": 0.15275461971759796, "4796": 0.3683255612850189, "4886": 1.259437084197998, "4937": 0.5528968572616577, "4962": 0.10906458646059036, "5034": 1.0506030321121216, "5072": 0.20739519596099854, "5158": 0.1970241367816925, "5250": 0.5662899017333984, "5258": 0.23556606471538544, "5320": 0.21372433006763458, "5324": 0.6754127144813538, "5387": 0.2018241584300995, "5393": 0.11951763927936554, "5416": 0.0770333781838417, "5449": 0.018384648486971855, "5450": 0.3910386264324188, "5452": 0.45499902963638306, "5478": 0.24401791393756866, "5482": 0.272677481174469, "5527": 0.18411032855510712, "5675": 0.009718249551951885, "5714": 0.8500841856002808, "5738": 0.4944818615913391, "5741": 0.04767346754670143, "5748": 0.2493593990802765, "5769": 0.20977331697940826, "5838": 0.1401015669107437, "5850": 0.06429435312747955, "5876": 0.07159364968538284, "5942": 0.16442140936851501, "6074": 0.5871354341506958, "6083": 0.06612417846918106, "6164": 0.3005385100841522, "6177": 0.6118015646934509, "6187": 0.9886114001274109, "6245": 0.2983669638633728, "6327": 0.757441520690918, "6370": 0.08603433519601822, "6573": 0.804835319519043, "6592": 0.20580662786960602, "6740": 0.2317005842924118, "6753": 0.12038381397724152, "6774": 0.4132472574710846, "6827": 0.6338034868240356, "6833": 1.001607894897461, "6869": 0.48068851232528687, "6872": 0.11256109178066254, "6911": 0.1064341589808464, "6922": 0.47158926725387573, "6942": 0.011650617234408855, "6958": 0.15442965924739838, "7013": 0.12470348179340363, "7077": 0.11343330889940262, "7082": 0.4770587682723999, "7085": 0.6629094481468201, "7096": 0.015504186972975731, "7324": 1.1702059507369995, "7337": 1.0409941673278809, "7366": 0.08513788133859634, "7388": 0.32129061222076416, "7461": 0.0797421783208847, "7473": 0.08871890604496002, "7485": 0.10731173306703568, "7614": 0.05786345899105072, "7645": 0.6128603219985962, "7654": 0.026025565341114998, "7711": 0.1751343309879303, "7755": 0.5947071313858032, "7790": 1.0788878202438354, "7816": 0.1677299439907074, "8010": 0.26296505331993103, "8039": 0.5127768516540527, "8089": 0.3034266233444214, "8153": 0.27342069149017334, "8171": 0.6603899002075195, "8250": 0.5016035437583923, "8287": 0.37035053968429565, "8290": 0.08244366943836212, "8292": 0.009718249551951885, "8303": 0.35950297117233276, "8470": 0.22626367211341858, "8496": 0.5104349255561829, "8878": 1.1281205415725708, "9006": 0.083342544734478, "9007": 0.5209306478500366, "9041": 0.4337083101272583, "9228": 0.4734157919883728, "9276": 0.10906458646059036, "9323": 0.11430477350950241, "9330": 0.22937409579753876, "9350": 0.9583619832992554, "9412": 0.29981520771980286, "9420": 0.4330752193927765, "9495": 0.18167030811309814, "9513": 0.3554046154022217, "9597": 0.28082266449928284, "9699": 0.3877306580543518, "9832": 0.3870677351951599, "9997": 0.026025565341114998, "10163": 0.29109421372413635, "10250": 0.32058215141296387, "10288": 0.7124901413917542, "10445": 0.6048921346664429, "10507": 0.056018441915512085, "10509": 0.37102460861206055, "10572": 0.306306391954422, "10580": 0.18816383183002472, "10591": 0.7898768186569214, "10595": 0.812664806842804, "10623": 0.8264343738555908, "10738": 0.06246116757392883, "10744": 0.09761575609445572, "10769": 0.817850649356842, "10960": 0.4425300657749176, "11160": 0.4374985992908478, "11211": 0.16690383851528168, "11231": 1.0802149772644043, "11240": 0.8925741910934448, "11369": 0.6654226183891296, "11432": 0.6833335757255554, "11598": 0.619189441204071, "11655": 0.007782140281051397, "11717": 0.021256839856505394, "11835": 0.11951763927936554, "11937": 0.19381128251552582, "12141": 0.013579257763922215, "12222": 0.05046287178993225, "12247": 0.2105647772550583, "12328": 0.06977381557226181, "12403": 0.20818853378295898, "12495": 0.1602703034877777, "12530": 0.6989894509315491, "12562": 0.12986256182193756, "12732": 0.16359257698059082, "12943": 1.0409941673278809, "12987": 0.861702561378479, "13330": 0.12470348179340363, "13340": 1.0927356481552124, "13490": 1.076228141784668, "13538": 0.04207121208310127, "13595": 0.07431721687316895, "13773": 0.08603433519601822, "13776": 0.36494144797325134, "13791": 0.8901712894439697, "13806": 0.10467668622732162, "13831": 0.7863243818283081, "13833": 0.8264343738555908, "13853": 1.3745063543319702, "13911": 0.0354953333735466, "13922": 0.1685553640127182, "14120": 0.47036975622177124, "14193": 0.3070250153541565, "14313": 0.04394211992621422, "14505": 0.176772341132164, "14760": 0.22626367211341858, "14828": 0.4855078160762787, "14932": 0.18248429894447327, "15042": 1.1211429834365845, "15115": 0.043007105588912964, "15166": 0.37304413318634033, "15429": 1.6078741550445557, "15445": 0.2026219218969345, "15593": 0.09672962874174118, "15663": 0.3019835948944092, "15680": 0.07250232994556427, "15698": 0.016465263441205025, "15849": 0.018384648486971855, "15946": 0.09584271162748337, "15956": 0.1384023278951645, "16119": 0.0029254043474793434, "16136": 0.5811457633972168, "16285": 0.16276304423809052, "16305": 0.1011524572968483, "16389": 0.015504186972975731, "16412": 0.15442965924739838, "16453": 0.08692999184131622, "16639": 0.07250232994556427, "16691": 0.15943801403045654, "16771": 0.08603433519601822, "16803": 0.3777405619621277, "16882": 0.9287132620811462, "16910": 0.09761575609445572, "16952": 0.12038381397724152, "17379": 0.3388410806655884, "17441": 0.6369074583053589, "17603": 0.3241194784641266, "17643": 1.1935672760009766, "17820": 0.2830325961112976, "17830": 0.06977381557226181, "17890": 0.23787821829319, "18050": 1.0979610681533813, "18084": 0.0317181795835495, "18287": 0.009718249551951885, "18562": 0.9092346429824829, "18622": 0.7276995778083801, "18642": 0.13071982562541962, "18714": 0.6327666640281677, "19220": 0.35745587944984436, "19419": 0.8500841856002808, "19421": 0.15860503911972046, "19601": 0.13499516248703003, "19653": 0.4330752193927765, "19696": 0.007782140281051397, "19811": 0.02412080205976963, "19817": 0.9217445850372314, "19872": 0.4158279001712799, "20110": 0.8877626657485962, "20350": 0.12986256182193756, "20382": 0.016465263441205025, "20544": 0.7144040465354919, "20752": 0.47827014327049255, "20817": 0.02316705882549286, "20858": 0.603290855884552, "21017": 0.12814582884311676, "21144": 0.841701865196228, "21145": 0.36290550231933594, "21466": 0.25467249751091003, "21618": 0.22937409579753876, "21758": 0.3346569836139679, "21764": 0.3304552733898163, "21903": 0.36967599391937256, "21919": 0.3269403576850891, "21963": 0.30558720231056213, "21967": 0.45499902963638306, "22239": 0.02792670577764511, "22248": 0.36426326632499695, "22260": 0.06977381557226181, "22261": 0.04487626627087593, "22731": 0.13243216276168823, "22794": 1.0312920808792114, "22930": 0.27786844968795776, "23216": 0.7144040465354919, "23586": 0.5145297050476074, "23692": 0.055094651877880096, "23722": 0.034552380442619324, "23807": 0.058784693479537964, "23977": 0.006812678650021553, "24054": 0.9798521995544434, "24312": 0.07612881064414978, "24394": 0.21372433006763458, "24411": 0.030771657824516296, "24554": 0.02316705882549286, "24774": 0.1358480453491211, "24848": 0.11604541540145874, "25117": 0.0009760859538801014, "25194": 0.8658194541931152, "25354": 1.0073304176330566, "25419": 0.2990913391113281, "25456": 0.7565253376960754, "25580": 0.4481603503227234, "25714": 0.016465263441205025, "25761": 0.4248080551624298, "25992": 0.7755908370018005, "26058": 0.1751343309879303, "26243": 0.11081436276435852, "26288": 0.04953393340110779, "26402": 0.574020504951477, "26487": 0.043007105588912964, "26651": 0.09584271162748337, "26721": 0.817850649356842, "26773": 0.011650617234408855, "26786": 0.10555581003427505, "27099": 0.09584271162748337, "27295": 0.41840189695358276, "27325": 0.04487626627087593, "27854": 0.5601736903190613, "28228": 0.04487626627087593, "28516": 0.0606246218085289, "28619": 0.043007105588912964, "28674": 0.04487626627087593, "28728": 0.021256839856505394, "28774": 0.07341018319129944, "28788": 0.1602703034877777, "28848": 0.1905880719423294, "28993": 0.8583967685699463, "29248": 0.010684899985790253} | 13760557 | Degranulation of mast cells in response to Ag or the calcium mobilizing agent, thapsigargin, is dependent on emptying of intracellular stores of Ca(2+) and the ensuing influx of external Ca(2+), also referred to as store-operated calcium entry. However, it is unlikely that the calcium release-activated calcium channel is the sole mechanism for the entry of Ca(2+) because Sr(2+) and other divalent cations also permeate and support degranulation in stimulated mast cells. In this study we show that influx of Ca(2+) and Sr(2+) as well as degranulation are dependent on the presence of the canonical transient receptor potential (TRPC) channel protein TRPC5, in addition to STIM1 and Orai1, as demonstrated by knock down of each of these proteins by inhibitory RNAs in a rat mast cell (RBL-2H3) line. Overexpression of STIM1 and Orai1, which are known to be essential components of calcium release-activated calcium channel, allows entry of Ca(2+) but not Sr(2+), whereas overexpression of STIM1 and TRPC5 allows entry of both Ca(2+) and Sr(2+). These and other observations suggest that the Sr(2+)-permeable TRPC5 associates with STIM1 and Orai1 in a stoichiometric manner to enhance entry of Ca(2+) to generate a signal for degranulation. | Canonical transient receptor potential 5 channel in conjunction with Orai1 and STIM1 allows Sr2+ entry, optimal influx of Ca2+, and degranulation in a rat mast cell line. |
{"1011": 0.27786844968795776, "1052": 0.7710843086242676, "1156": 0.0770333781838417, "2002": 0.7286425232887268, "2004": 0.055094651877880096, "2005": 0.3588210940361023, "2007": 0.2607102394104004, "2008": 0.08603433519601822, "2011": 0.1718502640724182, "2015": 0.3381449282169342, "2024": 0.20580662786960602, "2029": 0.35334911942481995, "2057": 0.17431432008743286, "2076": 0.23633737862110138, "2078": 0.45499902963638306, "2079": 0.2160874605178833, "2087": 0.029824240133166313, "2091": 0.03360854089260101, "2099": 0.7426811456680298, "2109": 0.1212492436170578, "2124": 0.5127768516540527, "2146": 0.2763880789279938, "2179": 0.06520967930555344, "2182": 0.10379679501056671, "2190": 0.3519764244556427, "2247": 0.013579257763922215, "2292": 0.7845434546470642, "2361": 0.11168810725212097, "2491": 0.3723714053630829, "2504": 0.21922965347766876, "2512": 0.981317400932312, "2515": 0.22079704701900482, "2523": 0.5827828645706177, "2529": 0.32341301441192627, "2532": 1.2460440397262573, "2535": 0.679875910282135, "2538": 0.4855078160762787, "2659": 0.11517547070980072, "2695": 0.8433839678764343, "2721": 0.5528968572616577, "2863": 0.4831010699272156, "2869": 0.015504186972975731, "2896": 0.44753631949424744, "2920": 0.12986256182193756, "3189": 0.026025565341114998, "3283": 0.7463917136192322, "3378": 0.7009293437004089, "3445": 0.5990082025527954, "3466": 0.2539152204990387, "3526": 0.3930181860923767, "3597": 0.5903874635696411, "3619": 0.5104349255561829, "3623": 0.5557019114494324, "3625": 0.2837681770324707, "3670": 0.3810817003250122, "3747": 0.08154398202896118, "3796": 0.02412080205976963, "3798": 0.4374985992908478, "3800": 0.22859740257263184, "3818": 0.26446542143821716, "3853": 0.7647408246994019, "3896": 0.11778303235769272, "3952": 0.006812678650021553, "4023": 0.009718249551951885, "4263": 0.02316705882549286, "4286": 0.1602703034877777, "4315": 0.6202403903007507, "4359": 0.32553088665008545, "4395": 0.46853771805763245, "4442": 0.5404602885246277, "4456": 0.6059582233428955, "4539": 0.6197150945663452, "4667": 1.04512357711792, "4758": 0.38905516266822815, "4852": 0.1401015669107437, "4937": 0.5990082025527954, "4962": 0.5973974466323853, "4972": 0.5517725944519043, "5250": 0.7305257320404053, "5360": 0.018384648486971855, "5421": 0.255429208278656, "5449": 1.2471669912338257, "5547": 0.2689530849456787, "5599": 0.1751343309879303, "5668": 0.004870930220931768, "5732": 0.04767346754670143, "6064": 0.10026945173740387, "6378": 0.15359249711036682, "6430": 0.4196864068508148, "6494": 0.6451379656791687, "6540": 0.7047978043556213, "6591": 0.13670019805431366, "6668": 0.13925230503082275, "6678": 0.23247487843036652, "6689": 0.567951500415802, "6761": 0.32553088665008545, "6897": 0.2394166737794876, "6914": 0.23402166366577148, "6970": 0.9724938273429871, "7077": 0.01934296265244484, "7290": 0.0752234235405922, "7337": 0.22937409579753876, "7366": 0.21530038118362427, "7403": 0.1913948506116867, "7457": 0.5466978549957275, "7461": 0.255429208278656, "7711": 0.6451379656791687, "7783": 0.175953671336174, "7816": 0.2478361576795578, "7889": 0.4709797203540802, "8031": 1.0601204633712769, "8153": 0.022212404757738113, "8161": 0.06520967930555344, "8171": 0.6778947114944458, "8247": 0.27342069149017334, "8290": 0.28670501708984375, "8292": 0.21765978634357452, "8303": 0.3824150264263153, "8319": 0.5540198087692261, "8360": 0.2689530849456787, "8898": 0.33953672647476196, "8924": 0.29328158497810364, "9007": 0.48068851232528687, "9099": 0.5596157908439636, "9165": 0.17431432008743286, "9211": 0.9271688461303711, "9412": 0.08782484382390976, "9416": 0.347847044467926, "9513": 0.255429208278656, "9516": 0.11168810725212097, "9521": 0.009718249551951885, "9756": 0.1212492436170578, "9869": 0.6989894509315491, "9885": 0.34577593207359314, "10266": 0.18004031479358673, "10548": 0.38041436672210693, "10572": 0.15526613593101501, "10695": 0.679875910282135, "10737": 0.22001366317272186, "10738": 0.2576959431171417, "10851": 0.03266380727291107, "10924": 0.8161250352859497, "11403": 0.31132611632347107, "11409": 1.3028278350830078, "11598": 0.2493593990802765, "11649": 1.2250384092330933, "11835": 0.1212492436170578, "11981": 0.3409265875816345, "11993": 0.3656192123889923, "12022": 0.8845420479774475, "12115": 0.04674193635582924, "12222": 0.16110190749168396, "12287": 0.3870677351951599, "12719": 0.0058422754518687725, "12789": 0.5979346632957458, "12987": 1.5663347244262695, "13024": 0.4132472574710846, "13228": 0.6202403903007507, "13331": 0.1751343309879303, "13416": 0.0913962796330452, "13656": 0.11604541540145874, "13699": 0.5313173532485962, "13791": 0.1970241367816925, "13845": 0.5021947622299194, "13922": 0.3297532796859741, "13993": 0.10993985831737518, "14080": 0.3850763738155365, "14126": 0.11343330889940262, "14163": 0.040196798741817474, "14187": 0.39696553349494934, "14193": 1.2883929014205933, "14357": 0.13157635927200317, "14442": 0.06977381557226181, "14480": 0.3676496744155884, "14486": 0.012615402229130268, "14828": 0.026025565341114998, "14830": 0.6482070088386536, "14931": 0.1384023278951645, "15115": 0.2637155055999756, "15176": 0.08603433519601822, "15527": 0.05417001247406006, "15543": 0.1677299439907074, "15663": 0.11168810725212097, "15680": 0.7248653769493103, "15876": 1.1738357543945312, "16119": 0.5696102976799011, "16221": 0.129004567861557, "16285": 0.11517547070980072, "16505": 0.9915141463279724, "16599": 0.6000806093215942, "16605": 0.02792670577764511, "16745": 0.450652539730072, "16913": 1.0116009712219238, "17146": 0.06337817758321762, "17379": 0.49626702070236206, "17465": 1.1141164302825928, "17637": 0.33115679025650024, "17913": 0.3464667797088623, "18357": 0.09761575609445572, "18549": 0.5495203733444214, "18595": 0.8013357520103455, "18714": 0.016465263441205025, "18969": 0.38574060797691345, "19220": 0.1229778528213501, "19301": 0.9225212931632996, "19317": 0.5191890001296997, "19601": 0.026025565341114998, "19653": 0.46486347913742065, "20299": 0.4770587682723999, "20350": 1.0953518152236938, "20817": 0.5069117546081543, "20858": 0.19220098853111267, "21081": 0.8212929964065552, "21122": 0.03360854089260101, "21360": 0.09050461649894714, "21575": 0.10379679501056671, "21618": 0.3027053773403168, "21903": 0.3012613356113434, "21991": 0.055094651877880096, "22422": 0.036437395960092545, "22483": 0.11168810725212097, "22907": 0.025073638185858727, "23216": 0.24325250089168549, "23235": 0.9186317324638367, "23586": 0.6664261221885681, "23737": 0.14602625370025635, "23758": 0.043007105588912964, "23900": 0.12038381397724152, "23924": 0.06429435312747955, "24051": 0.2674594223499298, "24054": 1.0966572761535645, "24278": 0.12814582884311676, "24950": 0.3339579105377197, "25194": 0.013579257763922215, "25409": 0.036437395960092545, "25456": 0.9100211262702942, "25476": 0.2184450328350067, "25502": 0.755608320236206, "25644": 0.045809537172317505, "25932": 0.036437395960092545, "26402": 0.7144040465354919, "26451": 0.46055975556373596, "26524": 0.8813109993934631, "26534": 0.1970241367816925, "26601": 0.15023678541183472, "26773": 0.23402166366577148, "26775": 1.0030416250228882, "26944": 0.15275461971759796, "27022": 0.2983669638633728, "27598": 0.5433003902435303, "27697": 0.1510767638683319, "27710": 0.0009760859538801014, "27790": 0.45994341373443604, "27822": 0.05046287178993225, "27989": 0.012615402229130268, "28696": 0.08064348995685577, "28711": 1.0512858629226685, "28715": 0.2089812457561493, "28848": 1.0960047245025635} | 13763195 | Mammalian long intergenic noncoding RNAs (lincRNAs) are best known for modulating transcription. Here we report a posttranscriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a posttranscriptional inhibitor of translation. | LincRNA-p21 suppresses target mRNA translation. |
{"1039": 0.6363908052444458, "1045": 0.8272887468338013, "1054": 0.9348671436309814, "1058": 0.1212492436170578, "1996": 0.06612417846918106, "1998": 0.11430477350950241, "2000": 0.2516399025917053, "2005": 0.3177432417869568, "2011": 0.2478361576795578, "2021": 0.04674193635582924, "2029": 0.20739519596099854, "2048": 0.026025565341114998, "2050": 0.3750596046447754, "2053": 0.11691460013389587, "2064": 0.503966212272644, "2069": 0.18816383183002472, "2073": 0.08513788133859634, "2079": 0.1011524572968483, "2083": 0.6260011196136475, "2099": 0.49030399322509766, "2109": 0.22859740257263184, "2114": 0.1332872211933136, "2119": 0.5415972471237183, "2126": 0.38041436672210693, "2128": 0.19862671196460724, "2129": 0.13755162060260773, "2135": 0.083342544734478, "2168": 0.11691460013389587, "2224": 0.24248650670051575, "2235": 0.5696102976799011, "2278": 0.5579402446746826, "2291": 0.5662899017333984, "2306": 0.06429435312747955, "2312": 0.8195732831954956, "2339": 0.16359257698059082, "2366": 0.1889725625514984, "2389": 0.5712664127349854, "2445": 0.3177432417869568, "2462": 0.056018441915512085, "2470": 0.11778303235769272, "2478": 0.16607704758644104, "2488": 0.12556517124176025, "2502": 0.1332872211933136, "2507": 0.034552380442619324, "2515": 0.055094651877880096, "2535": 0.20022670924663544, "2571": 0.010684899985790253, "2582": 0.06429435312747955, "2594": 0.055094651877880096, "2609": 0.4950772523880005, "2612": 0.13499516248703003, "2615": 0.31845372915267944, "2640": 0.10555581003427505, "2677": 0.3177432417869568, "2738": 0.0174254160374403, "2741": 0.007782140281051397, "2799": 0.7934166193008423, "2817": 0.18816383183002472, "2819": 0.06154331564903259, "2825": 0.5887627601623535, "2881": 0.33675122261047363, "2884": 0.26146242022514343, "2913": 0.3283478021621704, "2915": 0.9857001900672913, "3001": 0.3464667797088623, "3024": 0.19541899859905243, "3073": 0.083342544734478, "3081": 0.26296505331993103, "3085": 0.3547199070453644, "3112": 0.1401015669107437, "3130": 0.27786844968795776, "3144": 0.41001203656196594, "3170": 0.27342069149017334, "3233": 0.15275461971759796, "3273": 0.1212492436170578, "3302": 0.841701865196228, "3344": 0.17759032547473907, "3356": 0.6123310327529907, "3447": 0.8247235417366028, "3469": 0.14602625370025635, "3495": 0.49982786178588867, "3512": 0.08064348995685577, "3567": 0.23092569410800934, "3568": 0.016465263441205025, "3597": 0.15359249711036682, "3609": 0.5267143249511719, "3622": 0.9013357162475586, "3639": 0.08692999184131622, "3647": 0.176772341132164, "3659": 0.3897167444229126, "3665": 0.04207121208310127, "3710": 0.5421652793884277, "3723": 0.11951763927936554, "3800": 0.3127557039260864, "3806": 0.1994270235300064, "3818": 0.056018441915512085, "3853": 0.0842406153678894, "3860": 0.5860490798950195, "3891": 0.40611594915390015, "3908": 0.06520967930555344, "3921": 0.13243216276168823, "3971": 0.0752234235405922, "3973": 0.0606246218085289, "3989": 0.19541899859905243, "4012": 0.38308101892471313, "4047": 0.5903874635696411, "4072": 0.24325250089168549, "4111": 0.5805994272232056, "4118": 0.3077431619167328, "4119": 0.45623743534088135, "4130": 0.011650617234408855, "4176": 0.6322478652000427, "4182": 0.17431432008743286, "4240": 0.5139457583427429, "4244": 0.34577593207359314, "4287": 0.058784693479537964, "4308": 0.4318077862262726, "4355": 0.7276995778083801, "4492": 0.025073638185858727, "4522": 0.08782484382390976, "4539": 0.9798521995544434, "4573": 0.6684301495552063, "4588": 0.3662964701652527, "4607": 0.045809537172317505, "4621": 0.21135559678077698, "4651": 0.24859806895256042, "4652": 0.1332872211933136, "4663": 0.09317722171545029, "4714": 0.08154398202896118, "4719": 0.5805994272232056, "4725": 0.272677481174469, "4820": 0.14095009863376617, "4921": 0.53589928150177, "4928": 0.19782574474811554, "4993": 0.13670019805431366, "5016": 0.05694137513637543, "5050": 0.21372433006763458, "5056": 0.0038986403960734606, "5123": 0.7380234599113464, "5147": 0.6249561905860901, "5359": 0.8332487344741821, "5449": 0.0019512200960889459, "5549": 0.1332872211933136, "5555": 0.13925230503082275, "5656": 0.6629094481468201, "5812": 0.20421554148197174, "5847": 0.9037119746208191, "6011": 0.1685553640127182, "6028": 0.15023678541183472, "6033": 0.30558720231056213, "6061": 0.3005385100841522, "6087": 0.20580662786960602, "6099": 0.30558720231056213, "6162": 0.5751199722290039, "6215": 0.40546512603759766, "6388": 0.014542185701429844, "6461": 0.15943801403045654, "6464": 0.19862671196460724, "6585": 0.037378571927547455, "6612": 0.5573811531066895, "6614": 0.07884006202220917, "6726": 0.953857421875, "6741": 0.05970508232712746, "6773": 0.04487626627087593, "6812": 0.6430866718292236, "6819": 0.28082266449928284, "6855": 0.07431721687316895, "6871": 0.6369074583053589, "6873": 0.11604541540145874, "6887": 0.38905516266822815, "6959": 0.9987343549728394, "6970": 0.04207121208310127, "7012": 0.04953393340110779, "7028": 0.13670019805431366, "7125": 0.06795065850019455, "7171": 1.0775588750839233, "7174": 0.13243216276168823, "7218": 0.15023678541183472, "7242": 0.16359257698059082, "7315": 0.07068414986133575, "7337": 0.11343330889940262, "7438": 0.007782140281051397, "7645": 0.1994270235300064, "7709": 0.14095009863376617, "7768": 0.3027053773403168, "7790": 0.4286321699619293, "7860": 0.42735910415649414, "7865": 0.4126010537147522, "7885": 0.11604541540145874, "7889": 0.8255793452262878, "7975": 0.0606246218085289, "8000": 0.75193190574646, "8047": 0.007782140281051397, "8116": 0.6823468804359436, "8127": 0.0058422754518687725, "8153": 0.23324857652187347, "8315": 0.03925827145576477, "8360": 0.6363908052444458, "8469": 0.11778303235769272, "8564": 0.8957691192626953, "8578": 0.036437395960092545, "8650": 0.08692999184131622, "8700": 1.0464962720870972, "8729": 0.0174254160374403, "8778": 0.17840765416622162, "8803": 0.151916041970253, "8885": 0.3134697377681732, "8902": 0.129004567861557, "8970": 0.011650617234408855, "8977": 0.034552380442619324, "9067": 0.02792670577764511, "9080": 1.1369311809539795, "9099": 0.15693697333335876, "9207": 0.21293537318706512, "9276": 0.5450005531311035, "9289": 0.1619328260421753, "9323": 0.848413348197937, "9350": 0.1477125883102417, "9359": 0.07431721687316895, "9373": 0.0174254160374403, "9416": 1.035461664199829, "9468": 0.14349138736724854, "9474": 0.5244048833847046, "9513": 0.1913948506116867, "9535": 1.0001721382141113, "9544": 0.7086513638496399, "9623": 0.18654440343379974, "9687": 0.1212492436170578, "9689": 0.20818853378295898, "9777": 0.22782009840011597, "9820": 0.19622190296649933, "9932": 0.5506471395492554, "9942": 0.5381823778152466, "9972": 0.9613537192344666, "10003": 0.7836518287658691, "10047": 0.3743882179260254, "10111": 0.24859806895256042, "10327": 0.40285754203796387, "10368": 0.2409527748823166, "10572": 0.8925741910934448, "10586": 0.18167030811309814, "10831": 0.3084607720375061, "10910": 0.36290550231933594, "10967": 0.0606246218085289, "11290": 0.026025565341114998, "11311": 0.9886114001274109, "11432": 0.4196864068508148, "11475": 0.8152611255645752, "11528": 0.3388410806655884, "11595": 0.17922431230545044, "11604": 0.06520967930555344, "11629": 0.036437395960092545, "11667": 0.16359257698059082, "11767": 0.2409527748823166, "11860": 0.7791815400123596, "11890": 0.32905077934265137, "12157": 0.3012613356113434, "12171": 0.21372433006763458, "12274": 0.2711893916130066, "12326": 0.013579257763922215, "12328": 1.0271050930023193, "12412": 0.04207121208310127, "12436": 0.8877626657485962, "12540": 0.055094651877880096, "12637": 0.1332872211933136, "12681": 0.02887592278420925, "12702": 0.7978238463401794, "12732": 0.3949938118457794, "12754": 0.21293537318706512, "12771": 0.6286086440086365, "12859": 0.6588751673698425, "12997": 0.29400965571403503, "13070": 0.13243216276168823, "13075": 0.19541899859905243, "13181": 0.6548244953155518, "13186": 1.0808777809143066, "13341": 0.8281423449516296, "13434": 0.5909284353256226, "13626": 0.15610189735889435, "13685": 0.01934296265244484, "14066": 0.0038986403960734606, "14084": 0.007782140281051397, "14126": 0.6960725784301758, "14163": 0.9591107368469238, "14301": 0.11168810725212097, "14536": 0.09406650811433792, "14570": 0.2561853528022766, "14656": 0.42608439922332764, "14693": 1.278652548789978, "14695": 0.08513788133859634, "14708": 0.21214580535888672, "14874": 0.3963087201118469, "14925": 0.35677260160446167, "14958": 0.052318159490823746, "15042": 0.02316705882549286, "15273": 0.9591107368469238, "15384": 0.15860503911972046, "15403": 0.9155091643333435, "15615": 0.10291612148284912, "15651": 0.04207121208310127, "15663": 0.23015019297599792, "15877": 0.15275461971759796, "15923": 0.20421554148197174, "15946": 0.15526613593101501, "16289": 0.014542185701429844, "16409": 0.24248650670051575, "16453": 0.058784693479537964, "16636": 0.06977381557226181, "16700": 0.0009760859538801014, "16844": 0.9302552938461304, "16910": 0.36426326632499695, "16972": 0.13755162060260773, "17034": 0.018384648486971855, "17191": 0.09761575609445572, "17258": 0.28155985474586487, "17341": 0.2749055027961731, "17404": 1.4283655881881714, "17727": 0.5455666780471802, "17886": 0.4812922179698944, "18020": 0.09672962874174118, "18058": 0.5092619061470032, "18191": 0.38308101892471313, "18227": 0.4944818615913391, "18400": 0.056018441915512085, "18447": 0.38174858689308167, "18453": 0.27044451236724854, "18717": 1.0828639268875122, "18759": 0.22626367211341858, "18868": 0.3374483287334442, "18891": 0.15777134895324707, "19023": 0.04207121208310127, "19126": 0.9929623603820801, "19132": 0.2145126610994339, "19136": 0.23092569410800934, "19230": 0.22782009840011597, "19274": 0.09495500475168228, "19357": 0.3864043951034546, "19362": 0.9013357162475586, "19653": 0.8349450826644897, "19699": 0.026976587250828743, "19723": 0.05139094591140747, "19737": 0.22937409579753876, "19792": 0.03925827145576477, "19818": 0.6096806526184082, "19857": 0.25845035910606384, "20014": 1.1941591501235962, "20219": 0.034552380442619324, "20502": 0.08871890604496002, "20536": 0.6048921346664429, "20614": 0.3070250153541565, "20735": 0.11430477350950241, "20868": 0.6233867406845093, "20876": 0.6107416749000549, "21025": 0.5232481360435486, "21102": 0.055094651877880096, "21114": 0.08603433519601822, "21150": 0.14179791510105133, "21307": 0.39367714524269104, "21497": 0.6075552701950073, "21554": 0.010684899985790253, "21670": 0.35334911942481995, "21759": 0.6170841455459595, "21781": 0.13243216276168823, "22069": 0.1332872211933136, "22110": 0.25845035910606384, "22144": 0.27342069149017334, "22318": 0.3346569836139679, "22471": 1.0874829292297363, "22499": 0.20580662786960602, "22524": 0.13499516248703003, "22634": 0.10993985831737518, "22648": 0.7105726003646851, "22834": 0.4926934838294983, "22931": 0.18411032855510712, "22945": 1.0546929836273193, "23041": 0.8941729068756104, "23420": 0.2881702482700348, "23820": 0.2763880789279938, "23854": 0.4794800877571106, "24010": 0.23787821829319, "24093": 0.12728634476661682, "24264": 0.3084607720375061, "24269": 0.19782574474811554, "24286": 0.3374483287334442, "24290": 0.029824240133166313, "24442": 0.05786345899105072, "24479": 0.0029254043474793434, "24495": 0.020300358533859253, "24531": 0.42735910415649414, "24582": 0.7755908370018005, "24965": 1.1109062433242798, "25032": 0.055094651877880096, "25292": 0.0038986403960734606, "25553": 0.013579257763922215, "25714": 0.12642613053321838, "25765": 0.5751199722290039, "25778": 0.19622190296649933, "25916": 0.2470736801624298, "26243": 0.10818854719400406, "26282": 0.07159364968538284, "26396": 0.0029254043474793434, "26445": 0.0913962796330452, "26591": 0.0174254160374403, "26708": 0.040196798741817474, "26721": 1.0546929836273193, "26835": 0.9432673454284668, "27046": 0.04113444685935974, "27199": 0.4041621685028076, "27441": 0.3339579105377197, "27781": 0.0029254043474793434, "27815": 0.037378571927547455, "27920": 0.3995884954929352, "27969": 0.12038381397724152, "27998": 0.38041436672210693, "28156": 0.42926809191703796, "28170": 0.21214580535888672, "28389": 0.3127557039260864, "28475": 0.15693697333335876, "28667": 1.1012130975723267, "28689": 0.8973627090454102, "28748": 0.41065993905067444, "28775": 0.00875066313892603, "28815": 0.2749055027961731, "28896": 1.34847891330719, "28965": 0.35128939151763916, "28991": 0.7629209756851196, "29207": 0.1685553640127182, "29278": 0.20739519596099854, "29290": 0.36967599391937256, "29361": 0.13925230503082275, "29525": 0.09228714555501938} | 13764090 | Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa. | Large intestine-targeted nanoparticle-releasing oral vaccine to control genitorectal viral infection |
{"1014": 0.36290550231933594, "1018": 0.05694137513637543, "1019": 0.09672962874174118, "1022": 0.11865071207284927, "1998": 0.1064341589808464, "2012": 0.4337083101272583, "2034": 0.9108069539070129, "2043": 0.08244366943836212, "2044": 0.06520967930555344, "2051": 0.20580662786960602, "2062": 0.3106105625629425, "2076": 0.3910386264324188, "2077": 0.015504186972975731, "2084": 0.28670501708984375, "2086": 0.4980490207672119, "2090": 0.8772575259208679, "2095": 0.15023678541183472, "2116": 0.19220098853111267, "2137": 0.6420594453811646, "2141": 0.7333439588546753, "2142": 0.20022670924663544, "2146": 0.04674193635582924, "2149": 0.37371641397476196, "2166": 0.00875066313892603, "2214": 0.4349733293056488, "2220": 0.2470736801624298, "2241": 0.4267219603061676, "2273": 0.5707147121429443, "2287": 1.2175520658493042, "2304": 0.36967599391937256, "2308": 0.817850649356842, "2313": 0.6461620330810547, "2317": 0.6980181336402893, "2336": 0.013579257763922215, "2339": 0.09050461649894714, "2383": 0.3070250153541565, "2385": 0.4425300657749176, "2388": 0.08692999184131622, "2411": 0.0019512200960889459, "2426": 0.5404602885246277, "2450": 0.6011518239974976, "2470": 0.306306391954422, "2482": 0.07793712615966797, "2491": 0.8583967685699463, "2511": 0.812664806842804, "2515": 0.1994270235300064, "2523": 0.7144040465354919, "2553": 0.7239188551902771, "2558": 0.7124901413917542, "2599": 0.25239890813827515, "2637": 0.11256109178066254, "2641": 0.029824240133166313, "2687": 0.35060185194015503, "2695": 0.35745587944984436, "2707": 0.1734936386346817, "2724": 0.2800849378108978, "2754": 0.05694137513637543, "2775": 0.27342069149017334, "2807": 0.2637155055999756, "2812": 0.006812678650021553, "2817": 0.6664261221885681, "2818": 0.3588210940361023, "2824": 0.4349733293056488, "2828": 0.2622140049934387, "2844": 0.05970508232712746, "2846": 0.21372433006763458, "2863": 0.07159364968538284, "2906": 0.8885661959648132, "2913": 0.5936289429664612, "2927": 0.06337817758321762, "2931": 0.4431571960449219, "2951": 0.1221139207482338, "3020": 0.15442965924739838, "3057": 0.3084607720375061, "3060": 1.0030416250228882, "3078": 0.14939609169960022, "3080": 0.06154331564903259, "3083": 0.5952457785606384, "3088": 0.5197699069976807, "3141": 0.35677260160446167, "3188": 0.0317181795835495, "3225": 0.05970508232712746, "3273": 0.36900100111961365, "3276": 0.5707147121429443, "3278": 0.22937409579753876, "3322": 0.04113444685935974, "3336": 0.6619023680686951, "3347": 0.0009760859538801014, "3351": 0.16359257698059082, "3378": 0.7898768186569214, "3382": 0.2160874605178833, "3391": 0.08871890604496002, "3395": 0.07250232994556427, "3404": 0.0317181795835495, "3426": 0.2696990668773651, "3445": 0.4286321699619293, "3446": 0.3012613356113434, "3466": 0.304147332906723, "3497": 0.3588210940361023, "3517": 0.022212404757738113, "3540": 0.2711893916130066, "3549": 0.42225050926208496, "3556": 0.052318159490823746, "3560": 0.7220231294631958, "3572": 0.47158926725387573, "3618": 0.056018441915512085, "3623": 0.3601844012737274, "3647": 0.1751343309879303, "3653": 0.20022670924663544, "3747": 0.09850110858678818, "3801": 0.3903779089450836, "3867": 0.2160874605178833, "3891": 1.1236859560012817, "3893": 0.6719275116920471, "3896": 0.29619070887565613, "3915": 0.18411032855510712, "3930": 0.0842406153678894, "3979": 0.0009760859538801014, "3988": 0.23015019297599792, "3989": 0.014542185701429844, "4094": 0.08513788133859634, "4102": 0.319873183965683, "4106": 0.24248650670051575, "4127": 0.2969166338443756, "4182": 1.1917895078659058, "4226": 0.10906458646059036, "4237": 0.2822965085506439, "4254": 0.12728634476661682, "4295": 0.3077431619167328, "4328": 0.18329764902591705, "4358": 0.20660123229026794, "4414": 0.2026219218969345, "4456": 1.3248759508132935, "4502": 0.6118015646934509, "4647": 0.16359257698059082, "4652": 0.05786345899105072, "4758": 0.5629584193229675, "4793": 0.23864774405956268, "4795": 0.25995752215385437, "4800": 0.3381449282169342, "4841": 0.49626702070236206, "4975": 0.17922431230545044, "5002": 0.015504186972975731, "5003": 0.20660123229026794, "5069": 0.09050461649894714, "5105": 0.10906458646059036, "5323": 0.3743882179260254, "5345": 0.9710156321525574, "5360": 0.47463157773017883, "5387": 0.6471850275993347, "5400": 0.23402166366577148, "5403": 1.2605451345443726, "5428": 0.32553088665008545, "5531": 0.4093637466430664, "5535": 0.6769026517868042, "5537": 0.05970508232712746, "5593": 0.15275461971759796, "5636": 0.3269403576850891, "5668": 0.16110190749168396, "5700": 0.20102575421333313, "5769": 0.08603433519601822, "5798": 0.026976587250828743, "5799": 0.23092569410800934, "5816": 0.09850110858678818, "5876": 0.762009859085083, "5907": 0.12384103983640671, "5986": 0.0797421783208847, "6022": 0.053244512528181076, "6048": 0.15023678541183472, "6075": 0.052318159490823746, "6086": 0.03266380727291107, "6165": 0.2674594223499298, "6249": 0.03360854089260101, "6428": 0.31204116344451904, "6431": 0.2184450328350067, "6438": 0.0842406153678894, "6463": 0.7482418417930603, "6529": 0.1384023278951645, "6553": 0.7086513638496399, "6584": 0.0019512200960889459, "6721": 0.04207121208310127, "6747": 0.3485364317893982, "6761": 0.12986256182193756, "6818": 0.04113444685935974, "6875": 0.417115718126297, "6897": 0.045809537172317505, "6914": 0.011650617234408855, "6950": 0.23633737862110138, "6959": 0.0009760859538801014, "6970": 0.016465263441205025, "6993": 0.4673144817352295, "7012": 0.11865071207284927, "7017": 0.45870962738990784, "7023": 1.1356772184371948, "7080": 0.24248650670051575, "7091": 0.05970508232712746, "7189": 0.4950772523880005, "7382": 0.33115679025650024, "7388": 1.3112845420837402, "7403": 0.0317181795835495, "7411": 0.28743788599967957, "7457": 0.3141832649707794, "7461": 0.6813592314720154, "7507": 0.4531385898590088, "7524": 0.06886265426874161, "7551": 0.10906458646059036, "7570": 0.29400965571403503, "7591": 1.0423725843429565, "7691": 0.2852376699447632, "7711": 0.5186077356338501, "7778": 0.46853771805763245, "7790": 0.09228714555501938, "7831": 0.6064908504486084, "7870": 0.0058422754518687725, "7987": 0.4337083101272583, "8092": 0.06154331564903259, "8211": 0.34577593207359314, "8249": 0.018384648486971855, "8290": 0.045809537172317505, "8302": 0.42990362644195557, "8329": 0.18329764902591705, "8376": 0.33605360984802246, "8445": 0.0606246218085289, "8449": 0.0842406153678894, "8450": 0.304147332906723, "8536": 0.07159364968538284, "8557": 0.056018441915512085, "8599": 0.04674193635582924, "8661": 0.2501201331615448, "8833": 0.5472630262374878, "8840": 0.6102113127708435, "8865": 0.10203468054533005, "8924": 0.638455867767334, "9002": 0.10467668622732162, "9147": 0.0913962796330452, "9153": 0.07884006202220917, "9253": 0.23787821829319, "9280": 0.036437395960092545, "9336": 0.21922965347766876, "9363": 0.10906458646059036, "9367": 0.10026945173740387, "9556": 0.2561853528022766, "9560": 0.12986256182193756, "9592": 0.21293537318706512, "9657": 0.1751343309879303, "9723": 0.29036402702331543, "9750": 0.02316705882549286, "9756": 0.41195443272590637, "9765": 0.1751343309879303, "9867": 0.22859740257263184, "9905": 0.1332872211933136, "9962": 0.0009760859538801014, "10032": 0.5427330136299133, "10035": 0.5220900774002075, "10173": 0.15693697333335876, "10197": 0.37102460861206055, "10238": 1.0894558429718018, "10280": 0.2652147710323334, "10316": 0.018384648486971855, "10383": 0.5718178153038025, "10426": 0.43875885009765625, "10494": 0.18978065252304077, "10527": 0.469759464263916, "10671": 0.6512666940689087, "10744": 0.1693800985813141, "10755": 0.026025565341114998, "10760": 0.0842406153678894, "10769": 0.6430866718292236, "10823": 0.1693800985813141, "10831": 0.791648268699646, "10834": 0.3588210940361023, "10857": 0.34300774335861206, "10867": 0.3141832649707794, "10928": 0.018384648486971855, "10984": 0.6218147873878479, "11119": 0.03266380727291107, "11326": 0.6011518239974976, "11393": 0.07250232994556427, "11650": 0.4462870955467224, "11655": 0.08782484382390976, "11658": 0.00875066313892603, "11704": 0.14179791510105133, "11709": 0.06154331564903259, "11714": 0.043007105588912964, "11968": 0.9108069539070129, "12098": 0.10731173306703568, "12411": 0.1384023278951645, "12435": 0.1946154683828354, "12461": 0.42096930742263794, "12473": 0.1332872211933136, "12503": 0.22782009840011597, "12520": 0.32199856638908386, "12596": 0.13499516248703003, "12682": 0.8780695199966431, "12826": 0.2622140049934387, "13013": 0.7417513132095337, "13047": 0.29109421372413635, "13070": 0.08961215615272522, "13105": 0.21372433006763458, "13120": 0.10731173306703568, "13356": 0.33605360984802246, "13453": 0.13157635927200317, "13483": 1.2012346982955933, "13531": 0.3777405619621277, "13599": 0.2990913391113281, "13640": 0.045809537172317505, "13656": 0.6848117709159851, "13833": 0.6394867897033691, "13852": 0.15777134895324707, "14025": 0.8764448165893555, "14171": 0.22079704701900482, "14267": 0.2018241584300995, "14298": 0.2501201331615448, "14396": 0.016465263441205025, "14627": 0.37304413318634033, "14639": 0.7898768186569214, "14644": 0.07250232994556427, "14760": 0.37640097737312317, "14766": 0.4487839937210083, "14925": 0.014542185701429844, "15124": 0.8065804839134216, "15258": 0.15275461971759796, "15301": 0.6684301495552063, "15306": 0.27934664487838745, "15308": 0.16690383851528168, "15429": 0.009718249551951885, "15559": 0.10818854719400406, "15689": 0.06246116757392883, "15847": 0.0174254160374403, "15982": 0.19220098853111267, "16007": 0.18978065252304077, "16014": 0.512191891670227, "16026": 0.7491656541824341, "16211": 0.14179791510105133, "16330": 0.3034266233444214, "16387": 0.056018441915512085, "16505": 0.5651806592941284, "16515": 0.7370892763137817, "16519": 0.12038381397724152, "16593": 0.1401015669107437, "16725": 0.23402166366577148, "16824": 0.004870930220931768, "16902": 0.6664261221885681, "16989": 0.06337817758321762, "17060": 0.13670019805431366, "17245": 0.052318159490823746, "17376": 0.15943801403045654, "17489": 0.15023678541183472, "17547": 0.14349138736724854, "17631": 0.2184450328350067, "17635": 0.3134697377681732, "17819": 0.06977381557226181, "18002": 0.6517757177352905, "18076": 0.3750596046447754, "18130": 0.21765978634357452, "18158": 0.0029254043474793434, "18178": 0.27564704418182373, "18240": 0.15693697333335876, "18250": 0.3982778787612915, "18539": 0.20501139760017395, "18609": 0.05417001247406006, "18714": 0.6664261221885681, "18949": 0.43434104323387146, "19037": 0.31132611632347107, "19064": 0.4487839937210083, "19158": 0.30989447236061096, "19188": 0.49923527240753174, "19345": 0.10026945173740387, "19680": 0.09761575609445572, "19696": 0.013579257763922215, "19824": 0.28597161173820496, "20100": 0.10906458646059036, "20272": 0.3499138653278351, "20360": 0.18167030811309814, "20367": 0.2667117714881897, "20390": 0.14349138736724854, "20598": 0.18573370575904846, "20662": 0.603290855884552, "20752": 0.7076893448829651, "21009": 0.19541899859905243, "21081": 0.9440274834632874, "21230": 0.052318159490823746, "21326": 0.07793712615966797, "21371": 0.09228714555501938, "21434": 0.659380316734314, "21499": 0.0174254160374403, "21879": 0.7665573358535767, "21961": 0.02792670577764511, "22313": 0.05970508232712746, "22471": 0.18978065252304077, "22794": 0.05046287178993225, "22835": 0.1913948506116867, "22963": 0.2018241584300995, "22991": 0.5607312321662903, "23368": 0.6000806093215942, "23555": 0.021256839856505394, "23579": 0.0019512200960889459, "23637": 0.12986256182193756, "23676": 0.15359249711036682, "23737": 0.16690383851528168, "23862": 0.755608320236206, "23900": 0.5021947622299194, "23926": 0.014542185701429844, "24081": 0.013579257763922215, "24133": 0.09938567131757736, "24155": 0.25845035910606384, "24278": 0.18573370575904846, "24353": 0.34715715050697327, "24759": 0.2830325961112976, "25022": 0.7163142561912537, "25032": 0.14686977863311768, "25222": 0.034552380442619324, "25409": 0.9907892942428589, "25937": 0.045809537172317505, "26033": 0.015504186972975731, "26163": 0.0354953333735466, "26237": 1.0492360591888428, "26445": 0.10818854719400406, "26462": 0.04860413447022438, "26563": 0.8500841856002808, "26578": 0.0174254160374403, "26702": 0.04487626627087593, "27162": 0.5156965255737305, "27794": 0.1946154683828354, "27881": 0.01934296265244484, "28093": 0.32764431834220886, "28207": 0.28082266449928284, "28321": 0.040196798741817474, "28436": 0.37102460861206055, "28507": 0.1064341589808464, "28687": 0.40806588530540466, "28808": 1.12938392162323, "29458": 0.25694093108177185, "29477": 0.7124901413917542} | 13765757 | Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women. | Timing of menarche and first full-term birth in relation to breast cancer risk. |
{"1011": 0.23710809648036957, "1013": 0.14602625370025635, "1014": 0.31489628553390503, "1017": 0.21687394380569458, "1018": 0.05046287178993225, "1026": 0.014542185701429844, "1041": 0.2493593990802765, "1048": 0.9568626880645752, "1050": 0.06337817758321762, "1052": 0.1873544454574585, "1056": 0.4950772523880005, "2004": 0.24018502235412598, "2007": 0.29400965571403503, "2012": 0.7018978595733643, "2020": 0.04767346754670143, "2026": 0.6497380137443542, "2044": 0.3916989266872406, "2046": 0.28450319170951843, "2048": 0.34370049834251404, "2069": 0.020300358533859253, "2093": 0.026025565341114998, "2099": 0.8707374930381775, "2124": 0.15359249711036682, "2128": 0.26820653676986694, "2130": 0.04767346754670143, "2140": 0.19622190296649933, "2146": 0.2493593990802765, "2187": 0.6907027959823608, "2193": 0.04674193635582924, "2199": 0.17431432008743286, "2203": 0.004870930220931768, "2222": 0.09495500475168228, "2290": 0.20580662786960602, "2302": 0.28670501708984375, "2331": 0.6563454270362854, "2350": 0.06612417846918106, "2351": 0.2478361576795578, "2364": 0.33675122261047363, "2378": 0.48670899868011475, "2397": 0.9333322048187256, "2410": 0.0770333781838417, "2422": 0.8281423449516296, "2465": 0.4113073945045471, "2467": 0.06886265426874161, "2487": 0.5133614540100098, "2504": 0.04394211992621422, "2540": 0.8039615154266357, "2560": 0.7764897346496582, "2592": 0.20580662786960602, "2628": 0.2711893916130066, "2632": 0.8509185314178467, "2641": 0.18329764902591705, "2649": 0.10026945173740387, "2668": 0.6714286804199219, "2706": 0.1946154683828354, "2720": 0.06703783571720123, "2765": 0.38308101892471313, "2785": 0.030771657824516296, "2812": 0.09228714555501938, "2817": 0.10291612148284912, "2819": 0.5244048833847046, "2828": 0.5162794589996338, "2846": 0.1734936386346817, "2864": 0.5033760666847229, "2869": 0.058784693479537964, "2871": 0.24248650670051575, "2920": 0.5145297050476074, "2936": 0.06977381557226181, "2981": 0.9052929878234863, "3089": 0.6244332790374756, "3115": 0.7951818704605103, "3176": 0.08961215615272522, "3231": 0.23402166366577148, "3258": 0.5968599319458008, "3280": 0.09850110858678818, "3351": 1.2198615074157715, "3378": 0.7057625651359558, "3395": 0.2223619967699051, "3445": 0.18248429894447327, "3446": 0.07068414986133575, "3463": 0.6107416749000549, "3517": 0.20501139760017395, "3527": 0.7818660736083984, "3556": 0.27712854743003845, "3582": 0.012615402229130268, "3623": 0.20501139760017395, "3642": 0.06429435312747955, "3643": 0.27712854743003845, "3694": 0.17759032547473907, "3695": 0.25845035910606384, "3742": 0.817850649356842, "3747": 0.6275664567947388, "3867": 0.10818854719400406, "3872": 1.004473328590393, "3891": 0.6828403472900391, "3904": 0.7201237678527832, "3935": 0.8780695199966431, "3949": 0.659380316734314, "3977": 0.1602703034877777, "4003": 0.6338034868240356, "4013": 0.8238670229911804, "4022": 0.7592713832855225, "4094": 0.21687394380569458, "4102": 0.5584990978240967, "4106": 0.1905880719423294, "4115": 0.7182208299636841, "4118": 0.32199856638908386, "4127": 0.6296497583389282, "4135": 0.1905880719423294, "4146": 0.03831886500120163, "4167": 0.7656494975090027, "4225": 0.1619328260421753, "4242": 0.27044451236724854, "4281": 0.777387797832489, "4295": 0.2881702482700348, "4297": 0.2493593990802765, "4340": 0.5180262327194214, "4358": 0.04487626627087593, "4403": 0.7408206462860107, "4431": 0.5584990978240967, "4456": 0.2607102394104004, "4464": 0.08064348995685577, "4466": 0.12986256182193756, "4469": 0.9225212931632996, "4488": 0.034552380442619324, "4531": 0.08782484382390976, "4583": 0.151916041970253, "4588": 0.36697331070899963, "4597": 0.3084607720375061, "4649": 0.1229778528213501, "4654": 0.401551216840744, "4677": 0.9440274834632874, "4685": 0.0029254043474793434, "4696": 0.08871890604496002, "4724": 0.37707099318504333, "4725": 0.42544642090797424, "4758": 0.053244512528181076, "4781": 0.39433568716049194, "4795": 0.1477125883102417, "4852": 0.47827014327049255, "4942": 0.7417513132095337, "4949": 0.0842406153678894, "4962": 0.28963330388069153, "5022": 0.47036975622177124, "5050": 0.3077431619167328, "5083": 0.304147332906723, "5105": 0.7047978043556213, "5250": 0.23633737862110138, "5300": 0.04207121208310127, "5345": 0.7028654217720032, "5360": 0.16524957120418549, "5387": 0.5607312321662903, "5397": 0.777387797832489, "5400": 0.04767346754670143, "5418": 0.7295845746994019, "5461": 0.29981520771980286, "5468": 0.4831010699272156, "5531": 0.18329764902591705, "5536": 0.8332487344741821, "5579": 0.8195732831954956, "5603": 0.151916041970253, "5622": 0.03360854089260101, "5646": 0.1221139207482338, "5709": 0.20102575421333313, "5739": 0.7163142561912537, "5761": 0.28670501708984375, "5776": 0.48430517315864563, "5836": 0.34577593207359314, "5845": 0.47827014327049255, "5852": 0.06337817758321762, "5876": 0.5838727951049805, "5950": 0.9186317324638367, "5997": 0.06612417846918106, "6020": 0.8517522215843201, "6022": 0.5393219590187073, "6028": 0.7314660549163818, "6190": 0.5607312321662903, "6219": 0.8013357520103455, "6321": 0.3615458607673645, "6463": 0.8517522215843201, "6493": 0.7701805830001831, "6540": 0.15526613593101501, "6612": 0.2317005842924118, "6624": 0.8004589080810547, "6632": 0.3949938118457794, "6653": 0.6950984001159668, "6677": 0.05139094591140747, "6678": 0.3241194784641266, "6702": 0.6664261221885681, "6757": 0.3757305145263672, "6758": 0.034552380442619324, "6839": 0.4855078160762787, "6845": 0.026976587250828743, "6864": 1.2932277917861938, "6909": 0.956112265586853, "6914": 0.3318578004837036, "6937": 0.3170322775840759, "7017": 0.40285754203796387, "7023": 1.141931176185608, "7028": 0.06154331564903259, "7060": 0.659380316734314, "7065": 0.09406650811433792, "7091": 0.2763880789279938, "7103": 0.0058422754518687725, "7233": 0.8649974465370178, "7242": 0.24018502235412598, "7277": 0.7038320899009705, "7341": 0.011650617234408855, "7356": 0.15359249711036682, "7403": 0.18167030811309814, "7438": 0.5069117546081543, "7457": 0.03360854089260101, "7461": 0.0770333781838417, "7485": 0.012615402229130268, "7497": 0.20739519596099854, "7591": 0.8764448165893555, "7594": 0.6296497583389282, "7604": 0.0842406153678894, "7645": 0.08692999184131622, "7691": 0.14264501631259918, "7718": 0.020300358533859253, "7790": 0.11604541540145874, "7831": 0.43244171142578125, "7934": 0.7674643993377686, "8015": 0.010684899985790253, "8060": 0.979118824005127, "8092": 0.43812891840934753, "8153": 0.6931471824645996, "8442": 0.15860503911972046, "8449": 0.6043586730957031, "8569": 0.6882523894309998, "8609": 0.5301685929298401, "8649": 0.3381449282169342, "8674": 0.18411032855510712, "8715": 0.20580662786960602, "8733": 0.6420594453811646, "8740": 0.026025565341114998, "8859": 0.4734157919883728, "8980": 0.7854343056678772, "9031": 0.4145384132862091, "9099": 1.0485517978668213, "9141": 0.07884006202220917, "9174": 0.14095009863376617, "9181": 0.053244512528181076, "9239": 0.056018441915512085, "9312": 0.055094651877880096, "9367": 0.04767346754670143, "9412": 0.6573580503463745, "9442": 0.22157983481884003, "9447": 0.04953393340110779, "9556": 0.21293537318706512, "9560": 0.6921701431274414, "9626": 0.39433568716049194, "9657": 0.08064348995685577, "9723": 0.0009760859538801014, "9839": 0.40220460295677185, "10047": 0.43434104323387146, "10074": 0.495672345161438, "10173": 0.659380316734314, "10174": 0.15610189735889435, "10194": 0.9240728616714478, "10318": 0.09406650811433792, "10426": 0.6892333030700684, "10448": 0.0174254160374403, "10497": 0.9225212931632996, "10572": 0.09406650811433792, "10611": 0.19622190296649933, "10787": 0.3248254358768463, "10817": 0.06520967930555344, "10831": 0.22782009840011597, "10857": 0.19782574474811554, "10859": 1.0326838493347168, "10903": 0.3127557039260864, "10928": 0.026976587250828743, "11156": 0.045809537172317505, "11207": 0.07068414986133575, "11236": 0.2394166737794876, "11252": 0.27044451236724854, "11311": 0.176772341132164, "11320": 0.07884006202220917, "11326": 0.004870930220931768, "11363": 0.6212902665138245, "11436": 0.014542185701429844, "11441": 0.4980490207672119, "11487": 0.009718249551951885, "11522": 0.12470348179340363, "11598": 0.5882205963134766, "11616": 0.8057082891464233, "11674": 0.11604541540145874, "11678": 0.26446542143821716, "11704": 0.025073638185858727, "11709": 0.31132611632347107, "11721": 0.7683706283569336, "11787": 0.5489565134048462, "12044": 0.31560876965522766, "12126": 0.2749055027961731, "12269": 0.18492233753204346, "12318": 0.20501139760017395, "12335": 0.4450363218784332, "12349": 0.0174254160374403, "12375": 0.5930894017219543, "12381": 0.8517522215843201, "12435": 0.18004031479358673, "12650": 0.8748174905776978, "12765": 0.2034190446138382, "12798": 0.12384103983640671, "12826": 0.15023678541183472, "12884": 0.890972912311554, "13024": 0.020300358533859253, "13092": 0.10993985831737518, "13105": 0.6070231795310974, "13341": 0.19381128251552582, "13356": 0.306306391954422, "13400": 0.32199856638908386, "13441": 0.3683255612850189, "13465": 0.969535231590271, "13483": 0.9805850982666016, "13599": 0.33115679025650024, "13656": 0.20739519596099854, "13671": 0.0058422754518687725, "13692": 0.7144040465354919, "13876": 0.4400174915790558, "14025": 0.6144463419914246, "14085": 0.7755908370018005, "14095": 0.33953672647476196, "14155": 0.2576959431171417, "14171": 0.6430866718292236, "14234": 0.0606246218085289, "14267": 0.1718502640724182, "14357": 0.09050461649894714, "14482": 0.16359257698059082, "14494": 0.5957841277122498, "14613": 0.1064341589808464, "14639": 0.6512666940689087, "14766": 0.030771657824516296, "14900": 0.39696553349494934, "15050": 1.2140778303146362, "15306": 0.6064908504486084, "15316": 0.1064341589808464, "15354": 0.3077431619167328, "15476": 0.1808556467294693, "15527": 0.49626702070236206, "15559": 0.997294545173645, "15596": 0.07793712615966797, "15680": 0.27564704418182373, "16014": 0.6410312056541443, "16069": 1.1671710014343262, "16134": 0.4450363218784332, "16185": 0.13499516248703003, "16221": 0.8780695199966431, "16238": 0.13243216276168823, "16264": 0.1710275560617447, "16330": 0.0317181795835495, "16344": 1.2290464639663696, "16367": 0.2918238639831543, "16381": 0.040196798741817474, "16463": 0.11256109178066254, "16474": 0.469759464263916, "16505": 0.07431721687316895, "16670": 0.20501139760017395, "16706": 0.058784693479537964, "16853": 0.45499902963638306, "16882": 1.0587663650512695, "16921": 0.7601850032806396, "16924": 0.11430477350950241, "17011": 0.932563841342926, "17076": 0.10203468054533005, "17080": 0.8829278349876404, "17134": 0.3374483287334442, "17208": 0.012615402229130268, "17245": 0.18492233753204346, "17404": 0.014542185701429844, "17459": 0.4654768109321594, "17464": 0.48430517315864563, "17503": 0.07068414986133575, "17547": 0.6118015646934509, "17703": 0.0606246218085289, "17715": 0.06795065850019455, "17760": 0.306306391954422, "17785": 0.11604541540145874, "17816": 1.2649650573730469, "18133": 0.2763880789279938, "18349": 0.016465263441205025, "18419": 0.12384103983640671, "18439": 0.17759032547473907, "18452": 0.13414156436920166, "18749": 0.0019512200960889459, "18834": 0.7163142561912537, "18994": 0.23556606471538544, "19037": 1.0788878202438354, "19064": 0.25467249751091003, "19113": 0.040196798741817474, "19158": 0.4794800877571106, "19335": 0.2969166338443756, "19701": 1.1076855659484863, "19939": 0.0606246218085289, "20037": 0.6588751673698425, "20045": 0.1913948506116867, "20155": 0.009718249551951885, "20214": 0.07431721687316895, "20226": 0.16524957120418549, "20350": 0.02412080205976963, "20427": 0.2918238639831543, "20569": 0.42416930198669434, "20614": 0.8022117614746094, "20932": 0.176772341132164, "21050": 0.7755908370018005, "21150": 0.04767346754670143, "21262": 0.1677299439907074, "21425": 0.05139094591140747, "21449": 0.3248254358768463, "21718": 0.1221139207482338, "21879": 0.6823468804359436, "21887": 0.15693697333335876, "21903": 0.17020416259765625, "21945": 0.04487626627087593, "21961": 0.2409527748823166, "21976": 0.22001366317272186, "22010": 0.5186077356338501, "22153": 1.20182204246521, "22166": 0.6435998678207397, "22291": 0.24401791393756866, "22415": 1.12938392162323, "22423": 0.15023678541183472, "22575": 0.7463917136192322, "22931": 0.1602703034877777, "22935": 1.0868242979049683, "22961": 0.7898768186569214, "22963": 0.1212492436170578, "23041": 0.7086513638496399, "23163": 0.08871890604496002, "23191": 0.05139094591140747, "23247": 0.014542185701429844, "23737": 0.0038986403960734606, "23833": 0.0606246218085289, "23900": 0.06520967930555344, "24081": 0.7987030148506165, "24110": 0.02887592278420925, "24335": 0.5438674688339233, "24412": 0.41001203656196594, "24497": 0.04394211992621422, "24501": 0.3683255612850189, "24714": 0.3910386264324188, "24755": 0.7408206462860107, "24759": 0.026025565341114998, "24848": 0.020300358533859253, "25032": 0.0913962796330452, "25070": 0.8509185314178467, "25117": 0.8893690705299377, "25226": 0.0842406153678894, "25331": 0.19381128251552582, "25604": 0.07159364968538284, "25708": 0.0038986403960734606, "25714": 0.018384648486971855, "26163": 0.35128939151763916, "26226": 0.5010119676589966, "26243": 0.2976420819759369, "26268": 0.5450005531311035, "26279": 0.1384023278951645, "26404": 0.371698260307312, "26535": 0.25088030099868774, "26739": 0.13243216276168823, "26745": 0.8965662121772766, "26837": 0.30917787551879883, "26886": 0.17922431230545044, "27011": 0.5010119676589966, "27144": 0.016465263441205025, "27159": 0.06977381557226181, "27339": 0.14179791510105133, "27354": 0.12470348179340363, "27532": 0.0019512200960889459, "27697": 0.23092569410800934, "27710": 1.2387138605117798, "27781": 0.011650617234408855, "27790": 0.1221139207482338, "27811": 0.22079704701900482, "28093": 0.15610189735889435, "28353": 0.35334911942481995, "28436": 0.27044451236724854, "28527": 1.1506214141845703, "28578": 0.9013357162475586, "28648": 0.23787821829319, "28697": 0.004870930220931768, "28715": 0.15943801403045654, "28873": 0.1677299439907074, "29166": 0.052318159490823746, "29299": 0.5947071313858032, "29458": 0.6603899002075195, "29657": 0.19541899859905243} | 13768432 | BACKGROUND The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. METHODS AND RESULTS Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). CONCLUSIONS There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. | Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis |
{"1003": 0.0842406153678894, "1017": 0.38574060797691345, "1020": 0.129004567861557, "1022": 0.2470736801624298, "1023": 0.043007105588912964, "1038": 0.42735910415649414, "1043": 0.4855078160762787, "1997": 0.4855078160762787, "1998": 0.23479416966438293, "2001": 0.09228714555501938, "2011": 0.07250232994556427, "2012": 0.3777405619621277, "2015": 0.2990913391113281, "2020": 0.030771657824516296, "2039": 0.06520967930555344, "2042": 0.021256839856505394, "2043": 0.1905880719423294, "2057": 0.11951763927936554, "2058": 0.23015019297599792, "2062": 0.056018441915512085, "2071": 0.1401015669107437, "2072": 0.6603899002075195, "2075": 0.16607704758644104, "2084": 0.00875066313892603, "2086": 0.42990362644195557, "2088": 0.6970458030700684, "2093": 0.08692999184131622, "2095": 0.37907835841178894, "2104": 0.009718249551951885, "2106": 0.09406650811433792, "2109": 0.30917787551879883, "2111": 0.16359257698059082, "2116": 0.5174443125724792, "2120": 0.3346569836139679, "2129": 0.06703783571720123, "2146": 0.22157983481884003, "2152": 0.3248254358768463, "2155": 0.02316705882549286, "2166": 0.6773988008499146, "2169": 0.06429435312747955, "2172": 0.20580662786960602, "2177": 0.23633737862110138, "2184": 0.07884006202220917, "2193": 0.41840189695358276, "2241": 0.012615402229130268, "2248": 0.38174858689308167, "2250": 0.2983669638633728, "2287": 0.7258110046386719, "2303": 0.2954642176628113, "2313": 0.8013357520103455, "2321": 0.29109421372413635, "2325": 1.068206787109375, "2331": 0.6634125709533691, "2336": 0.3662964701652527, "2339": 0.016465263441205025, "2351": 0.18573370575904846, "2353": 0.09228714555501938, "2355": 0.030771657824516296, "2381": 0.01934296265244484, "2405": 0.06246116757392883, "2408": 0.3141832649707794, "2421": 0.36697331070899963, "2423": 0.33953672647476196, "2426": 0.08692999184131622, "2443": 0.5612884759902954, "2445": 0.029824240133166313, "2454": 0.5478278398513794, "2470": 0.681853175163269, "2478": 0.0354953333735466, "2491": 0.21922965347766876, "2504": 0.6181373596191406, "2509": 0.18004031479358673, "2511": 0.10467668622732162, "2522": 0.42608439922332764, "2539": 0.21372433006763458, "2558": 0.3897167444229126, "2590": 0.4932899475097656, "2591": 0.1710275560617447, "2620": 0.07431721687316895, "2668": 0.3191637098789215, "2702": 0.31489628553390503, "2730": 0.17267228662967682, "2740": 0.4203280806541443, "2764": 0.44753631949424744, "2775": 0.42225050926208496, "2795": 0.0174254160374403, "2817": 0.7969439625740051, "2866": 0.03925827145576477, "2883": 0.5838727951049805, "2901": 0.841701865196228, "2913": 0.7124901413917542, "2922": 0.23633737862110138, "2944": 0.5640701055526733, "2951": 0.7352184057235718, "2967": 0.04207121208310127, "2988": 0.08961215615272522, "3020": 0.040196798741817474, "3024": 0.06795065850019455, "3025": 0.37035053968429565, "3058": 0.28155985474586487, "3073": 0.0317181795835495, "3120": 0.29400965571403503, "3141": 0.10818854719400406, "3189": 0.259204238653183, "3252": 0.4145384132862091, "3273": 0.23556606471538544, "3276": 0.21687394380569458, "3278": 0.2223619967699051, "3280": 0.36086538434028625, "3344": 0.1229778528213501, "3348": 0.03925827145576477, "3350": 0.9147270321846008, "3378": 0.18816383183002472, "3399": 0.3464667797088623, "3426": 0.23633737862110138, "3435": 0.2184450328350067, "3439": 0.07431721687316895, "3445": 0.18816383183002472, "3446": 0.4980490207672119, "3452": 0.016465263441205025, "3463": 0.22937409579753876, "3465": 0.07612881064414978, "3497": 0.06154331564903259, "3556": 0.043007105588912964, "3563": 0.6254787445068359, "3616": 0.13414156436920166, "3618": 0.036437395960092545, "3623": 0.029824240133166313, "3635": 0.2674594223499298, "3640": 0.14939609169960022, "3643": 0.6471850275993347, "3647": 0.3325583338737488, "3742": 0.5968599319458008, "3778": 0.7210738658905029, "3795": 1.2192846536636353, "3798": 0.5635144114494324, "3808": 0.2652147710323334, "3867": 0.3127557039260864, "3891": 1.2210142612457275, "3896": 0.0174254160374403, "3930": 0.4248080551624298, "3940": 0.043007105588912964, "3979": 0.4462870955467224, "4044": 0.13670019805431366, "4053": 0.10203468054533005, "4094": 0.18654440343379974, "4102": 0.29619070887565613, "4106": 0.42735910415649414, "4118": 0.23479416966438293, "4146": 0.1221139207482338, "4216": 0.36967599391937256, "4229": 0.21372433006763458, "4254": 0.18167030811309814, "4275": 0.4330752193927765, "4281": 0.8917738795280457, "4286": 0.045809537172317505, "4295": 0.9052929878234863, "4319": 0.42161011695861816, "4328": 0.8796916007995605, "4358": 0.565735399723053, "4398": 0.49864232540130615, "4413": 0.5662899017333984, "4456": 0.8238670229911804, "4464": 0.46486347913742065, "4481": 0.11168810725212097, "4483": 0.2881702482700348, "4544": 0.8187123537063599, "4551": 0.07793712615966797, "4595": 0.06612417846918106, "4601": 0.12642613053321838, "4636": 0.5244048833847046, "4664": 0.3910386264324188, "4675": 0.5127768516540527, "4725": 0.4356052577495575, "4758": 0.46853771805763245, "4769": 0.06337817758321762, "4770": 0.4938860833644867, "4795": 0.5762182474136353, "4804": 0.15526613593101501, "4853": 0.14602625370025635, "4926": 0.42225050926208496, "4942": 0.38441169261932373, "4969": 0.5528968572616577, "5002": 0.5930894017219543, "5029": 0.1751343309879303, "5043": 0.037378571927547455, "5084": 0.36967599391937256, "5100": 0.1332872211933136, "5179": 0.6441128253936768, "5197": 0.6754127144813538, "5201": 0.12038381397724152, "5221": 0.06337817758321762, "5229": 0.055094651877880096, "5292": 0.04674193635582924, "5300": 0.40481385588645935, "5320": 0.2034190446138382, "5345": 0.7934166193008423, "5368": 0.0606246218085289, "5387": 0.7528522610664368, "5388": 0.27342069149017334, "5401": 0.19541899859905243, "5468": 0.1401015669107437, "5473": 0.259204238653183, "5531": 0.0058422754518687725, "5593": 0.5629584193229675, "5610": 0.5528968572616577, "5699": 0.2447827309370041, "5761": 0.15023678541183472, "5786": 0.02887592278420925, "5790": 0.2145126610994339, "5816": 0.45499902963638306, "5819": 0.1011524572968483, "5850": 0.4041621685028076, "5857": 0.6369074583053589, "5871": 0.6862877607345581, "5876": 0.8600510358810425, "5950": 0.854249119758606, "5981": 0.5086748600006104, "5986": 0.04113444685935974, "6086": 0.7934166193008423, "6123": 0.7863243818283081, "6165": 0.48850810527801514, "6263": 0.40089741349220276, "6441": 0.8004589080810547, "6480": 0.27044451236724854, "6553": 0.14095009863376617, "6648": 0.22392450273036957, "6677": 0.7426811456680298, "6691": 0.680370569229126, "6721": 0.5629584193229675, "6747": 0.6684301495552063, "6787": 0.11604541540145874, "6937": 0.016465263441205025, "6947": 0.08064348995685577, "6950": 0.0317181795835495, "7011": 0.6000806093215942, "7012": 0.7417513132095337, "7017": 0.5295937061309814, "7080": 0.22859740257263184, "7108": 0.7389566898345947, "7170": 0.25995752215385437, "7189": 0.3170322775840759, "7355": 0.41840189695358276, "7386": 0.1485546976327896, "7524": 1.1236859560012817, "7595": 0.3163207769393921, "7667": 0.7610978484153748, "7680": 0.21687394380569458, "7689": 0.4462870955467224, "7705": 0.9724938273429871, "7711": 0.04767346754670143, "7721": 0.06520967930555344, "7778": 0.791648268699646, "7784": 0.3615458607673645, "7809": 0.2719337046146393, "7831": 0.48068851232528687, "7865": 0.07068414986133575, "7870": 0.8264343738555908, "7882": 0.12728634476661682, "8020": 0.23864774405956268, "8249": 0.026976587250828743, "8280": 0.20739519596099854, "8332": 0.20977331697940826, "8353": 0.1332872211933136, "8554": 0.4831010699272156, "8569": 0.6446255445480347, "8664": 0.3084607720375061, "8732": 0.3615458607673645, "8737": 0.3283478021621704, "8787": 0.6389714479446411, "8800": 0.07159364968538284, "8817": 0.07793712615966797, "8985": 0.004870930220931768, "9002": 0.28082266449928284, "9098": 0.1808556467294693, "9181": 0.5957841277122498, "9312": 0.151916041970253, "9324": 0.565735399723053, "9373": 0.637939989566803, "9422": 0.6764062643051147, "9530": 0.11778303235769272, "9556": 0.757441520690918, "9560": 0.41195443272590637, "9582": 0.16442140936851501, "9662": 0.07612881064414978, "9765": 0.11691460013389587, "9776": 0.23092569410800934, "9874": 0.7047978043556213, "10035": 0.6773988008499146, "10173": 0.10993985831737518, "10174": 0.39433568716049194, "10197": 0.6487176418304443, "10415": 0.6931471824645996, "10426": 0.6764062643051147, "10505": 0.10379679501056671, "10548": 0.07341018319129944, "10611": 0.25694093108177185, "10752": 0.8492490649223328, "10755": 0.6892333030700684, "10776": 0.20580662786960602, "10796": 0.75193190574646, "10831": 1.0506030321121216, "10857": 0.1602703034877777, "10859": 1.2732000350952148, "10880": 0.848413348197937, "11019": 0.007782140281051397, "11179": 0.688742995262146, "11310": 0.10818854719400406, "11534": 0.11168810725212097, "11629": 0.014542185701429844, "11643": 0.31132611632347107, "11704": 0.21372433006763458, "11709": 0.13925230503082275, "11967": 0.6244332790374756, "11980": 0.5784112811088562, "12046": 0.7827593088150024, "12123": 0.846739649772644, "12130": 0.5822374224662781, "12265": 0.6553317308425903, "12374": 0.30989447236061096, "12435": 0.17431432008743286, "12490": 0.026025565341114998, "12596": 0.9178520441055298, "12603": 0.04487626627087593, "12654": 0.817850649356842, "12765": 0.08244366943836212, "12786": 0.4126010537147522, "12826": 0.18167030811309814, "12876": 0.16690383851528168, "12878": 0.7951818704605103, "12906": 0.6118015646934509, "12959": 0.014542185701429844, "13047": 0.012615402229130268, "13105": 0.4002431631088257, "13143": 0.7809720039367676, "13265": 0.554580807685852, "13356": 0.6149744987487793, "13359": 0.37371641397476196, "13436": 0.28082266449928284, "13543": 0.42225050926208496, "13597": 0.083342544734478, "13599": 0.20977331697940826, "13827": 0.8349450826644897, "13912": 0.28963330388069153, "13938": 0.08961215615272522, "14155": 0.29109421372413635, "14171": 0.18004031479358673, "14230": 0.1889725625514984, "14358": 0.34508460760116577, "14379": 0.4944818615913391, "14396": 0.18978065252304077, "14451": 0.06795065850019455, "14506": 0.29036402702331543, "14549": 0.3409265875816345, "14729": 0.5063233375549316, "14817": 0.2447827309370041, "15001": 0.3897167444229126, "15170": 0.7086513638496399, "15306": 0.0058422754518687725, "15356": 0.058784693479537964, "15396": 0.009718249551951885, "15412": 0.8400169610977173, "15451": 0.010684899985790253, "15509": 0.052318159490823746, "15556": 0.12642613053321838, "15559": 0.7408206462860107, "15596": 0.9409833550453186, "15877": 0.15359249711036682, "15901": 0.20022670924663544, "15982": 0.7426811456680298, "16014": 0.037378571927547455, "16033": 0.6059582233428955, "16065": 0.7239188551902771, "16068": 0.19782574474811554, "16087": 0.014542185701429844, "16134": 0.6275664567947388, "16149": 0.42096930742263794, "16268": 0.11951763927936554, "16311": 0.3134697377681732, "16330": 0.38574060797691345, "16452": 0.9650808572769165, "16459": 0.08961215615272522, "16478": 0.0019512200960889459, "16796": 0.37102460861206055, "16820": 0.5618454217910767, "16884": 0.7601850032806396, "16902": 0.029824240133166313, "16928": 0.755608320236206, "16935": 0.0913962796330452, "17159": 0.41195443272590637, "17208": 0.3743882179260254, "17245": 0.2689530849456787, "17253": 0.34577593207359314, "17371": 0.755608320236206, "17522": 0.6739205718040466, "17531": 0.08961215615272522, "17537": 0.020300358533859253, "17613": 0.6139179468154907, "17631": 0.3346569836139679, "17760": 0.4752389192581177, "17832": 0.02792670577764511, "17867": 0.6960725784301758, "17943": 0.25694093108177185, "17961": 0.15693697333335876, "18089": 0.15023678541183472, "18130": 0.23479416966438293, "18191": 0.02792670577764511, "18422": 0.37707099318504333, "18423": 0.7610978484153748, "18509": 1.3610767126083374, "18539": 0.4330752193927765, "18701": 0.08603433519601822, "18723": 0.8550800085067749, "18886": 0.6291293501853943, "18949": 0.33953672647476196, "19037": 0.12642613053321838, "19064": 0.2786078155040741, "19107": 0.7086513638496399, "19132": 0.12038381397724152, "19188": 0.46853771805763245, "19229": 0.16359257698059082, "19235": 0.7925328612327576, "19450": 0.03360854089260101, "19518": 0.151916041970253, "19548": 0.16524957120418549, "19883": 0.17020416259765625, "20077": 0.021256839856505394, "20155": 0.13157635927200317, "20177": 0.22859740257263184, "20272": 0.4228905141353607, "20304": 0.3248254358768463, "20390": 0.11343330889940262, "20482": 0.12470348179340363, "20592": 0.11430477350950241, "20767": 0.18004031479358673, "20794": 0.4926934838294983, "20871": 0.3423145115375519, "21081": 0.22392450273036957, "21453": 0.5506471395492554, "21796": 0.034552380442619324, "21933": 0.7057625651359558, "22010": 0.6603899002075195, "22393": 0.2026219218969345, "22423": 0.07250232994556427, "22634": 0.2763880789279938, "22835": 0.38441169261932373, "22963": 0.22001366317272186, "23041": 0.010684899985790253, "23260": 0.15693697333335876, "23572": 0.012615402229130268, "23900": 0.15943801403045654, "24094": 0.25239890813827515, "24142": 0.013579257763922215, "24155": 0.4132472574710846, "24203": 0.5557019114494324, "24290": 0.06246116757392883, "24370": 0.5784112811088562, "24552": 0.401551216840744, "24665": 0.24325250089168549, "24710": 0.10467668622732162, "24757": 0.11517547070980072, "24768": 0.29981520771980286, "25022": 0.4673144817352295, "25121": 0.20501139760017395, "25135": 0.5990082025527954, "25221": 0.06886265426874161, "25352": 0.46117570996284485, "25353": 0.5979346632957458, "25409": 0.3870677351951599, "25434": 0.5707147121429443, "25480": 0.08154398202896118, "25524": 0.20739519596099854, "25613": 0.1510767638683319, "26163": 0.2231435477733612, "26237": 0.06795065850019455, "26319": 0.42735910415649414, "26462": 0.3883931338787079, "26835": 0.347847044467926, "27758": 0.5805994272232056, "27794": 0.8400169610977173, "28025": 0.15442965924739838, "28093": 0.43938836455345154, "28321": 0.3750596046447754, "28465": 0.3743882179260254, "28488": 0.07341018319129944, "29048": 0.11865071207284927, "29191": 0.0752234235405922, "29299": 0.5220900774002075, "29361": 0.16690383851528168, "29446": 0.13414156436920166} | 13770184 | BACKGROUND The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING Bill & Melinda Gates Foundation. | Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 |
{"1011": 0.06977381557226181, "1019": 0.18816383183002472, "1038": 0.5893046259880066, "1044": 0.2976420819759369, "1053": 0.5957841277122498, "1054": 0.6389714479446411, "2002": 1.0512858629226685, "2003": 0.24325250089168549, "2013": 0.1485546976327896, "2014": 0.41840189695358276, "2024": 0.3784096837043762, "2029": 0.18978065252304077, "2060": 0.11691460013389587, "2063": 0.12728634476661682, "2078": 0.4228905141353607, "2079": 0.2990913391113281, "2104": 0.20501139760017395, "2109": 0.0842406153678894, "2116": 0.13499516248703003, "2128": 0.5573811531066895, "2140": 0.14518201351165771, "2155": 0.9515975713729858, "2169": 0.35334911942481995, "2176": 0.06154331564903259, "2177": 0.06795065850019455, "2179": 0.09406650811433792, "2188": 0.6107416749000549, "2266": 0.42735910415649414, "2274": 0.44753631949424744, "2339": 0.022212404757738113, "2372": 0.4177590310573578, "2377": 0.05970508232712746, "2407": 0.32341301441192627, "2421": 0.17922431230545044, "2426": 0.10026945173740387, "2443": 0.1064341589808464, "2470": 0.5168620347976685, "2515": 0.20739519596099854, "2529": 0.9710156321525574, "2535": 0.5968599319458008, "2549": 0.4400174915790558, "2590": 0.6086184978485107, "2920": 0.1751343309879303, "2945": 0.6911921501159668, "2950": 0.0606246218085289, "3036": 0.26820653676986694, "3125": 0.11865071207284927, "3141": 0.09050461649894714, "3248": 0.1602703034877777, "3278": 0.35677260160446167, "3289": 0.18492233753204346, "3344": 0.010684899985790253, "3366": 1.0735615491867065, "3378": 0.12470348179340363, "3468": 0.2969166338443756, "3508": 0.2034190446138382, "3526": 0.3416208028793335, "3615": 0.3374483287334442, "3619": 0.15359249711036682, "3625": 0.09850110858678818, "3670": 0.1229778528213501, "3800": 0.15943801403045654, "3853": 0.5712664127349854, "3860": 0.045809537172317505, "4047": 0.02792670577764511, "4127": 0.021256839856505394, "4160": 1.534006953239441, "4187": 0.5455666780471802, "4226": 0.1384023278951645, "4254": 0.36697331070899963, "4256": 0.37974658608436584, "4286": 0.8366385698318481, "4295": 0.49864232540130615, "4310": 0.4818955361843109, "4395": 0.5387523174285889, "4442": 0.1477125883102417, "4450": 0.20660123229026794, "4824": 0.3248254358768463, "4962": 0.7710843086242676, "4972": 0.39893341064453125, "5014": 0.1229778528213501, "5070": 0.012615402229130268, "5197": 0.5696102976799011, "5224": 0.29328158497810364, "5250": 1.1369311809539795, "5292": 0.11081436276435852, "5369": 0.3949938118457794, "5425": 0.32129061222076416, "5441": 0.4855078160762787, "5449": 0.4518963396549225, "5500": 0.08513788133859634, "5537": 0.12814582884311676, "5596": 0.07431721687316895, "5680": 0.2409527748823166, "5792": 0.23092569410800934, "5799": 0.5478278398513794, "5826": 0.5238267183303833, "6032": 0.7925328612327576, "6064": 0.9470623731613159, "6190": 0.21922965347766876, "6540": 0.6228629946708679, "6560": 0.040196798741817474, "6590": 0.4873090982437134, "6697": 1.151856780052185, "6792": 0.21765978634357452, "6897": 0.1212492436170578, "6924": 0.4190443754196167, "7065": 0.19782574474811554, "7192": 0.603290855884552, "7337": 0.030771657824516296, "7366": 0.2501201331615448, "7403": 0.7500885725021362, "7461": 0.13243216276168823, "7505": 0.08961215615272522, "7741": 0.3283478021621704, "7772": 0.05417001247406006, "7784": 0.31489628553390503, "7870": 0.36086538434028625, "7883": 0.04953393340110779, "7900": 0.18978065252304077, "8001": 0.28963330388069153, "8080": 0.022212404757738113, "8171": 1.1437997817993164, "8290": 0.5584990978240967, "8291": 0.3012613356113434, "8347": 0.10467668622732162, "8360": 0.18329764902591705, "8498": 0.36290550231933594, "8553": 0.016465263441205025, "8583": 0.9115922451019287, "8640": 0.1510767638683319, "8678": 0.018384648486971855, "8715": 0.5495203733444214, "8822": 0.40546512603759766, "8991": 0.5767669677734375, "9007": 0.8666408061981201, "9096": 0.04860413447022438, "9099": 0.12814582884311676, "9165": 0.5893046259880066, "9211": 0.9084475636482239, "9319": 0.3554046154022217, "9363": 0.7229714393615723, "9412": 0.3897167444229126, "9536": 0.012615402229130268, "9589": 0.07159364968538284, "9799": 0.10379679501056671, "9867": 1.1616848707199097, "10266": 0.7647408246994019, "10315": 0.1905880719423294, "10327": 0.8143964409828186, "10461": 0.08244366943836212, "10539": 0.11691460013389587, "10737": 0.010684899985790253, "10738": 0.014542185701429844, "10788": 0.47158926725387573, "10861": 0.47584590315818787, "10958": 0.1751343309879303, "11022": 0.5762182474136353, "11106": 0.05970508232712746, "11109": 0.18167030811309814, "11326": 0.15442965924739838, "11598": 0.5033760666847229, "11631": 0.17020416259765625, "11835": 0.472198486328125, "12115": 0.19381128251552582, "12137": 0.03925827145576477, "12317": 0.08244366943836212, "12534": 0.2231435477733612, "12562": 0.5590575933456421, "12631": 0.09406650811433792, "12667": 0.14264501631259918, "12702": 0.3662964701652527, "12987": 0.5495203733444214, "13458": 1.086165428161621, "13671": 0.5010119676589966, "13675": 0.08692999184131622, "13728": 1.0444365739822388, "13922": 0.029824240133166313, "14080": 0.009718249551951885, "14193": 0.8813109993934631, "14240": 1.2759300470352173, "14471": 0.42353010177612305, "14480": 0.25694093108177185, "14494": 0.19541899859905243, "14670": 0.15610189735889435, "14702": 0.36697331070899963, "14800": 0.009718249551951885, "15059": 0.18004031479358673, "15258": 0.2105647772550583, "15527": 0.05417001247406006, "15543": 0.20102575421333313, "15826": 0.02412080205976963, "16167": 0.1889725625514984, "16221": 0.3381449282169342, "16285": 0.6538092494010925, "16360": 0.4673144817352295, "16387": 0.011650617234408855, "16706": 0.4974553883075714, "16731": 0.22937409579753876, "17341": 0.5517725944519043, "17345": 0.07612881064414978, "17600": 0.1994270235300064, "17654": 0.3864043951034546, "17785": 0.17267228662967682, "18231": 0.0174254160374403, "18260": 0.25088030099868774, "18419": 0.8837352395057678, "18515": 0.6405166387557983, "18549": 0.39893341064453125, "19115": 0.1384023278951645, "19341": 1.1537069082260132, "19500": 0.02412080205976963, "19610": 0.06795065850019455, "19723": 0.175953671336174, "19995": 1.001607894897461, "20226": 0.04674193635582924, "20784": 0.14518201351165771, "20880": 0.3241194784641266, "20996": 0.3084607720375061, "21114": 0.7220231294631958, "21162": 0.015504186972975731, "21252": 0.0019512200960889459, "21262": 0.7153595685958862, "21557": 0.0009760859538801014, "21647": 0.841701865196228, "21766": 0.16690383851528168, "21903": 0.14095009863376617, "21935": 0.5127768516540527, "22026": 0.4425300657749176, "22207": 0.4512746334075928, "22415": 0.13755162060260773, "22931": 0.16110190749168396, "23079": 0.07431721687316895, "23277": 1.185243844985962, "23350": 0.12556517124176025, "23797": 0.1889725625514984, "23900": 0.058784693479537964, "24024": 0.026025565341114998, "24169": 0.4374985992908478, "24501": 0.015504186972975731, "25269": 0.3297532796859741, "25524": 0.41840189695358276, "25743": 0.05970508232712746, "26147": 0.5341835021972656, "26296": 0.28082266449928284, "26534": 0.05786345899105072, "26835": 0.12556517124176025, "27276": 0.037378571927547455, "27697": 0.07793712615966797, "27790": 0.22157983481884003, "28024": 0.37907835841178894, "28389": 0.2667117714881897, "28498": 0.06337817758321762, "28667": 1.346956491470337, "28696": 1.0742288827896118, "28828": 0.1619328260421753, "28829": 0.2501201331615448, "28835": 0.22704219818115234, "29206": 0.28963330388069153} | 13771184 | RecQ helicases are an important family of genome surveillance proteins conserved from bacteria to humans. Each of the five human RecQ helicases plays critical roles in genome maintenance and stability, and the RecQ protein family members are often referred to as guardians of the genome. The importance of these proteins in cellular homeostasis is underscored by the fact that defects in BLM, WRN, and RECQL4 are linked to distinct heritable human disease syndromes. Each human RecQ helicase has a unique set of protein-interacting partners, and these interactions dictate its specialized functions in genome maintenance, including DNA repair, recombination, replication, and transcription. Human RecQ helicases also interact with each other, and these interactions have significant impact on enzyme function. Future research goals in this field include a better understanding of the division of labor among the human RecQ helicases and learning how human RecQ helicases collaborate and cooperate to enhance genome stability. | Human RecQ helicases in DNA repair, recombination, and replication. |
{"1011": 0.12986256182193756, "1039": 0.5232481360435486, "1044": 0.25845035910606384, "1053": 0.35950297117233276, "1055": 0.24631060659885406, "1056": 0.45623743534088135, "1999": 0.13670019805431366, "2000": 0.6902132034301758, "2002": 0.42990362644195557, "2005": 0.5646255612373352, "2006": 0.06977381557226181, "2007": 0.026976587250828743, "2011": 0.04953393340110779, "2020": 0.10379679501056671, "2029": 0.058784693479537964, "2038": 0.14264501631259918, "2042": 0.013579257763922215, "2044": 0.22001366317272186, "2050": 0.32199856638908386, "2051": 0.3963087201118469, "2094": 0.16110190749168396, "2099": 0.1011524572968483, "2106": 0.01934296265244484, "2109": 0.41840189695358276, "2121": 0.2852376699447632, "2140": 0.9256220459938049, "2146": 0.06703783571720123, "2147": 0.26296505331993103, "2152": 0.3283478021621704, "2177": 0.42096930742263794, "2179": 0.0913962796330452, "2206": 0.17922431230545044, "2241": 0.4419025182723999, "2290": 0.2749055027961731, "2303": 0.10555581003427505, "2320": 0.22001366317272186, "2401": 0.0317181795835495, "2410": 0.083342544734478, "2470": 0.10555581003427505, "2491": 0.3864043951034546, "2504": 0.3519764244556427, "2515": 0.16359257698059082, "2531": 0.6064908504486084, "2532": 0.0770333781838417, "2545": 0.6394867897033691, "2546": 0.3615458607673645, "2556": 0.37102460861206055, "2560": 0.8143964409828186, "2571": 0.11517547070980072, "2594": 0.030771657824516296, "2613": 0.23633737862110138, "2659": 0.1510767638683319, "2668": 0.5685047507286072, "2675": 0.2493593990802765, "2677": 0.09317722171545029, "2696": 0.00875066313892603, "2721": 0.5528968572616577, "2764": 0.08961215615272522, "2765": 0.2539152204990387, "2817": 0.2786078155040741, "2822": 0.6086184978485107, "2859": 0.9225212931632996, "2913": 0.12814582884311676, "2920": 0.5893046259880066, "2951": 0.02316705882549286, "2967": 0.2317005842924118, "3141": 0.1734936386346817, "3148": 0.28082266449928284, "3231": 0.2749055027961731, "3269": 0.7408206462860107, "3273": 0.38041436672210693, "3278": 0.1332872211933136, "3344": 0.5618454217910767, "3372": 0.06886265426874161, "3378": 0.07341018319129944, "3388": 0.31560876965522766, "3424": 0.4770587682723999, "3433": 0.6149744987487793, "3445": 0.42096930742263794, "3447": 0.6338034868240356, "3462": 0.9115922451019287, "3463": 0.5860490798950195, "3466": 0.6709295511245728, "3491": 0.18329764902591705, "3556": 0.3622259199619293, "3591": 0.07793712615966797, "3593": 0.6573580503463745, "3597": 0.15943801403045654, "3603": 0.0038986403960734606, "3623": 0.27934664487838745, "3670": 0.7314660549163818, "3671": 0.40220460295677185, "3718": 0.026976587250828743, "3742": 0.5762182474136353, "3787": 0.07250232994556427, "3795": 0.3409265875816345, "3798": 0.5584990978240967, "3858": 0.016465263441205025, "3896": 0.6212902665138245, "3909": 0.319873183965683, "3949": 0.732405424118042, "3979": 0.07250232994556427, "3981": 0.11951763927936554, "4045": 0.037378571927547455, "4054": 0.6482070088386536, "4106": 0.7934166193008423, "4118": 0.347847044467926, "4146": 0.6970458030700684, "4162": 0.6170841455459595, "4179": 0.4974553883075714, "4187": 0.6989894509315491, "4221": 0.04207121208310127, "4235": 0.3547199070453644, "4244": 0.2969166338443756, "4264": 0.6823468804359436, "4281": 0.7809720039367676, "4287": 0.02887592278420925, "4295": 0.6441128253936768, "4304": 0.6583697199821472, "4319": 0.1994270235300064, "4340": 0.021256839856505394, "4353": 0.5220900774002075, "4359": 0.04207121208310127, "4453": 0.6553317308425903, "4456": 0.1332872211933136, "4484": 0.05786345899105072, "4539": 0.11951763927936554, "4632": 0.6202403903007507, "4646": 0.04674193635582924, "4663": 0.045809537172317505, "4668": 0.7220231294631958, "4677": 0.8845420479774475, "4705": 0.2607102394104004, "4710": 0.674915611743927, "4725": 0.45870962738990784, "4747": 0.013579257763922215, "4758": 0.4158279001712799, "4812": 0.4374985992908478, "4819": 0.06703783571720123, "4830": 0.25845035910606384, "4877": 0.12642613053321838, "4962": 0.6006163358688354, "4969": 0.16110190749168396, "5034": 0.574020504951477, "5038": 0.4728073179721832, "5072": 0.2622140049934387, "5144": 0.06246116757392883, "5159": 0.16442140936851501, "5162": 0.4002431631088257, "5178": 0.9037119746208191, "5228": 0.20501139760017395, "5250": 0.5139457583427429, "5360": 0.14686977863311768, "5387": 0.28890204429626465, "5402": 0.7248653769493103, "5413": 1.0423725843429565, "5418": 0.440646231174469, "5423": 1.039613962173462, "5436": 0.5220900774002075, "5468": 0.3027053773403168, "5500": 0.940220832824707, "5524": 0.39433568716049194, "5546": 0.1734936386346817, "5547": 0.011650617234408855, "5604": 0.13925230503082275, "5622": 0.823009729385376, "5648": 0.4824984669685364, "5761": 0.23092569410800934, "5783": 0.1994270235300064, "5796": 0.5973974466323853, "5799": 0.07341018319129944, "5802": 0.022212404757738113, "5811": 0.09850110858678818, "5813": 0.8509185314178467, "5816": 0.5313173532485962, "5845": 0.5629584193229675, "5850": 0.18004031479358673, "5852": 0.08782484382390976, "5860": 0.6970458030700684, "5876": 0.4500300884246826, "5901": 0.11865071207284927, "5911": 0.040196798741817474, "5915": 0.6639154553413391, "5983": 0.0058422754518687725, "6022": 0.8997484445571899, "6064": 0.35060185194015503, "6074": 0.03266380727291107, "6132": 0.15526613593101501, "6135": 0.15526613593101501, "6177": 0.3810817003250122, "6370": 0.12986256182193756, "6381": 0.5244048833847046, "6388": 0.06612417846918106, "6459": 0.21372433006763458, "6529": 0.010684899985790253, "6540": 0.016465263441205025, "6551": 0.1212492436170578, "6590": 0.06886265426874161, "6611": 0.10731173306703568, "6612": 0.03266380727291107, "6638": 0.8400169610977173, "6666": 0.05417001247406006, "6693": 0.14602625370025635, "6709": 0.08782484382390976, "6757": 0.7537717819213867, "6810": 0.053244512528181076, "6845": 0.08064348995685577, "6869": 0.09761575609445572, "6897": 0.27786844968795776, "6906": 0.06977381557226181, "6922": 0.5301685929298401, "7012": 0.021256839856505394, "7060": 0.19622190296649933, "7093": 0.20102575421333313, "7096": 0.34577593207359314, "7099": 0.11691460013389587, "7233": 0.3995884954929352, "7242": 0.19381128251552582, "7265": 0.4624064862728119, "7328": 0.05046287178993225, "7337": 0.755608320236206, "7356": 0.030771657824516296, "7361": 0.1751343309879303, "7366": 0.18654440343379974, "7403": 0.46363574266433716, "7405": 0.32199856638908386, "7438": 0.66441810131073, "7457": 0.04674193635582924, "7461": 0.3916989266872406, "7473": 0.5984715819358826, "7563": 0.08244366943836212, "7594": 0.5151132941246033, "7599": 0.22079704701900482, "7616": 0.43623676896095276, "7629": 0.2231435477733612, "7644": 0.34300774335861206, "7645": 0.09850110858678818, "7704": 0.4673144817352295, "7711": 0.5220900774002075, "7718": 0.30989447236061096, "7816": 0.7239188551902771, "7842": 0.13755162060260773, "7856": 0.3325583338737488, "7870": 0.6970458030700684, "7885": 0.18654440343379974, "7911": 0.2026219218969345, "7932": 0.38041436672210693, "8000": 0.7791815400123596, "8031": 0.8699195384979248, "8040": 1.3862943649291992, "8077": 0.1751343309879303, "8168": 0.41001203656196594, "8171": 0.4974553883075714, "8193": 0.30486753582954407, "8202": 0.0019512200960889459, "8281": 0.3325583338737488, "8290": 0.176772341132164, "8319": 0.040196798741817474, "8337": 0.029824240133166313, "8344": 0.016465263441205025, "8469": 0.018384648486971855, "8516": 0.5209306478500366, "8556": 0.22079704701900482, "8564": 0.574020504951477, "8621": 0.6233867406845093, "8674": 0.10993985831737518, "8700": 0.791648268699646, "8720": 0.15359249711036682, "8738": 0.6075552701950073, "8758": 0.8973627090454102, "8820": 0.2447827309370041, "8830": 0.46608972549438477, "8859": 0.2719337046146393, "8878": 0.056018441915512085, "8913": 0.012615402229130268, "8943": 0.33115679025650024, "8980": 0.7182208299636841, "9007": 0.4349733293056488, "9102": 0.13925230503082275, "9165": 0.5957841277122498, "9336": 0.15023678541183472, "9350": 0.3353555500507355, "9526": 0.0058422754518687725, "9556": 0.07250232994556427, "9597": 0.6312094330787659, "9670": 0.1946154683828354, "9756": 0.02316705882549286, "9766": 0.19782574474811554, "9785": 0.38374659419059753, "9821": 0.39367714524269104, "9839": 0.2983669638633728, "9885": 0.2247048318386078, "9911": 1.0533316135406494, "10003": 0.0770333781838417, "10010": 0.669430673122406, "10090": 0.23015019297599792, "10092": 0.678390383720398, "10174": 0.13925230503082275, "10242": 0.33953672647476196, "10266": 0.10993985831737518, "10318": 0.6207655072212219, "10381": 0.2447827309370041, "10509": 0.2561853528022766, "10548": 0.39367714524269104, "10556": 0.19381128251552582, "10572": 0.791648268699646, "10595": 0.637939989566803, "10610": 0.5483922958374023, "10665": 0.8238670229911804, "10738": 0.8600510358810425, "10751": 0.7500885725021362, "10752": 0.5947071313858032, "10847": 0.5151132941246033, "10857": 0.004870930220931768, "10903": 0.02316705882549286, "10929": 0.03925827145576477, "10960": 0.07341018319129944, "10980": 0.16110190749168396, "11022": 0.4132472574710846, "11077": 0.23247487843036652, "11115": 0.11604541540145874, "11179": 0.29328158497810364, "11211": 0.7067264318466187, "11290": 1.0478670597076416, "11382": 0.24401791393756866, "11423": 0.5336109399795532, "11432": 0.5461324453353882, "11538": 0.28963330388069153, "11709": 0.13414156436920166, "11761": 0.15023678541183472, "11835": 0.014542185701429844, "11867": 0.0913962796330452, "12099": 0.05786345899105072, "12123": 0.2478361576795578, "12204": 0.6301699280738831, "12210": 0.3127557039260864, "12222": 0.5618454217910767, "12318": 0.2976420819759369, "12328": 1.1375575065612793, "12353": 0.04953393340110779, "12377": 0.3304552733898163, "12381": 0.306306391954422, "12448": 0.09850110858678818, "12462": 0.043007105588912964, "12488": 0.15610189735889435, "12707": 0.013579257763922215, "12709": 0.3870677351951599, "12732": 0.6275664567947388, "12737": 0.3170322775840759, "12941": 0.04113444685935974, "12987": 0.42225050926208496, "13012": 0.6773988008499146, "13153": 0.8004589080810547, "13194": 0.19782574474811554, "13241": 0.1913948506116867, "13341": 0.004870930220931768, "13441": 0.4450363218784332, "13458": 0.7067264318466187, "13531": 0.07612881064414978, "13671": 0.0842406153678894, "13786": 0.1734936386346817, "13832": 0.12814582884311676, "13859": 0.006812678650021553, "13871": 0.3824150264263153, "13887": 0.6649205088615417, "13922": 0.09495500475168228, "14061": 0.030771657824516296, "14120": 0.14349138736724854, "14155": 0.12470348179340363, "14229": 0.11604541540145874, "14320": 0.5244048833847046, "14471": 0.08961215615272522, "14667": 0.040196798741817474, "14671": 0.11951763927936554, "14760": 0.21372433006763458, "14811": 0.5116065740585327, "14817": 0.2478361576795578, "14956": 0.8433839678764343, "15000": 1.0960047245025635, "15008": 1.360575795173645, "15113": 0.026025565341114998, "15154": 0.04767346754670143, "15176": 0.38308101892471313, "15303": 0.020300358533859253, "15315": 0.20022670924663544, "15472": 0.6275664567947388, "15569": 0.11256109178066254, "15578": 0.4891071021556854, "15660": 0.07793712615966797, "15788": 0.27934664487838745, "15869": 0.022212404757738113, "15878": 0.8600510358810425, "15901": 0.16524957120418549, "15946": 0.12642613053321838, "16012": 0.8255793452262878, "16026": 0.1401015669107437, "16134": 0.45870962738990784, "16221": 0.09761575609445572, "16285": 0.14939609169960022, "16330": 0.10026945173740387, "16369": 0.09050461649894714, "16452": 0.6950984001159668, "16478": 0.24554696679115295, "16480": 0.6833335757255554, "16515": 0.3339579105377197, "16549": 0.3353555500507355, "16578": 0.2447827309370041, "16642": 0.02316705882549286, "16670": 0.020300358533859253, "16811": 0.3423145115375519, "16910": 0.757441520690918, "17119": 0.4311734735965729, "17261": 0.15359249711036682, "17404": 0.07341018319129944, "17561": 0.09672962874174118, "17643": 0.022212404757738113, "17663": 0.14264501631259918, "17670": 0.6149744987487793, "17710": 1.0094679594039917, "17718": 0.7863243818283081, "17782": 0.7647408246994019, "17785": 0.11168810725212097, "17789": 0.034552380442619324, "17826": 0.2689530849456787, "17908": 0.6202403903007507, "17948": 0.08871890604496002, "18089": 1.0257055759429932, "18178": 0.14939609169960022, "18349": 0.11081436276435852, "18428": 0.1510767638683319, "18452": 0.2493593990802765, "18647": 0.13157635927200317, "18714": 0.0317181795835495, "18803": 0.007782140281051397, "18804": 0.8805016279220581, "18853": 0.2918238639831543, "19009": 0.672426164150238, "19101": 0.920189380645752, "19387": 0.35950297117233276, "19388": 0.2160874605178833, "19649": 0.12642613053321838, "19653": 0.5696102976799011, "19780": 0.1619328260421753, "19825": 0.4002431631088257, "19826": 0.25088030099868774, "19872": 0.07068414986133575, "19942": 0.2105647772550583, "20026": 0.755608320236206, "20155": 0.9005423784255981, "20194": 0.8949713706970215, "20228": 0.3777405619621277, "20253": 0.09672962874174118, "20353": 0.32129061222076416, "20496": 0.02412080205976963, "20752": 0.011650617234408855, "20799": 0.007782140281051397, "20806": 0.1619328260421753, "20817": 0.06429435312747955, "20968": 0.12470348179340363, "21081": 0.010684899985790253, "21150": 0.40546512603759766, "21270": 0.11778303235769272, "21391": 0.08692999184131622, "21453": 0.9076598286628723, "21497": 0.14939609169960022, "21531": 0.5646255612373352, "21575": 0.23092569410800934, "21618": 0.13414156436920166, "21709": 0.7638313174247742, "21716": 0.6118015646934509, "21939": 0.11081436276435852, "22026": 0.5336109399795532, "22419": 0.6075552701950073, "22420": 0.4311734735965729, "22423": 0.02412080205976963, "22447": 0.018384648486971855, "22499": 0.00875066313892603, "22586": 0.13925230503082275, "22618": 0.012615402229130268, "22916": 0.5069117546081543, "22923": 0.020300358533859253, "22975": 0.8973627090454102, "22987": 0.2247048318386078, "22989": 0.08782484382390976, "23067": 0.08692999184131622, "23191": 0.08244366943836212, "23274": 0.056018441915512085, "23309": 0.5398913025856018, "23444": 0.02792670577764511, "23572": 0.19782574474811554, "23586": 0.3019835948944092, "23683": 0.22548456490039825, "23760": 0.8349450826644897, "23924": 0.6000806093215942, "23990": 0.11256109178066254, "24054": 0.4512746334075928, "24110": 0.47463157773017883, "24158": 1.1720224618911743, "24171": 0.34922540187835693, "24203": 0.24554696679115295, "24229": 0.05970508232712746, "24269": 0.16607704758644104, "24278": 0.3318578004837036, "24328": 0.37907835841178894, "24366": 0.48068851232528687, "24448": 0.37102460861206055, "24458": 0.15275461971759796, "24513": 0.3077431619167328, "24516": 0.347847044467926, "24552": 0.9798521995544434, "24562": 0.08961215615272522, "24769": 0.08064348995685577, "24848": 0.15023678541183472, "24914": 0.1677299439907074, "24952": 0.8238670229911804, "24991": 0.20580662786960602, "25176": 0.08513788133859634, "25269": 0.9115922451019287, "25329": 0.5197699069976807, "25456": 0.19220098853111267, "25458": 0.2674594223499298, "25510": 0.8332487344741821, "25524": 0.9739698171615601, "25643": 0.8255793452262878, "25714": 0.20739519596099854, "26083": 0.2478361576795578, "26163": 0.022212404757738113, "26261": 0.7683706283569336, "26402": 0.8600510358810425, "26605": 0.1946154683828354, "26769": 0.040196798741817474, "26773": 0.4537591338157654, "26787": 0.1710275560617447, "27144": 0.23092569410800934, "27216": 0.2822965085506439, "27373": 0.4145384132862091, "27753": 0.2837681770324707, "27766": 0.036437395960092545, "27833": 1.1994705200195312, "27928": 0.21293537318706512, "27965": 0.03266380727291107, "28156": 0.27786844968795776, "28207": 0.757441520690918, "28389": 0.04674193635582924, "28517": 0.05139094591140747, "28621": 0.045809537172317505, "28691": 0.03925827145576477, "28699": 0.5278670787811279, "28848": 0.5180262327194214, "28948": 0.10203468054533005, "29159": 1.4874467849731445, "29237": 0.11430477350950241, "29244": 0.12038381397724152, "29290": 0.022212404757738113, "29295": 0.08513788133859634, "29490": 0.2447827309370041} | 13774178 | BACKGROUND Schisandra, a globally distributed plant, has been widely applied for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China. In the present work, a rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics was conducted to investigate the intervention effect of Schisandra chinensis lignans (SCL) on hyperlipidemia mice induced by high-fat diet (HFD). METHODS Hyperlipidemia mice were orally administered with SCL (100 mg/kg) once a day for 4 weeks. Serum biochemistry assay of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) was conducted to confirm the treatment of SCL on lipid regulation. Metabolomics analysis on serum samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of liver lipid metabolism, sterol regulatory element-binding proteins (SREBPs) and its related gene expressions were measured by quantitative real-time polymerase chain reaction (RT-PCR) for investigating the underlying mechanism. RESULTS Oral administration of SCL significantly decreased the serum levels of TC, TG and LDL-c and increased the serum level of HDL-c in the hyperlipidemia mice, and no effect of SCL on blood lipid levels was observed in control mice. Serum samples were scattered in the PCA scores plots in response to the control, HFD and SCL group. Totally, thirteen biomarkers were identified and nine of them were recovered to the normal levels after SCL treatment. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, the anti-hyperlipidemia mechanisms of SCL may be involved in the following metabolic pathways: tricarboxylic acid (TCA) cycle, synthesis of ketone body and cholesterol, choline metabolism and fatty acid metabolism. Meanwhile, SCL significantly inhibited the mRNA expression level of hepatic lipogenesis genes such as SREBP-1c, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), and decreased the mRNA expression of liver X receptor α (LXRα). Moreover, SCL also significantly decreased the expression level of SREBP-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in the liver of hyperlipidemia mice. CONCLUSION Anti-hyperlipidemia effect of SCL was confirmed by both serum biochemistry and metabolomics analysis. The mechanism may be related to the down-regulation of LXRα/SREBP-1c/FAS/ACC and SREBP2/HMGCR signaling pathways. | Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice |
{"1011": 0.2983669638633728, "1015": 0.2034190446138382, "1019": 0.9092346429824829, "1042": 0.08244366943836212, "1056": 0.1221139207482338, "1999": 0.02887592278420925, "2002": 0.28890204429626465, "2007": 0.12814582884311676, "2008": 0.13925230503082275, "2011": 0.319873183965683, "2028": 0.007782140281051397, "2029": 0.38308101892471313, "2033": 0.5968599319458008, "2041": 0.04113444685935974, "2046": 0.15442965924739838, "2064": 0.05046287178993225, "2072": 0.08692999184131622, "2076": 0.3297532796859741, "2079": 0.16442140936851501, "2102": 1.1147572994232178, "2110": 0.15275461971759796, "2155": 0.9857001900672913, "2163": 0.11778303235769272, "2173": 0.5898461937904358, "2177": 0.08961215615272522, "2179": 0.02316705882549286, "2187": 0.6011518239974976, "2203": 0.8649974465370178, "2213": 0.1485546976327896, "2232": 0.6011518239974976, "2251": 0.010684899985790253, "2255": 0.27786844968795776, "2265": 0.0317181795835495, "2274": 0.77198725938797, "2278": 0.674915611743927, "2362": 0.37907835841178894, "2378": 0.03266380727291107, "2407": 0.00875066313892603, "2433": 0.35745587944984436, "2458": 0.052318159490823746, "2475": 0.45932671427726746, "2487": 0.680370569229126, "2515": 0.20102575421333313, "2535": 0.1873544454574585, "2549": 0.6296497583389282, "2550": 0.07068414986133575, "2560": 0.15275461971759796, "2594": 0.1751343309879303, "2629": 0.791648268699646, "2690": 0.18004031479358673, "2705": 0.38041436672210693, "2719": 0.05046287178993225, "2777": 0.13499516248703003, "2920": 0.06886265426874161, "2922": 0.040196798741817474, "2945": 0.6054253578186035, "2947": 0.058784693479537964, "2953": 0.37707099318504333, "3022": 0.04767346754670143, "3054": 0.9021284580230713, "3170": 0.03925827145576477, "3215": 0.679875910282135, "3217": 0.5646255612373352, "3226": 0.31560876965522766, "3252": 0.07341018319129944, "3311": 0.36358460783958435, "3366": 0.272677481174469, "3367": 0.2786078155040741, "3372": 0.12642613053321838, "3375": 0.022212404757738113, "3378": 0.5685047507286072, "3384": 0.02412080205976963, "3406": 0.14518201351165771, "3445": 0.4145384132862091, "3491": 0.25239890813827515, "3511": 0.30917787551879883, "3526": 0.6764062643051147, "3550": 0.10379679501056671, "3563": 0.007782140281051397, "3587": 0.6461620330810547, "3593": 0.1970241367816925, "3596": 0.25995752215385437, "3623": 0.3141832649707794, "3625": 0.022212404757738113, "3670": 0.520350456237793, "3785": 0.25845035910606384, "3853": 0.4374985992908478, "3914": 0.15693697333335876, "3922": 0.15275461971759796, "3930": 0.018384648486971855, "3935": 0.08692999184131622, "3965": 0.04207121208310127, "4022": 0.4770587682723999, "4063": 0.7656494975090027, "4117": 0.09317722171545029, "4167": 0.14602625370025635, "4195": 0.015504186972975731, "4332": 0.05417001247406006, "4359": 0.4286321699619293, "4442": 0.8306987881660461, "4515": 0.12814582884311676, "4566": 0.08154398202896118, "4697": 0.20739519596099854, "4758": 0.0770333781838417, "4765": 0.3743882179260254, "4833": 0.4412745535373688, "4860": 0.15023678541183472, "4958": 0.6254787445068359, "4962": 0.7665573358535767, "4972": 0.30917787551879883, "4991": 0.6075552701950073, "5016": 0.8997484445571899, "5017": 0.8272887468338013, "5072": 0.083342544734478, "5228": 0.12814582884311676, "5250": 0.28450319170951843, "5257": 0.0029254043474793434, "5292": 0.08961215615272522, "5421": 0.009718249551951885, "5441": 0.0019512200960889459, "5449": 0.2576959431171417, "5537": 0.0019512200960889459, "5547": 0.06429435312747955, "5616": 0.11604541540145874, "5666": 0.77198725938797, "5788": 0.0038986403960734606, "6064": 0.9409833550453186, "6169": 0.791648268699646, "6310": 0.5640701055526733, "6499": 0.6704301834106445, "6562": 0.35813871026039124, "6622": 0.007782140281051397, "6627": 0.052318159490823746, "6806": 0.7473171949386597, "7230": 0.6369074583053589, "7293": 0.812664806842804, "7337": 0.16276304423809052, "7356": 0.030771657824516296, "7361": 0.4794800877571106, "7366": 0.3409265875816345, "7382": 0.12038381397724152, "7403": 0.4067663550376892, "7457": 0.2830325961112976, "7461": 0.022212404757738113, "7584": 0.31204116344451904, "7645": 0.2231435477733612, "7711": 0.2954642176628113, "7816": 0.5021947622299194, "7872": 1.1431772708892822, "7898": 0.025073638185858727, "7900": 0.16524957120418549, "7974": 0.24018502235412598, "8000": 1.1487655639648438, "8153": 0.255429208278656, "8171": 0.33953672647476196, "8306": 0.05786345899105072, "8335": 0.5450005531311035, "8360": 0.17267228662967682, "8449": 0.7592713832855225, "8469": 0.2659635543823242, "8578": 0.2026219218969345, "8586": 0.04953393340110779, "8602": 0.030771657824516296, "8713": 0.7018978595733643, "8760": 0.2018241584300995, "8878": 0.500420093536377, "8915": 1.333663821220398, "9006": 0.27934664487838745, "9007": 1.261651873588562, "9069": 0.41195443272590637, "9096": 0.5145297050476074, "9113": 0.14602625370025635, "9165": 0.45251765847206116, "9319": 0.16276304423809052, "9350": 0.4709797203540802, "9376": 0.8901712894439697, "9496": 0.8517522215843201, "9530": 0.15275461971759796, "9556": 0.25694093108177185, "9610": 0.6522845029830933, "9686": 1.0271050930023193, "10057": 0.11778303235769272, "10074": 0.5789587497711182, "10463": 0.6970458030700684, "10548": 0.2105647772550583, "10572": 0.7845434546470642, "10610": 0.8433839678764343, "10737": 0.00875066313892603, "10738": 0.42225050926208496, "10744": 0.0354953333735466, "10799": 0.05786345899105072, "10814": 0.7417513132095337, "10882": 0.3443928062915802, "10976": 0.5952457785606384, "11008": 0.8433839678764343, "11022": 0.5381823778152466, "11055": 0.03925827145576477, "11265": 0.37974658608436584, "11338": 0.3269403576850891, "11368": 0.7674643993377686, "11432": 0.31560876965522766, "11601": 0.1718502640724182, "11835": 0.12728634476661682, "12222": 0.8731874823570251, "12328": 1.1012130975723267, "12380": 0.678390383720398, "12402": 0.45251765847206116, "12458": 1.1870332956314087, "12516": 0.9379299283027649, "12618": 0.8433839678764343, "12649": 0.012615402229130268, "12719": 0.4374985992908478, "12732": 0.05139094591140747, "12837": 0.43244171142578125, "12987": 0.9455460906028748, "13113": 0.7942996621131897, "13122": 0.7907629609107971, "13321": 0.812664806842804, "13323": 1.2181298732757568, "13458": 0.1734936386346817, "13655": 0.010684899985790253, "13791": 0.48970574140548706, "13880": 0.056018441915512085, "13908": 0.04394211992621422, "13922": 0.21214580535888672, "14080": 0.8039615154266357, "14193": 0.10026945173740387, "14227": 1.452418565750122, "14399": 0.6916812658309937, "14595": 0.036437395960092545, "14795": 0.021256839856505394, "14800": 0.04860413447022438, "14828": 0.2026219218969345, "14925": 0.5098485946655273, "14974": 0.5267143249511719, "15053": 0.18167030811309814, "15074": 0.04767346754670143, "15176": 0.6543170213699341, "15315": 0.49923527240753174, "15527": 0.2667117714881897, "15543": 0.07612881064414978, "15575": 0.09850110858678818, "15758": 0.2637155055999756, "15770": 0.7295845746994019, "15911": 0.472198486328125, "15946": 0.18978065252304077, "16221": 0.18167030811309814, "16257": 0.10379679501056671, "16285": 1.2732000350952148, "16315": 0.29473719000816345, "16360": 0.6931471824645996, "16401": 0.1946154683828354, "16530": 0.5871354341506958, "16661": 0.2830325961112976, "16706": 0.3910386264324188, "16844": 0.5033760666847229, "16862": 0.13499516248703003, "16921": 0.18654440343379974, "16980": 0.469759464263916, "17063": 0.0029254043474793434, "17163": 1.0492360591888428, "17379": 0.8238670229911804, "17441": 0.18411032855510712, "17637": 0.30917787551879883, "18037": 0.7314660549163818, "18260": 0.5151132941246033, "18479": 0.5920094847679138, "18700": 0.30558720231056213, "18714": 0.1358480453491211, "19269": 0.052318159490823746, "19335": 0.10818854719400406, "19362": 0.7674643993377686, "19610": 0.6149744987487793, "19620": 0.2741633653640747, "19653": 0.609149694442749, "19817": 0.5478278398513794, "19884": 0.6699305176734924, "20228": 0.5255602598190308, "20492": 0.012615402229130268, "20544": 0.6872705817222595, "20582": 1.0802149772644043, "20585": 0.19862671196460724, "20752": 0.1011524572968483, "21032": 0.26296505331993103, "21246": 0.006812678650021553, "21575": 0.23092569410800934, "21618": 0.26446542143821716, "21697": 0.05694137513637543, "21903": 0.3757305145263672, "22117": 0.02887592278420925, "22311": 0.8264343738555908, "22330": 0.17840765416622162, "22444": 0.12038381397724152, "22471": 0.7592713832855225, "22595": 1.2129170894622803, "22663": 0.17020416259765625, "22931": 0.10291612148284912, "22974": 0.9717550277709961, "23130": 0.04394211992621422, "23192": 0.05970508232712746, "23216": 0.18004031479358673, "23706": 0.1229778528213501, "23737": 0.15610189735889435, "23760": 0.06703783571720123, "23797": 0.03360854089260101, "24054": 0.05970508232712746, "24169": 0.3134697377681732, "24269": 0.2711893916130066, "24312": 0.02316705882549286, "24374": 0.3283478021621704, "24663": 0.01934296265244484, "24848": 0.06703783571720123, "25002": 0.21687394380569458, "25003": 1.0519683361053467, "25032": 0.8143964409828186, "25170": 0.08961215615272522, "25194": 0.045809537172317505, "25451": 0.5968599319458008, "25644": 0.06612417846918106, "25708": 0.9240728616714478, "25714": 0.8583967685699463, "26042": 0.1718502640724182, "26402": 0.13157635927200317, "26534": 0.23787821829319, "26601": 0.036437395960092545, "26773": 0.6970458030700684, "27321": 0.27712854743003845, "27381": 1.1888195276260376, "27487": 0.07431721687316895, "28086": 1.2991054058074951, "28156": 0.3897167444229126, "28283": 0.755608320236206, "28522": 0.9256220459938049, "28691": 0.10026945173740387, "28774": 0.9425065517425537, "29206": 1.0001721382141113, "29290": 0.2852376699447632, "29516": 0.05970508232712746, "29598": 0.6603899002075195} | 13777138 | TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs. | Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. |
{"1009": 0.32270604372024536, "1011": 0.2983669638633728, "1019": 0.18573370575904846, "1021": 0.6075552701950073, "1052": 0.38308101892471313, "1055": 0.5110208988189697, "2003": 0.06337817758321762, "2008": 0.045809537172317505, "2011": 0.3019835948944092, "2015": 0.7800771594047546, "2024": 0.306306391954422, "2029": 0.3106105625629425, "2064": 0.0038986403960734606, "2072": 0.7086513638496399, "2076": 0.21293537318706512, "2090": 0.15943801403045654, "2091": 0.3070250153541565, "2094": 0.0174254160374403, "2099": 0.083342544734478, "2110": 0.21372433006763458, "2117": 0.09228714555501938, "2121": 0.056018441915512085, "2163": 0.5232481360435486, "2176": 0.3409265875816345, "2177": 0.3519764244556427, "2179": 0.1685553640127182, "2274": 0.06154331564903259, "2278": 0.45251765847206116, "2313": 0.02887592278420925, "2361": 0.6280876994132996, "2458": 0.36426326632499695, "2462": 0.436867892742157, "2475": 0.6054253578186035, "2487": 0.22782009840011597, "2515": 0.007782140281051397, "2522": 0.17431432008743286, "2535": 0.45932671427726746, "2537": 0.025073638185858727, "2550": 0.25845035910606384, "2581": 1.0933903455734253, "2590": 0.5301685929298401, "2629": 0.848413348197937, "2698": 0.2607102394104004, "2750": 0.03831886500120163, "2846": 0.1221139207482338, "2898": 0.4132472574710846, "2920": 0.40806588530540466, "2953": 1.0389231443405151, "2967": 0.13243216276168823, "3161": 0.861702561378479, "3252": 0.009718249551951885, "3276": 0.53589928150177, "3278": 0.06520967930555344, "3375": 1.0533316135406494, "3378": 0.35334911942481995, "3436": 0.3683255612850189, "3445": 0.3106105625629425, "3449": 0.4400174915790558, "3491": 0.12470348179340363, "3508": 0.3027053773403168, "3526": 0.6022219061851501, "3539": 0.8583967685699463, "3558": 0.3601844012737274, "3563": 0.0019512200960889459, "3603": 0.23324857652187347, "3614": 0.3409265875816345, "3623": 0.3930181860923767, "3625": 0.1477125883102417, "3670": 0.7482418417930603, "3853": 0.13157635927200317, "3965": 0.3956514894962311, "4023": 0.23479416966438293, "4160": 0.6563454270362854, "4263": 0.13925230503082275, "4371": 0.5584990978240967, "4395": 0.469759464263916, "4417": 0.45870962738990784, "4442": 0.7463917136192322, "4453": 0.33115679025650024, "4456": 1.013020396232605, "4523": 0.3034266233444214, "4539": 0.9470623731613159, "4691": 0.11430477350950241, "4742": 0.026025565341114998, "4758": 0.16276304423809052, "4949": 0.20739519596099854, "4962": 0.7692760229110718, "5012": 0.02887592278420925, "5197": 0.14264501631259918, "5228": 0.2954642176628113, "5250": 0.6155022978782654, "5258": 0.0058422754518687725, "5391": 0.3850763738155365, "5449": 0.3903779089450836, "5537": 0.034552380442619324, "5642": 0.7305257320404053, "5668": 0.8065804839134216, "5799": 0.26446542143821716, "5856": 0.6543170213699341, "6064": 0.48430517315864563, "6129": 1.0641717910766602, "6169": 0.6165571808815002, "6550": 0.1751343309879303, "6573": 0.6254787445068359, "6591": 0.22626367211341858, "6622": 0.007782140281051397, "6624": 0.0019512200960889459, "6709": 0.2749055027961731, "6911": 0.014542185701429844, "6942": 0.7445381283760071, "7077": 0.02316705882549286, "7080": 0.08154398202896118, "7137": 0.20818853378295898, "7237": 0.22548456490039825, "7324": 0.9598589539527893, "7337": 0.2674594223499298, "7341": 0.2622140049934387, "7356": 0.025073638185858727, "7366": 0.2231435477733612, "7367": 0.7528522610664368, "7403": 0.5483922958374023, "7457": 0.5145297050476074, "7645": 0.09050461649894714, "7698": 0.5244048833847046, "7711": 0.19220098853111267, "7770": 0.8796916007995605, "7816": 0.25694093108177185, "7872": 1.1325355768203735, "7889": 1.0087559223175049, "8031": 0.6048921346664429, "8153": 0.083342544734478, "8171": 0.5301685929298401, "8176": 0.037378571927547455, "8186": 0.5903874635696411, "8197": 1.3449229001998901, "8290": 0.034552380442619324, "8303": 1.2533208131790161, "8327": 0.3615458607673645, "8349": 0.05970508232712746, "8360": 0.6054253578186035, "8713": 0.77198725938797, "8827": 0.129004567861557, "8878": 0.42225050926208496, "8890": 0.0174254160374403, "8991": 0.15610189735889435, "9007": 0.5601736903190613, "9033": 0.8039615154266357, "9090": 0.8715548515319824, "9165": 0.8400169610977173, "9397": 0.08871890604496002, "9416": 0.6704301834106445, "9496": 0.6744182109832764, "9686": 0.8933739066123962, "10099": 0.021256839856505394, "10176": 0.3084607720375061, "10253": 0.04953393340110779, "10266": 0.21293537318706512, "10381": 0.6170841455459595, "10591": 0.5244048833847046, "10595": 0.0058422754518687725, "10599": 0.24401791393756866, "10637": 0.06520967930555344, "10738": 0.2741633653640747, "10744": 0.026025565341114998, "10752": 0.03266380727291107, "10769": 0.4950772523880005, "10814": 0.8492490649223328, "10975": 0.48610860109329224, "11008": 0.8212929964065552, "11022": 0.6043586730957031, "11211": 0.06520967930555344, "11254": 0.0913962796330452, "11369": 0.43244171142578125, "11423": 0.2026219218969345, "11598": 0.10993985831737518, "11601": 0.043007105588912964, "11772": 0.29981520771980286, "11835": 0.03266380727291107, "11916": 0.755608320236206, "11991": 0.2696990668773651, "12115": 0.8492490649223328, "12222": 0.37102460861206055, "12375": 0.574020504951477, "12402": 0.4891071021556854, "12528": 0.27934664487838745, "12673": 0.3423145115375519, "12719": 0.2089812457561493, "12789": 0.08244366943836212, "12987": 1.299638032913208, "13458": 0.7389566898345947, "13656": 0.3757305145263672, "13712": 0.3423145115375519, "13759": 0.06703783571720123, "13791": 0.12814582884311676, "13833": 0.6254787445068359, "13908": 0.7352184057235718, "13922": 0.05970508232712746, "14080": 0.33953672647476196, "14126": 0.5127768516540527, "14187": 0.6181373596191406, "14193": 0.46363574266433716, "14255": 0.32553088665008545, "14397": 0.29473719000816345, "14471": 0.025073638185858727, "14494": 0.1905880719423294, "14719": 0.1332872211933136, "14828": 0.045809537172317505, "15053": 0.09050461649894714, "15059": 0.083342544734478, "15113": 0.05046287178993225, "15420": 1.185243844985962, "15527": 0.14939609169960022, "15543": 0.41840189695358276, "15660": 0.014542185701429844, "15924": 0.9783848524093628, "16007": 0.1677299439907074, "16081": 0.5033760666847229, "16119": 1.035461664199829, "16221": 0.2918238639831543, "16285": 0.40546512603759766, "16341": 0.48970574140548706, "16360": 0.9798521995544434, "16387": 0.9409833550453186, "16389": 0.011650617234408855, "16453": 0.02412080205976963, "16706": 0.2493593990802765, "16834": 0.0354953333735466, "16840": 0.3012613356113434, "16902": 0.8374842405319214, "16913": 0.8600510358810425, "17715": 0.6764062643051147, "17782": 0.8161250352859497, "18089": 0.7370892763137817, "18095": 0.8442239761352539, "18136": 0.38574060797691345, "18231": 0.06795065850019455, "18274": 1.538210391998291, "18404": 0.16359257698059082, "19355": 0.13157635927200317, "19432": 0.07159364968538284, "19563": 0.015504186972975731, "19653": 0.23247487843036652, "19811": 0.4537591338157654, "19824": 0.3409265875816345, "19962": 0.7370892763137817, "20110": 0.500420093536377, "20228": 0.6112717390060425, "20363": 1.076228141784668, "20467": 0.7755908370018005, "20544": 0.18492233753204346, "20817": 0.5596157908439636, "21081": 0.18654440343379974, "21104": 0.022212404757738113, "21112": 0.07612881064414978, "21150": 0.3526630103588104, "21326": 0.5483922958374023, "21370": 0.1602703034877777, "21434": 0.28890204429626465, "21453": 0.32129061222076416, "21508": 0.2018241584300995, "21618": 0.1477125883102417, "21647": 0.018384648486971855, "21716": 0.9842413663864136, "21903": 0.16110190749168396, "21967": 0.083342544734478, "22026": 0.07068414986133575, "22303": 0.0913962796330452, "22327": 0.22157983481884003, "22422": 1.1549384593963623, "22694": 0.15860503911972046, "22851": 0.2969166338443756, "22863": 0.9455460906028748, "22922": 0.0038986403960734606, "23586": 0.45994341373443604, "23737": 0.22626367211341858, "23767": 0.02887592278420925, "23797": 0.07884006202220917, "23900": 0.6921701431274414, "24054": 0.2478361576795578, "24312": 0.15610189735889435, "24670": 0.6233867406845093, "25039": 0.4500300884246826, "25206": 0.04953393340110779, "25409": 0.5756692886352539, "25416": 0.025073638185858727, "25456": 0.2223619967699051, "25468": 0.02792670577764511, "25502": 0.38308101892471313, "25524": 0.03925827145576477, "25582": 0.659380316734314, "25761": 0.1734936386346817, "25879": 0.04113444685935974, "25932": 0.7124901413917542, "26141": 1.5280922651290894, "26189": 0.10555581003427505, "26244": 0.11168810725212097, "26356": 1.061472773551941, "26402": 0.2531573474407196, "26408": 0.013579257763922215, "26512": 0.29328158497810364, "26520": 0.2696990668773651, "26534": 0.33953672647476196, "26572": 1.2980393171310425, "26638": 0.3443928062915802, "26773": 0.07341018319129944, "27144": 0.0354953333735466, "27216": 0.1221139207482338, "27794": 0.9340999722480774, "27846": 0.04487626627087593, "27854": 0.1930064558982849, "28086": 1.197703242301941, "28295": 1.0471819639205933, "28569": 0.31489628553390503, "28848": 0.8004589080810547, "29206": 0.05417001247406006} | 13777706 | Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism. | Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs |
{"1011": 0.1930064558982849, "1015": 0.5551415085792542, "1021": 0.15860503911972046, "1039": 0.5517725944519043, "1040": 0.08154398202896118, "1041": 0.1221139207482338, "1043": 0.18573370575904846, "1047": 0.42608439922332764, "2007": 0.11430477350950241, "2008": 0.10467668622732162, "2028": 0.14686977863311768, "2029": 0.20580662786960602, "2036": 0.36900100111961365, "2063": 0.3622259199619293, "2066": 0.8748174905776978, "2076": 0.034552380442619324, "2090": 0.34370049834251404, "2099": 0.8559102416038513, "2109": 0.12728634476661682, "2124": 0.2531573474407196, "2140": 0.5324648022651672, "2171": 0.02887592278420925, "2178": 0.026025565341114998, "2213": 0.3325583338737488, "2243": 0.9162907600402832, "2334": 0.7220231294631958, "2378": 0.5562619566917419, "2379": 0.22079704701900482, "2389": 0.2954642176628113, "2397": 0.036437395960092545, "2475": 0.5773153901100159, "2478": 0.04767346754670143, "2487": 0.7086513638496399, "2515": 0.28670501708984375, "2535": 0.7286425232887268, "2539": 0.23092569410800934, "2556": 0.43623676896095276, "2575": 0.5860490798950195, "2582": 0.2447827309370041, "2595": 0.43875885009765625, "2629": 0.5455666780471802, "2698": 0.06429435312747955, "2714": 0.10818854719400406, "2734": 0.11517547070980072, "2817": 0.1751343309879303, "2865": 0.6233867406845093, "2869": 0.04207121208310127, "2901": 0.06795065850019455, "2913": 0.36290550231933594, "2920": 0.08692999184131622, "2947": 0.011650617234408855, "2953": 0.3416208028793335, "3130": 0.2976420819759369, "3217": 0.0770333781838417, "3273": 0.0752234235405922, "3283": 0.23247487843036652, "3286": 0.45994341373443604, "3351": 0.03925827145576477, "3378": 0.03925827145576477, "3393": 0.4831010699272156, "3406": 0.3870677351951599, "3424": 0.6926587820053101, "3433": 0.8306987881660461, "3445": 0.030771657824516296, "3463": 0.006812678650021553, "3518": 0.13071982562541962, "3525": 0.06795065850019455, "3526": 0.5427330136299133, "3593": 0.49864232540130615, "3603": 0.05786345899105072, "3623": 0.1358480453491211, "3625": 0.04767346754670143, "3640": 0.05139094591140747, "3670": 0.5086748600006104, "3674": 0.09406650811433792, "3695": 0.47463157773017883, "3853": 0.3177432417869568, "3917": 0.7692760229110718, "4013": 0.6363908052444458, "4081": 0.259204238653183, "4134": 0.5364705324172974, "4168": 0.3750596046447754, "4263": 0.659380316734314, "4346": 0.05417001247406006, "4395": 0.6123310327529907, "4442": 0.630689799785614, "4453": 0.2983669638633728, "4456": 0.28890204429626465, "4539": 0.07793712615966797, "4642": 1.1592369079589844, "4742": 0.46363574266433716, "4745": 0.29255300760269165, "4800": 0.8298473954200745, "4939": 1.0601204633712769, "4957": 0.6699305176734924, "4962": 0.6634125709533691, "4972": 0.1734936386346817, "5017": 1.105748176574707, "5072": 0.06703783571720123, "5173": 0.6989894509315491, "5228": 0.13071982562541962, "5250": 0.5800528526306152, "5302": 0.5444341897964478, "5326": 0.15442965924739838, "5393": 0.2711893916130066, "5423": 0.7665573358535767, "5449": 0.1401015669107437, "5547": 0.08154398202896118, "5666": 0.3910386264324188, "5668": 0.1905880719423294, "5705": 0.3526630103588104, "5769": 0.3127557039260864, "5794": 0.5324648022651672, "5799": 0.5244048833847046, "5813": 0.09228714555501938, "5887": 0.9240728616714478, "6064": 0.08244366943836212, "6083": 0.4518963396549225, "6194": 0.0009760859538801014, "6370": 0.07250232994556427, "6483": 0.17267228662967682, "6591": 0.4177590310573578, "6592": 0.6522845029830933, "6693": 0.823009729385376, "6869": 0.2954642176628113, "6873": 0.5116065740585327, "6897": 0.5010119676589966, "6968": 0.6223390698432922, "6971": 0.2741633653640747, "7127": 0.28450319170951843, "7246": 0.5778634548187256, "7337": 0.23556606471538544, "7366": 0.23092569410800934, "7403": 0.2696990668773651, "7457": 0.1619328260421753, "7755": 0.13499516248703003, "7939": 0.732405424118042, "8000": 1.0519683361053467, "8031": 0.4356052577495575, "8114": 0.1994270235300064, "8161": 0.3304552733898163, "8171": 0.417115718126297, "8197": 0.07431721687316895, "8290": 0.7086513638496399, "8360": 0.3949938118457794, "8445": 0.056018441915512085, "8449": 0.7163142561912537, "8469": 0.09761575609445572, "8525": 0.32553088665008545, "8733": 0.176772341132164, "8878": 0.29619070887565613, "9007": 0.2881702482700348, "9099": 0.7473171949386597, "9104": 0.33953672647476196, "9165": 0.5151132941246033, "9230": 0.791648268699646, "9280": 0.24401791393756866, "9350": 0.44753631949424744, "9358": 0.4400174915790558, "9496": 0.24018502235412598, "9530": 0.09938567131757736, "9556": 0.2674594223499298, "9574": 0.0019512200960889459, "9597": 0.07159364968538284, "9821": 0.1229778528213501, "10047": 0.04767346754670143, "10085": 0.31560876965522766, "10210": 0.22704219818115234, "10253": 0.7314660549163818, "10258": 0.6522845029830933, "10266": 0.6064908504486084, "10359": 0.23787821829319, "10381": 0.2539152204990387, "10395": 0.08603433519601822, "10507": 1.0540125370025635, "10556": 0.01934296265244484, "10572": 0.49030399322509766, "10663": 0.3325583338737488, "10744": 0.022212404757738113, "10769": 1.3279863595962524, "10889": 0.46363574266433716, "10960": 0.5438674688339233, "11211": 0.9922385215759277, "11263": 0.7592713832855225, "11311": 0.9363996982574463, "11382": 0.0606246218085289, "11383": 0.19541899859905243, "11432": 0.29473719000816345, "11455": 0.22859740257263184, "11461": 0.6482070088386536, "11521": 0.472198486328125, "11835": 0.40089741349220276, "12123": 0.8641747236251831, "12190": 1.2721059322357178, "12319": 0.0019512200960889459, "12328": 1.2421036958694458, "12541": 0.23324857652187347, "12562": 0.3353555500507355, "12631": 0.03925827145576477, "12731": 0.15442965924739838, "13024": 0.5990082025527954, "13366": 0.6000806093215942, "13369": 0.6664261221885681, "13626": 0.5506471395492554, "13767": 0.15943801403045654, "13791": 0.7201237678527832, "13833": 1.3001704216003418, "13922": 0.13670019805431366, "14061": 0.46853771805763245, "14067": 0.2667117714881897, "14074": 0.13157635927200317, "14120": 0.3070250153541565, "14187": 0.5220900774002075, "14228": 0.18248429894447327, "14321": 0.030771657824516296, "14322": 0.07341018319129944, "14357": 0.39367714524269104, "14828": 0.20660123229026794, "14905": 0.6400018334388733, "15403": 0.3464667797088623, "15680": 0.8567397594451904, "16012": 0.2223619967699051, "16026": 0.18654440343379974, "16147": 0.9232974052429199, "16221": 0.052318159490823746, "16226": 0.732405424118042, "16505": 0.10379679501056671, "16643": 0.45499902963638306, "16862": 0.3554046154022217, "17076": 0.6654226183891296, "17250": 0.5168620347976685, "17366": 0.4794800877571106, "17379": 0.26446542143821716, "17441": 0.0770333781838417, "17598": 0.8004589080810547, "17788": 0.2696990668773651, "17856": 0.956112265586853, "17971": 1.3535370826721191, "18053": 0.7314660549163818, "18119": 0.09050461649894714, "18120": 0.11430477350950241, "18178": 1.3998736143112183, "18211": 0.996573805809021, "18228": 0.2026219218969345, "18231": 0.016465263441205025, "18243": 0.9256220459938049, "18291": 0.5324648022651672, "18612": 0.4450363218784332, "18714": 0.24171993136405945, "18715": 0.0842406153678894, "18827": 0.18978065252304077, "18861": 0.15023678541183472, "18888": 0.23402166366577148, "18900": 0.6543170213699341, "18938": 0.12384103983640671, "18954": 0.7683706283569336, "19317": 0.37102460861206055, "19321": 0.9147270321846008, "19653": 0.7934166193008423, "19780": 0.5640701055526733, "19872": 0.26146242022514343, "20132": 0.5330380201339722, "20187": 1.0533316135406494, "20350": 0.006812678650021553, "20544": 0.2674594223499298, "20752": 0.06246116757392883, "20817": 0.7333439588546753, "20974": 1.4478377103805542, "21471": 0.006812678650021553, "21486": 0.1011524572968483, "21733": 0.7182208299636841, "21890": 0.603290855884552, "21903": 0.7370892763137817, "21919": 0.04113444685935974, "21926": 1.2012346982955933, "21935": 0.05046287178993225, "22025": 0.1751343309879303, "22262": 0.045809537172317505, "22330": 0.10993985831737518, "22648": 0.7610978484153748, "22684": 0.32553088665008545, "22806": 0.4709797203540802, "22907": 0.3963087201118469, "22931": 0.03360854089260101, "23041": 0.5421652793884277, "23150": 0.15943801403045654, "23216": 0.07068414986133575, "23586": 0.3339579105377197, "23616": 0.906871497631073, "23737": 0.8973627090454102, "23833": 0.1358480453491211, "23924": 0.11865071207284927, "24004": 0.6739205718040466, "24054": 0.5261374711990356, "24269": 0.8715548515319824, "24278": 0.8813109993934631, "24418": 0.4002431631088257, "24594": 0.2637155055999756, "24848": 0.08154398202896118, "25456": 0.24325250089168549, "25499": 0.7342816591262817, "25714": 0.6911921501159668, "26402": 0.8550800085067749, "26632": 0.5909284353256226, "26651": 0.19541899859905243, "27133": 0.6394867897033691, "27144": 1.0430610179901123, "27321": 0.08961215615272522, "27487": 0.06612417846918106, "27781": 0.0354953333735466, "27854": 1.2094266414642334, "27989": 0.9333322048187256, "28156": 0.16524957120418549, "28227": 0.3910386264324188, "28314": 0.16524957120418549, "28667": 0.5433003902435303, "28674": 0.8500841856002808, "28873": 0.7389566898345947, "29290": 0.2852376699447632, "29304": 0.5778634548187256} | 13778710 | Chemokine-like receptor 1 (CMKLR1), also known as ChemR23, and chemokine (C-C motif) receptor-like 2 (CCRL2) are 7-transmembrane receptors that were cloned in the late 1990s based on their homology to known G-protein-coupled receptors. They were previously orphan receptors without any known biological roles; however, recent studies identified ligands for these receptors and their functions have begun to be unveiled. The plasma protein-derived chemoattractant chemerin is a ligand for CMKLR1 and activation of CMKLR1 with chemerin induces the migration of macrophages and dendritic cells (DCs) in vitro, suggesting a proinflammatory role. However, in vivo studies using CMKLR-deficient mice suggest an anti-inflammatory role for this receptor, possibly due to the recruitment of tolerogenic plasmacytoid DCs. Chemerin/CMKLR1 interaction also promotes adipogenesis and angiogenesis. The anti-inflammatory lipid mediator, resolving E1, is another CMKLR1 ligand and it inhibits leukocyte infiltration and proinflammatory gene expression. These divergent results suggest that CMKLR1 is a multifunctional receptor. The chemokine CCL5 and CCL19 are reported to bind to CCRL2. Like Duffy antigen for chemokine receptor (DARC), D6 and CCX-CKR, CCRL2 does not signal, but it constitutively recycles, potentially reducing local concentration of CCL5 and CCL19 and subsequent immune responses. Surprisingly, chemerin, a ligand for CMKLR1, is a ligand for CCRL2. CCRL2 binds chemerin and increases local chemerin concentration to efficiently present it to CMKLR1 on nearby cells, providing a link between CCRL2 and CMKLR1. Although these findings suggest an anti-inflammatory role, a recent study using CCRL2-deficient mice indicates a proinflammatory role; thus, CCRL2 may also be multifunctional. Further studies using CMKLR1- or CCRL2-deficient mice are needed to further define the role of these receptors in immune responses and other cellular processes. | Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties. |
{"1017": 0.2539152204990387, "1039": 0.7182208299636841, "1058": 0.5914691090583801, "2003": 0.015504186972975731, "2011": 0.4818955361843109, "2013": 0.28963330388069153, "2024": 0.14179791510105133, "2029": 0.05046287178993225, "2045": 0.1358480453491211, "2076": 0.07793712615966797, "2078": 0.07341018319129944, "2079": 0.21372433006763458, "2083": 0.33325836062431335, "2091": 0.28082266449928284, "2119": 0.1332872211933136, "2170": 0.3723714053630829, "2179": 0.29109421372413635, "2220": 0.06246116757392883, "2229": 0.5696102976799011, "2278": 1.1153976917266846, "2306": 0.20660123229026794, "2334": 0.5098485946655273, "2339": 0.04207121208310127, "2378": 0.7809720039367676, "2407": 0.18816383183002472, "2415": 0.02792670577764511, "2433": 0.4673144817352295, "2442": 0.1710275560617447, "2507": 0.37035053968429565, "2509": 0.21214580535888672, "2515": 0.1677299439907074, "2527": 0.06703783571720123, "2529": 0.46363574266433716, "2535": 0.2409527748823166, "2550": 0.07159364968538284, "2594": 0.2607102394104004, "2638": 0.9021284580230713, "2659": 0.22626367211341858, "2664": 0.24171993136405945, "2668": 0.06703783571720123, "2719": 0.15023678541183472, "2765": 0.41647201776504517, "2828": 0.40806588530540466, "2856": 0.0029254043474793434, "2890": 0.02316705882549286, "2920": 0.14095009863376617, "2925": 0.2478361576795578, "2947": 0.08871890604496002, "2969": 0.7827593088150024, "3117": 0.4728073179721832, "3161": 0.083342544734478, "3209": 0.14095009863376617, "3226": 0.7182208299636841, "3227": 0.33325836062431335, "3298": 0.2749055027961731, "3350": 0.7201237678527832, "3370": 0.25845035910606384, "3378": 0.07159364968538284, "3463": 0.20421554148197174, "3491": 0.15526613593101501, "3525": 0.35060185194015503, "3526": 0.9769153594970703, "3550": 0.08961215615272522, "3563": 0.04767346754670143, "3595": 0.0606246218085289, "3596": 0.32129061222076416, "3597": 0.18329764902591705, "3619": 0.5805994272232056, "3625": 0.5936289429664612, "3674": 0.4196864068508148, "3796": 0.3683255612850189, "3800": 0.0038986403960734606, "3853": 0.1384023278951645, "3930": 0.5707147121429443, "3949": 0.29036402702331543, "3957": 0.27786844968795776, "3989": 0.6714286804199219, "4005": 0.06154331564903259, "4050": 0.07068414986133575, "4062": 0.02316705882549286, "4072": 0.10993985831737518, "4125": 0.5920094847679138, "4127": 0.45994341373443604, "4130": 0.025073638185858727, "4167": 0.2822965085506439, "4195": 0.7537717819213867, "4286": 0.28670501708984375, "4439": 0.21765978634357452, "4442": 1.1462857723236084, "4453": 0.34922540187835693, "4456": 1.3423751592636108, "4469": 0.5784112811088562, "4517": 0.45870962738990784, "4539": 0.0019512200960889459, "4649": 0.36086538434028625, "4654": 0.45437926054000854, "4678": 0.8567397594451904, "4742": 0.4938860833644867, "4921": 0.010684899985790253, "4937": 0.6451379656791687, "4939": 0.020300358533859253, "4962": 0.5551415085792542, "4975": 0.055094651877880096, "5117": 0.6212902665138245, "5182": 0.0770333781838417, "5250": 0.08692999184131622, "5258": 0.11951763927936554, "5267": 0.14349138736724854, "5320": 0.1229778528213501, "5387": 0.4770587682723999, "5533": 0.25995752215385437, "5643": 0.006812678650021553, "5716": 0.27342069149017334, "5850": 0.025073638185858727, "5876": 0.6160298585891724, "5991": 0.24248650670051575, "6026": 0.0842406153678894, "6074": 0.06795065850019455, "6169": 1.1102628707885742, "6177": 0.27934664487838745, "6234": 0.10731173306703568, "6459": 0.058784693479537964, "6461": 0.3409265875816345, "6541": 1.022197961807251, "6593": 1.02149498462677, "6648": 0.20102575421333313, "6657": 0.8600510358810425, "6761": 0.23864774405956268, "6914": 0.5893046259880066, "6922": 0.5914691090583801, "7076": 0.3034266233444214, "7242": 0.5523349046707153, "7246": 0.22859740257263184, "7275": 0.9900637865066528, "7337": 0.6348392367362976, "7356": 0.02792670577764511, "7366": 0.255429208278656, "7403": 0.3346569836139679, "7438": 0.06612417846918106, "7531": 1.0137293338775635, "7578": 0.1212492436170578, "7645": 0.23092569410800934, "7755": 0.5478278398513794, "7790": 0.637939989566803, "7872": 1.420846700668335, "7934": 0.0174254160374403, "8123": 0.8550800085067749, "8147": 0.1401015669107437, "8153": 0.38308101892471313, "8247": 1.005902886390686, "8292": 0.010684899985790253, "8526": 0.3464667797088623, "8534": 0.004870930220931768, "8578": 0.46608972549438477, "8586": 0.20977331697940826, "8663": 0.06977381557226181, "8754": 0.03360854089260101, "8878": 0.24248650670051575, "9006": 0.2689530849456787, "9007": 0.3262358605861664, "9031": 0.06612417846918106, "9100": 0.28670501708984375, "9153": 0.13414156436920166, "9165": 0.6410312056541443, "9253": 0.7067264318466187, "9297": 0.43244171142578125, "9336": 0.10379679501056671, "9416": 0.1212492436170578, "9468": 0.5871354341506958, "9530": 0.06154331564903259, "9626": 0.44753631949424744, "9793": 0.1718502640724182, "10085": 0.04487626627087593, "10507": 0.2089812457561493, "10572": 0.5272908806800842, "10580": 0.0038986403960734606, "10595": 0.42353010177612305, "10610": 0.25467249751091003, "10624": 0.3615458607673645, "10722": 0.11951763927936554, "10744": 0.12470348179340363, "10782": 0.21765978634357452, "10851": 0.5278670787811279, "10956": 0.20102575421333313, "11234": 0.053244512528181076, "11265": 0.08782484382390976, "11443": 0.1011524572968483, "11601": 0.28670501708984375, "11973": 0.036437395960092545, "12115": 0.4654768109321594, "12123": 0.5151132941246033, "12222": 0.1485546976327896, "12247": 0.036437395960092545, "12402": 0.6482070088386536, "12407": 0.007782140281051397, "12477": 0.7426811456680298, "12530": 0.04207121208310127, "12562": 0.27712854743003845, "12732": 0.6629094481468201, "12798": 0.6149744987487793, "12854": 0.0606246218085289, "13013": 1.0101795196533203, "13046": 0.4734157919883728, "13197": 0.05139094591140747, "13330": 0.15526613593101501, "13368": 0.11256109178066254, "13441": 0.12986256182193756, "13595": 0.07068414986133575, "13656": 1.3118107318878174, "13791": 0.1619328260421753, "13833": 0.08782484382390976, "13910": 0.953857421875, "14524": 0.5301685929298401, "14769": 0.8941729068756104, "14828": 0.41840189695358276, "14988": 0.09584271162748337, "15370": 0.2089812457561493, "15660": 0.1332872211933136, "15946": 0.1221139207482338, "15986": 0.5540198087692261, "16007": 0.5860490798950195, "16026": 0.31132611632347107, "16074": 0.11430477350950241, "16257": 0.00875066313892603, "16285": 0.08513788133859634, "16387": 0.5773153901100159, "16463": 0.05417001247406006, "16480": 0.31132611632347107, "16492": 0.018384648486971855, "16505": 0.27564704418182373, "16649": 0.18816383183002472, "16670": 0.12038381397724152, "16677": 0.0019512200960889459, "16745": 0.9294845461845398, "16771": 0.16690383851528168, "16882": 0.9440274834632874, "16910": 0.680370569229126, "16913": 0.07250232994556427, "17261": 0.11081436276435852, "17379": 0.06703783571720123, "17820": 1.04512357711792, "17890": 1.0137293338775635, "18178": 0.674915611743927, "18349": 0.38308101892471313, "18436": 0.02316705882549286, "18439": 0.13925230503082275, "18514": 0.040196798741817474, "18595": 0.7881022095680237, "18714": 0.4132472574710846, "18804": 0.39367714524269104, "18856": 0.013579257763922215, "18886": 0.7898768186569214, "19589": 0.23556606471538544, "19601": 0.06520967930555344, "19653": 0.5762182474136353, "19824": 0.5914691090583801, "19872": 0.175953671336174, "20014": 0.9131608605384827, "20045": 0.13755162060260773, "20116": 1.3520222902297974, "20194": 0.8731874823570251, "20199": 0.19381128251552582, "20350": 0.16110190749168396, "20360": 0.820433497428894, "20544": 0.07068414986133575, "20576": 0.24018502235412598, "20582": 1.2948341369628906, "20687": 0.8117979168891907, "20752": 0.3750596046447754, "20852": 0.24401791393756866, "20875": 0.32764431834220886, "20900": 0.21293537318706512, "21032": 0.8161250352859497, "21081": 0.6543170213699341, "21434": 1.2215901613235474, "21471": 0.19220098853111267, "21754": 0.06612417846918106, "21770": 0.8699195384979248, "21823": 0.34300774335861206, "21864": 0.9515975713729858, "21906": 0.11517547070980072, "21919": 0.21922965347766876, "22318": 0.03831886500120163, "22330": 0.26296505331993103, "22694": 0.016465263441205025, "23216": 0.10555581003427505, "23586": 0.47036975622177124, "23737": 0.2231435477733612, "24004": 0.1751343309879303, "24054": 0.5584990978240967, "24255": 0.29036402702331543, "24269": 0.9886114001274109, "24374": 0.7333439588546753, "24759": 0.04487626627087593, "24848": 1.0587663650512695, "24854": 0.7258110046386719, "24873": 0.0029254043474793434, "25409": 0.9463045597076416, "25456": 0.43875885009765625, "25468": 0.2983669638633728, "25502": 0.7067264318466187, "25714": 1.160461664199829, "25778": 0.25467249751091003, "26402": 0.8682814836502075, "26520": 0.09317722171545029, "26616": 0.7086513638496399, "26721": 0.9680526852607727, "27144": 0.6265231370925903, "27152": 0.7500885725021362, "27166": 0.22157983481884003, "27321": 0.13414156436920166, "27343": 0.3588210940361023, "27777": 0.09050461649894714, "27854": 0.007782140281051397, "27881": 0.45870962738990784, "28086": 0.29473719000816345, "28207": 0.3077431619167328, "28522": 0.29255300760269165, "28711": 0.11604541540145874, "28723": 0.0038986403960734606, "28788": 0.24554696679115295, "28873": 0.04953393340110779, "29109": 0.3381449282169342, "29217": 0.04394211992621422, "29290": 0.1221139207482338} | 13779605 | There is mounting evidence that tumors are initiated by a rare subset of cells called cancer stem cells (CSCs). CSCs are generally quiescent, self-renew, form tumors at low numbers, and give rise to the heterogeneous cell types found within a tumor. CSCs isolated from multiple tumor types differentiate both in vivo and in vitro when cultured in serum, yet the factors responsible for their differentiation have not yet been identified. Here we show that vitronectin is the component of human serum driving stem cell differentiation through an integrin alpha V beta 3-dependent mechanism. CSCs cultured on vitronectin result in downregulation of stem cell genes, modulation of differentiation markers, and loss of beta-catenin nuclear localization. Blocking integrin alpha V beta 3 inhibits differentiation and subsequently tumor formation. Thus, CSCs must be engaged by one or more extracellular signals to differentiate and initiate tumor formation, defining a new axis for future novel therapies aimed at both the extrinsic and intracellular pathways. | Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation. |
{"1015": 0.42926809191703796, "1018": 0.020300358533859253, "1051": 0.2539152204990387, "2003": 0.036437395960092545, "2011": 0.36086538434028625, "2015": 0.21372433006763458, "2025": 0.1229778528213501, "2028": 0.20818853378295898, "2043": 0.18167030811309814, "2046": 0.32129061222076416, "2061": 0.1510767638683319, "2064": 0.08692999184131622, "2076": 0.4891071021556854, "2083": 0.12556517124176025, "2124": 0.1685553640127182, "2128": 0.8022117614746094, "2129": 0.10731173306703568, "2135": 0.21372433006763458, "2139": 0.14686977863311768, "2169": 0.18004031479358673, "2170": 0.26146242022514343, "2203": 0.7969439625740051, "2207": 0.6471850275993347, "2291": 0.22704219818115234, "2339": 0.11256109178066254, "2358": 0.8550800085067749, "2433": 0.49982786178588867, "2475": 0.6451379656791687, "2487": 0.9123768210411072, "2497": 0.0842406153678894, "2515": 0.06337817758321762, "2535": 0.5133614540100098, "2550": 0.39696553349494934, "2561": 0.3683255612850189, "2649": 0.025073638185858727, "2659": 0.3012613356113434, "2713": 0.8691008687019348, "2717": 0.347847044467926, "2719": 0.13925230503082275, "2744": 0.18329764902591705, "2765": 0.1358480453491211, "2832": 0.401551216840744, "2920": 0.5805994272232056, "2953": 0.469759464263916, "3001": 0.05970508232712746, "3133": 0.0913962796330452, "3161": 0.3248254358768463, "3169": 0.38174858689308167, "3223": 0.272677481174469, "3227": 0.24171993136405945, "3283": 0.736154317855835, "3333": 0.6522845029830933, "3370": 0.15610189735889435, "3426": 0.06154331564903259, "3431": 0.18329764902591705, "3433": 0.1619328260421753, "3463": 0.07884006202220917, "3466": 0.5174443125724792, "3491": 0.03360854089260101, "3498": 0.841701865196228, "3508": 0.5882205963134766, "3526": 0.8349450826644897, "3550": 0.4444103240966797, "3573": 0.48068851232528687, "3596": 0.24171993136405945, "3617": 0.9915141463279724, "3625": 0.04113444685935974, "3853": 0.21214580535888672, "3896": 0.16607704758644104, "3965": 0.44566190242767334, "4072": 0.2160874605178833, "4195": 0.2561853528022766, "4211": 0.44753631949424744, "4395": 0.3084607720375061, "4400": 0.20977331697940826, "4403": 0.25845035910606384, "4415": 0.3170322775840759, "4442": 0.8625272512435913, "4443": 1.033379077911377, "4515": 0.05139094591140747, "4525": 0.41001203656196594, "4530": 0.9886114001274109, "4566": 0.09850110858678818, "4571": 0.22859740257263184, "4588": 0.3325583338737488, "4607": 0.5139457583427429, "4668": 0.0317181795835495, "4722": 0.762009859085083, "4742": 1.068206787109375, "4921": 0.19782574474811554, "5158": 0.5174443125724792, "5159": 0.46363574266433716, "5250": 0.22157983481884003, "5258": 0.4873090982437134, "5259": 0.3499138653278351, "5320": 0.2317005842924118, "5412": 0.34300774335861206, "5421": 0.32058215141296387, "5449": 0.6451379656791687, "5452": 0.3916989266872406, "5527": 0.2674594223499298, "5549": 0.732405424118042, "5567": 0.2447827309370041, "5668": 0.8004589080810547, "5714": 1.0782235860824585, "5738": 0.4190443754196167, "5741": 0.32129061222076416, "5748": 0.13157635927200317, "5975": 0.026976587250828743, "6164": 0.1358480453491211, "6177": 0.15860503911972046, "6187": 0.6059582233428955, "6194": 0.17840765416622162, "6210": 0.10467668622732162, "6370": 0.026025565341114998, "6433": 0.1905880719423294, "6512": 0.8459017872810364, "6529": 0.09406650811433792, "6591": 0.18492233753204346, "6689": 0.0317181795835495, "6693": 0.36426326632499695, "6774": 0.272677481174469, "6827": 0.3615458607673645, "6895": 0.5805994272232056, "6897": 0.25845035910606384, "6922": 0.3923587501049042, "7085": 0.669430673122406, "7137": 0.42926809191703796, "7182": 0.45994341373443604, "7262": 0.09317722171545029, "7290": 0.10906458646059036, "7336": 0.20660123229026794, "7337": 0.47463157773017883, "7356": 0.07612881064414978, "7358": 0.036437395960092545, "7361": 0.6059582233428955, "7366": 0.5903874635696411, "7461": 0.11865071207284927, "7510": 0.5010119676589966, "7531": 0.6244332790374756, "7565": 0.5244048833847046, "7568": 0.3353555500507355, "7580": 0.5336109399795532, "7645": 0.0009760859538801014, "7686": 0.5596157908439636, "7712": 0.36426326632499695, "7755": 0.9162907600402832, "7790": 0.0317181795835495, "7816": 0.0019512200960889459, "8004": 0.49030399322509766, "8039": 0.3910386264324188, "8082": 0.6301699280738831, "8153": 0.22937409579753876, "8171": 0.3339579105377197, "8184": 0.17020416259765625, "8250": 0.846739649772644, "8287": 0.38041436672210693, "8339": 0.7791815400123596, "8345": 0.6848117709159851, "8523": 1.0868242979049683, "8878": 1.086165428161621, "8918": 0.8666408061981201, "9005": 0.0606246218085289, "9007": 0.14686977863311768, "9010": 0.650757372379303, "9125": 0.2881702482700348, "9185": 1.1906025409698486, "9285": 0.10291612148284912, "9377": 0.07159364968538284, "9575": 0.06246116757392883, "9771": 0.3615458607673645, "9808": 1.0193830728530884, "10066": 0.045809537172317505, "10163": 0.22079704701900482, "10250": 0.12642613053321838, "10322": 0.0797421783208847, "10445": 0.7782850861549377, "10572": 0.34715715050697327, "10595": 0.17020416259765625, "10769": 0.11168810725212097, "10804": 0.11604541540145874, "10814": 0.9568626880645752, "10842": 0.4574742913246155, "10889": 0.39367714524269104, "11138": 0.32270604372024536, "11207": 0.9447870850563049, "11240": 0.890972912311554, "11583": 0.47036975622177124, "11787": 0.016465263441205025, "11889": 1.070887804031372, "11949": 0.19782574474811554, "12016": 0.2089812457561493, "12061": 0.4151833653450012, "12126": 0.26820653676986694, "12247": 0.12728634476661682, "12495": 0.10731173306703568, "12562": 0.22392450273036957, "12732": 0.18573370575904846, "13013": 0.07431721687316895, "13248": 0.890972912311554, "13330": 0.30989447236061096, "13490": 0.15693697333335876, "13494": 0.6931471824645996, "13536": 0.21765978634357452, "13595": 0.0354953333735466, "13617": 0.5080875158309937, "13791": 1.1683861017227173, "13833": 0.3622259199619293, "13851": 0.052318159490823746, "13853": 1.6611998081207275, "13907": 0.41195443272590637, "13909": 0.255429208278656, "14061": 0.45994341373443604, "14374": 0.6980181336402893, "14442": 0.014542185701429844, "14477": 0.8517522215843201, "14505": 0.10467668622732162, "14774": 0.1693800985813141, "14828": 1.005902886390686, "14905": 0.7067264318466187, "14909": 0.3723714053630829, "14932": 0.037378571927547455, "15192": 0.2969166338443756, "15261": 0.19541899859905243, "15340": 0.7482418417930603, "15431": 0.09406650811433792, "15663": 0.16524957120418549, "15677": 0.777387797832489, "15850": 0.07341018319129944, "16012": 0.010684899985790253, "16055": 0.417115718126297, "16058": 0.11951763927936554, "16127": 0.30558720231056213, "16215": 0.014542185701429844, "16315": 0.5301685929298401, "16326": 0.04113444685935974, "16648": 0.23247487843036652, "16690": 0.17922431230545044, "16882": 0.9857001900672913, "17160": 0.19622190296649933, "17379": 0.4794800877571106, "17441": 0.7510106563568115, "17523": 0.3381449282169342, "17637": 0.5461324453353882, "17820": 0.6348392367362976, "17880": 0.11081436276435852, "17890": 0.47766464948654175, "18050": 1.2358801364898682, "18622": 0.791648268699646, "18714": 0.24018502235412598, "18846": 0.007782140281051397, "18896": 0.2983669638633728, "18987": 0.2954642176628113, "19220": 0.2667117714881897, "19389": 0.6921701431274414, "19601": 0.08513788133859634, "19653": 0.16110190749168396, "19723": 0.8567397594451904, "19857": 0.8517522215843201, "19872": 0.14518201351165771, "19957": 0.5370414853096008, "20030": 1.1555536985397339, "20045": 0.6327666640281677, "20382": 1.2969720363616943, "20544": 0.8383291959762573, "20752": 0.1685553640127182, "20763": 0.02792670577764511, "20766": 0.13243216276168823, "20858": 0.2837681770324707, "20868": 0.010684899985790253, "20998": 0.007782140281051397, "21112": 0.176772341132164, "21346": 0.7898768186569214, "21466": 0.2741633653640747, "21477": 0.6664261221885681, "21758": 0.25995752215385437, "21903": 0.10291612148284912, "21919": 0.6410312056541443, "21967": 0.41065993905067444, "22008": 0.1677299439907074, "22184": 0.6619023680686951, "22239": 0.10203468054533005, "22261": 0.011650617234408855, "22330": 0.0038986403960734606, "22595": 0.43875885009765625, "22834": 0.0797421783208847, "22969": 0.43244171142578125, "23216": 0.2622140049934387, "23318": 0.06795065850019455, "23563": 0.8315495252609253, "23586": 0.02316705882549286, "23638": 0.04394211992621422, "23750": 0.006812678650021553, "24411": 0.010684899985790253, "24454": 0.5551415085792542, "24554": 0.1751343309879303, "24635": 0.8272887468338013, "24644": 0.22392450273036957, "24959": 0.06795065850019455, "25100": 0.9628462791442871, "25194": 0.5685047507286072, "25323": 0.7907629609107971, "25354": 1.3960126638412476, "25458": 0.00875066313892603, "25502": 0.022212404757738113, "25533": 0.09495500475168228, "25580": 0.5438674688339233, "25711": 0.36358460783958435, "25761": 0.43053874373435974, "25971": 0.09406650811433792, "26243": 0.27044451236724854, "26396": 0.1734936386346817, "26616": 0.2576959431171417, "26721": 1.1487655639648438, "26942": 0.7791815400123596, "27295": 0.040196798741817474, "27526": 0.02887592278420925, "27774": 0.026976587250828743, "27854": 0.15275461971759796, "28041": 0.33675122261047363, "28078": 0.24171993136405945, "29088": 0.4879087805747986, "29089": 0.09672962874174118, "29105": 0.8764448165893555, "29320": 0.2018241584300995} | 13780287 | When cells are activated by calcium-mobilizing agonists at low, physiological concentrations, the resulting calcium signals generally take the form of repetitive regenerative discharges of stored calcium, termed calcium oscillations [1]. These intracellular calcium oscillations have long fascinated biologists as a mode of digitized intracellular signaling. Recent work has highlighted the role of calcium influx as an essential component of calcium oscillations [2]. This influx occurs through a process known as store-operated calcium entry, which is initiated by calcium sensor proteins, STIM1 and STIM2, in the endoplasmic reticulum [3]. STIM2 is activated by changes in endoplasmic reticulum calcium near the resting level, whereas a threshold of calcium depletion is required for STIM1 activation [4]. Here we show that, surprisingly, it is STIM1 and not STIM2 that is exclusively involved in calcium entry during calcium oscillations. The implication is that each oscillation produces a transient drop in endoplasmic reticulum calcium and that this drop is sufficient to transiently activate STIM1. This transient activation of STIM1 can be observed in some cells by total internal reflection fluorescence microscopy. This arrangement nicely provides a clearly defined and unambiguous signaling system, translating a digital calcium release signal into calcium influx that can signal to downstream effectors. | STIM1 Is a Calcium Sensor Specialized for Digital Signaling |
{"1003": 0.17840765416622162, "1014": 0.37640097737312317, "1017": 0.3409265875816345, "1057": 0.565735399723053, "2005": 0.012615402229130268, "2011": 0.0752234235405922, "2043": 0.1734936386346817, "2051": 0.42225050926208496, "2058": 0.14179791510105133, "2087": 0.3560888469219208, "2093": 0.5816917419433594, "2095": 0.19220098853111267, "2109": 0.6970458030700684, "2111": 0.5045560002326965, "2116": 0.4855078160762787, "2120": 0.7047978043556213, "2137": 0.4151833653450012, "2142": 0.7163142561912537, "2149": 0.6563454270362854, "2151": 0.27564704418182373, "2163": 0.3982778787612915, "2193": 0.04953393340110779, "2204": 0.0317181795835495, "2214": 0.24018502235412598, "2224": 0.6970458030700684, "2262": 0.5957841277122498, "2287": 0.6734226942062378, "2289": 0.4374985992908478, "2308": 0.11430477350950241, "2313": 0.8366385698318481, "2324": 0.14179791510105133, "2335": 0.1913948506116867, "2353": 0.2026219218969345, "2367": 0.23015019297599792, "2378": 0.04487626627087593, "2391": 0.0029254043474793434, "2408": 0.6096806526184082, "2426": 0.4462870955467224, "2429": 0.020300358533859253, "2470": 0.23787821829319, "2478": 0.4132472574710846, "2504": 0.5415972471237183, "2512": 0.7791815400123596, "2526": 0.6989894509315491, "2591": 0.3381449282169342, "2637": 0.40546512603759766, "2679": 0.3283478021621704, "2685": 0.3325583338737488, "2691": 0.3325583338737488, "2711": 0.045809537172317505, "2740": 0.9739698171615601, "2759": 0.7398891448974609, "2779": 0.2223619967699051, "2817": 0.07431721687316895, "2822": 0.1751343309879303, "2846": 0.15860503911972046, "2951": 0.659380316734314, "2966": 0.2696990668773651, "2967": 0.0009760859538801014, "3060": 0.09406650811433792, "3103": 0.11604541540145874, "3151": 0.06246116757392883, "3155": 0.19622190296649933, "3189": 0.6931471824645996, "3207": 0.45870962738990784, "3231": 0.46853771805763245, "3264": 0.10993985831737518, "3265": 0.35060185194015503, "3273": 0.1677299439907074, "3278": 0.053244512528181076, "3445": 0.28082266449928284, "3446": 0.42096930742263794, "3463": 0.22157983481884003, "3465": 0.06612417846918106, "3479": 0.495672345161438, "3508": 0.22782009840011597, "3594": 0.5438674688339233, "3623": 0.09850110858678818, "3633": 0.25845035910606384, "3770": 0.23633737862110138, "3775": 0.14264501631259918, "3798": 0.4437839686870575, "3842": 0.3070250153541565, "3862": 0.17759032547473907, "3867": 0.7028654217720032, "3915": 0.5849615335464478, "3921": 1.0389231443405151, "4048": 0.2674594223499298, "4102": 0.5816917419433594, "4106": 0.3012613356113434, "4117": 0.4818955361843109, "4118": 0.23092569410800934, "4127": 0.0606246218085289, "4141": 0.07068414986133575, "4146": 0.1229778528213501, "4200": 0.3877306580543518, "4217": 0.13071982562541962, "4235": 0.24554696679115295, "4286": 0.022212404757738113, "4311": 0.4837033152580261, "4357": 0.6543170213699341, "4358": 0.42161011695861816, "4387": 0.6233867406845093, "4480": 0.1693800985813141, "4489": 0.22626367211341858, "4505": 0.13499516248703003, "4522": 0.06520967930555344, "4621": 0.14264501631259918, "4639": 0.8534175157546997, "4725": 0.37102460861206055, "4761": 0.18167030811309814, "4841": 0.7009293437004089, "4846": 0.03266380727291107, "4989": 0.27712854743003845, "5002": 0.846739649772644, "5050": 0.06520967930555344, "5067": 0.2493593990802765, "5159": 0.2822965085506439, "5198": 0.2231435477733612, "5422": 0.12986256182193756, "5428": 0.15943801403045654, "5461": 0.0009760859538801014, "5468": 0.04207121208310127, "5535": 0.036437395960092545, "5546": 0.02887592278420925, "5604": 0.4337083101272583, "5636": 0.4938860833644867, "5709": 0.05786345899105072, "5761": 0.029824240133166313, "5762": 0.3560888469219208, "5799": 0.0317181795835495, "5850": 0.0354953333735466, "5852": 0.319873183965683, "5966": 0.45994341373443604, "6001": 1.0305955410003662, "6070": 0.018384648486971855, "6075": 0.24171993136405945, "6165": 0.18978065252304077, "6217": 0.5232481360435486, "6420": 0.026976587250828743, "6459": 0.7163142561912537, "6666": 0.053244512528181076, "6696": 0.8366385698318481, "6721": 0.09050461649894714, "6747": 0.6233867406845093, "6831": 0.8004589080810547, "6912": 0.03266380727291107, "7017": 0.8349450826644897, "7073": 0.0354953333735466, "7076": 0.3750596046447754, "7080": 0.42096930742263794, "7099": 0.5267143249511719, "7242": 0.31132611632347107, "7276": 0.07431721687316895, "7316": 0.3353555500507355, "7399": 0.9394577741622925, "7402": 0.8022117614746094, "7452": 0.21922965347766876, "7461": 0.0058422754518687725, "7636": 0.6902132034301758, "7718": 0.3547199070453644, "7778": 0.0913962796330452, "7784": 0.1485546976327896, "7809": 0.1873544454574585, "7831": 0.574020504951477, "7863": 0.8475768566131592, "7941": 0.7305257320404053, "7965": 0.6064908504486084, "8107": 0.9717550277709961, "8137": 0.05139094591140747, "8168": 0.3464667797088623, "8192": 0.4248080551624298, "8281": 0.37640097737312317, "8321": 0.006812678650021553, "8358": 0.010684899985790253, "8386": 0.0842406153678894, "8525": 0.36290550231933594, "8554": 0.2652147710323334, "8738": 0.3297532796859741, "8907": 0.21687394380569458, "8920": 0.08154398202896118, "9053": 0.3963087201118469, "9152": 0.06795065850019455, "9272": 0.5139457583427429, "9312": 0.0174254160374403, "9426": 0.42990362644195557, "9530": 0.0354953333735466, "9556": 0.2089812457561493, "9580": 0.020300358533859253, "9582": 0.5116065740585327, "9610": 1.1431772708892822, "9765": 0.2317005842924118, "9871": 0.4764525294303894, "9874": 0.7898768186569214, "10020": 0.5450005531311035, "10035": 0.755608320236206, "10147": 0.030771657824516296, "10197": 0.5729197263717651, "10390": 0.1994270235300064, "10422": 0.13243216276168823, "10426": 0.007782140281051397, "10513": 0.22079704701900482, "10640": 0.055094651877880096, "10662": 0.2026219218969345, "10930": 0.304147332906723, "11005": 0.01934296265244484, "11100": 0.48430517315864563, "11201": 0.11081436276435852, "11233": 0.36358460783958435, "11234": 0.4537591338157654, "11475": 0.5762182474136353, "11507": 0.036437395960092545, "11837": 0.1970241367816925, "12265": 0.7201237678527832, "12332": 0.05417001247406006, "12353": 0.25088030099868774, "12435": 0.32129061222076416, "12448": 0.6862877607345581, "12550": 0.19622190296649933, "12596": 0.23479416966438293, "12654": 0.004870930220931768, "12826": 0.2561853528022766, "12876": 0.3588210940361023, "12878": 0.8022117614746094, "12955": 0.3262358605861664, "13046": 0.21922965347766876, "13272": 1.258327841758728, "13316": 0.10467668622732162, "13599": 0.3141832649707794, "13711": 1.0236024856567383, "13751": 0.2667117714881897, "13804": 0.1332872211933136, "13843": 1.094698429107666, "14085": 0.021256839856505394, "14266": 0.15860503911972046, "14286": 0.05139094591140747, "14592": 0.12814582884311676, "14617": 0.1485546976327896, "14667": 0.07884006202220917, "14702": 0.2689530849456787, "14729": 0.48610860109329224, "14773": 0.7629209756851196, "14890": 0.09495500475168228, "14971": 0.012615402229130268, "15157": 0.45623743534088135, "15158": 0.06337817758321762, "15982": 0.7969439625740051, "15995": 0.11256109178066254, "16134": 0.38308101892471313, "16227": 0.16524957120418549, "16330": 0.23864774405956268, "16462": 0.1011524572968483, "16578": 0.17840765416622162, "16965": 0.020300358533859253, "17036": 0.6123310327529907, "17237": 0.0606246218085289, "17242": 1.1598494052886963, "17261": 0.083342544734478, "17504": 0.03360854089260101, "17522": 0.7220231294631958, "17663": 0.4794800877571106, "17908": 0.0913962796330452, "17984": 0.03831886500120163, "18208": 0.22001366317272186, "18215": 0.6128603219985962, "18240": 0.4311734735965729, "18414": 0.015504186972975731, "18539": 0.2160874605178833, "18577": 0.3588210940361023, "18816": 1.0828639268875122, "18925": 0.12384103983640671, "18949": 0.21530038118362427, "19004": 0.11256109178066254, "19300": 0.33605360984802246, "19394": 0.28963330388069153, "19541": 0.23787821829319, "19982": 0.25467249751091003, "20155": 0.06154331564903259, "20272": 0.9754437208175659, "20435": 0.2160874605178833, "20480": 0.09850110858678818, "20576": 0.18816383183002472, "20621": 0.2689530849456787, "20632": 0.09672962874174118, "20900": 0.2160874605178833, "21053": 1.4358283281326294, "21146": 0.1332872211933136, "21150": 0.13243216276168823, "21881": 0.1011524572968483, "21882": 0.05139094591140747, "22835": 0.09495500475168228, "22930": 0.03831886500120163, "22963": 0.2983669638633728, "23048": 0.25995752215385437, "23284": 0.13755162060260773, "23368": 0.2607102394104004, "23444": 0.5500838756561279, "23555": 0.016465263441205025, "23732": 0.12814582884311676, "24155": 0.24554696679115295, "24658": 0.15610189735889435, "24873": 0.5033760666847229, "25094": 0.2674594223499298, "25531": 0.09850110858678818, "25546": 0.19782574474811554, "25654": 0.7827593088150024, "25860": 0.49626702070236206, "25947": 0.1734936386346817, "25981": 0.08782484382390976, "26215": 0.20739519596099854, "26319": 0.3077431619167328, "26378": 0.12556517124176025, "26591": 0.06612417846918106, "26629": 0.006812678650021553, "27348": 0.4512746334075928, "27400": 0.23556606471538544, "27794": 0.009718249551951885, "27805": 0.2089812457561493, "27891": 0.09406650811433792, "27937": 0.07341018319129944, "28093": 0.176772341132164, "28268": 0.16524957120418549, "28321": 0.6548244953155518, "28403": 0.8658194541931152, "28436": 0.009718249551951885} | 13782317 | OBJECTIVE This report presents national estimates of the use of complementary health approaches among adults in the United States across three time points. Trends in the use of selected complementary health approaches are compared for 2002, 2007, and 2012, and differences by selected demographic characteristics are also examined. METHODS Combined data from 88,962 adults aged 18 and over collected as part of the 2002, 2007, and 2012 National Health Interview Survey were analyzed for this report. Sample data were weighted to produce national estimates that are representative of the civilian noninstitutionalized U.S. adult population. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. RESULTS Although the use of individual approaches varied across the three time points, nonvitamin, nonmineral dietary supplements remained the most popular complementary health approach used. The use of yoga, tai chi, and qi gong increased linearly across the three time points; among these three approaches, yoga accounted for approximately 80% of the prevalence. The use of any complementary health approach also differed by selected sociodemographic characteristics. The most notable observed differences in use were by age and Hispanic or Latino origin and race. | Trends in the use of complementary health approaches among adults: United States, 2002-2012. |
{"1011": 0.18816383183002472, "1044": 0.38374659419059753, "1996": 0.07068414986133575, "1997": 0.21214580535888672, "1999": 0.09495500475168228, "2002": 0.45499902963638306, "2007": 0.05694137513637543, "2010": 1.4161186218261719, "2014": 0.04953393340110779, "2029": 0.14349138736724854, "2032": 0.03360854089260101, "2037": 0.04767346754670143, "2038": 0.12814582884311676, "2044": 0.08692999184131622, "2049": 0.5562619566917419, "2075": 0.1751343309879303, "2076": 0.021256839856505394, "2079": 0.4311734735965729, "2090": 0.3485364317893982, "2109": 0.1477125883102417, "2110": 0.3877306580543518, "2128": 0.33115679025650024, "2163": 0.52266925573349, "2209": 0.2223619967699051, "2339": 0.1946154683828354, "2377": 0.6212902665138245, "2389": 0.22859740257263184, "2515": 0.3297532796859741, "2535": 0.8861536383628845, "2571": 0.23324857652187347, "2590": 0.2667117714881897, "2669": 0.5712664127349854, "2695": 0.6734226942062378, "2920": 0.33115679025650024, "2962": 0.15275461971759796, "3005": 0.34715715050697327, "3014": 0.11604541540145874, "3132": 0.12814582884311676, "3161": 0.755608320236206, "3248": 0.5104349255561829, "3252": 1.024303913116455, "3375": 0.5063233375549316, "3378": 0.2089812457561493, "3419": 0.5651806592941284, "3452": 0.5045560002326965, "3466": 0.2667117714881897, "3508": 0.2652147710323334, "3563": 0.012615402229130268, "3625": 0.36426326632499695, "3670": 0.05694137513637543, "3747": 0.7144040465354919, "3800": 0.24554696679115295, "3853": 0.5579402446746826, "3896": 0.22859740257263184, "4023": 0.13243216276168823, "4072": 0.3027053773403168, "4115": 0.013579257763922215, "4187": 0.1718502640724182, "4240": 0.030771657824516296, "4254": 0.04953393340110779, "4395": 0.846739649772644, "4403": 0.036437395960092545, "4563": 0.8965662121772766, "4588": 0.34023189544677734, "4685": 0.0606246218085289, "4758": 0.03266380727291107, "4958": 0.44753631949424744, "4962": 0.8332487344741821, "4972": 0.4938860833644867, "5071": 0.04394211992621422, "5090": 0.7951818704605103, "5105": 0.34370049834251404, "5144": 0.0317181795835495, "5197": 0.12642613053321838, "5224": 0.2034190446138382, "5250": 1.1109062433242798, "5258": 0.007782140281051397, "5302": 0.17020416259765625, "5360": 0.15023678541183472, "5441": 0.4574742913246155, "5449": 0.7987030148506165, "5524": 1.276475191116333, "5680": 0.9769153594970703, "5967": 0.13414156436920166, "6032": 0.15275461971759796, "6064": 1.0587663650512695, "6121": 0.16442140936851501, "6129": 0.678885817527771, "6194": 0.1229778528213501, "6310": 0.5016035437583923, "6383": 0.17431432008743286, "6459": 0.18654440343379974, "6529": 0.037378571927547455, "6560": 0.02412080205976963, "6622": 0.40285754203796387, "6653": 0.890972912311554, "6698": 0.1011524572968483, "6761": 0.0058422754518687725, "6789": 0.011650617234408855, "6827": 0.5483922958374023, "6897": 0.00875066313892603, "6970": 0.6420594453811646, "7192": 0.7510106563568115, "7277": 0.6497380137443542, "7337": 0.2184450328350067, "7366": 0.38174858689308167, "7403": 0.6254787445068359, "7461": 0.4330752193927765, "7578": 0.40611594915390015, "7711": 0.36697331070899963, "7770": 0.7105726003646851, "7784": 0.06154331564903259, "7816": 0.7220231294631958, "7868": 0.10203468054533005, "7964": 0.6254787445068359, "7969": 0.1401015669107437, "8092": 0.7067264318466187, "8171": 1.167778730392456, "8290": 0.6348392367362976, "8332": 0.9929623603820801, "8347": 0.1873544454574585, "8349": 0.6872705817222595, "8360": 0.8534175157546997, "8386": 0.004870930220931768, "8466": 0.013579257763922215, "8498": 0.22157983481884003, "8776": 0.21214580535888672, "8878": 0.29473719000816345, "9007": 0.1946154683828354, "9033": 0.5590575933456421, "9099": 0.09406650811433792, "9165": 0.7276995778083801, "9211": 0.06795065850019455, "9247": 0.7333439588546753, "9319": 0.4944818615913391, "9556": 0.28670501708984375, "9589": 0.040196798741817474, "10176": 0.8074519634246826, "10266": 0.9240728616714478, "10315": 0.41065993905067444, "10381": 0.7845434546470642, "10438": 0.0029254043474793434, "10595": 0.18978065252304077, "10737": 0.09850110858678818, "10738": 0.3723714053630829, "11115": 1.0735615491867065, "11835": 0.5290185213088989, "12210": 0.2034190446138382, "12222": 0.47827014327049255, "12335": 0.07612881064414978, "12546": 0.32129061222076416, "12662": 0.09228714555501938, "12719": 0.8517522215843201, "12761": 0.08603433519601822, "12987": 0.1905880719423294, "13135": 0.0770333781838417, "13323": 1.0848461389541626, "13458": 0.29400965571403503, "13502": 0.35334911942481995, "13531": 0.2881702482700348, "13671": 0.6128603219985962, "13791": 0.11430477350950241, "13922": 0.23324857652187347, "14045": 0.05046287178993225, "14074": 0.7067264318466187, "14080": 0.7286425232887268, "14163": 0.004870930220931768, "14193": 0.9485763907432556, "14321": 0.3106105625629425, "14336": 0.2711893916130066, "14442": 0.040196798741817474, "14471": 0.4617912769317627, "14494": 0.18411032855510712, "14670": 0.07431721687316895, "14679": 0.950843095779419, "14774": 0.1485546976327896, "14800": 0.12728634476661682, "15059": 0.13755162060260773, "15176": 0.4679262638092041, "15380": 0.15693697333335876, "15420": 0.6669275164604187, "15663": 0.2561853528022766, "16221": 0.35745587944984436, "16238": 0.1212492436170578, "16285": 0.13071982562541962, "16371": 0.4794800877571106, "16389": 0.9425065517425537, "16463": 0.21922965347766876, "16530": 0.34577593207359314, "16705": 0.21530038118362427, "16706": 0.9005423784255981, "17241": 0.1905880719423294, "17459": 0.6704301834106445, "18804": 0.009718249551951885, "18856": 0.04767346754670143, "19209": 0.2026219218969345, "19293": 0.08064348995685577, "19362": 0.8383291959762573, "19476": 0.015504186972975731, "19500": 0.06795065850019455, "19852": 0.4132472574710846, "19995": 0.5838727951049805, "20363": 1.2117549180984497, "20544": 0.05139094591140747, "21114": 0.736154317855835, "21508": 0.018384648486971855, "21575": 0.35813871026039124, "21618": 0.34922540187835693, "21647": 0.9371650815010071, "21716": 1.0123108625411987, "21903": 0.09938567131757736, "21935": 0.22937409579753876, "21967": 0.3077431619167328, "22166": 0.6149744987487793, "22170": 0.3170322775840759, "22694": 0.08871890604496002, "22718": 0.15023678541183472, "23283": 0.1332872211933136, "23758": 0.1332872211933136, "23767": 0.27342069149017334, "24051": 0.043007105588912964, "25426": 0.1229778528213501, "25562": 0.23864774405956268, "25644": 0.20421554148197174, "25761": 0.27934664487838745, "25870": 0.28450319170951843, "26296": 0.39762192964553833, "26773": 0.4734157919883728, "26874": 0.6369074583053589, "27142": 0.7701805830001831, "27570": 0.14433705806732178, "27642": 0.8212929964065552, "27749": 0.40481385588645935, "28024": 0.3601844012737274, "28667": 0.469759464263916, "29060": 0.4914994537830353, "29206": 0.9225212931632996, "29226": 0.0038986403960734606} | 13790144 | Histone proteins play essential structural and functional roles in the transition between active and inactive chromatin states. Although histones have a high degree of conservation due to constraints to maintain the overall structure of the nucleosomal octameric core, variants have evolved to assume diverse roles in gene regulation and epigenetic silencing. Histone variants, post-translational modifications and interactions with chromatin remodeling complexes influence DNA replication, transcription, repair and recombination. The authors review recent findings on the structure of chromatin that confirm previous interparticle interactions observed in crystal structures. | Histone structure and nucleosome stability. |
{"1003": 0.03925827145576477, "1014": 0.27044451236724854, "1018": 0.006812678650021553, "1023": 0.0606246218085289, "1039": 0.13670019805431366, "1997": 0.18654440343379974, "2001": 0.06886265426874161, "2012": 0.20580662786960602, "2018": 0.13414156436920166, "2019": 0.40481385588645935, "2034": 0.05694137513637543, "2039": 0.016465263441205025, "2043": 0.26446542143821716, "2051": 0.2954642176628113, "2053": 0.14433705806732178, "2076": 0.11430477350950241, "2077": 0.17020416259765625, "2086": 0.21765978634357452, "2087": 0.025073638185858727, "2092": 0.21293537318706512, "2095": 0.16524957120418549, "2101": 0.40089741349220276, "2109": 0.04674193635582924, "2116": 0.4356052577495575, "2120": 0.46853771805763245, "2141": 0.8861536383628845, "2146": 0.29036402702331543, "2166": 0.17759032547473907, "2193": 0.3177432417869568, "2206": 0.14095009863376617, "2213": 0.304147332906723, "2214": 0.3777405619621277, "2220": 0.3163207769393921, "2241": 0.17922431230545044, "2287": 1.0101795196533203, "2309": 0.07793712615966797, "2313": 0.6674286723136902, "2321": 0.2026219218969345, "2336": 0.7314660549163818, "2348": 0.2954642176628113, "2349": 0.2741633653640747, "2364": 0.07612881064414978, "2365": 0.21530038118362427, "2382": 0.33605360984802246, "2383": 0.3304552733898163, "2384": 0.27934664487838745, "2388": 0.14939609169960022, "2389": 0.2501201331615448, "2397": 0.27342069149017334, "2411": 0.18004031479358673, "2423": 0.32553088665008545, "2459": 0.055094651877880096, "2470": 0.2674594223499298, "2511": 0.7755908370018005, "2522": 0.35403475165367126, "2523": 0.6684301495552063, "2526": 0.016465263441205025, "2539": 0.13071982562541962, "2541": 0.4537591338157654, "2558": 0.6123310327529907, "2560": 0.1384023278951645, "2592": 0.14264501631259918, "2599": 0.045809537172317505, "2628": 0.20818853378295898, "2640": 0.2026219218969345, "2641": 0.2160874605178833, "2659": 0.09938567131757736, "2660": 0.23633737862110138, "2691": 0.2659635543823242, "2695": 0.5773153901100159, "2733": 0.38574060797691345, "2744": 0.6588751673698425, "2750": 0.058784693479537964, "2765": 0.0752234235405922, "2775": 0.7408206462860107, "2779": 0.0770333781838417, "2817": 0.5398913025856018, "2844": 0.06612417846918106, "2846": 0.8748174905776978, "2866": 0.21765978634357452, "2871": 0.5483922958374023, "2902": 0.1477125883102417, "2913": 0.4873090982437134, "2920": 0.05786345899105072, "2930": 0.0029254043474793434, "2951": 0.2741633653640747, "2966": 0.28670501708984375, "2988": 0.025073638185858727, "3020": 0.3084607720375061, "3041": 0.401551216840744, "3134": 0.5517725944519043, "3141": 0.40546512603759766, "3188": 0.04767346754670143, "3251": 0.15860503911972046, "3273": 0.34508460760116577, "3276": 0.503966212272644, "3278": 0.030771657824516296, "3334": 0.8837352395057678, "3336": 0.861702561378479, "3378": 0.7482418417930603, "3380": 0.15610189735889435, "3382": 0.09761575609445572, "3401": 0.1477125883102417, "3408": 0.07884006202220917, "3445": 0.04394211992621422, "3446": 0.42735910415649414, "3463": 0.2918238639831543, "3465": 0.07341018319129944, "3466": 0.12556517124176025, "3476": 0.6634125709533691, "3484": 0.40871503949165344, "3497": 0.151916041970253, "3517": 0.10467668622732162, "3540": 0.12814582884311676, "3547": 0.26296505331993103, "3556": 0.15693697333335876, "3566": 0.0029254043474793434, "3570": 0.10906458646059036, "3572": 0.030771657824516296, "3582": 0.5618454217910767, "3616": 0.06612417846918106, "3618": 0.1485546976327896, "3642": 0.06612417846918106, "3643": 0.07612881064414978, "3647": 0.3526630103588104, "3653": 0.9348671436309814, "3671": 0.06154331564903259, "3808": 0.025073638185858727, "3867": 0.37640097737312317, "3891": 1.1381834745407104, "3917": 0.10731173306703568, "3938": 0.7067264318466187, "3979": 0.05786345899105072, "3981": 0.16607704758644104, "4008": 0.4624064862728119, "4029": 0.37907835841178894, "4094": 0.0174254160374403, "4102": 0.08154398202896118, "4146": 0.05139094591140747, "4167": 0.5607312321662903, "4182": 1.1935672760009766, "4229": 0.2852376699447632, "4236": 0.4624064862728119, "4260": 0.5495203733444214, "4261": 0.3784096837043762, "4268": 0.11081436276435852, "4270": 0.5718178153038025, "4295": 0.06977381557226181, "4328": 0.09495500475168228, "4340": 0.3910386264324188, "4358": 0.11691460013389587, "4413": 0.7583568692207336, "4428": 0.5151132941246033, "4450": 0.7872136831283569, "4453": 0.22001366317272186, "4464": 0.05046287178993225, "4595": 0.3877306580543518, "4652": 0.10818854719400406, "4701": 0.24171993136405945, "4746": 0.04767346754670143, "4795": 0.18492233753204346, "4842": 0.18654440343379974, "4957": 0.6186635494232178, "5002": 0.013579257763922215, "5046": 0.8366385698318481, "5068": 0.48430517315864563, "5120": 1.1102628707885742, "5158": 0.24018502235412598, "5175": 0.2763880789279938, "5187": 0.19862671196460724, "5201": 0.24018502235412598, "5258": 0.36697331070899963, "5323": 0.1685553640127182, "5345": 0.9037119746208191, "5359": 0.7827593088150024, "5360": 0.669430673122406, "5387": 0.7925328612327576, "5388": 0.34922540187835693, "5400": 0.20739519596099854, "5427": 0.6931471824645996, "5428": 0.0752234235405922, "5468": 0.3824150264263153, "5508": 0.004870930220931768, "5511": 0.26146242022514343, "5519": 0.11517547070980072, "5535": 0.14179791510105133, "5537": 0.2247048318386078, "5585": 0.5601736903190613, "5593": 0.14264501631259918, "5594": 0.16524957120418549, "5646": 0.40285754203796387, "5679": 0.7191727757453918, "5700": 0.058784693479537964, "5718": 0.07612881064414978, "5761": 0.26446542143821716, "5788": 0.39762192964553833, "5790": 0.006812678650021553, "5799": 0.5261374711990356, "5809": 0.5197699069976807, "5816": 0.956112265586853, "5824": 0.21765978634357452, "5842": 0.1873544454574585, "5857": 0.14939609169960022, "5876": 0.6435998678207397, "5950": 0.08154398202896118, "5986": 0.15693697333335876, "6022": 0.06337817758321762, "6075": 0.32199856638908386, "6123": 0.7987030148506165, "6163": 0.27044451236724854, "6165": 0.3615458607673645, "6205": 0.3883931338787079, "6273": 0.15023678541183472, "6325": 0.09672962874174118, "6405": 0.524982750415802, "6428": 0.151916041970253, "6463": 0.2659635543823242, "6508": 1.005902886390686, "6522": 0.026025565341114998, "6691": 0.3464667797088623, "6694": 0.7201237678527832, "6721": 0.0752234235405922, "6747": 0.3910386264324188, "6818": 0.4002431631088257, "6875": 0.8306987881660461, "6911": 0.11256109178066254, "6927": 0.08244366943836212, "6959": 1.0828639268875122, "6993": 0.25239890813827515, "7012": 0.22937409579753876, "7017": 0.5767669677734375, "7023": 1.0298984050750732, "7080": 0.2231435477733612, "7108": 0.030771657824516296, "7162": 0.5729197263717651, "7189": 0.5220900774002075, "7290": 0.42608439922332764, "7388": 0.32341301441192627, "7403": 0.255429208278656, "7411": 0.08154398202896118, "7461": 0.3297532796859741, "7505": 0.23402166366577148, "7551": 0.0913962796330452, "7594": 0.35334911942481995, "7619": 0.6512666940689087, "7644": 0.02887592278420925, "7645": 0.010684899985790253, "7685": 0.06246116757392883, "7691": 0.4617912769317627, "7778": 0.29619070887565613, "7784": 0.22392450273036957, "7790": 0.09228714555501938, "7843": 0.16690383851528168, "7863": 0.8973627090454102, "7913": 0.04113444685935974, "7959": 0.10203468054533005, "8020": 0.306306391954422, "8023": 0.06337817758321762, "8116": 0.37907835841178894, "8178": 0.28963330388069153, "8189": 0.04674193635582924, "8196": 0.16524957120418549, "8211": 0.014542185701429844, "8292": 0.31845372915267944, "8329": 0.2447827309370041, "8394": 0.05046287178993225, "8483": 0.42353010177612305, "8536": 0.2034190446138382, "8643": 0.07793712615966797, "8674": 0.0009760859538801014, "8715": 0.567397952079773, "8800": 0.06612417846918106, "8819": 0.38441169261932373, "8832": 0.13071982562541962, "8924": 0.6265231370925903, "9002": 0.674915611743927, "9053": 0.1401015669107437, "9280": 0.0009760859538801014, "9289": 0.3464667797088623, "9367": 0.306306391954422, "9556": 0.037378571927547455, "9560": 0.5168620347976685, "9582": 0.3897167444229126, "9626": 0.5376120805740356, "9657": 0.2247048318386078, "9723": 0.2637155055999756, "9886": 0.1946154683828354, "9977": 0.39762192964553833, "10003": 0.19862671196460724, "10010": 0.07068414986133575, "10032": 1.0506030321121216, "10035": 0.10731173306703568, "10066": 0.06612417846918106, "10141": 0.23633737862110138, "10173": 0.32129061222076416, "10174": 0.11517547070980072, "10184": 0.10379679501056671, "10238": 0.12038381397724152, "10254": 0.14602625370025635, "10280": 0.47827014327049255, "10426": 0.020300358533859253, "10441": 0.06977381557226181, "10507": 0.07250232994556427, "10527": 0.9021284580230713, "10539": 0.052318159490823746, "10624": 0.13071982562541962, "10640": 0.14264501631259918, "10768": 0.11691460013389587, "10831": 0.8022117614746094, "10834": 0.7934166193008423, "10857": 0.28890204429626465, "10903": 0.4673144817352295, "10975": 0.02792670577764511, "10984": 0.6415454745292664, "11062": 0.3519764244556427, "11100": 0.6502478122711182, "11156": 0.10379679501056671, "11207": 0.1229778528213501, "11324": 0.15943801403045654, "11326": 0.08603433519601822, "11383": 0.15275461971759796, "11601": 0.13670019805431366, "11656": 0.14095009863376617, "11667": 0.06612417846918106, "11683": 0.4709797203540802, "11702": 0.3339579105377197, "11709": 0.05694137513637543, "11795": 0.05786345899105072, "11983": 0.49030399322509766, "12130": 0.4794800877571106, "12322": 0.11865071207284927, "12353": 0.018384648486971855, "12380": 0.5080875158309937, "12412": 0.15860503911972046, "12435": 0.3248254358768463, "12503": 0.18411032855510712, "12515": 0.1751343309879303, "12516": 0.08692999184131622, "12667": 0.04953393340110779, "12740": 0.10906458646059036, "12763": 0.1212492436170578, "12771": 0.6244332790374756, "13047": 0.24248650670051575, "13105": 0.5495203733444214, "13120": 0.20977331697940826, "13180": 0.007782140281051397, "13328": 0.04394211992621422, "13356": 0.5021947622299194, "13483": 0.9409833550453186, "13494": 0.015504186972975731, "13531": 0.025073638185858727, "13655": 0.2652147710323334, "13923": 0.04394211992621422, "14025": 0.6296497583389282, "14267": 0.17922431230545044, "14302": 0.10203468054533005, "14396": 0.15359249711036682, "14412": 0.9893379211425781, "14625": 0.05417001247406006, "14800": 0.16607704758644104, "14874": 0.15275461971759796, "14966": 0.00875066313892603, "15050": 0.04113444685935974, "15053": 0.1332872211933136, "15087": 0.04860413447022438, "15157": 0.6102113127708435, "15258": 0.15693697333335876, "15354": 0.10467668622732162, "15559": 0.34922540187835693, "15584": 1.0144377946853638, "15643": 0.037378571927547455, "15756": 0.17020416259765625, "15758": 0.3191637098789215, "15855": 0.24631060659885406, "15946": 0.06703783571720123, "16014": 0.5336109399795532, "16021": 0.25694093108177185, "16186": 0.029824240133166313, "16211": 0.1677299439907074, "16216": 0.7629209756851196, "16222": 0.08154398202896118, "16231": 0.8366385698318481, "16381": 0.0009760859538801014, "16452": 0.055094651877880096, "16463": 0.04767346754670143, "16515": 0.2837681770324707, "16593": 0.11951763927936554, "16605": 0.40546512603759766, "16725": 0.8731874823570251, "16745": 0.7314660549163818, "16884": 0.3388410806655884, "16902": 0.5063233375549316, "16989": 0.4818955361843109, "17060": 0.10555581003427505, "17208": 0.14433705806732178, "17237": 0.18816383183002472, "17245": 0.05417001247406006, "17463": 0.07612881064414978, "17489": 0.08064348995685577, "17547": 0.23324857652187347, "17660": 0.14433705806732178, "17706": 0.29109421372413635, "17819": 0.09761575609445572, "18130": 0.04674193635582924, "18133": 1.1641268730163574, "18250": 0.42735910415649414, "18279": 0.26146242022514343, "18419": 0.41840189695358276, "18422": 0.026976587250828743, "18439": 1.1456648111343384, "18509": 0.04113444685935974, "18583": 0.15610189735889435, "18609": 0.22001366317272186, "18687": 0.4349733293056488, "18749": 0.025073638185858727, "18949": 0.6064908504486084, "18976": 0.0354953333735466, "19064": 0.42735910415649414, "19188": 0.5584990978240967, "19199": 0.01934296265244484, "19362": 0.6451379656791687, "19465": 0.43434104323387146, "19470": 0.04953393340110779, "19723": 0.2493593990802765, "19761": 0.2749055027961731, "19804": 0.09495500475168228, "19833": 0.04207121208310127, "20100": 0.9944084882736206, "20116": 0.2247048318386078, "20155": 0.026025565341114998, "20272": 1.1786550283432007, "20367": 0.6011518239974976, "20469": 0.10379679501056671, "20576": 0.33605360984802246, "20588": 0.7389566898345947, "20612": 0.24325250089168549, "20662": 0.8933739066123962, "20828": 0.17759032547473907, "21011": 0.960606575012207, "21111": 0.0038986403960734606, "21150": 0.0797421783208847, "21262": 0.4450363218784332, "21371": 0.7629209756851196, "21539": 0.5517725944519043, "21557": 0.17840765416622162, "21608": 0.23092569410800934, "21621": 0.08961215615272522, "21778": 0.015504186972975731, "21799": 0.3560888469219208, "21906": 0.37907835841178894, "21963": 0.1212492436170578, "22010": 0.053244512528181076, "22313": 0.16524957120418549, "22432": 0.1873544454574585, "22740": 0.2516399025917053, "22813": 0.2184450328350067, "22835": 0.03831886500120163, "23130": 0.18411032855510712, "23238": 0.33325836062431335, "23259": 0.10379679501056671, "23260": 0.19220098853111267, "23534": 0.5844172835350037, "23614": 0.3784096837043762, "23676": 0.401551216840744, "23900": 0.40741631388664246, "24226": 0.056018441915512085, "24558": 0.22937409579753876, "24624": 0.5421652793884277, "24919": 0.04487626627087593, "25022": 0.6989894509315491, "25121": 0.18329764902591705, "25137": 0.10291612148284912, "25213": 0.015504186972975731, "25269": 1.154322862625122, "25344": 0.045809537172317505, "25426": 0.04860413447022438, "25635": 0.07431721687316895, "25714": 0.034552380442619324, "25719": 0.05139094591140747, "25863": 0.03266380727291107, "25972": 0.684319257736206, "26163": 0.020300358533859253, "26305": 0.0038986403960734606, "26331": 0.009718249551951885, "26462": 0.18167030811309814, "26563": 0.2247048318386078, "26578": 0.16607704758644104, "26708": 0.5898461937904358, "26906": 0.03360854089260101, "26914": 0.3750596046447754, "26927": 0.15610189735889435, "26994": 0.03925827145576477, "27159": 0.020300358533859253, "27162": 0.7028654217720032, "27166": 0.20421554148197174, "27312": 0.9717550277709961, "27480": 1.1217793226242065, "27532": 0.18492233753204346, "27615": 0.0752234235405922, "27642": 0.22548456490039825, "27678": 0.38574060797691345, "27794": 0.9333322048187256, "27815": 0.42353010177612305, "28086": 0.1693800985813141, "28093": 0.3084607720375061, "28155": 0.0797421783208847, "28159": 1.1671710014343262, "28207": 0.2089812457561493, "28297": 0.07612881064414978, "28436": 0.19622190296649933, "28569": 0.35060185194015503, "28685": 0.175953671336174, "28711": 0.06154331564903259, "28774": 0.08064348995685577, "28828": 0.2478361576795578, "28950": 0.02412080205976963, "29048": 0.0174254160374403, "29242": 0.23556606471538544, "29361": 0.0038986403960734606, "29392": 0.06795065850019455, "29458": 0.28890204429626465, "29477": 0.10026945173740387} | 13791044 | CONTEXT Although preterm delivery is a well-established risk factor for cerebral palsy (CP), preterm deliveries contribute only a minority of affected infants. There is little information on the relation of CP risk to gestational age in the term range, where most CP occurs. OBJECTIVE To determine whether timing of birth in the term and postterm period is associated with risk of CP. DESIGN, SETTING, AND PARTICIPANTS Population-based follow-up study using the Medical Birth Registry of Norway to identify 1,682,441 singleton children born in the years 1967-2001 with a gestational age of 37 through 44 weeks and no congenital anomalies. The cohort was followed up through 2005 by linkage to other national registries. MAIN OUTCOME MEASURES Absolute and relative risk of CP for children surviving to at least 4 years of age. RESULTS Of the cohort of term and postterm children, 1938 were registered with CP in the National Insurance Scheme. Infants born at 40 weeks had the lowest risk of CP, with a prevalence of 0.99/1000 (95% confidence interval [CI], 0.90-1.08). Risk for CP was higher with earlier or later delivery, with a prevalence at 37 weeks of 1.91/1000 (95% CI, 1.58-2.25) and a relative risk (RR) of 1.9 (95% CI, 1.6-2.4), a prevalence at 38 weeks of 1.25/1000 (95% CI, 1.07-1.42) and an RR of 1.3 (95% CI, 1.1-1.6), a prevalence at 42 weeks of 1.36/1000 (95% CI, 1.19-1.53) and an RR of 1.4 (95% CI, 1.2-1.6), and a prevalence after 42 weeks of 1.44 (95% CI, 1.15-1.72) and an RR of 1.4 (95% CI, 1.1-1.8). These associations were even stronger in a subset with gestational age based on ultrasound measurements: at 37 weeks the prevalence was 1.17/1000 (95% CI, 0.30-2.04) and the relative risk was 3.7 (95% CI, 1.5-9.1). At 42 weeks the prevalence was 0.85/1000 (95% CI, 0.33-1.38) and the relative risk was 2.4 (95% CI, 1.1-5.3). Adjustment for infant sex, maternal age, and various socioeconomic measures had little effect. CONCLUSION Compared with delivery at 40 weeks' gestation, delivery at 37 or 38 weeks or at 42 weeks or later was associated with an increased risk of CP. | Cerebral palsy among term and postterm births. |
{"1015": 0.27342069149017334, "1018": 0.1384023278951645, "2011": 0.4177590310573578, "2025": 0.10467668622732162, "2033": 0.07159364968538284, "2046": 0.2622140049934387, "2064": 0.2447827309370041, "2075": 0.06154331564903259, "2076": 0.5495203733444214, "2079": 0.09672962874174118, "2090": 0.27786844968795776, "2094": 0.1358480453491211, "2099": 0.10555581003427505, "2128": 0.27712854743003845, "2182": 0.21214580535888672, "2203": 0.5584990978240967, "2239": 0.3784096837043762, "2245": 0.36697331070899963, "2265": 0.0354953333735466, "2271": 0.0019512200960889459, "2290": 0.16110190749168396, "2309": 0.5427330136299133, "2339": 0.16110190749168396, "2350": 0.49030399322509766, "2361": 0.17922431230545044, "2397": 0.05417001247406006, "2439": 0.1913948506116867, "2487": 0.7565253376960754, "2489": 0.5347557663917542, "2497": 0.3304552733898163, "2512": 0.34370049834251404, "2515": 0.3554046154022217, "2529": 0.24325250089168549, "2535": 0.009718249551951885, "2549": 0.5920094847679138, "2550": 0.0752234235405922, "2587": 0.9409833550453186, "2659": 0.0317181795835495, "2730": 0.500420093536377, "2765": 0.33325836062431335, "2825": 0.04394211992621422, "2832": 0.45994341373443604, "2971": 0.34922540187835693, "3065": 0.0009760859538801014, "3102": 0.7276995778083801, "3278": 0.02316705882549286, "3279": 0.5562619566917419, "3291": 0.1229778528213501, "3308": 0.1718502640724182, "3338": 0.8374842405319214, "3344": 0.06246116757392883, "3366": 0.43053874373435974, "3370": 0.053244512528181076, "3375": 0.8298473954200745, "3378": 0.09050461649894714, "3426": 0.1693800985813141, "3436": 0.025073638185858727, "3463": 0.27342069149017334, "3466": 0.11168810725212097, "3471": 0.0770333781838417, "3491": 0.30917787551879883, "3501": 0.10993985831737518, "3508": 0.812664806842804, "3526": 0.5278670787811279, "3540": 0.9980146884918213, "3560": 0.48008447885513306, "3631": 0.4419025182723999, "3633": 0.2026219218969345, "3693": 0.7610978484153748, "3714": 0.8957691192626953, "3768": 0.13670019805431366, "3860": 0.2622140049934387, "3879": 0.18492233753204346, "3896": 0.02792670577764511, "3930": 0.11256109178066254, "3965": 0.27712854743003845, "3972": 0.66441810131073, "3995": 0.45251765847206116, "4039": 0.11256109178066254, "4047": 0.7389566898345947, "4053": 0.30486753582954407, "4286": 0.014542185701429844, "4287": 0.006812678650021553, "4288": 0.6155022978782654, "4295": 0.2493593990802765, "4373": 0.8829278349876404, "4394": 0.10026945173740387, "4442": 0.6989894509315491, "4456": 0.7333439588546753, "4478": 0.16110190749168396, "4515": 0.6011518239974976, "4558": 0.04767346754670143, "4652": 0.5313173532485962, "4678": 0.013579257763922215, "4755": 0.20421554148197174, "4911": 0.37707099318504333, "4945": 0.29473719000816345, "4962": 0.7009293437004089, "5054": 0.7201237678527832, "5123": 0.4512746334075928, "5158": 0.007782140281051397, "5187": 0.9379299283027649, "5201": 0.1734936386346817, "5214": 0.15610189735889435, "5241": 0.6338034868240356, "5258": 0.029824240133166313, "5278": 0.0606246218085289, "5320": 0.23864774405956268, "5326": 0.14518201351165771, "5343": 0.7863243818283081, "5358": 0.25845035910606384, "5360": 0.043007105588912964, "5387": 0.6410312056541443, "5410": 0.2231435477733612, "5429": 0.5984715819358826, "5519": 0.015504186972975731, "5566": 1.04512357711792, "5591": 0.32905077934265137, "5622": 0.8901712894439697, "5670": 0.7610978484153748, "5703": 0.6989894509315491, "5799": 0.06429435312747955, "5854": 0.15359249711036682, "5857": 0.21372433006763458, "5876": 0.6603899002075195, "6032": 0.022212404757738113, "6033": 0.31489628553390503, "6064": 1.2655161619186401, "6194": 0.15610189735889435, "6310": 0.08603433519601822, "6313": 0.1619328260421753, "6364": 0.37707099318504333, "6409": 0.13071982562541962, "6418": 0.151916041970253, "6460": 0.3560888469219208, "6496": 1.0382318496704102, "6553": 0.0770333781838417, "6637": 0.1873544454574585, "6691": 0.42608439922332764, "6761": 0.004870930220931768, "6914": 0.11604541540145874, "6942": 0.10291612148284912, "6975": 0.35745587944984436, "6999": 0.10291612148284912, "7035": 0.0009760859538801014, "7178": 0.09050461649894714, "7192": 1.2140778303146362, "7337": 0.23864774405956268, "7366": 0.20580662786960602, "7403": 0.7463917136192322, "7440": 0.2852376699447632, "7461": 0.09406650811433792, "7507": 0.18816383183002472, "7561": 0.7491656541824341, "7645": 0.33325836062431335, "7730": 0.5438674688339233, "7790": 0.8941729068756104, "7807": 0.9045027494430542, "7870": 0.16359257698059082, "7883": 0.09584271162748337, "7900": 0.1677299439907074, "7901": 0.18329764902591705, "7987": 1.1858406066894531, "8018": 1.0986123085021973, "8020": 0.5393219590187073, "8031": 0.21135559678077698, "8081": 0.24248650670051575, "8093": 0.5057345628738403, "8246": 0.058784693479537964, "8347": 0.08064348995685577, "8428": 0.32199856638908386, "8536": 0.043007105588912964, "8552": 0.26296505331993103, "8563": 0.4855078160762787, "8650": 0.17020416259765625, "8715": 0.11604541540145874, "8729": 0.5718178153038025, "8735": 0.42735910415649414, "8761": 0.14686977863311768, "8776": 0.09317722171545029, "8980": 0.2674594223499298, "8991": 0.1011524572968483, "9002": 0.3864043951034546, "9007": 0.19782574474811554, "9041": 0.1734936386346817, "9165": 0.4450363218784332, "9239": 0.630689799785614, "9253": 0.11778303235769272, "9285": 0.4849066734313965, "9336": 0.06795065850019455, "9412": 0.018384648486971855, "9474": 0.09938567131757736, "9530": 0.16359257698059082, "9564": 0.8941729068756104, "9740": 0.13670019805431366, "9794": 0.5696102976799011, "10077": 0.12384103983640671, "10109": 0.15442965924739838, "10148": 0.35813871026039124, "10315": 0.6793810129165649, "10341": 0.33115679025650024, "10375": 0.19541899859905243, "10381": 0.30558720231056213, "10450": 0.987156867980957, "10580": 0.06520967930555344, "10595": 0.0842406153678894, "10671": 0.10993985831737518, "10697": 0.5261374711990356, "10723": 0.23556606471538544, "10744": 0.11081436276435852, "10840": 0.04953393340110779, "11019": 0.06520967930555344, "11158": 0.19782574474811554, "11160": 0.12814582884311676, "11215": 0.11343330889940262, "11369": 0.11256109178066254, "11674": 0.1718502640724182, "11968": 0.8475768566131592, "12014": 0.34508460760116577, "12042": 0.3409265875816345, "12130": 1.0144377946853638, "12363": 0.5139457583427429, "12394": 0.010684899985790253, "12452": 0.24401791393756866, "12530": 0.5104349255561829, "12554": 0.20102575421333313, "12636": 0.03266380727291107, "12650": 0.026025565341114998, "12732": 0.6634125709533691, "12765": 0.16110190749168396, "12898": 0.574020504951477, "12958": 0.3743882179260254, "13070": 0.07341018319129944, "13228": 0.9021284580230713, "13366": 0.6149744987487793, "13368": 0.8357921838760376, "13369": 0.08692999184131622, "13442": 0.14095009863376617, "13458": 0.347847044467926, "13656": 0.8600510358810425, "13665": 0.7482418417930603, "13671": 1.1185935735702515, "13765": 0.13755162060260773, "13995": 0.09317722171545029, "14067": 0.11343330889940262, "14080": 0.1510767638683319, "14163": 0.2976420819759369, "14190": 0.5387523174285889, "14192": 0.16359257698059082, "14193": 0.16524957120418549, "14386": 0.052318159490823746, "14427": 0.22626367211341858, "14442": 0.2696990668773651, "14471": 0.20421554148197174, "14494": 1.0933903455734253, "14591": 0.055094651877880096, "14626": 0.3897167444229126, "14627": 0.04767346754670143, "14639": 0.08064348995685577, "14800": 0.1693800985813141, "14828": 0.053244512528181076, "14856": 0.7182208299636841, "14863": 0.6374238729476929, "15059": 0.15610189735889435, "15074": 0.1602703034877777, "15420": 0.11865071207284927, "15445": 0.04113444685935974, "15451": 0.17759032547473907, "15527": 0.9739698171615601, "15577": 0.7500885725021362, "15671": 0.1710275560617447, "15778": 0.18492233753204346, "15804": 0.07159364968538284, "15924": 0.11343330889940262, "16007": 0.23402166366577148, "16221": 1.1487655639648438, "16238": 0.4556184411048889, "16263": 0.6181373596191406, "16341": 0.02412080205976963, "16487": 0.13670019805431366, "16505": 0.7182208299636841, "16530": 0.03925827145576477, "16605": 0.3870677351951599, "16680": 0.02792670577764511, "16705": 0.06612417846918106, "16706": 1.0533316135406494, "16765": 0.09050461649894714, "16803": 0.01934296265244484, "16884": 0.7009293437004089, "16910": 0.7210738658905029, "17159": 0.11691460013389587, "17598": 0.2105647772550583, "17707": 0.3601844012737274, "17824": 1.1369311809539795, "17850": 1.533164143562317, "17935": 0.14602625370025635, "18077": 0.674915611743927, "18130": 0.1229778528213501, "18189": 0.2223619967699051, "18227": 0.46363574266433716, "18234": 0.07159364968538284, "18340": 0.2954642176628113, "18419": 1.034073829650879, "18516": 0.7647408246994019, "18653": 0.4624064862728119, "18699": 1.185243844985962, "18771": 0.0058422754518687725, "18888": 0.9857001900672913, "19009": 0.8281423449516296, "19112": 0.04674193635582924, "19141": 0.1401015669107437, "19345": 0.00875066313892603, "19470": 0.27044451236724854, "19500": 0.32764431834220886, "19583": 0.21135559678077698, "19653": 0.11778303235769272, "20045": 0.016465263441205025, "20120": 0.5063233375549316, "20132": 0.7987030148506165, "20275": 0.09850110858678818, "20360": 0.31560876965522766, "20397": 0.0029254043474793434, "20502": 0.010684899985790253, "20518": 1.3233171701431274, "20624": 0.7057625651359558, "20870": 0.06795065850019455, "21081": 0.34370049834251404, "21114": 1.1653456687927246, "21197": 0.8450632095336914, "21262": 1.1462857723236084, "21371": 0.22157983481884003, "21407": 0.03360854089260101, "21434": 0.6181373596191406, "21537": 0.25239890813827515, "21557": 0.24631060659885406, "21647": 1.0492360591888428, "21716": 0.7898768186569214, "21726": 0.37707099318504333, "21770": 0.3127557039260864, "21891": 1.067535400390625, "21903": 0.09050461649894714, "22026": 0.0009760859538801014, "22207": 0.018384648486971855, "22219": 0.6709295511245728, "22275": 0.29619070887565613, "22422": 0.016465263441205025, "22571": 0.022212404757738113, "23393": 0.9394577741622925, "23586": 0.6744182109832764, "23737": 0.4734157919883728, "23760": 0.47584590315818787, "23892": 0.43938836455345154, "23924": 0.021256839856505394, "24004": 1.1350497007369995, "24054": 0.4926934838294983, "24251": 0.8332487344741821, "24278": 0.21922965347766876, "24388": 0.9576126337051392, "24394": 0.2018241584300995, "24473": 0.34023189544677734, "24759": 0.034552380442619324, "24854": 0.29981520771980286, "24899": 0.18248429894447327, "25077": 0.4374985992908478, "25409": 0.11604541540145874, "25456": 0.2800849378108978, "25817": 0.12470348179340363, "25874": 0.30989447236061096, "26001": 0.13071982562541962, "26206": 0.05970508232712746, "26296": 0.890972912311554, "26305": 0.04953393340110779, "26402": 0.42608439922332764, "26601": 0.06795065850019455, "26657": 0.09317722171545029, "26702": 0.07884006202220917, "26872": 0.10818854719400406, "26874": 0.8238670229911804, "27029": 0.010684899985790253, "27118": 0.03925827145576477, "27218": 0.820433497428894, "27642": 0.4770587682723999, "27651": 0.1221139207482338, "27989": 0.34023189544677734, "28024": 0.44753631949424744, "28032": 0.609149694442749, "28227": 0.7258110046386719, "28290": 0.025073638185858727, "28327": 0.8748174905776978, "28424": 0.3930181860923767, "28450": 0.3034266233444214, "28466": 0.2763880789279938, "28548": 0.0019512200960889459, "28616": 0.09672962874174118, "28667": 1.0257055759429932, "28685": 0.1064341589808464, "28828": 0.31132611632347107, "28829": 0.9805850982666016, "28927": 0.7683706283569336, "28929": 0.0752234235405922, "29125": 0.15860503911972046, "29206": 1.0874829292297363, "29238": 0.03266380727291107} | 13791206 | Defective DNA repair by homologous recombination (HR) is thought to be a major contributor to tumorigenesis in individuals carrying Brca1 mutations. Here, we show that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4. Loss of 53BP1 alleviates hypersensitivity of Brca1 mutant cells to PARP inhibition and restores error-free repair by HR. Mechanistically, 53BP1 deletion promotes ATM-dependent processing of broken DNA ends to produce recombinogenic single-stranded DNA competent for HR. In contrast, Lig4 deficiency does not rescue the HR defect in Brca1 mutant cells but prevents the joining of chromatid breaks into chromosome rearrangements. Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations. | 53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks |
{"1998": 0.05786345899105072, "2004": 0.0058422754518687725, "2013": 0.5427330136299133, "2015": 0.3963087201118469, "2020": 0.1930064558982849, "2033": 0.7942996621131897, "2038": 0.02412080205976963, "2045": 0.0029254043474793434, "2060": 0.25239890813827515, "2070": 0.27786844968795776, "2073": 0.14095009863376617, "2080": 0.0606246218085289, "2088": 0.1994270235300064, "2090": 0.1510767638683319, "2106": 0.2184450328350067, "2111": 0.5882205963134766, "2116": 0.567397952079773, "2124": 0.0029254043474793434, "2137": 0.43875885009765625, "2155": 0.15526613593101501, "2177": 0.4574742913246155, "2179": 0.4914994537830353, "2193": 0.28155985474586487, "2195": 0.0019512200960889459, "2264": 0.42161011695861816, "2272": 0.2034190446138382, "2306": 0.40481385588645935, "2307": 0.3923587501049042, "2313": 0.8925741910934448, "2339": 0.23864774405956268, "2358": 0.16110190749168396, "2367": 0.23015019297599792, "2381": 0.2763880789279938, "2406": 0.3777405619621277, "2408": 0.44566190242767334, "2424": 0.18654440343379974, "2426": 0.5209306478500366, "2427": 0.23556606471538544, "2451": 0.011650617234408855, "2470": 0.28450319170951843, "2515": 0.016465263441205025, "2523": 0.3897167444229126, "2529": 0.567397952079773, "2555": 0.5186077356338501, "2591": 0.24401791393756866, "2637": 0.08513788133859634, "2647": 0.6064908504486084, "2664": 0.03831886500120163, "2679": 0.36900100111961365, "2691": 0.05046287178993225, "2695": 0.02792670577764511, "2714": 0.0058422754518687725, "2761": 0.15526613593101501, "2789": 0.24171993136405945, "2796": 0.38308101892471313, "2802": 0.19381128251552582, "2817": 0.34508460760116577, "2822": 0.0354953333735466, "2844": 0.037378571927547455, "2885": 0.26296505331993103, "2898": 0.4425300657749176, "2913": 0.37102460861206055, "2945": 0.1751343309879303, "2947": 0.10026945173740387, "2951": 0.15359249711036682, "2966": 0.09228714555501938, "2967": 0.6286086440086365, "2981": 0.2983669638633728, "2986": 0.9857001900672913, "3009": 0.23864774405956268, "3014": 0.02316705882549286, "3019": 0.04487626627087593, "3032": 0.29109421372413635, "3060": 0.08871890604496002, "3097": 0.2652147710323334, "3128": 0.9194108247756958, "3141": 0.30558720231056213, "3226": 0.7809720039367676, "3265": 0.28082266449928284, "3273": 0.53589928150177, "3276": 0.08692999184131622, "3278": 0.5427330136299133, "3290": 1.58732008934021, "3334": 0.2749055027961731, "3344": 0.23479416966438293, "3348": 0.029824240133166313, "3350": 0.006812678650021553, "3365": 0.10379679501056671, "3378": 0.3346569836139679, "3421": 0.16359257698059082, "3451": 1.001607894897461, "3463": 0.05970508232712746, "3497": 0.5800528526306152, "3528": 0.11517547070980072, "3550": 0.2954642176628113, "3597": 0.07159364968538284, "3603": 0.17267228662967682, "3633": 0.6369074583053589, "3653": 0.7898768186569214, "3734": 0.00875066313892603, "3745": 0.07612881064414978, "3795": 0.18248429894447327, "3802": 0.16690383851528168, "3837": 0.09228714555501938, "3989": 0.09228714555501938, "4004": 0.7764897346496582, "4021": 0.33605360984802246, "4044": 0.0842406153678894, "4094": 0.8989537954330444, "4183": 0.20102575421333313, "4187": 0.10906458646059036, "4207": 0.15610189735889435, "4245": 0.07068414986133575, "4279": 0.21372433006763458, "4281": 0.3070250153541565, "4286": 0.5562619566917419, "4310": 0.3743882179260254, "4321": 0.09850110858678818, "4328": 0.6451379656791687, "4348": 0.6907027959823608, "4453": 0.006812678650021553, "4483": 0.07068414986133575, "4531": 0.1677299439907074, "4602": 0.18573370575904846, "4655": 0.3923587501049042, "4659": 0.043007105588912964, "4666": 0.04487626627087593, "4748": 0.4734157919883728, "4761": 0.5562619566917419, "4767": 0.14179791510105133, "4839": 0.10818854719400406, "4841": 0.3995884954929352, "4858": 0.12986256182193756, "4864": 0.06429435312747955, "4895": 0.014542185701429844, "4916": 1.504077434539795, "4942": 0.5278670787811279, "4962": 0.8658194541931152, "4969": 0.49030399322509766, "5050": 0.15777134895324707, "5173": 0.1011524572968483, "5182": 0.015504186972975731, "5336": 0.09228714555501938, "5418": 0.7610978484153748, "5500": 0.04767346754670143, "5542": 0.42608439922332764, "5579": 0.11430477350950241, "5636": 1.12938392162323, "5664": 0.013579257763922215, "5762": 0.5051454305648804, "5802": 0.15777134895324707, "5836": 0.11865071207284927, "5917": 0.3012613356113434, "5921": 0.015504186972975731, "5966": 0.08871890604496002, "6022": 0.1332872211933136, "6064": 0.7854343056678772, "6147": 0.1477125883102417, "6219": 0.2034190446138382, "6284": 1.1941591501235962, "6338": 0.1808556467294693, "6447": 0.0009760859538801014, "6459": 0.4425300657749176, "6496": 0.812664806842804, "6505": 0.7314660549163818, "6529": 0.1332872211933136, "6552": 0.11343330889940262, "6590": 0.06703783571720123, "6622": 0.09495500475168228, "6648": 0.014542185701429844, "6696": 0.5517725944519043, "6698": 0.15943801403045654, "6820": 0.6374238729476929, "6844": 0.8383291959762573, "6887": 0.07068414986133575, "6897": 0.35060185194015503, "6914": 0.2247048318386078, "6934": 0.9568626880645752, "6937": 0.14179791510105133, "6946": 0.2689530849456787, "6950": 0.06612417846918106, "7017": 0.021256839856505394, "7060": 0.8997484445571899, "7080": 0.9333322048187256, "7145": 0.04953393340110779, "7162": 0.025073638185858727, "7243": 0.2493593990802765, "7275": 0.7182208299636841, "7297": 0.11081436276435852, "7321": 0.37371641397476196, "7322": 0.07793712615966797, "7356": 0.17759032547473907, "7366": 0.0009760859538801014, "7402": 0.3318578004837036, "7403": 1.2889312505722046, "7440": 0.29981520771980286, "7443": 0.006812678650021553, "7444": 0.1221139207482338, "7489": 0.3750596046447754, "7507": 0.36967599391937256, "7521": 0.33605360984802246, "7523": 0.04767346754670143, "7551": 0.1619328260421753, "7578": 0.8195732831954956, "7718": 0.013579257763922215, "7784": 0.1930064558982849, "7810": 0.43875885009765625, "7885": 0.09317722171545029, "7900": 0.4537591338157654, "8092": 0.15442965924739838, "8119": 0.02887592278420925, "8137": 0.25088030099868774, "8168": 0.08692999184131622, "8200": 0.025073638185858727, "8205": 0.18329764902591705, "8213": 0.06886265426874161, "8281": 0.016465263441205025, "8292": 0.22626367211341858, "8349": 0.401551216840744, "8358": 0.7710843086242676, "8374": 0.03925827145576477, "8386": 0.9440274834632874, "8478": 0.8195732831954956, "8481": 0.4400174915790558, "8578": 0.5925496220588684, "8609": 0.8893690705299377, "8757": 0.42926809191703796, "8807": 0.319873183965683, "8893": 0.04953393340110779, "8898": 0.33675122261047363, "8906": 1.0587663650512695, "8924": 0.35813871026039124, "8948": 0.4673144817352295, "8991": 0.8715548515319824, "9031": 1.018678069114685, "9048": 0.08513788133859634, "9064": 0.0029254043474793434, "9147": 0.1808556467294693, "9165": 0.8509185314178467, "9174": 0.3499138653278351, "9183": 0.7800771594047546, "9230": 0.38441169261932373, "9287": 0.6538092494010925, "9331": 0.5607312321662903, "9426": 0.052318159490823746, "9487": 0.010684899985790253, "9513": 0.05417001247406006, "9539": 0.46608972549438477, "9556": 0.2501201331615448, "9610": 0.011650617234408855, "9613": 0.0317181795835495, "9671": 0.3423145115375519, "9757": 0.48670899868011475, "9762": 0.00875066313892603, "9815": 0.12038381397724152, "9869": 0.36426326632499695, "9905": 0.007782140281051397, "9983": 0.18411032855510712, "10056": 0.6674286723136902, "10176": 0.3106105625629425, "10199": 0.040196798741817474, "10357": 0.15275461971759796, "10483": 0.00875066313892603, "10505": 0.3416208028793335, "10662": 0.512191891670227, "10744": 0.26146242022514343, "10748": 0.841701865196228, "10847": 0.022212404757738113, "10924": 0.00875066313892603, "11056": 0.176772341132164, "11156": 0.04767346754670143, "11192": 0.6358738541603088, "11219": 0.2089812457561493, "11234": 0.012615402229130268, "11377": 1.133164644241333, "11560": 0.053244512528181076, "11663": 0.0606246218085289, "11767": 0.0770333781838417, "11787": 0.39893341064453125, "11983": 0.34508460760116577, "12158": 0.08513788133859634, "12260": 0.13670019805431366, "12319": 0.3662964701652527, "12334": 0.3897167444229126, "12477": 0.9162907600402832, "12493": 0.5341835021972656, "12608": 0.175953671336174, "12631": 0.11604541540145874, "12795": 0.34715715050697327, "12839": 0.25995752215385437, "12878": 0.22001366317272186, "12955": 0.40546512603759766, "13032": 0.6228629946708679, "13139": 0.055094651877880096, "13186": 0.004870930220931768, "13221": 0.3027053773403168, "13321": 0.47463157773017883, "13447": 0.19622190296649933, "13458": 0.9820492267608643, "13481": 0.6980181336402893, "13578": 0.0029254043474793434, "13811": 0.026025565341114998, "13874": 0.5267143249511719, "14144": 0.319873183965683, "14163": 0.08603433519601822, "14286": 0.10379679501056671, "14388": 0.2539152204990387, "14398": 0.16690383851528168, "14402": 0.23015019297599792, "14471": 0.9209672808647156, "14494": 0.15860503911972046, "14561": 0.08154398202896118, "14729": 0.2409527748823166, "14735": 0.29109421372413635, "14800": 0.6573580503463745, "14890": 0.7124901413917542, "14906": 0.1710275560617447, "14947": 0.5860490798950195, "15053": 0.055094651877880096, "15112": 0.14686977863311768, "15157": 0.004870930220931768, "15215": 0.18329764902591705, "15370": 0.18816383183002472, "15460": 0.06886265426874161, "15643": 0.013579257763922215, "15671": 0.00875066313892603, "15758": 0.25088030099868774, "15945": 0.07884006202220917, "15982": 0.5092619061470032, "16012": 0.08064348995685577, "16221": 0.2493593990802765, "16275": 0.045809537172317505, "16452": 0.36967599391937256, "16505": 0.45994341373443604, "16512": 0.030771657824516296, "16515": 0.8973627090454102, "16530": 0.06886265426874161, "16578": 0.030771657824516296, "16643": 0.9500881433486938, "16706": 0.37707099318504333, "16836": 0.08244366943836212, "16882": 0.013579257763922215, "17194": 0.5404602885246277, "17431": 0.05139094591140747, "17450": 0.15610189735889435, "17522": 0.01934296265244484, "17819": 0.026976587250828743, "17921": 0.12728634476661682, "18076": 0.03360854089260101, "18095": 0.021256839856505394, "18240": 1.0775588750839233, "18273": 0.2026219218969345, "18275": 0.2089812457561493, "18278": 0.11951763927936554, "18771": 0.036437395960092545, "18855": 0.7067264318466187, "18925": 0.18411032855510712, "18953": 0.0174254160374403, "18969": 0.18978065252304077, "19068": 0.5718178153038025, "19293": 0.029824240133166313, "19345": 0.8550800085067749, "19539": 0.29255300760269165, "19612": 0.025073638185858727, "20248": 0.04674193635582924, "20272": 0.08603433519601822, "20392": 0.16442140936851501, "20547": 0.8682814836502075, "20576": 0.1221139207482338, "20582": 0.6466736793518066, "20731": 0.07068414986133575, "20806": 0.053244512528181076, "20852": 0.151916041970253, "20969": 0.5267143249511719, "21011": 0.5145297050476074, "21032": 0.22626367211341858, "21571": 0.3106105625629425, "21697": 0.09850110858678818, "21754": 0.4879087805747986, "21770": 0.20421554148197174, "21891": 0.08154398202896118, "21988": 0.12642613053321838, "22026": 0.7987030148506165, "22107": 0.42225050926208496, "22126": 0.21293537318706512, "22648": 0.7537717819213867, "22694": 0.034552380442619324, "22887": 0.2160874605178833, "23079": 0.00875066313892603, "23282": 0.016465263441205025, "23284": 0.40546512603759766, "23328": 0.1477125883102417, "23368": 0.37974658608436584, "23399": 0.0174254160374403, "23610": 0.16359257698059082, "23803": 0.016465263441205025, "23900": 0.05694137513637543, "24004": 0.10379679501056671, "24374": 0.39762192964553833, "24715": 0.09938567131757736, "24784": 0.0174254160374403, "24854": 0.3423145115375519, "24904": 0.43623676896095276, "24908": 0.22001366317272186, "25080": 0.04394211992621422, "25169": 0.175953671336174, "25206": 0.4158279001712799, "25245": 0.47158926725387573, "25469": 0.35677260160446167, "25524": 0.5086748600006104, "25630": 0.06337817758321762, "25882": 1.2353124618530273, "26005": 0.045809537172317505, "26064": 0.1229778528213501, "26125": 0.8861536383628845, "26266": 0.15526613593101501, "26285": 0.036437395960092545, "26305": 0.7665573358535767, "26563": 0.2689530849456787, "26569": 0.1011524572968483, "26684": 0.018384648486971855, "26741": 0.4349733293056488, "26874": 0.19862671196460724, "26923": 0.14264501631259918, "26954": 0.04860413447022438, "27135": 0.40546512603759766, "27152": 0.7267557382583618, "27343": 0.15526613593101501, "27360": 0.07431721687316895, "27642": 0.3325583338737488, "27694": 0.19220098853111267, "27794": 0.6970458030700684, "28290": 0.11517547070980072, "28295": 0.045809537172317505, "28321": 0.3005385100841522, "28370": 0.6338034868240356, "28395": 0.040196798741817474, "28436": 0.5301685929298401, "28637": 0.15693697333335876, "28667": 0.4311734735965729, "28911": 0.22157983481884003, "28922": 0.06795065850019455, "29206": 0.11081436276435852, "29415": 0.45623743534088135, "29488": 0.16359257698059082, "29606": 0.21214580535888672} | 13791788 | Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide. | The genetics of Mexico recapitulates Native American substructure and affects biomedical traits |
{"1045": 0.3106105625629425, "1047": 0.6312094330787659, "1999": 0.034552380442619324, "2003": 0.21687394380569458, "2005": 0.10906458646059036, "2011": 0.24018502235412598, "2012": 0.5376120805740356, "2024": 0.40351006388664246, "2029": 0.014542185701429844, "2048": 0.10993985831737518, "2054": 0.036437395960092545, "2072": 0.9929623603820801, "2076": 0.02887592278420925, "2079": 0.2470736801624298, "2090": 0.09938567131757736, "2091": 0.27712854743003845, "2124": 0.1970241367816925, "2128": 0.07068414986133575, "2135": 0.1808556467294693, "2155": 0.4891071021556854, "2179": 0.20102575421333313, "2188": 0.6573580503463745, "2266": 0.36494144797325134, "2290": 0.1221139207482338, "2291": 0.21687394380569458, "2310": 0.7182208299636841, "2339": 0.034552380442619324, "2372": 0.29473719000816345, "2378": 0.347847044467926, "2421": 0.11778303235769272, "2433": 0.1064341589808464, "2483": 0.3106105625629425, "2487": 0.05970508232712746, "2515": 0.2184450328350067, "2523": 0.3339579105377197, "2535": 0.2719337046146393, "2566": 0.5517725944519043, "2571": 0.5573811531066895, "2618": 0.5427330136299133, "2719": 0.2089812457561493, "2734": 0.2409527748823166, "2850": 0.6699305176734924, "2852": 0.3810817003250122, "2865": 0.8366385698318481, "2920": 0.0913962796330452, "2943": 0.6573580503463745, "2945": 0.20818853378295898, "2951": 0.23864774405956268, "2970": 0.5990082025527954, "3001": 0.3248254358768463, "3141": 0.44753631949424744, "3145": 0.20977331697940826, "3173": 0.03360854089260101, "3191": 0.053244512528181076, "3223": 0.5168620347976685, "3252": 0.2822965085506439, "3302": 0.9635916948318481, "3333": 0.5936289429664612, "3366": 0.010684899985790253, "3370": 0.07341018319129944, "3372": 0.10203468054533005, "3375": 0.8796916007995605, "3378": 0.12470348179340363, "3573": 0.5795059204101562, "3593": 1.061472773551941, "3597": 0.7656494975090027, "3605": 0.31845372915267944, "3625": 0.07250232994556427, "3665": 0.8877626657485962, "3755": 0.10906458646059036, "3800": 0.08603433519601822, "3853": 0.6059582233428955, "3949": 0.1384023278951645, "4018": 0.6451379656791687, "4072": 0.24631060659885406, "4195": 0.6709295511245728, "4244": 0.2470736801624298, "4319": 0.2918238639831543, "4328": 0.14179791510105133, "4453": 0.3027053773403168, "4530": 1.216973900794983, "4654": 0.3388410806655884, "4700": 0.47584590315818787, "4747": 0.6578640341758728, "4758": 0.2531573474407196, "4962": 0.7995813488960266, "4972": 0.48430517315864563, "5014": 0.20660123229026794, "5072": 0.18167030811309814, "5090": 0.11865071207284927, "5178": 0.7333439588546753, "5193": 0.3304552733898163, "5250": 0.7683706283569336, "5302": 0.24631060659885406, "5324": 0.3723714053630829, "5326": 0.53589928150177, "5347": 0.347847044467926, "5393": 0.04113444685935974, "5423": 1.4432357549667358, "5435": 1.0172666311264038, "5478": 0.1718502640724182, "5512": 0.5893046259880066, "5527": 0.9739698171615601, "5666": 0.7537717819213867, "5680": 0.22859740257263184, "5716": 0.23864774405956268, "5725": 0.8065804839134216, "5769": 0.2711893916130066, "5787": 0.176772341132164, "5812": 0.5914691090583801, "5850": 0.3949938118457794, "5918": 0.20580662786960602, "5942": 0.21372433006763458, "6064": 0.21530038118362427, "6096": 0.04953393340110779, "6137": 0.23324857652187347, "6177": 0.4248080551624298, "6178": 0.043007105588912964, "6190": 0.2667117714881897, "6381": 0.23402166366577148, "6392": 0.6902132034301758, "6459": 0.11604541540145874, "6508": 0.5584990978240967, "6537": 0.15777134895324707, "6573": 0.4196864068508148, "6598": 0.052318159490823746, "6622": 0.6170841455459595, "6638": 0.09672962874174118, "6709": 0.009718249551951885, "6731": 0.5936289429664612, "6873": 0.762009859085083, "6887": 0.5220900774002075, "6897": 0.07884006202220917, "6903": 0.33605360984802246, "6922": 0.2493593990802765, "6986": 1.2035820484161377, "7040": 0.02887592278420925, "7127": 0.0354953333735466, "7297": 0.04487626627087593, "7324": 0.7934166193008423, "7328": 0.2719337046146393, "7337": 0.3297532796859741, "7358": 0.13499516248703003, "7366": 0.36967599391937256, "7403": 0.6425731778144836, "7453": 0.4926934838294983, "7485": 1.0986123085021973, "7510": 0.45251765847206116, "7645": 0.014542185701429844, "7685": 0.7333439588546753, "7694": 0.16276304423809052, "7698": 0.5461324453353882, "7711": 0.3554046154022217, "7816": 0.8169882297515869, "7987": 0.6989894509315491, "8000": 0.7426811456680298, "8071": 0.3034266233444214, "8091": 0.9673105478286743, "8171": 0.6563454270362854, "8250": 0.861702561378479, "8281": 0.045809537172317505, "8290": 0.680370569229126, "8328": 0.14349138736724854, "8332": 0.026976587250828743, "8360": 0.20501139760017395, "8486": 0.469759464263916, "8621": 0.5849615335464478, "8636": 0.3877306580543518, "8872": 1.3238370418548584, "8883": 0.25239890813827515, "8924": 0.2447827309370041, "9007": 0.7047978043556213, "9010": 0.6170841455459595, "9096": 0.11865071207284927, "9165": 0.8699195384979248, "9231": 0.20421554148197174, "9380": 0.1905880719423294, "9386": 0.0029254043474793434, "9687": 0.4974553883075714, "9728": 0.20022670924663544, "9821": 0.8306987881660461, "9972": 0.6332852244377136, "10029": 0.11256109178066254, "10099": 0.3870677351951599, "10266": 0.8550800085067749, "10591": 0.3034266233444214, "10595": 0.04207121208310127, "10737": 0.14939609169960022, "10738": 0.8740028142929077, "10752": 0.01934296265244484, "10893": 0.026025565341114998, "10956": 0.05970508232712746, "11022": 0.8837352395057678, "11094": 0.32270604372024536, "11099": 1.0073304176330566, "11146": 0.016465263441205025, "11211": 0.0174254160374403, "11369": 0.24631060659885406, "11548": 0.02316705882549286, "11595": 0.0606246218085289, "11835": 0.5540198087692261, "11876": 0.09495500475168228, "11957": 0.02412080205976963, "11983": 0.036437395960092545, "12123": 0.03831886500120163, "12222": 0.7144040465354919, "12247": 0.036437395960092545, "12328": 0.7258110046386719, "12649": 0.0009760859538801014, "12732": 0.669430673122406, "12761": 0.2852376699447632, "12944": 0.2478361576795578, "12987": 1.0894558429718018, "13012": 0.9576126337051392, "13046": 0.030771657824516296, "13153": 0.823009729385376, "13197": 0.045809537172317505, "13433": 0.07612881064414978, "13458": 0.0606246218085289, "13461": 0.8161250352859497, "13463": 0.083342544734478, "13512": 0.014542185701429844, "13791": 0.11081436276435852, "13833": 0.16524957120418549, "13922": 0.11256109178066254, "14067": 0.319873183965683, "14151": 0.006812678650021553, "14193": 0.06154331564903259, "14289": 0.13499516248703003, "14309": 0.07884006202220917, "14454": 0.7445381283760071, "14471": 0.2160874605178833, "14774": 0.8583967685699463, "14793": 0.08154398202896118, "14828": 0.06246116757392883, "14879": 0.5849615335464478, "15000": 0.20501139760017395, "15026": 0.7295845746994019, "15115": 0.7592713832855225, "15176": 0.8109301924705505, "15379": 0.14686977863311768, "15420": 0.5324648022651672, "15484": 0.26446542143821716, "15543": 0.04394211992621422, "15663": 0.08871890604496002, "15695": 0.7537717819213867, "16012": 0.603290855884552, "16221": 0.03831886500120163, "16285": 0.637939989566803, "16480": 0.07612881064414978, "16483": 0.3485364317893982, "16515": 0.9500881433486938, "16531": 0.469759464263916, "16627": 0.05970508232712746, "16910": 0.5290185213088989, "17119": 0.680370569229126, "17424": 0.42990362644195557, "17448": 0.48008447885513306, "17695": 0.1619328260421753, "17878": 0.014542185701429844, "17938": 0.12384103983640671, "17971": 0.022212404757738113, "18089": 0.11081436276435852, "18260": 0.21214580535888672, "18276": 0.3930181860923767, "18622": 0.9240728616714478, "18898": 0.5133614540100098, "19003": 0.46117570996284485, "19101": 0.28743788599967957, "19137": 0.777387797832489, "19293": 0.03831886500120163, "19570": 0.9500881433486938, "19601": 0.1710275560617447, "19723": 0.13925230503082275, "19852": 0.24631060659885406, "19872": 0.803087055683136, "19995": 0.9673105478286743, "20064": 0.020300358533859253, "20125": 0.2470736801624298, "20350": 0.16276304423809052, "20582": 0.8433839678764343, "20960": 0.7389566898345947, "21032": 0.06246116757392883, "21252": 0.38905516266822815, "21500": 0.06886265426874161, "21575": 0.4374985992908478, "21618": 0.9084475636482239, "21903": 0.1229778528213501, "21935": 0.3995884954929352, "22718": 0.1485546976327896, "22869": 0.9108069539070129, "23150": 0.0038986403960734606, "23267": 0.6181373596191406, "23296": 1.2204381227493286, "23389": 0.31845372915267944, "23586": 0.7389566898345947, "23737": 0.010684899985790253, "23977": 0.37640097737312317, "24019": 0.05046287178993225, "24054": 0.6254787445068359, "24124": 0.7248653769493103, "24169": 0.05139094591140747, "24314": 0.08961215615272522, "24324": 0.49030399322509766, "24345": 0.129004567861557, "24374": 0.0770333781838417, "24848": 0.2145126610994339, "25456": 0.4487839937210083, "25643": 1.1506214141845703, "25644": 0.6415454745292664, "25711": 0.6553317308425903, "26083": 1.1198691129684448, "26261": 0.9783848524093628, "26328": 0.07612881064414978, "26394": 0.3743882179260254, "26402": 0.9515975713729858, "26773": 0.7791815400123596, "27126": 1.5263959169387817, "27133": 0.9842413663864136, "27235": 1.0553730726242065, "27321": 0.5069117546081543, "27642": 0.07612881064414978, "27777": 0.06154331564903259, "27833": 0.47463157773017883, "27915": 0.6664261221885681, "27965": 0.11081436276435852, "28498": 0.8941729068756104, "28517": 1.0080435276031494, "28696": 1.0285027027130127, "28848": 0.14179791510105133, "28976": 0.06337817758321762} | 13794374 | Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets. | COPI Complex Is a Regulator of Lipid Homeostasis |
{"1018": 0.6714286804199219, "1039": 0.46853771805763245, "1056": 1.0815403461456299, "1999": 0.04487626627087593, "2005": 0.09495500475168228, "2009": 0.6583697199821472, "2024": 0.020300358533859253, "2029": 0.15943801403045654, "2043": 0.04487626627087593, "2046": 0.15275461971759796, "2076": 0.5098485946655273, "2079": 0.41647201776504517, "2099": 0.6317287683486938, "2102": 0.056018441915512085, "2109": 0.0606246218085289, "2112": 0.012615402229130268, "2121": 0.4337083101272583, "2176": 0.5364705324172974, "2209": 0.07793712615966797, "2278": 0.2223619967699051, "2290": 0.2034190446138382, "2377": 0.5800528526306152, "2393": 0.5925496220588684, "2458": 0.24631060659885406, "2475": 0.23710809648036957, "2487": 0.40089741349220276, "2515": 0.24018502235412598, "2529": 0.2501201331615448, "2535": 0.7809720039367676, "2537": 0.3903779089450836, "2545": 0.2976420819759369, "2549": 1.2494091987609863, "2550": 0.2105647772550583, "2575": 0.04953393340110779, "2581": 0.06337817758321762, "2590": 0.08782484382390976, "2828": 0.21687394380569458, "2865": 0.6970458030700684, "2890": 0.6461620330810547, "2897": 0.28743788599967957, "2920": 0.9052929878234863, "2959": 0.41840189695358276, "3012": 0.016465263441205025, "3145": 0.2317005842924118, "3161": 0.10467668622732162, "3170": 0.12728634476661682, "3223": 0.12642613053321838, "3248": 0.4412745535373688, "3276": 0.06337817758321762, "3319": 0.2089812457561493, "3378": 0.10555581003427505, "3433": 0.6275664567947388, "3436": 0.2247048318386078, "3526": 1.2204381227493286, "3563": 0.12814582884311676, "3603": 0.1221139207482338, "3625": 0.2719337046146393, "3670": 0.009718249551951885, "3729": 1.4132709503173828, "3800": 0.11256109178066254, "3853": 0.6212902665138245, "3965": 0.09317722171545029, "4127": 0.2674594223499298, "4187": 0.6980181336402893, "4286": 0.17840765416622162, "4295": 0.4126010537147522, "4343": 0.2089812457561493, "4395": 0.7305257320404053, "4442": 1.2666174173355103, "4456": 0.35334911942481995, "4958": 0.4248080551624298, "4962": 0.11778303235769272, "4972": 0.5936289429664612, "5012": 0.15023678541183472, "5094": 0.24171993136405945, "5182": 0.034552380442619324, "5387": 0.35950297117233276, "5418": 0.5313173532485962, "5456": 0.3615458607673645, "5589": 0.27342069149017334, "5714": 0.4481603503227234, "5876": 0.4419025182723999, "5918": 0.20739519596099854, "6125": 0.3615458607673645, "6459": 0.037378571927547455, "6509": 0.025073638185858727, "6550": 0.09228714555501938, "6624": 0.3499138653278351, "6789": 0.1685553640127182, "6869": 0.21530038118362427, "7060": 0.4400174915790558, "7126": 0.15777134895324707, "7137": 0.0174254160374403, "7336": 0.2145126610994339, "7337": 0.037378571927547455, "7356": 0.0354953333735466, "7366": 0.15359249711036682, "7485": 0.17759032547473907, "7711": 0.08603433519601822, "7772": 0.09406650811433792, "7816": 0.4950772523880005, "7870": 0.4311734735965729, "8153": 0.18329764902591705, "8285": 0.613389253616333, "8360": 0.19862671196460724, "8449": 0.040196798741817474, "8790": 0.0913962796330452, "8878": 0.6533012986183167, "9099": 0.1718502640724182, "9125": 0.4437839686870575, "9358": 0.151916041970253, "9597": 0.15023678541183472, "10509": 0.02792670577764511, "10586": 0.25995752215385437, "10738": 0.16110190749168396, "10769": 0.030771657824516296, "10938": 0.04394211992621422, "10960": 0.5021947622299194, "11311": 0.9256220459938049, "12222": 0.4002431631088257, "12562": 0.23479416966438293, "12987": 0.020300358533859253, "13070": 0.04487626627087593, "13321": 0.6270449161529541, "13345": 0.07068414986133575, "13595": 0.010684899985790253, "13656": 0.5629584193229675, "13791": 0.8973627090454102, "13833": 0.22001366317272186, "13908": 0.20580662786960602, "14120": 0.0770333781838417, "14193": 1.0748957395553589, "14228": 0.12384103983640671, "14340": 0.45870962738990784, "14828": 0.49923527240753174, "15176": 0.37640097737312317, "15238": 0.5313173532485962, "15403": 1.024303913116455, "15581": 0.10993985831737518, "15743": 1.0382318496704102, "16048": 0.2089812457561493, "16215": 0.9310253858566284, "16530": 0.18816383183002472, "16576": 0.5573811531066895, "16706": 0.0606246218085289, "17250": 0.27342069149017334, "17252": 0.4349733293056488, "17257": 0.12038381397724152, "17301": 0.5500838756561279, "17404": 0.22859740257263184, "17441": 0.3554046154022217, "18120": 0.3877306580543518, "18191": 0.04860413447022438, "18419": 0.2034190446138382, "18715": 1.1911962032318115, "18856": 0.05139094591140747, "19293": 0.9987343549728394, "19852": 0.3027053773403168, "19872": 0.1889725625514984, "20467": 0.16524957120418549, "20544": 0.5871354341506958, "20582": 1.0165601968765259, "20752": 0.04113444685935974, "20766": 0.04487626627087593, "21032": 0.6848117709159851, "21262": 0.11691460013389587, "21434": 0.3134697377681732, "21575": 0.11951763927936554, "21618": 0.129004567861557, "21697": 0.08513788133859634, "21919": 0.09228714555501938, "22022": 0.04767346754670143, "22330": 0.8143964409828186, "22907": 0.08513788133859634, "22931": 0.3269403576850891, "22932": 0.12986256182193756, "22975": 1.0802149772644043, "23041": 0.8837352395057678, "23689": 0.6317287683486938, "23746": 0.05970508232712746, "24374": 0.4926934838294983, "24395": 0.5393219590187073, "24529": 0.18573370575904846, "25194": 0.24248650670051575, "25605": 0.1384023278951645, "25761": 0.04113444685935974, "26180": 1.072225570678711, "26419": 0.08513788133859634, "26435": 0.07341018319129944, "26773": 0.45994341373443604, "26775": 0.1358480453491211, "26835": 0.9178520441055298, "27321": 0.37304413318634033, "27343": 0.0770333781838417, "27395": 0.755608320236206, "27781": 0.1751343309879303, "28788": 0.6181373596191406, "28829": 0.2719337046146393, "28873": 0.401551216840744, "28896": 0.15693697333335876, "29206": 0.8893690705299377, "29610": 0.0770333781838417} | 13798951 | CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation. | Differentiation of effector CD4 T cell populations (*). |
{"1011": 0.08603433519601822, "1014": 0.23864774405956268, "1044": 0.1994270235300064, "1048": 0.1619328260421753, "1997": 0.08154398202896118, "1999": 0.25845035910606384, "2000": 0.19782574474811554, "2002": 0.6838265657424927, "2007": 0.13499516248703003, "2013": 0.036437395960092545, "2022": 0.08603433519601822, "2029": 0.17267228662967682, "2041": 0.004870930220931768, "2051": 0.1685553640127182, "2063": 0.1685553640127182, "2064": 0.36086538434028625, "2076": 0.28082266449928284, "2109": 0.020300358533859253, "2129": 0.26446542143821716, "2140": 0.15526613593101501, "2146": 0.3262358605861664, "2152": 0.31132611632347107, "2202": 0.014542185701429844, "2241": 0.38374659419059753, "2278": 0.1905880719423294, "2291": 0.21372433006763458, "2309": 0.7791815400123596, "2378": 0.5729197263717651, "2386": 0.7352184057235718, "2424": 0.2447827309370041, "2425": 0.05786345899105072, "2427": 0.6011518239974976, "2478": 0.04860413447022438, "2484": 0.07431721687316895, "2504": 0.39893341064453125, "2544": 0.37640097737312317, "2549": 0.6902132034301758, "2561": 0.9225212931632996, "2668": 0.9379299283027649, "2696": 0.5330380201339722, "2705": 0.5800528526306152, "2721": 0.04674193635582924, "2764": 0.2184450328350067, "2765": 0.3170322775840759, "2795": 0.01934296265244484, "2825": 0.052318159490823746, "2832": 0.21293537318706512, "2846": 0.3588210940361023, "2854": 0.13071982562541962, "2855": 0.030771657824516296, "2864": 0.5936289429664612, "2878": 0.6583697199821472, "2951": 0.0009760859538801014, "2972": 0.055094651877880096, "3014": 0.5033760666847229, "3074": 0.6233867406845093, "3096": 0.045809537172317505, "3112": 0.2247048318386078, "3115": 0.33953672647476196, "3132": 0.012615402229130268, "3143": 0.010684899985790253, "3144": 0.5092619061470032, "3155": 0.5215105414390564, "3226": 0.1889725625514984, "3231": 0.5816917419433594, "3284": 0.19782574474811554, "3406": 0.04953393340110779, "3435": 0.10555581003427505, "3452": 0.3676496744155884, "3463": 0.5871354341506958, "3549": 0.014542185701429844, "3584": 0.7500885725021362, "3653": 0.8109301924705505, "3718": 0.11168810725212097, "3775": 0.5057345628738403, "3798": 0.36426326632499695, "3816": 0.3683255612850189, "3898": 0.03360854089260101, "3929": 0.5495203733444214, "3963": 0.5811457633972168, "3968": 0.5139457583427429, "3977": 0.00875066313892603, "3981": 0.052318159490823746, "3989": 0.23633737862110138, "4009": 0.43875885009765625, "4094": 0.029824240133166313, "4098": 0.04674193635582924, "4106": 0.4849066734313965, "4115": 0.05139094591140747, "4118": 0.9100211262702942, "4135": 0.3070250153541565, "4146": 0.13670019805431366, "4180": 0.1212492436170578, "4237": 0.2749055027961731, "4315": 1.094698429107666, "4340": 0.6624060273170471, "4358": 0.014542185701429844, "4383": 0.4794800877571106, "4403": 0.8649974465370178, "4453": 0.14686977863311768, "4487": 0.39762192964553833, "4488": 0.18411032855510712, "4531": 0.2493593990802765, "4555": 0.49626702070236206, "4617": 0.2531573474407196, "4632": 0.4196864068508148, "4663": 0.31489628553390503, "4668": 0.05046287178993225, "4684": 0.09317722171545029, "4685": 0.30989447236061096, "4710": 0.5220900774002075, "4719": 0.28743788599967957, "4725": 0.7610978484153748, "4747": 0.7907629609107971, "4781": 0.04953393340110779, "5041": 0.450652539730072, "5067": 0.5267143249511719, "5072": 0.29109421372413635, "5097": 0.026025565341114998, "5140": 0.12814582884311676, "5147": 0.20818853378295898, "5216": 0.0019512200960889459, "5250": 0.5295937061309814, "5278": 0.09938567131757736, "5292": 0.10203468054533005, "5301": 0.29400965571403503, "5302": 0.4879087805747986, "5335": 0.1994270235300064, "5391": 0.6492279767990112, "5422": 0.10291612148284912, "5425": 0.24018502235412598, "5445": 0.040196798741817474, "5459": 0.7934166193008423, "5461": 0.36426326632499695, "5468": 0.47584590315818787, "5531": 0.030771657824516296, "5545": 0.09761575609445572, "5576": 0.06977381557226181, "5604": 0.27934664487838745, "5638": 0.8195732831954956, "5643": 0.07159364968538284, "5646": 0.7124901413917542, "5648": 0.8281423449516296, "5666": 0.8433839678764343, "5709": 0.1229778528213501, "5760": 0.01934296265244484, "5761": 0.018384648486971855, "5787": 0.7220231294631958, "5852": 0.16690383851528168, "5867": 0.06703783571720123, "5911": 0.4855078160762787, "5930": 0.9900637865066528, "5967": 0.21214580535888672, "5997": 0.06246116757392883, "6022": 0.2089812457561493, "6028": 0.5855054259300232, "6064": 0.2184450328350067, "6162": 0.3409265875816345, "6310": 0.7934166193008423, "6364": 0.37707099318504333, "6366": 0.12470348179340363, "6370": 0.14939609169960022, "6407": 0.030771657824516296, "6434": 0.7182208299636841, "6522": 1.2985725402832031, "6537": 0.688742995262146, "6583": 0.5370414853096008, "6643": 0.04860413447022438, "6693": 0.9037119746208191, "6698": 0.2539152204990387, "6709": 0.2516399025917053, "6731": 0.04953393340110779, "6757": 0.4158279001712799, "6845": 0.6128603219985962, "6855": 0.2478361576795578, "6882": 0.5822374224662781, "6887": 0.6011518239974976, "6895": 0.5197699069976807, "6914": 0.09228714555501938, "6942": 0.9115922451019287, "7017": 0.2394166737794876, "7065": 0.3903779089450836, "7076": 0.09317722171545029, "7096": 0.37974658608436584, "7099": 0.7220231294631958, "7233": 0.7124901413917542, "7237": 0.6813592314720154, "7275": 0.2394166737794876, "7312": 0.6853039860725403, "7317": 0.06337817758321762, "7485": 0.23556606471538544, "7551": 0.04207121208310127, "7591": 1.0403043031692505, "7594": 0.3388410806655884, "7610": 0.9470623731613159, "7633": 0.053244512528181076, "7645": 0.05786345899105072, "7709": 0.5027855634689331, "7718": 0.23633737862110138, "7753": 0.757441520690918, "7790": 0.5255602598190308, "7809": 0.05046287178993225, "7863": 0.02792670577764511, "7901": 0.8323994874954224, "8031": 0.14939609169960022, "8073": 0.5618454217910767, "8117": 0.15943801403045654, "8122": 0.056018441915512085, "8145": 0.4914994537830353, "8161": 0.10379679501056671, "8168": 0.535327672958374, "8171": 0.28155985474586487, "8279": 0.08513788133859634, "8285": 0.2719337046146393, "8321": 0.7987030148506165, "8428": 0.5478278398513794, "8516": 0.5903874635696411, "8602": 1.3858059644699097, "8649": 0.46670228242874146, "8674": 0.06246116757392883, "8745": 1.0735615491867065, "8778": 0.1485546976327896, "8853": 0.42990362644195557, "8885": 0.5685047507286072, "8913": 0.6980181336402893, "8980": 0.6583697199821472, "9007": 0.06246116757392883, "9128": 0.4286321699619293, "9276": 0.6813592314720154, "9284": 0.010684899985790253, "9334": 0.45994341373443604, "9412": 0.18329764902591705, "9447": 0.040196798741817474, "9614": 0.11168810725212097, "9839": 0.01934296265244484, "9888": 0.10291612148284912, "9896": 0.2622140049934387, "10125": 0.014542185701429844, "10174": 0.21687394380569458, "10329": 0.1751343309879303, "10381": 0.42225050926208496, "10426": 0.35334911942481995, "10438": 0.026025565341114998, "10480": 0.319873183965683, "10610": 0.5707147121429443, "10640": 0.7370892763137817, "10698": 0.14349138736724854, "10750": 0.8600510358810425, "10751": 0.09495500475168228, "10788": 0.8298473954200745, "10903": 0.08603433519601822, "11020": 0.11691460013389587, "11099": 0.4093637466430664, "11156": 0.6430866718292236, "11163": 0.32270604372024536, "11207": 0.11168810725212097, "11307": 0.04394211992621422, "11326": 0.1693800985813141, "11375": 0.41065993905067444, "11444": 0.8264343738555908, "11487": 0.6223390698432922, "11658": 0.11691460013389587, "11674": 1.105748176574707, "11709": 0.10379679501056671, "11718": 0.9115922451019287, "11847": 0.009718249551951885, "11991": 1.0506030321121216, "12123": 1.2781087160110474, "12126": 0.030771657824516296, "12322": 0.010684899985790253, "12335": 0.6000806093215942, "12381": 0.3784096837043762, "12477": 0.5186077356338501, "12515": 0.6280876994132996, "12530": 0.07612881064414978, "12546": 0.2409527748823166, "12565": 0.4425300657749176, "12618": 0.8559102416038513, "12719": 0.7182208299636841, "12737": 0.5027855634689331, "12850": 0.18492233753204346, "12978": 0.9673105478286743, "13013": 0.020300358533859253, "13113": 0.03266380727291107, "13151": 0.4873090982437134, "13153": 0.22001366317272186, "13365": 0.06429435312747955, "13400": 0.23247487843036652, "13511": 0.822151780128479, "13594": 0.11604541540145874, "13625": 0.06612417846918106, "13791": 0.036437395960092545, "13792": 0.05139094591140747, "13887": 0.23479416966438293, "14061": 0.8633513450622559, "14080": 0.6461620330810547, "14125": 0.3084607720375061, "14127": 0.9907892942428589, "14171": 0.3743882179260254, "14234": 0.02887592278420925, "14277": 0.2674594223499298, "14358": 0.022212404757738113, "14386": 0.0038986403960734606, "14413": 0.3012613356113434, "14443": 0.6714286804199219, "14570": 0.3963087201118469, "14639": 0.8400169610977173, "14676": 0.40611594915390015, "14817": 0.38041436672210693, "14841": 0.18329764902591705, "14879": 0.1693800985813141, "14961": 0.08064348995685577, "14971": 0.2800849378108978, "15042": 0.03266380727291107, "15113": 0.03266380727291107, "15115": 0.7067264318466187, "15149": 0.020300358533859253, "15154": 0.0913962796330452, "15222": 0.8332487344741821, "15472": 1.2290464639663696, "15502": 0.5127768516540527, "15796": 0.1221139207482338, "15901": 0.09672962874174118, "15924": 0.7960633039474487, "16014": 0.15442965924739838, "16134": 0.6921701431274414, "16189": 0.2749055027961731, "16215": 0.7863243818283081, "16227": 0.6970458030700684, "16360": 0.8893690705299377, "16367": 0.7426811456680298, "16463": 0.5127768516540527, "16567": 0.8941729068756104, "16578": 0.5021947622299194, "16731": 0.12470348179340363, "16840": 0.026025565341114998, "17208": 0.2741633653640747, "17427": 0.05417001247406006, "17463": 0.18654440343379974, "17544": 0.2160874605178833, "17698": 0.2539152204990387, "17822": 0.1384023278951645, "17826": 0.8492490649223328, "17908": 0.5562619566917419, "17996": 1.117955207824707, "18017": 0.3824150264263153, "18422": 0.4950772523880005, "18433": 0.09317722171545029, "18479": 0.0842406153678894, "18554": 0.1602703034877777, "18600": 0.5301685929298401, "18700": 0.14939609169960022, "18847": 0.4568560719490051, "18856": 0.021256839856505394, "18925": 0.4400174915790558, "19034": 0.4356052577495575, "19037": 0.6149744987487793, "19158": 0.14433705806732178, "19309": 0.7258110046386719, "19362": 0.940220832824707, "19425": 0.319873183965683, "19466": 0.18329764902591705, "19610": 0.7295845746994019, "19857": 0.630689799785614, "19933": 0.22626367211341858, "19948": 0.06246116757392883, "20030": 0.9470623731613159, "20037": 0.3750596046447754, "20155": 0.38574060797691345, "20177": 0.3077431619167328, "20194": 0.9886114001274109, "20253": 0.13243216276168823, "20282": 1.0464962720870972, "20302": 0.1693800985813141, "20377": 0.02887592278420925, "20960": 0.7144040465354919, "21101": 0.00875066313892603, "21104": 0.839173436164856, "21118": 0.05417001247406006, "21252": 0.32199856638908386, "21336": 0.31132611632347107, "21716": 0.6902132034301758, "21718": 0.33605360984802246, "21770": 0.35745587944984436, "21948": 0.04953393340110779, "21961": 0.029824240133166313, "21969": 0.11778303235769272, "22184": 0.5607312321662903, "22248": 0.4196864068508148, "22330": 0.8707374930381775, "22618": 0.1889725625514984, "22718": 0.3141832649707794, "22731": 0.10993985831737518, "22799": 0.22626367211341858, "22916": 0.26820653676986694, "23163": 0.6699305176734924, "23247": 0.052318159490823746, "23270": 0.8091925978660583, "23274": 0.09850110858678818, "23310": 0.03360854089260101, "23521": 0.14433705806732178, "23559": 0.02887592278420925, "23706": 0.9139442443847656, "23736": 0.09050461649894714, "23943": 0.020300358533859253, "24004": 1.2324692010879517, "24081": 0.45994341373443604, "24110": 0.27564704418182373, "24171": 0.7115318179130554, "24324": 0.2018241584300995, "24327": 0.06977381557226181, "24345": 0.18411032855510712, "24471": 0.22937409579753876, "24848": 0.1677299439907074, "24854": 0.10818854719400406, "25002": 0.03360854089260101, "25003": 0.05786345899105072, "25006": 0.05786345899105072, "25060": 0.055094651877880096, "25458": 0.2674594223499298, "25643": 1.0655186176300049, "25714": 0.04953393340110779, "25952": 0.11343330889940262, "25971": 0.34300774335861206, "26226": 0.6441128253936768, "26236": 0.2983669638633728, "26394": 0.3163207769393921, "26563": 0.056018441915512085, "27059": 0.1011524572968483, "27152": 0.5596157908439636, "27321": 0.12384103983640671, "27351": 0.1384023278951645, "27896": 0.11081436276435852, "28144": 0.09672962874174118, "28293": 0.11168810725212097, "28406": 0.38308101892471313, "28414": 1.1616848707199097, "28527": 0.24401791393756866, "28591": 0.1384023278951645, "28613": 0.06977381557226181, "28648": 0.7845434546470642, "29160": 0.6466736793518066, "29336": 0.35677260160446167, "29458": 0.026025565341114998, "29490": 0.5370414853096008} | 13801259 | We have developed a modified version of our fully automated column-switching HPLC method for determining total plasma homocysteine based on single-column (reversed-phase) separation. Homocysteine, cysteine, and cysteinylglycine in plasma (total concentrations), acid-precipitated plasma (non-protein-bound concentrations), and urine can be determined. The derivatization and chromatography were performed automatically by a sample processor. The successful separation of all thiol species (within 15 min) was accomplished by accurate adjustment of the pH of the mobile phase to 3.65 (plasma) or 3.50 (acid-precipitated plasma, urine). Maximal fluorescence yield of cysteine, cysteinylglycine, and, to a lesser degree, homocysteine was dependent on optimal concentrations of EDTA and dithioerythritol during reduction (with NaBH4) and derivatization (with monobromobimane). The method is sensitive (detection limit approximately 0.05 pmol) and has a high degree of precision (CV < 5%). The sample output is approximately 70 samples in 24 h. Serum and heparin plasma can also be analyzed. Hemolysis up to approximately 2.0 g/L of hemoglobin did not interfere with the analytical recovery of homocysteine or cysteine. Collection of blood, separation of plasma from whole blood, and acid precipitation must be standardized to obtain reproducible thiol results. Our modifications and the standardization of blood-sampling procedures have substantially improved the method and broadened its applications. | Homocysteine and other thiols in plasma and urine: automated determination and sample stability. |
{"1011": 0.1619328260421753, "1055": 0.05139094591140747, "2000": 0.026976587250828743, "2015": 0.5936289429664612, "2054": 0.04674193635582924, "2064": 0.05139094591140747, "2087": 0.2830325961112976, "2109": 0.3963087201118469, "2111": 0.14686977863311768, "2114": 0.4248080551624298, "2214": 0.5450005531311035, "2216": 0.020300358533859253, "2224": 0.33953672647476196, "2241": 0.9194108247756958, "2278": 0.29981520771980286, "2287": 0.8764448165893555, "2291": 0.2881702482700348, "2339": 0.14518201351165771, "2349": 0.04767346754670143, "2389": 0.08244366943836212, "2443": 0.05970508232712746, "2458": 0.23787821829319, "2470": 0.8600510358810425, "2478": 0.25845035910606384, "2488": 0.20660123229026794, "2512": 0.20022670924663544, "2529": 0.6744182109832764, "2535": 0.022212404757738113, "2580": 0.055094651877880096, "2590": 0.010684899985790253, "2640": 0.016465263441205025, "2664": 0.31489628553390503, "2671": 0.12986256182193756, "2691": 0.5590575933456421, "2695": 0.4974553883075714, "2750": 0.018384648486971855, "2764": 0.7482418417930603, "2817": 0.12986256182193756, "2825": 0.06977381557226181, "2832": 0.2749055027961731, "2913": 0.1619328260421753, "2944": 0.7854343056678772, "2966": 0.16442140936851501, "2974": 0.7692760229110718, "2999": 0.4002431631088257, "3001": 0.43053874373435974, "3024": 0.043007105588912964, "3026": 0.6086184978485107, "3073": 0.052318159490823746, "3080": 0.4311734735965729, "3145": 0.016465263441205025, "3231": 0.2719337046146393, "3273": 0.2160874605178833, "3291": 0.22157983481884003, "3294": 0.18329764902591705, "3303": 0.22001366317272186, "3305": 0.37707099318504333, "3314": 0.0174254160374403, "3319": 0.48850810527801514, "3330": 0.0058422754518687725, "3399": 0.2990913391113281, "3424": 0.16442140936851501, "3426": 0.5092619061470032, "3443": 0.21214580535888672, "3471": 0.37102460861206055, "3515": 0.6461620330810547, "3522": 0.2394166737794876, "3526": 1.0123108625411987, "3563": 0.554580807685852, "3594": 0.12642613053321838, "3603": 0.07250232994556427, "3638": 0.5174443125724792, "3695": 0.45870962738990784, "3697": 0.1718502640724182, "3728": 0.6522845029830933, "3802": 0.8583967685699463, "3818": 0.14349138736724854, "3891": 0.5849615335464478, "3898": 0.2089812457561493, "3935": 0.12470348179340363, "3949": 0.4450363218784332, "4039": 0.1677299439907074, "4045": 0.21372433006763458, "4118": 0.0913962796330452, "4119": 0.6139179468154907, "4132": 0.5685047507286072, "4141": 0.23710809648036957, "4146": 0.11604541540145874, "4167": 0.4770587682723999, "4215": 0.3416208028793335, "4275": 0.7755908370018005, "4286": 0.52266925573349, "4295": 0.9546096324920654, "4319": 0.10467668622732162, "4397": 0.0913962796330452, "4442": 1.0815403461456299, "4453": 0.47827014327049255, "4456": 0.29036402702331543, "4503": 0.23324857652187347, "4526": 0.021256839856505394, "4541": 0.00875066313892603, "4719": 0.011650617234408855, "4725": 0.0029254043474793434, "4748": 1.3610767126083374, "4765": 0.7951818704605103, "4769": 0.0174254160374403, "4786": 0.39893341064453125, "4793": 0.07250232994556427, "4824": 0.603290855884552, "4958": 0.043007105588912964, "4962": 0.5968599319458008, "4975": 0.3388410806655884, "5022": 0.45437926054000854, "5038": 0.10291612148284912, "5082": 0.32553088665008545, "5173": 0.8366385698318481, "5301": 0.0019512200960889459, "5302": 0.08603433519601822, "5319": 0.3864043951034546, "5320": 0.5887627601623535, "5387": 0.255429208278656, "5421": 0.1930064558982849, "5422": 0.255429208278656, "5449": 1.0101795196533203, "5535": 0.030771657824516296, "5604": 0.3409265875816345, "5672": 0.5893046259880066, "5770": 0.05694137513637543, "5776": 0.5607312321662903, "5850": 0.3027053773403168, "5852": 0.07612881064414978, "5876": 0.4512746334075928, "5906": 0.17922431230545044, "5911": 0.018384648486971855, "5967": 0.06429435312747955, "6001": 0.11430477350950241, "6028": 0.14602625370025635, "6064": 0.1401015669107437, "6110": 1.1076855659484863, "6169": 0.11604541540145874, "6179": 0.09938567131757736, "6194": 0.07068414986133575, "6305": 0.12470348179340363, "6388": 0.06520967930555344, "6419": 0.30558720231056213, "6475": 0.5278670787811279, "6529": 0.015504186972975731, "6612": 0.6410312056541443, "6627": 0.3560888469219208, "6635": 0.46055975556373596, "6666": 0.1685553640127182, "6709": 0.32764431834220886, "6779": 0.17267228662967682, "6786": 0.6862877607345581, "6848": 0.24401791393756866, "6887": 0.28670501708984375, "6897": 0.014542185701429844, "6936": 0.26820653676986694, "6950": 0.13414156436920166, "6994": 0.2881702482700348, "7013": 0.04860413447022438, "7155": 0.0058422754518687725, "7242": 1.0755622386932373, "7248": 0.5238267183303833, "7337": 0.8691008687019348, "7355": 0.3757305145263672, "7366": 0.09850110858678818, "7403": 0.6613984704017639, "7645": 0.08064348995685577, "7681": 0.07068414986133575, "7718": 0.19782574474811554, "7860": 0.8715548515319824, "7870": 0.77198725938797, "7872": 1.325913906097412, "7885": 0.14518201351165771, "7900": 0.11604541540145874, "7976": 0.03360854089260101, "8040": 0.23479416966438293, "8153": 0.1685553640127182, "8182": 0.19541899859905243, "8190": 0.17267228662967682, "8280": 0.40806588530540466, "8315": 0.4311734735965729, "8720": 0.5685047507286072, "8761": 0.21214580535888672, "9099": 0.22859740257263184, "9165": 0.7047978043556213, "9336": 0.06520967930555344, "9349": 0.0019512200960889459, "9373": 0.619189441204071, "9412": 0.09406650811433792, "9468": 0.21765978634357452, "9496": 0.8022117614746094, "9750": 0.7728893756866455, "9793": 0.12384103983640671, "9849": 0.1751343309879303, "10003": 0.09850110858678818, "10015": 0.777387797832489, "10091": 0.30558720231056213, "10368": 0.5952457785606384, "10539": 0.75193190574646, "10572": 1.1911962032318115, "10595": 0.8633513450622559, "10660": 0.2516399025917053, "10699": 0.5021947622299194, "10744": 0.6950984001159668, "10753": 0.2976420819759369, "10787": 0.2034190446138382, "10831": 0.3106105625629425, "10840": 0.07884006202220917, "10847": 0.02316705882549286, "10859": 0.006812678650021553, "10976": 0.2409527748823166, "11008": 0.8941729068756104, "11020": 1.3165339231491089, "11160": 0.06429435312747955, "11326": 0.6684301495552063, "11548": 0.15359249711036682, "11601": 0.12814582884311676, "11643": 0.7889899015426636, "11913": 0.13755162060260773, "11916": 0.08154398202896118, "12126": 0.006812678650021553, "12151": 0.32129061222076416, "12153": 0.025073638185858727, "12238": 0.36697331070899963, "12328": 0.14518201351165771, "12402": 0.3262358605861664, "12504": 0.5080875158309937, "12520": 0.5104349255561829, "12546": 0.14686977863311768, "12550": 0.04860413447022438, "12562": 0.4145384132862091, "12637": 0.1221139207482338, "12697": 0.029824240133166313, "12786": 0.026025565341114998, "12944": 0.022212404757738113, "12997": 1.4450790882110596, "13046": 0.5827828645706177, "13102": 0.07793712615966797, "13376": 0.3127557039260864, "13441": 0.22937409579753876, "13685": 0.08871890604496002, "13711": 0.14264501631259918, "13720": 0.2852376699447632, "13874": 0.36967599391937256, "14440": 0.37102460861206055, "14471": 0.2837681770324707, "14573": 0.2696990668773651, "14622": 0.02792670577764511, "14667": 0.16524957120418549, "14679": 0.06429435312747955, "14780": 0.2763880789279938, "14800": 0.19220098853111267, "14847": 0.09672962874174118, "14997": 0.42608439922332764, "15007": 0.2539152204990387, "15069": 0.7258110046386719, "15189": 0.41001203656196594, "15258": 0.5523349046707153, "15262": 0.08692999184131622, "15841": 0.07159364968538284, "15873": 0.6369074583053589, "15909": 0.6410312056541443, "15946": 0.5209306478500366, "15995": 0.6430866718292236, "16014": 0.06612417846918106, "16134": 0.11691460013389587, "16221": 0.05417001247406006, "16364": 0.0058422754518687725, "16462": 0.02412080205976963, "16474": 0.1011524572968483, "16515": 0.7028654217720032, "16661": 0.03266380727291107, "16911": 0.09495500475168228, "17261": 0.3381449282169342, "17316": 0.09406650811433792, "17537": 0.1477125883102417, "17637": 0.23864774405956268, "18178": 0.07341018319129944, "18547": 0.3560888469219208, "19294": 0.2689530849456787, "19389": 0.0606246218085289, "19518": 0.47827014327049255, "19653": 0.7995813488960266, "19731": 0.9209672808647156, "19824": 0.17840765416622162, "19872": 0.1229778528213501, "20166": 0.1930064558982849, "20228": 0.7370892763137817, "20282": 0.7258110046386719, "20310": 0.42353010177612305, "20350": 0.11343330889940262, "20353": 0.17922431230545044, "20523": 0.04487626627087593, "20569": 0.5180262327194214, "20734": 0.40089741349220276, "20736": 0.1751343309879303, "20775": 0.025073638185858727, "20792": 0.08871890604496002, "20885": 0.10906458646059036, "20900": 0.5033760666847229, "20906": 0.27934664487838745, "21104": 0.09850110858678818, "21823": 0.07431721687316895, "21901": 1.5548497438430786, "22571": 0.3283478021621704, "22634": 0.21372433006763458, "22901": 0.004870930220931768, "22969": 0.1401015669107437, "23041": 0.13157635927200317, "23072": 0.7528522610664368, "23184": 0.7210738658905029, "23411": 0.16359257698059082, "23569": 0.32905077934265137, "23683": 0.23092569410800934, "23700": 0.037378571927547455, "23936": 0.4531385898590088, "24269": 0.14433705806732178, "24286": 0.03831886500120163, "24608": 0.5393219590187073, "24710": 0.5690577030181885, "24757": 0.19541899859905243, "24992": 0.006812678650021553, "25284": 0.14518201351165771, "25437": 0.14602625370025635, "25613": 0.010684899985790253, "25714": 0.25467249751091003, "25737": 0.07431721687316895, "26305": 0.015504186972975731, "26452": 0.009718249551951885, "26497": 0.11691460013389587, "26633": 0.10026945173740387, "27011": 0.07793712615966797, "27144": 0.2531573474407196, "27354": 0.0019512200960889459, "27605": 0.46853771805763245, "28086": 0.14179791510105133, "28228": 0.01934296265244484, "28405": 0.23247487843036652, "28487": 0.08513788133859634, "28518": 0.5590575933456421, "28767": 1.4927284717559814, "28788": 0.18329764902591705, "29290": 0.49864232540130615} | 13814480 | Alzheimer's disease (AD) is the most common cause of dementia in those over the age of 65. While a numerous of disease-causing genes and risk factors have been identified, the exact etiological mechanisms of AD are not yet completely understood, due to the inability to test theoretical hypotheses on non-postmortem and patient-specific research systems. The use of recently developed and optimized induced pluripotent stem cells (iPSCs) technology may provide a promising platform to create reliable models, not only for better understanding the etiopathological process of AD, but also for efficient anti-AD drugs screening. More importantly, human-sourced iPSCs may also provide a beneficial tool for cell-replacement therapy against AD. Although considerable progress has been achieved, a number of key challenges still require to be addressed in iPSCs research, including the identification of robust disease phenotypes in AD modeling and the clinical availabilities of iPSCs-based cell-replacement therapy in human. In this review, we highlight recent progresses of iPSCs research and discuss the translational challenges of AD patients-derived iPSCs in disease modeling and cell-replacement therapy. | Induced pluripotent stem cells in Alzheimer’s disease: applications for disease modeling and cell-replacement therapy |
{"1011": 0.14095009863376617, "1016": 0.21922965347766876, "1045": 0.03925827145576477, "1050": 0.520350456237793, "1060": 0.09050461649894714, "1999": 0.18978065252304077, "2000": 0.09317722171545029, "2003": 0.020300358533859253, "2004": 0.06154331564903259, "2011": 0.3077431619167328, "2012": 0.24401791393756866, "2029": 0.11691460013389587, "2033": 0.5272908806800842, "2044": 0.11168810725212097, "2053": 1.2959036827087402, "2064": 0.19862671196460724, "2071": 0.1930064558982849, "2078": 0.22392450273036957, "2089": 0.07612881064414978, "2109": 0.04207121208310127, "2114": 0.43623676896095276, "2120": 0.0752234235405922, "2121": 0.2447827309370041, "2135": 0.07159364968538284, "2139": 0.3191637098789215, "2193": 0.09050461649894714, "2203": 0.5278670787811279, "2278": 0.3963087201118469, "2302": 0.022212404757738113, "2331": 0.07793712615966797, "2365": 0.4002431631088257, "2475": 0.4318077862262726, "2487": 0.401551216840744, "2504": 0.01934296265244484, "2512": 0.5021947622299194, "2515": 0.21214580535888672, "2535": 0.2160874605178833, "2540": 0.2105647772550583, "2545": 0.06795065850019455, "2590": 0.38174858689308167, "2618": 1.2140778303146362, "2659": 0.11691460013389587, "2668": 0.11517547070980072, "2748": 0.45499902963638306, "2895": 0.055094651877880096, "2944": 0.3034266233444214, "2953": 0.5914691090583801, "2954": 0.0797421783208847, "3024": 0.02792670577764511, "3025": 0.04207121208310127, "3064": 0.16359257698059082, "3073": 0.16690383851528168, "3081": 0.013579257763922215, "3130": 0.46608972549438477, "3161": 0.1011524572968483, "3223": 0.151916041970253, "3273": 0.00875066313892603, "3278": 0.052318159490823746, "3366": 0.16276304423809052, "3375": 0.5347557663917542, "3378": 0.6043586730957031, "3424": 0.10555581003427505, "3433": 0.1332872211933136, "3450": 0.07431721687316895, "3466": 0.48008447885513306, "3490": 0.11168810725212097, "3491": 0.2830325961112976, "3508": 0.05046287178993225, "3522": 0.13499516248703003, "3560": 0.18167030811309814, "3630": 0.43244171142578125, "3639": 0.020300358533859253, "3640": 0.14179791510105133, "3642": 0.06154331564903259, "3686": 0.13157635927200317, "3695": 0.3297532796859741, "3728": 0.3339579105377197, "3853": 0.5381823778152466, "3860": 0.6451379656791687, "3893": 0.07793712615966797, "3896": 0.472198486328125, "3904": 0.5232481360435486, "3949": 0.4400174915790558, "4003": 0.6086184978485107, "4005": 0.03925827145576477, "4022": 0.12470348179340363, "4023": 0.5220900774002075, "4047": 0.7028654217720032, "4053": 0.5914691090583801, "4054": 0.4425300657749176, "4072": 0.4568560719490051, "4119": 0.5021947622299194, "4135": 0.15693697333335876, "4167": 0.22626367211341858, "4176": 0.04953393340110779, "4221": 0.6664261221885681, "4275": 0.026025565341114998, "4305": 0.678390383720398, "4319": 0.08154398202896118, "4359": 0.3005385100841522, "4372": 0.08064348995685577, "4442": 0.13157635927200317, "4453": 0.5021947622299194, "4456": 0.4537591338157654, "4496": 0.42225050926208496, "4539": 0.052318159490823746, "4544": 0.4673144817352295, "4570": 0.755608320236206, "4621": 0.06337817758321762, "4629": 0.2105647772550583, "4652": 0.15693697333335876, "4742": 0.4752389192581177, "4747": 0.3910386264324188, "4758": 0.05694137513637543, "4788": 0.08603433519601822, "4795": 0.26296505331993103, "4962": 0.040196798741817474, "4972": 0.2247048318386078, "4997": 0.6223390698432922, "5012": 0.23479416966438293, "5072": 0.5238267183303833, "5123": 0.40806588530540466, "5144": 0.11081436276435852, "5158": 0.14686977863311768, "5197": 0.09406650811433792, "5213": 0.9907892942428589, "5250": 0.09672962874174118, "5258": 0.35403475165367126, "5387": 0.36086538434028625, "5397": 0.371698260307312, "5403": 0.7537717819213867, "5423": 0.5483922958374023, "5441": 0.18492233753204346, "5524": 0.15777134895324707, "5531": 0.08782484382390976, "5547": 0.24325250089168549, "5582": 0.46853771805763245, "5591": 0.35950297117233276, "5643": 0.18329764902591705, "5668": 0.37640097737312317, "5675": 0.2711893916130066, "5688": 0.09672962874174118, "5770": 0.018384648486971855, "5783": 0.058784693479537964, "5788": 0.1384023278951645, "5812": 0.17922431230545044, "5845": 0.14518201351165771, "5850": 0.08782484382390976, "5876": 0.1401015669107437, "5892": 0.13157635927200317, "6022": 0.5466978549957275, "6024": 0.3297532796859741, "6032": 0.012615402229130268, "6099": 0.1808556467294693, "6305": 0.1677299439907074, "6370": 0.26146242022514343, "6441": 0.2394166737794876, "6459": 0.02412080205976963, "6499": 0.7105726003646851, "6528": 0.5478278398513794, "6540": 0.07884006202220917, "6541": 0.732405424118042, "6553": 0.32129061222076416, "6583": 0.09850110858678818, "6657": 0.48068851232528687, "6666": 0.1751343309879303, "6691": 0.037378571927547455, "6887": 0.4286321699619293, "6895": 0.25467249751091003, "6897": 0.6931471824645996, "6909": 0.1477125883102417, "6911": 0.6275664567947388, "6980": 0.7134475708007812, "6985": 0.02792670577764511, "7021": 0.007782140281051397, "7028": 0.28670501708984375, "7091": 0.1873544454574585, "7135": 0.23402166366577148, "7242": 0.21214580535888672, "7274": 0.4512746334075928, "7312": 0.630689799785614, "7328": 0.08154398202896118, "7337": 0.3423145115375519, "7361": 0.2637155055999756, "7366": 0.47036975622177124, "7438": 0.3416208028793335, "7461": 0.1619328260421753, "7507": 0.4437839686870575, "7542": 0.13755162060260773, "7616": 0.4132472574710846, "7629": 0.05417001247406006, "7645": 0.5723689198493958, "7677": 0.016465263441205025, "7691": 0.07159364968538284, "7722": 0.6212902665138245, "7755": 0.22548456490039825, "7790": 1.034073829650879, "7816": 0.0354953333735466, "7860": 0.34023189544677734, "7913": 0.00875066313892603, "8000": 0.935633659362793, "8071": 1.0492360591888428, "8153": 0.7845434546470642, "8161": 0.18329764902591705, "8315": 0.11343330889940262, "8360": 0.21372433006763458, "8382": 0.05970508232712746, "8428": 0.2976420819759369, "8522": 0.1064341589808464, "8524": 0.674915611743927, "8566": 0.2749055027961731, "8649": 0.31560876965522766, "8650": 0.016465263441205025, "8743": 1.1153976917266846, "8878": 0.07793712615966797, "8961": 0.6170841455459595, "9002": 0.2409527748823166, "9007": 0.5278670787811279, "9048": 0.2763880789279938, "9096": 0.7210738658905029, "9099": 0.3297532796859741, "9152": 1.390192985534668, "9319": 0.03266380727291107, "9350": 0.4425300657749176, "9474": 0.42096930742263794, "9513": 0.46363574266433716, "9614": 0.022212404757738113, "9947": 0.1930064558982849, "10092": 0.6502478122711182, "10124": 0.4190443754196167, "10163": 0.28890204429626465, "10196": 0.2394166737794876, "10210": 0.6420594453811646, "10368": 0.255429208278656, "10572": 0.9217445850372314, "10595": 0.037378571927547455, "10665": 0.9209672808647156, "10698": 0.1677299439907074, "10744": 0.022212404757738113, "10752": 0.4356052577495575, "10769": 0.42353010177612305, "11022": 0.57457035779953, "11244": 0.40806588530540466, "11265": 0.21214580535888672, "11311": 0.3134697377681732, "11432": 0.469759464263916, "11467": 0.25239890813827515, "11522": 0.10467668622732162, "11636": 0.5849615335464478, "11657": 0.38574060797691345, "11704": 1.0001721382141113, "11890": 0.4412745535373688, "12044": 0.5301685929298401, "12115": 0.15359249711036682, "12123": 0.15610189735889435, "12130": 0.12556517124176025, "12141": 0.07250232994556427, "12222": 0.037378571927547455, "12248": 0.10467668622732162, "12259": 0.4196864068508148, "12306": 0.3949938118457794, "12326": 0.05970508232712746, "12328": 1.0250049829483032, "12394": 0.05970508232712746, "12436": 0.6892333030700684, "12530": 0.46055975556373596, "12644": 0.12470348179340363, "12702": 0.4812922179698944, "12765": 0.846739649772644, "12835": 0.12728634476661682, "12987": 0.21293537318706512, "13070": 0.24631060659885406, "13136": 0.02412080205976963, "13181": 0.3297532796859741, "13250": 0.7086513638496399, "13316": 0.036437395960092545, "13341": 0.14179791510105133, "13345": 0.053244512528181076, "13356": 0.36358460783958435, "13365": 0.08782484382390976, "13366": 0.2247048318386078, "13416": 0.012615402229130268, "13441": 0.14095009863376617, "13490": 0.7286425232887268, "13656": 0.7426811456680298, "13776": 0.12556517124176025, "13791": 0.03925827145576477, "13806": 0.3963087201118469, "13833": 0.6435998678207397, "13922": 0.2089812457561493, "14014": 0.05139094591140747, "14095": 0.6862877607345581, "14114": 0.6563454270362854, "14399": 0.40806588530540466, "14480": 0.021256839856505394, "14573": 0.5069117546081543, "14828": 0.5849615335464478, "14856": 0.8845420479774475, "14956": 0.906871497631073, "14971": 0.9417452812194824, "15011": 0.129004567861557, "15050": 0.30486753582954407, "15306": 0.11430477350950241, "15316": 0.36290550231933594, "15403": 0.32199856638908386, "15420": 0.3547199070453644, "15519": 0.33605360984802246, "15637": 0.5729197263717651, "15663": 0.026025565341114998, "15869": 0.0752234235405922, "15946": 0.3662964701652527, "16012": 0.6714286804199219, "16127": 0.42608439922332764, "16149": 0.3656192123889923, "16231": 0.11081436276435852, "16285": 0.4425300657749176, "16341": 0.07159364968538284, "16360": 0.8517522215843201, "16371": 0.4203280806541443, "16429": 0.3134697377681732, "16505": 0.11256109178066254, "16605": 0.44753631949424744, "16839": 1.0080435276031494, "16880": 0.2674594223499298, "16882": 0.6389714479446411, "17063": 0.034552380442619324, "17119": 0.1889725625514984, "17212": 0.42416930198669434, "17235": 0.24631060659885406, "17250": 0.6233867406845093, "17261": 0.06886265426874161, "17379": 0.09317722171545029, "17631": 0.3560888469219208, "17698": 0.06795065850019455, "17760": 0.15359249711036682, "18089": 0.4196864068508148, "18178": 0.10291612148284912, "18227": 0.4926934838294983, "18260": 0.07793712615966797, "18491": 0.4920966327190399, "18642": 0.04953393340110779, "18647": 0.08782484382390976, "18699": 0.21687394380569458, "18714": 0.2749055027961731, "18804": 0.7463917136192322, "18886": 1.2873153686523438, "18888": 0.13499516248703003, "19092": 0.6980181336402893, "19319": 0.07250232994556427, "19332": 0.6435998678207397, "19389": 0.7818660736083984, "19577": 0.11430477350950241, "19653": 0.7701805830001831, "19739": 0.4500300884246826, "19879": 0.4374985992908478, "20051": 0.777387797832489, "20132": 0.4938860833644867, "20303": 0.10731173306703568, "20350": 0.06703783571720123, "20353": 0.25088030099868774, "20360": 0.022212404757738113, "20464": 0.6327666640281677, "20523": 0.9037119746208191, "20598": 0.2786078155040741, "20752": 0.1889725625514984, "20766": 0.034552380442619324, "20872": 0.07068414986133575, "20906": 0.21530038118362427, "20976": 0.0174254160374403, "21081": 0.14686977863311768, "21150": 0.12384103983640671, "21434": 0.4980490207672119, "21449": 0.15943801403045654, "21453": 0.19862671196460724, "21572": 0.52266925573349, "21656": 0.04394211992621422, "21709": 0.4462870955467224, "21800": 0.021256839856505394, "21903": 0.1384023278951645, "21919": 0.20421554148197174, "22214": 1.1281205415725708, "22330": 0.5151132941246033, "22423": 1.0735615491867065, "22535": 0.8323994874954224, "22571": 0.6420594453811646, "22641": 0.39762192964553833, "22779": 0.06703783571720123, "22930": 0.32764431834220886, "23060": 0.5244048833847046, "23079": 1.0999135971069336, "23296": 0.4673144817352295, "23572": 0.2719337046146393, "23586": 0.7408206462860107, "23737": 0.06703783571720123, "23924": 0.8074519634246826, "23961": 0.5506471395492554, "24054": 0.5990082025527954, "24203": 0.6950984001159668, "24269": 0.39367714524269104, "24278": 0.48008447885513306, "24312": 0.7665573358535767, "24335": 0.2145126610994339, "24345": 0.5162794589996338, "24394": 0.23556606471538544, "24842": 0.21765978634357452, "24848": 0.24171993136405945, "24978": 0.1946154683828354, "25006": 0.3141832649707794, "25456": 0.29981520771980286, "25608": 0.13925230503082275, "25714": 0.15023678541183472, "25950": 0.02792670577764511, "26387": 0.07612881064414978, "26402": 0.5347557663917542, "26557": 0.3325583338737488, "26702": 0.15860503911972046, "26721": 0.46853771805763245, "26785": 0.7809720039367676, "27373": 0.4974553883075714, "27854": 0.02887592278420925, "27937": 0.11517547070980072, "27969": 0.5139457583427429, "28156": 0.22079704701900482, "28215": 0.5116065740585327, "28227": 0.3177432417869568, "28466": 0.43623676896095276, "28548": 0.12038381397724152, "28817": 0.7096124291419983, "28991": 0.3850763738155365, "29090": 0.6892333030700684, "29122": 0.7610978484153748, "29166": 0.9037119746208191, "29290": 0.35813871026039124, "29349": 0.4531385898590088, "29607": 1.0409941673278809} | 13823200 | Nitrite (NO(2)(-)), previously viewed as a physiologically inert metabolite and biomarker of the endogenous vasodilator NO, was recently identified as an important biological NO reservoir in vasculature and tissues, where it contributes to hypoxic signaling, vasodilation, and cytoprotection after ischemia-reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin, deoxymyoglobin, xanthine oxidase, mitochondrial complexes, or NO synthase (NOS). We show that nitrite treatment, in sharp contrast with the worsening effect of NOS inhibition, significantly attenuates hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction, and mortality in a mouse shock model induced by a lethal tumor necrosis factor challenge. Mechanistically, nitrite-dependent protection was not associated with inhibition of mitochondrial complex I activity, as previously demonstrated for ischemia-reperfusion, but was largely abolished in mice deficient for the soluble guanylate cyclase (sGC) alpha1 subunit, one of the principal intracellular NO receptors and signal transducers in the cardiovasculature. Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were required. In conclusion, we show that nitrite can protect against toxicity in shock via sGC-dependent signaling, which may include hypoxic vasodilation necessary to maintain microcirculation and organ function, and cardioprotection. | Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase–dependent manner |
{"1014": 0.25845035910606384, "1022": 0.42735910415649414, "1023": 0.018384648486971855, "1997": 0.0038986403960734606, "2003": 0.025073638185858727, "2011": 0.22704219818115234, "2043": 0.15610189735889435, "2044": 0.6212902665138245, "2051": 0.5404602885246277, "2058": 0.3588210940361023, "2062": 0.2184450328350067, "2064": 0.24325250089168549, "2084": 0.11951763927936554, "2086": 0.469759464263916, "2090": 0.16359257698059082, "2095": 0.07793712615966797, "2098": 0.3297532796859741, "2144": 0.28743788599967957, "2146": 0.6430866718292236, "2181": 0.1384023278951645, "2206": 0.02792670577764511, "2214": 0.41065993905067444, "2220": 0.07884006202220917, "2260": 0.3241194784641266, "2287": 0.981317400932312, "2290": 0.17840765416622162, "2308": 0.7220231294631958, "2312": 0.13925230503082275, "2313": 0.5534584522247314, "2335": 0.09584271162748337, "2339": 0.25239890813827515, "2402": 0.33953672647476196, "2411": 0.29255300760269165, "2429": 0.1873544454574585, "2450": 0.4764525294303894, "2470": 0.20660123229026794, "2491": 0.817850649356842, "2515": 0.3084607720375061, "2523": 0.6420594453811646, "2524": 0.07159364968538284, "2553": 0.8517522215843201, "2560": 0.08244366943836212, "2599": 0.037378571927547455, "2625": 0.2478361576795578, "2632": 0.010684899985790253, "2674": 0.07250232994556427, "2706": 0.5051454305648804, "2753": 0.6244332790374756, "2765": 0.20421554148197174, "2779": 0.06703783571720123, "2809": 0.23324857652187347, "2812": 0.2089812457561493, "2817": 0.5860490798950195, "2844": 0.006812678650021553, "2846": 0.07068414986133575, "2863": 0.15023678541183472, "2913": 0.6197150945663452, "2920": 0.0752234235405922, "2931": 0.22001366317272186, "2972": 0.1332872211933136, "3026": 0.13071982562541962, "3041": 0.004870930220931768, "3080": 0.6389714479446411, "3176": 0.12728634476661682, "3204": 0.22157983481884003, "3231": 0.5381823778152466, "3251": 0.3601844012737274, "3258": 0.037378571927547455, "3273": 0.2223619967699051, "3278": 0.47402387857437134, "3344": 0.4831010699272156, "3350": 0.043007105588912964, "3365": 0.052318159490823746, "3378": 0.9147270321846008, "3382": 0.25694093108177185, "3435": 0.20102575421333313, "3445": 0.680370569229126, "3446": 0.18654440343379974, "3449": 0.056018441915512085, "3461": 0.25845035910606384, "3463": 0.42096930742263794, "3466": 0.1685553640127182, "3497": 0.1685553640127182, "3515": 0.4624064862728119, "3517": 0.17020416259765625, "3540": 0.15860503911972046, "3556": 0.10993985831737518, "3572": 0.3949938118457794, "3618": 0.5882205963134766, "3623": 0.4938860833644867, "3647": 0.29036402702331543, "3668": 0.3750596046447754, "3697": 0.5778634548187256, "3742": 0.3191637098789215, "3747": 0.4879087805747986, "3801": 0.02887592278420925, "3811": 0.2763880789279938, "3867": 0.4462870955467224, "3891": 1.0782235860824585, "3893": 0.21922965347766876, "3896": 0.13499516248703003, "3898": 0.736154317855835, "3920": 0.619189441204071, "3935": 0.48970574140548706, "3940": 0.4770587682723999, "3979": 0.22079704701900482, "3991": 0.4855078160762787, "4102": 0.4849066734313965, "4106": 0.04674193635582924, "4118": 0.3750596046447754, "4135": 0.034552380442619324, "4235": 0.02887592278420925, "4242": 0.2409527748823166, "4254": 0.08513788133859634, "4281": 0.9425065517425537, "4293": 0.4067663550376892, "4295": 0.1221139207482338, "4304": 1.3555532693862915, "4328": 0.055094651877880096, "4423": 0.3070250153541565, "4443": 0.3353555500507355, "4453": 0.09317722171545029, "4456": 1.210591435432434, "4468": 0.04487626627087593, "4531": 0.04767346754670143, "4600": 0.31132611632347107, "4647": 0.30558720231056213, "4654": 0.3141832649707794, "4725": 0.4624064862728119, "4758": 0.5139457583427429, "4771": 0.010684899985790253, "4793": 0.0038986403960734606, "4795": 0.29619070887565613, "4852": 0.1602703034877777, "4866": 1.2471669912338257, "4935": 0.07793712615966797, "4950": 0.1358480453491211, "4997": 0.8567397594451904, "5003": 0.9463045597076416, "5022": 0.10379679501056671, "5105": 0.10291612148284912, "5179": 0.5773153901100159, "5186": 0.13925230503082275, "5345": 0.7746911644935608, "5360": 0.04394211992621422, "5387": 0.41195443272590637, "5468": 0.35128939151763916, "5531": 0.15359249711036682, "5535": 0.1229778528213501, "5604": 0.2741633653640747, "5761": 0.20580662786960602, "5769": 0.02316705882549286, "5776": 0.13755162060260773, "5790": 0.04674193635582924, "5791": 0.020300358533859253, "5852": 0.21135559678077698, "5876": 0.26446542143821716, "5995": 0.0009760859538801014, "6022": 0.46117570996284485, "6061": 0.025073638185858727, "6075": 0.06795065850019455, "6118": 0.6202403903007507, "6196": 0.20818853378295898, "6377": 0.015504186972975731, "6387": 0.1401015669107437, "6444": 0.6461620330810547, "6463": 0.8748174905776978, "6587": 0.24554696679115295, "6612": 0.0317181795835495, "6698": 0.35334911942481995, "6747": 0.07159364968538284, "6851": 0.08244366943836212, "6924": 0.03360854089260101, "6937": 1.039613962173462, "7012": 0.2659635543823242, "7017": 0.820433497428894, "7023": 1.0519683361053467, "7080": 0.3750596046447754, "7091": 0.37371641397476196, "7108": 0.6160298585891724, "7382": 1.243794322013855, "7388": 1.2375813722610474, "7457": 0.2918238639831543, "7461": 0.25694093108177185, "7531": 0.08513788133859634, "7594": 0.5410289764404297, "7669": 0.11168810725212097, "7689": 0.6759096384048462, "7691": 0.07884006202220917, "7711": 0.38574060797691345, "7721": 0.24325250089168549, "7749": 0.23864774405956268, "7818": 0.24171993136405945, "7831": 0.40220460295677185, "7949": 0.19622190296649933, "7987": 0.3297532796859741, "8015": 0.043007105588912964, "8077": 0.8715548515319824, "8092": 0.07431721687316895, "8249": 0.030771657824516296, "8319": 0.3170322775840759, "8321": 0.16607704758644104, "8569": 0.3423145115375519, "8649": 0.38441169261932373, "8920": 0.129004567861557, "8924": 0.4794800877571106, "9089": 0.9363996982574463, "9253": 0.22859740257263184, "9280": 0.08871890604496002, "9335": 0.026976587250828743, "9336": 0.15860503911972046, "9363": 0.1677299439907074, "9367": 0.14095009863376617, "9376": 0.04767346754670143, "9377": 0.026976587250828743, "9412": 0.036437395960092545, "9480": 0.053244512528181076, "9556": 0.40546512603759766, "9560": 0.10291612148284912, "9592": 0.27342069149017334, "9603": 0.14939609169960022, "9626": 0.011650617234408855, "9657": 0.21765978634357452, "9723": 0.2447827309370041, "9742": 0.8772575259208679, "9750": 0.4518963396549225, "9756": 0.26296505331993103, "9839": 0.22859740257263184, "9844": 0.05970508232712746, "9888": 0.8666408061981201, "10032": 0.01934296265244484, "10174": 0.08513788133859634, "10238": 0.9994535446166992, "10349": 0.6123310327529907, "10368": 0.11865071207284927, "10539": 0.14179791510105133, "10640": 0.28082266449928284, "10788": 0.7969439625740051, "10831": 0.7510106563568115, "10847": 0.015504186972975731, "10880": 0.46608972549438477, "10903": 0.2990913391113281, "10928": 0.13243216276168823, "11047": 0.022212404757738113, "11118": 0.32199856638908386, "11156": 0.8682814836502075, "11176": 0.0174254160374403, "11326": 1.1406835317611694, "11360": 0.1693800985813141, "11441": 0.1401015669107437, "11487": 0.7305257320404053, "11616": 0.11343330889940262, "11655": 0.05786345899105072, "11664": 0.07159364968538284, "11792": 0.04953393340110779, "11806": 0.6911921501159668, "12117": 0.2089812457561493, "12126": 0.472198486328125, "12238": 0.823009729385376, "12246": 0.01934296265244484, "12381": 0.4920966327190399, "12435": 0.11081436276435852, "12503": 0.1510767638683319, "12520": 0.10906458646059036, "12546": 0.009718249551951885, "12565": 0.06337817758321762, "12604": 0.07341018319129944, "12682": 0.7737906575202942, "12826": 0.09228714555501938, "12884": 0.9348671436309814, "13047": 0.006812678650021553, "13105": 0.08603433519601822, "13483": 0.8340972661972046, "13589": 0.1946154683828354, "13594": 0.5069117546081543, "13599": 0.21214580535888672, "13656": 0.5313173532485962, "13705": 0.6543170213699341, "13893": 0.08064348995685577, "14025": 0.4450363218784332, "14155": 0.129004567861557, "14613": 0.17267228662967682, "14639": 0.012615402229130268, "14760": 0.28082266449928284, "14773": 0.18167030811309814, "15116": 0.013579257763922215, "15258": 0.020300358533859253, "15306": 0.6043586730957031, "15316": 0.022212404757738113, "15329": 0.08064348995685577, "15354": 0.11430477350950241, "15488": 0.08603433519601822, "15559": 0.12642613053321838, "15855": 0.0354953333735466, "15945": 0.0019512200960889459, "15982": 0.13499516248703003, "16007": 0.18816383183002472, "16014": 0.2493593990802765, "16030": 0.09761575609445572, "16134": 0.32129061222076416, "16211": 0.18492233753204346, "16330": 0.14518201351165771, "16474": 0.05970508232712746, "16593": 0.15860503911972046, "16778": 0.08603433519601822, "16902": 0.3304552733898163, "17464": 0.25088030099868774, "17503": 0.3248254358768463, "17631": 0.04394211992621422, "17759": 0.15693697333335876, "17820": 0.2447827309370041, "17890": 0.6931471824645996, "17961": 0.14433705806732178, "18075": 0.04953393340110779, "18568": 0.08154398202896118, "18886": 0.35060185194015503, "18949": 0.19381128251552582, "19034": 0.1064341589808464, "19035": 0.2990913391113281, "19064": 0.28963330388069153, "19188": 0.5301685929298401, "19441": 0.4158279001712799, "19762": 0.11168810725212097, "19824": 0.1358480453491211, "19875": 0.09050461649894714, "20272": 0.13670019805431366, "20288": 0.08244366943836212, "20502": 0.04953393340110779, "21016": 0.12470348179340363, "21081": 0.5021947622299194, "21150": 0.040196798741817474, "21434": 0.36426326632499695, "21879": 0.6144463419914246, "23900": 0.37304413318634033, "24279": 0.6461620330810547, "24759": 0.306306391954422, "24895": 0.304147332906723, "25022": 0.5133614540100098, "25121": 0.05970508232712746, "25145": 0.25845035910606384, "25202": 0.20660123229026794, "25409": 0.8764448165893555, "25437": 0.5139457583427429, "25949": 0.07884006202220917, "25952": 0.2160874605178833, "25971": 0.02316705882549286, "26163": 0.672426164150238, "26616": 0.22157983481884003, "26721": 0.052318159490823746, "26745": 0.053244512528181076, "27312": 0.1477125883102417, "27794": 0.06337817758321762, "27881": 0.009718249551951885, "28093": 0.1011524572968483, "28207": 0.15442965924739838, "28297": 0.16524957120418549, "28687": 0.1913948506116867, "29107": 0.07341018319129944, "29486": 0.3084607720375061} | 13831558 | BACKGROUND Extensive mammographic density is associated with an increased risk of breast cancer and makes the detection of cancer by mammography difficult, but the influence of density on risk according to method of cancer detection is unknown. METHODS We carried out three nested case-control studies in screened populations with 1112 matched case-control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. RESULTS As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. CONCLUSIONS Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor. | Mammographic density and the risk and detection of breast cancer. |
{"1013": 0.026976587250828743, "1014": 0.28963330388069153, "1019": 0.4487839937210083, "1023": 0.021256839856505394, "1038": 0.757441520690918, "2044": 0.151916041970253, "2090": 0.49923527240753174, "2111": 0.013579257763922215, "2116": 0.32553088665008545, "2152": 0.08603433519601822, "2177": 0.08692999184131622, "2179": 0.10203468054533005, "2193": 0.12814582884311676, "2273": 0.23015019297599792, "2287": 0.10379679501056671, "2303": 0.31132611632347107, "2308": 1.0285027027130127, "2313": 0.4158279001712799, "2386": 0.06977381557226181, "2426": 0.22548456490039825, "2450": 0.8625272512435913, "2470": 0.21214580535888672, "2475": 0.010684899985790253, "2491": 0.5092619061470032, "2502": 0.15359249711036682, "2522": 0.34508460760116577, "2523": 1.0788878202438354, "2538": 0.14095009863376617, "2553": 0.23092569410800934, "2558": 0.25694093108177185, "2566": 0.30989447236061096, "2625": 0.22859740257263184, "2641": 0.2026219218969345, "2654": 0.2160874605178833, "2695": 0.8425432443618774, "2779": 0.23402166366577148, "2817": 0.4818955361843109, "2827": 0.03925827145576477, "2846": 0.40741631388664246, "2861": 0.3318578004837036, "2863": 0.04767346754670143, "2894": 0.20501139760017395, "2913": 0.6149744987487793, "2931": 0.6254787445068359, "2946": 0.5393219590187073, "2951": 0.7370892763137817, "2981": 0.987156867980957, "3057": 0.14602625370025635, "3141": 0.37371641397476196, "3273": 0.21372433006763458, "3276": 0.6155022978782654, "3278": 0.650757372379303, "3350": 0.6902132034301758, "3378": 0.6941232681274414, "3382": 0.08603433519601822, "3445": 0.17431432008743286, "3446": 0.13071982562541962, "3466": 0.0029254043474793434, "3497": 0.15777134895324707, "3517": 0.06246116757392883, "3540": 0.10203468054533005, "3549": 0.7105726003646851, "3556": 0.3615458607673645, "3570": 0.5963221788406372, "3572": 0.5267143249511719, "3616": 0.06795065850019455, "3623": 0.3005385100841522, "3635": 0.9650808572769165, "3643": 0.15777134895324707, "3653": 0.5092619061470032, "3671": 0.36967599391937256, "3742": 0.6624060273170471, "3801": 0.4831010699272156, "3807": 0.03266380727291107, "3867": 0.12642613053321838, "3891": 1.0271050930023193, "3893": 0.75193190574646, "3896": 0.030771657824516296, "4090": 0.4770587682723999, "4094": 0.20501139760017395, "4102": 0.6608943343162537, "4106": 0.6522845029830933, "4206": 0.9363996982574463, "4254": 0.04674193635582924, "4295": 0.07884006202220917, "4297": 0.0174254160374403, "4298": 0.02316705882549286, "4304": 0.12556517124176025, "4328": 1.2244645357131958, "4336": 0.1212492436170578, "4456": 1.269914150238037, "4502": 0.7028654217720032, "4531": 0.011650617234408855, "4578": 1.0788878202438354, "4642": 0.8117979168891907, "4647": 0.17267228662967682, "4705": 0.956112265586853, "4758": 0.23324857652187347, "4765": 0.026976587250828743, "4795": 0.045809537172317505, "4800": 0.5816917419433594, "5003": 0.26146242022514343, "5043": 0.8357921838760376, "5092": 0.029824240133166313, "5139": 0.4041621685028076, "5159": 0.05694137513637543, "5300": 0.0174254160374403, "5345": 0.9333322048187256, "5360": 0.025073638185858727, "5387": 0.5968599319458008, "5393": 0.2749055027961731, "5482": 0.004870930220931768, "5547": 0.08871890604496002, "5594": 0.3084607720375061, "5769": 0.36697331070899963, "5790": 0.15442965924739838, "5799": 0.20739519596099854, "5808": 0.3019835948944092, "5816": 0.9317949414253235, "5876": 0.6343214511871338, "5907": 0.02792670577764511, "5950": 1.036847710609436, "5986": 0.1619328260421753, "6022": 0.23479416966438293, "6048": 0.20022670924663544, "6388": 0.02887592278420925, "6463": 0.23324857652187347, "6638": 0.18492233753204346, "6678": 0.14095009863376617, "6721": 0.06337817758321762, "6747": 0.1485546976327896, "6774": 0.029824240133166313, "6950": 0.004870930220931768, "7012": 0.2516399025917053, "7017": 0.40806588530540466, "7023": 1.1102628707885742, "7099": 0.029824240133166313, "7108": 0.08154398202896118, "7189": 0.5381823778152466, "7361": 0.1221139207482338, "7382": 0.57457035779953, "7388": 1.2948341369628906, "7399": 0.3526630103588104, "7457": 0.1477125883102417, "7461": 0.25995752215385437, "7535": 0.47036975622177124, "7610": 0.3381449282169342, "7619": 0.0009760859538801014, "7691": 0.1751343309879303, "7711": 0.2501201331615448, "7778": 0.2741633653640747, "7784": 0.37102460861206055, "7790": 0.12470348179340363, "7809": 0.07159364968538284, "7831": 0.6553317308425903, "7987": 0.5244048833847046, "7998": 0.052318159490823746, "8089": 0.053244512528181076, "8093": 0.8550800085067749, "8123": 0.26446542143821716, "8137": 0.029824240133166313, "8189": 0.10026945173740387, "8249": 0.03925827145576477, "8290": 0.8022117614746094, "8462": 0.36900100111961365, "8557": 0.4349733293056488, "8738": 0.036437395960092545, "8902": 0.012615402229130268, "8924": 0.8957691192626953, "9147": 0.08871890604496002, "9153": 0.1229778528213501, "9174": 0.401551216840744, "9228": 0.20102575421333313, "9253": 0.14349138736724854, "9280": 0.026025565341114998, "9289": 0.13243216276168823, "9312": 0.06795065850019455, "9324": 0.010684899985790253, "9336": 0.06795065850019455, "9380": 0.004870930220931768, "9381": 0.0770333781838417, "9539": 0.06429435312747955, "9556": 0.151916041970253, "9581": 0.013579257763922215, "9617": 0.06154331564903259, "9654": 0.17267228662967682, "9657": 0.09938567131757736, "9706": 0.04487626627087593, "9723": 0.1677299439907074, "9756": 0.3897167444229126, "9765": 0.15275461971759796, "10085": 0.06795065850019455, "10173": 0.18004031479358673, "10174": 0.07250232994556427, "10238": 0.13157635927200317, "10266": 0.5517725944519043, "10383": 0.7969439625740051, "10426": 0.19220098853111267, "10444": 0.11168810725212097, "10640": 0.20102575421333313, "10755": 0.8400169610977173, "10831": 0.6389714479446411, "10857": 0.1873544454574585, "10903": 0.19622190296649933, "10928": 0.037378571927547455, "11129": 0.12986256182193756, "11179": 0.5718178153038025, "11207": 0.0752234235405922, "11229": 0.0019512200960889459, "11326": 0.3963087201118469, "11365": 0.004870930220931768, "11655": 0.07431721687316895, "11678": 0.21687394380569458, "11702": 0.1229778528213501, "11709": 0.16359257698059082, "11835": 0.4444103240966797, "12283": 0.25845035910606384, "12407": 0.010684899985790253, "12412": 0.0058422754518687725, "12435": 0.2561853528022766, "12490": 0.06246116757392883, "12503": 0.20739519596099854, "12589": 0.36697331070899963, "12596": 0.09672962874174118, "12682": 0.8459017872810364, "12826": 0.36900100111961365, "12943": 0.043007105588912964, "13143": 0.9568626880645752, "13356": 0.09228714555501938, "13467": 0.3027053773403168, "13483": 0.9186317324638367, "13599": 0.3683255612850189, "13617": 0.06154331564903259, "13656": 0.4914994537830353, "14025": 0.5629584193229675, "14267": 0.3269403576850891, "14298": 0.043007105588912964, "14396": 0.10467668622732162, "14405": 0.9455460906028748, "14627": 0.14349138736724854, "14760": 0.3381449282169342, "14773": 0.2160874605178833, "14872": 0.14686977863311768, "15087": 0.04860413447022438, "15124": 0.7389566898345947, "15258": 0.07793712615966797, "15316": 0.25845035910606384, "15354": 0.5127768516540527, "15429": 0.10026945173740387, "15559": 0.04394211992621422, "15578": 0.3588210940361023, "15821": 0.09761575609445572, "15871": 0.18978065252304077, "15982": 0.19381128251552582, "16007": 0.2231435477733612, "16014": 0.3903779089450836, "16026": 0.12470348179340363, "16111": 0.3423145115375519, "16211": 0.3923587501049042, "16222": 0.18573370575904846, "16330": 0.21530038118362427, "16478": 0.3930181860923767, "16515": 0.9256220459938049, "16530": 0.13243216276168823, "16578": 0.2689530849456787, "16593": 0.11517547070980072, "16677": 0.11343330889940262, "16824": 0.052318159490823746, "16902": 0.6980181336402893, "17003": 0.21135559678077698, "17042": 0.7764897346496582, "17245": 0.2741633653640747, "17376": 0.14349138736724854, "17464": 0.672426164150238, "17503": 0.981317400932312, "17631": 0.016465263441205025, "17635": 0.0354953333735466, "17908": 0.3012613356113434, "17914": 0.05046287178993225, "18119": 0.5573811531066895, "18215": 0.1693800985813141, "18509": 0.0752234235405922, "18539": 0.18411032855510712, "18609": 0.04113444685935974, "18721": 0.2667117714881897, "18804": 0.02412080205976963, "18857": 0.6181373596191406, "18949": 0.39696553349494934, "18981": 0.04207121208310127, "19037": 0.16442140936851501, "19064": 0.4824984669685364, "19107": 0.9500881433486938, "19188": 0.26446542143821716, "19198": 0.21214580535888672, "19262": 0.8796916007995605, "19736": 0.010684899985790253, "19824": 0.1685553640127182, "19825": 0.1602703034877777, "20146": 0.05970508232712746, "20155": 0.020300358533859253, "20272": 0.1734936386346817, "20302": 0.06520967930555344, "20576": 0.32905077934265137, "20752": 0.10731173306703568, "20876": 0.0019512200960889459, "21081": 0.5893046259880066, "21120": 0.13670019805431366, "21371": 0.2607102394104004, "21382": 0.02316705882549286, "21434": 0.32905077934265137, "21486": 0.13499516248703003, "21499": 0.25694093108177185, "21608": 0.06886265426874161, "21639": 0.319873183965683, "21700": 0.016465263441205025, "21778": 0.09406650811433792, "21935": 0.018384648486971855, "22026": 0.07884006202220917, "22068": 0.10379679501056671, "22261": 0.0009760859538801014, "22307": 0.012615402229130268, "22963": 0.29328158497810364, "22991": 0.5069117546081543, "23260": 0.1401015669107437, "23444": 0.41195443272590637, "23651": 0.29981520771980286, "23900": 0.4654768109321594, "23924": 0.15693697333335876, "23926": 0.04487626627087593, "24004": 0.03925827145576477, "24327": 0.43623676896095276, "24353": 0.1970241367816925, "24552": 0.7182208299636841, "24759": 0.3339579105377197, "24895": 0.1619328260421753, "24915": 0.565735399723053, "25022": 0.7791815400123596, "25269": 1.1236859560012817, "25331": 0.4177590310573578, "25409": 0.8989537954330444, "25524": 0.2800849378108978, "25525": 1.2181298732757568, "25531": 0.10993985831737518, "25613": 0.07793712615966797, "26237": 0.49923527240753174, "26305": 0.04207121208310127, "26461": 0.371698260307312, "26563": 1.0835250616073608, "26656": 0.11691460013389587, "26786": 0.043007105588912964, "26914": 0.3177432417869568, "27133": 0.25694093108177185, "27400": 0.9302552938461304, "27487": 0.5466978549957275, "27694": 0.02887592278420925, "27794": 1.0788878202438354, "28093": 0.16607704758644104, "28207": 0.16607704758644104, "28268": 0.1693800985813141, "28309": 0.23402166366577148, "28321": 0.13071982562541962, "28436": 0.23864774405956268, "28489": 0.7960633039474487, "28578": 0.7276995778083801, "28739": 0.2689530849456787, "28977": 0.08692999184131622, "28993": 1.1381834745407104, "29299": 0.9379299283027649, "29311": 0.052318159490823746, "29458": 0.20421554148197174, "29477": 1.070887804031372} | 13831842 | The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women. | Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. |
{"1039": 0.3070250153541565, "1044": 0.06886265426874161, "1050": 0.2561853528022766, "1051": 0.41195443272590637, "1052": 0.41647201776504517, "1069": 0.1889725625514984, "2053": 0.4537591338157654, "2072": 0.0058422754518687725, "2080": 0.1401015669107437, "2094": 0.5197699069976807, "2095": 0.3499138653278351, "2109": 0.018384648486971855, "2116": 0.034552380442619324, "2166": 0.1229778528213501, "2172": 0.5174443125724792, "2177": 0.32199856638908386, "2226": 0.36426326632499695, "2241": 0.5860490798950195, "2250": 0.22157983481884003, "2275": 0.2105647772550583, "2278": 0.2394166737794876, "2282": 0.22001366317272186, "2302": 0.3381449282169342, "2326": 0.5324648022651672, "2329": 0.0058422754518687725, "2331": 0.8534175157546997, "2351": 0.1677299439907074, "2363": 0.0029254043474793434, "2403": 0.055094651877880096, "2414": 0.33325836062431335, "2470": 0.42353010177612305, "2475": 0.25995752215385437, "2478": 0.020300358533859253, "2483": 0.04953393340110779, "2491": 0.304147332906723, "2512": 1.0312920808792114, "2546": 0.3547199070453644, "2561": 0.20022670924663544, "2563": 0.4728073179721832, "2566": 0.8074519634246826, "2575": 0.16359257698059082, "2578": 0.3027053773403168, "2605": 0.006812678650021553, "2615": 0.15275461971759796, "2625": 0.06612417846918106, "2632": 0.021256839856505394, "2640": 0.6892333030700684, "2660": 0.08961215615272522, "2729": 0.619189441204071, "2740": 0.026976587250828743, "2779": 0.28890204429626465, "2794": 0.15777134895324707, "2804": 0.2881702482700348, "2817": 0.1873544454574585, "2866": 0.8559102416038513, "2881": 0.1913948506116867, "2885": 0.22392450273036957, "2902": 1.0001721382141113, "2944": 0.4974553883075714, "2951": 0.2969166338443756, "2966": 0.6543170213699341, "2983": 0.4617912769317627, "3024": 0.15359249711036682, "3073": 0.26446542143821716, "3115": 0.8600510358810425, "3131": 0.7163142561912537, "3144": 0.1946154683828354, "3161": 0.0797421783208847, "3171": 0.8517522215843201, "3197": 0.6970458030700684, "3280": 0.5045560002326965, "3296": 0.14349138736724854, "3361": 0.004870930220931768, "3378": 0.6970458030700684, "3446": 0.1011524572968483, "3463": 0.04674193635582924, "3465": 1.2824517488479614, "3466": 0.007782140281051397, "3508": 0.06612417846918106, "3512": 0.055094651877880096, "3643": 0.02887592278420925, "3695": 0.24554696679115295, "3701": 0.4673144817352295, "3725": 0.35950297117233276, "3811": 0.672426164150238, "3885": 0.12986256182193756, "3905": 0.57457035779953, "3947": 0.06337817758321762, "3949": 0.5952457785606384, "3976": 0.6674286723136902, "3979": 0.8973627090454102, "4094": 0.0317181795835495, "4102": 0.5562619566917419, "4106": 0.857568621635437, "4128": 0.0029254043474793434, "4185": 0.30917787551879883, "4229": 0.3353555500507355, "4275": 0.14264501631259918, "4292": 0.5415972471237183, "4295": 0.5903874635696411, "4297": 0.3325583338737488, "4322": 0.06703783571720123, "4346": 0.42990362644195557, "4358": 0.052318159490823746, "4359": 0.4770587682723999, "4468": 0.46486347913742065, "4576": 0.3750596046447754, "4610": 0.4938860833644867, "4621": 1.061472773551941, "4652": 0.00875066313892603, "4654": 0.5438674688339233, "4749": 0.3676496744155884, "4758": 0.6960725784301758, "4781": 0.29619070887565613, "4829": 0.9702757596969604, "4866": 0.15693697333335876, "4895": 0.4126010537147522, "4903": 0.083342544734478, "4909": 0.2786078155040741, "4914": 0.8957691192626953, "4945": 0.5662899017333984, "5022": 0.5495203733444214, "5057": 0.004870930220931768, "5084": 0.4132472574710846, "5143": 0.11778303235769272, "5171": 0.3743882179260254, "5292": 0.058784693479537964, "5301": 0.2531573474407196, "5335": 0.2145126610994339, "5345": 0.4113073945045471, "5366": 0.8161250352859497, "5427": 0.025073638185858727, "5468": 0.4145384132862091, "5505": 0.5133614540100098, "5543": 0.684319257736206, "5547": 0.3019835948944092, "5587": 0.004870930220931768, "5617": 0.1946154683828354, "5648": 0.7665573358535767, "5656": 0.7115318179130554, "5675": 0.23556606471538544, "5729": 0.129004567861557, "5761": 0.2409527748823166, "5776": 0.7436100244522095, "5815": 0.1734936386346817, "5842": 0.013579257763922215, "5845": 0.018384648486971855, "5859": 0.12556517124176025, "5970": 0.03831886500120163, "5996": 0.04207121208310127, "6131": 0.02887592278420925, "6143": 0.026025565341114998, "6190": 0.06246116757392883, "6275": 0.1011524572968483, "6363": 0.4794800877571106, "6388": 0.15526613593101501, "6421": 0.16110190749168396, "6449": 0.5584990978240967, "6450": 0.45623743534088135, "6463": 0.9893379211425781, "6464": 0.574020504951477, "6612": 0.10731173306703568, "6643": 0.19220098853111267, "6648": 0.6212902665138245, "6677": 0.46117570996284485, "6721": 0.7009293437004089, "6818": 0.5139457583427429, "6820": 0.23015019297599792, "6887": 0.6363908052444458, "6948": 0.2576959431171417, "7012": 0.7881022095680237, "7023": 0.7333439588546753, "7028": 0.1485546976327896, "7038": 0.6265231370925903, "7091": 0.175953671336174, "7142": 0.040196798741817474, "7197": 0.13925230503082275, "7200": 0.15275461971759796, "7242": 0.08513788133859634, "7312": 0.7898768186569214, "7355": 0.08513788133859634, "7408": 0.3423145115375519, "7438": 0.14518201351165771, "7444": 0.7389566898345947, "7505": 0.01934296265244484, "7551": 0.1970241367816925, "7594": 0.03925827145576477, "7597": 0.1946154683828354, "7620": 0.22548456490039825, "7667": 0.26296505331993103, "7712": 0.08871890604496002, "7722": 0.43875885009765625, "7831": 0.5021947622299194, "7861": 0.0797421783208847, "7863": 0.953857421875, "7870": 0.3297532796859741, "7873": 0.09672962874174118, "7885": 0.00875066313892603, "7922": 0.08603433519601822, "7941": 0.010684899985790253, "8010": 0.04113444685935974, "8064": 0.05970508232712746, "8114": 0.5517725944519043, "8122": 0.5773153901100159, "8161": 0.2719337046146393, "8197": 0.18978065252304077, "8292": 0.09672962874174118, "8323": 0.812664806842804, "8377": 0.013579257763922215, "8649": 0.02792670577764511, "8729": 0.08513788133859634, "8777": 0.4673144817352295, "8830": 0.1994270235300064, "8872": 0.4824984669685364, "8948": 0.5438674688339233, "9044": 0.32553088665008545, "9152": 0.12728634476661682, "9197": 0.2160874605178833, "9312": 0.27712854743003845, "9345": 0.2231435477733612, "9353": 0.24171993136405945, "9355": 0.0019512200960889459, "9468": 0.05970508232712746, "9511": 0.5336109399795532, "9556": 0.04674193635582924, "9560": 0.5290185213088989, "9617": 0.1229778528213501, "9634": 0.6877616047859192, "9808": 0.5444341897964478, "9871": 0.09495500475168228, "9883": 0.20580662786960602, "9932": 0.013579257763922215, "9942": 0.47402387857437134, "9944": 0.6451379656791687, "9992": 0.4425300657749176, "10128": 0.06703783571720123, "10174": 0.21922965347766876, "10197": 0.014542185701429844, "10256": 0.5387523174285889, "10507": 0.21372433006763458, "10611": 0.03831886500120163, "10732": 0.3995884954929352, "10771": 0.13243216276168823, "10790": 0.5238267183303833, "10903": 0.05139094591140747, "10933": 0.9100211262702942, "10961": 0.15275461971759796, "10995": 0.06337817758321762, "11095": 0.5584990978240967, "11100": 0.6911921501159668, "11192": 0.7951818704605103, "11231": 0.11691460013389587, "11236": 0.2800849378108978, "11325": 0.820433497428894, "11539": 0.05046287178993225, "11643": 0.3381449282169342, "11682": 0.7047978043556213, "11727": 0.21922965347766876, "11733": 0.6823468804359436, "11806": 1.02149498462677, "11888": 0.8091925978660583, "12044": 0.1401015669107437, "12302": 0.09584271162748337, "12353": 1.1394343376159668, "12435": 0.0009760859538801014, "12504": 0.2231435477733612, "12596": 0.04394211992621422, "12650": 0.5990082025527954, "12680": 0.3141832649707794, "12697": 0.23710809648036957, "12771": 0.01934296265244484, "12826": 0.17267228662967682, "12935": 0.4337083101272583, "12941": 0.3683255612850189, "12963": 0.38574060797691345, "13095": 0.037378571927547455, "13105": 0.46853771805763245, "13180": 0.15023678541183472, "13316": 0.22548456490039825, "13356": 0.7172679901123047, "13441": 0.259204238653183, "13483": 0.7445381283760071, "13592": 0.013579257763922215, "13599": 0.25467249751091003, "13811": 0.24325250089168549, "13958": 0.11604541540145874, "14025": 0.40481385588645935, "14155": 0.03360854089260101, "14358": 0.1384023278951645, "14384": 0.21687394380569458, "14534": 0.3012613356113434, "14545": 0.06795065850019455, "14785": 0.0913962796330452, "14840": 0.3297532796859741, "15030": 0.12728634476661682, "15050": 0.056018441915512085, "15238": 0.27342069149017334, "15277": 0.6709295511245728, "15306": 0.4673144817352295, "15318": 0.45251765847206116, "15338": 0.15023678541183472, "15354": 0.16690383851528168, "15384": 0.0797421783208847, "15877": 0.08513788133859634, "16085": 0.1401015669107437, "16157": 0.17922431230545044, "16169": 0.9394577741622925, "16259": 0.11865071207284927, "16302": 0.11865071207284927, "16330": 0.05786345899105072, "16367": 0.11343330889940262, "16405": 0.0009760859538801014, "16464": 0.9217445850372314, "16478": 0.03266380727291107, "16781": 0.35813871026039124, "17047": 0.5139457583427429, "17208": 0.3381449282169342, "17212": 0.21530038118362427, "17237": 0.4788752794265747, "17338": 0.41389304399490356, "17503": 1.0668635368347168, "17908": 0.3963087201118469, "17927": 0.23247487843036652, "18133": 0.304147332906723, "18154": 0.3248254358768463, "18288": 0.09584271162748337, "18422": 0.2478361576795578, "18583": 0.5080875158309937, "18730": 0.14939609169960022, "18834": 0.9131608605384827, "19098": 0.02887592278420925, "19329": 0.9194108247756958, "19413": 0.040196798741817474, "19478": 0.04767346754670143, "19518": 0.5393219590187073, "19531": 0.3084607720375061, "19536": 1.1573970317840576, "19761": 0.24171993136405945, "19960": 0.175953671336174, "20118": 0.4568560719490051, "20177": 0.04860413447022438, "20247": 0.7601850032806396, "20304": 0.4500300884246826, "20694": 0.3381449282169342, "20868": 0.06977381557226181, "20991": 0.004870930220931768, "21050": 0.9470623731613159, "21150": 0.7258110046386719, "21371": 0.01934296265244484, "21486": 0.04860413447022438, "21557": 0.0913962796330452, "21604": 0.029824240133166313, "21619": 0.3519764244556427, "21791": 0.37907835841178894, "21853": 0.11604541540145874, "21877": 0.12642613053321838, "21879": 0.6853039860725403, "21908": 1.0855059623718262, "21929": 0.053244512528181076, "22063": 0.07612881064414978, "22084": 0.44753631949424744, "22110": 0.021256839856505394, "22173": 0.3910386264324188, "22684": 0.0797421783208847, "22963": 0.05786345899105072, "23035": 0.09938567131757736, "23208": 0.03925827145576477, "23260": 0.052318159490823746, "23364": 0.10731173306703568, "23523": 0.03831886500120163, "23632": 0.5364705324172974, "23650": 0.09228714555501938, "23971": 0.15359249711036682, "24010": 0.09584271162748337, "24171": 0.49030399322509766, "24343": 0.2409527748823166, "24501": 0.6286086440086365, "24531": 0.14602625370025635, "24554": 0.010684899985790253, "24582": 0.20818853378295898, "24685": 0.40806588530540466, "24705": 0.08782484382390976, "24710": 0.06703783571720123, "24735": 0.13414156436920166, "24755": 0.23402166366577148, "24887": 0.46117570996284485, "24978": 0.53589928150177, "25006": 0.4113073945045471, "25095": 0.2990913391113281, "25284": 0.022212404757738113, "25619": 0.16442140936851501, "25986": 0.00875066313892603, "26180": 0.5255602598190308, "26226": 0.40806588530540466, "26478": 0.32341301441192627, "26777": 0.2018241584300995, "26897": 0.0009760859538801014, "26989": 0.08692999184131622, "27178": 0.025073638185858727, "27615": 0.0317181795835495, "27708": 0.02316705882549286, "27813": 0.3388410806655884, "27885": 0.9178520441055298, "27969": 0.04953393340110779, "28182": 0.1994270235300064, "28287": 0.014542185701429844, "28483": 0.8633513450622559, "28578": 0.9500881433486938, "28689": 0.007782140281051397, "28907": 0.24325250089168549, "28991": 0.1602703034877777, "29003": 0.1693800985813141, "29025": 0.12384103983640671, "29277": 0.04674193635582924} | 13843341 | OBJECTIVE To evaluate the cost effectiveness of standard treatment with and without the addition of ward based non-invasive ventilation in patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease. DESIGN Incremental cost effectiveness analysis of a randomised controlled trial. SETTING Medical wards in 14 hospitals in the United Kingdom. PARTICIPANTS The trial comprised 236 patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease and mild to moderate acidosis (pH 7.25-7.35) secondary to respiratory failure. The economic analysis compared the costs of treatment that these patients received after randomisation. MAIN OUTCOME MEASURE Incremental cost per in-hospital death. RESULTS 24/118 died in the group receiving standard treatment and 12/118 in the group receiving non-invasive ventilation (P=0.05). Allocation to the group receiving non-invasive ventilation was associated with a reduction in costs of 49362 pounds sterling (78741 dollars; 73109 euros), mainly through reduced use of intensive care units. The incremental cost effectiveness ratio was -645 pounds sterling per death avoided (95% confidence interval -2310 pounds sterling to 386 pounds sterling), indicating a dominant (more effective and less costly) strategy. Modelling of these data indicates that a typical UK hospital providing a non-invasive ventilation service will avoid six deaths and three to nine admissions to intensive care units per year, with an associated cost reduction of 12000-53000 pounds sterling per year. CONCLUSIONS Non-invasive ventilation is a highly cost effective treatment that both reduced total costs and improved mortality in hospital. | Cost effectiveness of ward based non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: economic analysis of randomised controlled trial. |
{"1009": 0.7500885725021362, "1011": 0.20421554148197174, "1013": 0.030771657824516296, "1014": 0.2394166737794876, "1017": 0.3353555500507355, "1019": 0.1358480453491211, "1039": 0.23556606471538544, "1044": 0.129004567861557, "1052": 0.03831886500120163, "1058": 0.1685553640127182, "2001": 0.3423145115375519, "2003": 0.011650617234408855, "2004": 0.25467249751091003, "2005": 0.23247487843036652, "2011": 0.04953393340110779, "2015": 0.3297532796859741, "2078": 0.7295845746994019, "2090": 0.2990913391113281, "2109": 0.6482070088386536, "2116": 0.15275461971759796, "2146": 0.16442140936851501, "2152": 0.6107416749000549, "2177": 0.36290550231933594, "2179": 0.09050461649894714, "2224": 0.3269403576850891, "2294": 0.42353010177612305, "2308": 0.39893341064453125, "2361": 0.04487626627087593, "2391": 0.46055975556373596, "2421": 0.056018441915512085, "2443": 0.23402166366577148, "2470": 0.37035053968429565, "2475": 0.755608320236206, "2478": 0.07793712615966797, "2482": 0.3656192123889923, "2506": 0.3743882179260254, "2509": 0.3127557039260864, "2523": 0.7969439625740051, "2529": 0.5551415085792542, "2558": 0.03266380727291107, "2615": 1.1287524700164795, "2706": 0.42608439922332764, "2734": 0.13925230503082275, "2750": 0.3191637098789215, "2815": 0.02412080205976963, "2817": 0.5461324453353882, "2846": 0.36494144797325134, "2863": 0.17840765416622162, "2898": 0.21922965347766876, "2913": 0.6400018334388733, "2966": 0.16524957120418549, "2967": 0.22704219818115234, "3020": 0.23324857652187347, "3115": 0.29473719000816345, "3204": 0.04860413447022438, "3231": 0.8583967685699463, "3273": 0.29981520771980286, "3276": 0.14518201351165771, "3284": 0.19220098853111267, "3319": 0.6613984704017639, "3378": 0.7258110046386719, "3463": 0.10993985831737518, "3556": 0.1485546976327896, "3563": 0.053244512528181076, "3594": 0.13925230503082275, "3603": 0.03266380727291107, "3619": 0.29255300760269165, "3643": 0.02792670577764511, "3670": 0.025073638185858727, "3686": 0.04953393340110779, "3694": 1.018678069114685, "3800": 0.029824240133166313, "3891": 0.7818660736083984, "3893": 0.12642613053321838, "3898": 0.15359249711036682, "3961": 0.0354953333735466, "3979": 0.7124901413917542, "4014": 1.2059240341186523, "4094": 0.12384103983640671, "4102": 0.175953671336174, "4106": 0.6233867406845093, "4118": 0.32270604372024536, "4179": 0.3027053773403168, "4286": 0.09850110858678818, "4351": 0.4926934838294983, "4391": 0.15943801403045654, "4431": 0.5174443125724792, "4453": 0.23402166366577148, "4456": 1.138809084892273, "4492": 0.2247048318386078, "4531": 0.06977381557226181, "4606": 0.18329764902591705, "4649": 0.8281423449516296, "4710": 0.36426326632499695, "4725": 0.4374985992908478, "4781": 0.19220098853111267, "4962": 0.5427330136299133, "4997": 0.6197150945663452, "5185": 0.00875066313892603, "5292": 0.02316705882549286, "5345": 0.9425065517425537, "5377": 0.5186077356338501, "5393": 0.11691460013389587, "5456": 0.026025565341114998, "5490": 0.5596157908439636, "5531": 0.036437395960092545, "5567": 0.15442965924739838, "5604": 0.757441520690918, "5719": 0.12642613053321838, "5737": 0.7647408246994019, "5741": 0.052318159490823746, "5769": 0.10731173306703568, "5816": 0.5607312321662903, "5852": 0.4879087805747986, "5986": 0.04767346754670143, "5997": 0.03360854089260101, "6022": 0.055094651877880096, "6025": 0.2394166737794876, "6028": 0.004870930220931768, "6048": 0.23247487843036652, "6064": 1.4075511693954468, "6118": 0.28890204429626465, "6179": 0.22859740257263184, "6210": 0.14264501631259918, "6282": 0.09495500475168228, "6388": 0.05139094591140747, "6415": 0.09406650811433792, "6431": 0.17431432008743286, "6522": 1.4441578388214111, "6600": 0.13157635927200317, "6612": 0.8989537954330444, "6635": 0.09938567131757736, "6643": 0.8845420479774475, "6692": 0.45623743534088135, "6709": 0.129004567861557, "6761": 0.255429208278656, "6819": 0.1485546976327896, "6873": 0.10731173306703568, "6914": 0.08961215615272522, "6976": 0.04113444685935974, "7012": 0.8057082891464233, "7017": 0.23787821829319, "7022": 0.49982786178588867, "7023": 1.035461664199829, "7099": 0.28890204429626465, "7142": 0.6517757177352905, "7174": 1.109619140625, "7289": 0.47766464948654175, "7366": 0.05139094591140747, "7403": 0.6970458030700684, "7478": 0.07612881064414978, "7551": 0.0058422754518687725, "7552": 0.0770333781838417, "7604": 0.10993985831737518, "7642": 0.13414156436920166, "7709": 0.46608972549438477, "7718": 0.48068851232528687, "7784": 0.06703783571720123, "7810": 0.4126010537147522, "7831": 0.5640701055526733, "7865": 0.8893690705299377, "7885": 0.14518201351165771, "8023": 0.004870930220931768, "8153": 0.272677481174469, "8168": 0.16524957120418549, "8182": 0.2990913391113281, "8197": 0.6160298585891724, "8259": 0.1221139207482338, "8290": 0.19541899859905243, "8292": 0.5267143249511719, "8319": 0.27786844968795776, "8335": 0.3499138653278351, "8358": 0.17840765416622162, "8385": 0.24554696679115295, "8386": 0.5069117546081543, "8400": 0.6867793202400208, "8483": 0.02412080205976963, "8553": 0.15442965924739838, "8609": 0.6744182109832764, "8720": 0.029824240133166313, "8778": 0.05694137513637543, "8853": 0.22937409579753876, "8924": 0.6492279767990112, "8939": 0.7755908370018005, "8991": 0.09850110858678818, "9031": 0.16524957120418549, "9165": 0.23787821829319, "9253": 0.7791815400123596, "9279": 0.0058422754518687725, "9312": 0.2674594223499298, "9336": 0.18654440343379974, "9349": 0.16359257698059082, "9367": 0.5838727951049805, "9398": 0.7728893756866455, "9426": 0.28670501708984375, "9463": 0.19862671196460724, "9513": 0.011650617234408855, "9556": 0.6139179468154907, "9657": 0.09850110858678818, "9671": 0.1358480453491211, "9690": 0.07431721687316895, "9820": 0.3499138653278351, "9867": 0.030771657824516296, "10061": 0.175953671336174, "10174": 0.23787821829319, "10194": 0.45623743534088135, "10266": 0.04113444685935974, "10374": 0.3141832649707794, "10465": 0.015504186972975731, "10480": 0.6502478122711182, "10502": 0.5701626539230347, "10539": 0.5718178153038025, "10665": 0.27786844968795776, "10694": 0.1011524572968483, "10788": 0.9240728616714478, "10831": 0.41065993905067444, "10843": 0.5827828645706177, "10847": 0.006812678650021553, "10862": 0.5057345628738403, "11156": 0.7276995778083801, "11326": 0.3777405619621277, "11328": 0.08782484382390976, "11487": 0.7009293437004089, "11616": 0.13243216276168823, "11704": 0.016465263441205025, "11709": 0.03266380727291107, "11718": 0.08603433519601822, "11778": 0.7665573358535767, "11888": 0.18492233753204346, "12115": 1.2364475727081299, "12146": 0.5690577030181885, "12368": 0.13414156436920166, "12407": 0.28670501708984375, "12435": 0.15777134895324707, "12596": 0.12986256182193756, "12826": 0.12642613053321838, "12987": 0.18492233753204346, "12997": 0.034552380442619324, "13070": 0.28082266449928284, "13434": 0.5393219590187073, "13458": 0.39893341064453125, "13483": 1.2284748554229736, "13523": 0.10379679501056671, "13599": 0.2184450328350067, "13633": 0.1510767638683319, "13656": 0.2954642176628113, "13699": 0.6989894509315491, "14025": 0.9687942266464233, "14280": 0.006812678650021553, "14301": 0.21293537318706512, "14358": 0.04394211992621422, "14471": 0.23864774405956268, "14516": 1.216395378112793, "14644": 0.500420093536377, "14678": 0.3141832649707794, "15088": 0.1734936386346817, "15113": 0.0317181795835495, "15149": 0.09584271162748337, "15192": 0.011650617234408855, "15252": 0.08513788133859634, "15258": 0.5404602885246277, "15304": 0.29328158497810364, "15330": 0.41001203656196594, "15396": 1.0080435276031494, "15844": 0.42735910415649414, "15873": 0.7610978484153748, "16007": 0.09761575609445572, "16014": 0.043007105588912964, "16134": 0.3297532796859741, "16157": 0.30917787551879883, "16221": 0.11517547070980072, "16227": 0.5827828645706177, "16268": 0.15610189735889435, "16330": 0.29036402702331543, "16367": 0.520350456237793, "16387": 0.9769153594970703, "16406": 0.43623676896095276, "16474": 0.29400965571403503, "16483": 0.3995884954929352, "16505": 0.8306987881660461, "16706": 0.40806588530540466, "16731": 0.08692999184131622, "16762": 0.3784096837043762, "16902": 0.5127768516540527, "16923": 0.8383291959762573, "17208": 0.5290185213088989, "17245": 0.25088030099868774, "17503": 0.8748174905776978, "17908": 0.2478361576795578, "18191": 0.6296497583389282, "18400": 0.16276304423809052, "18422": 0.18492233753204346, "18479": 0.1064341589808464, "18539": 0.07612881064414978, "18678": 0.052318159490823746, "18700": 0.05139094591140747, "18804": 0.8161250352859497, "18925": 0.08064348995685577, "19034": 0.3170322775840759, "19035": 0.7610978484153748, "19064": 0.21530038118362427, "19188": 0.058784693479537964, "19761": 0.07793712615966797, "19824": 0.21135559678077698, "19960": 0.18329764902591705, "20001": 0.15359249711036682, "20125": 0.09672962874174118, "20155": 0.11168810725212097, "20177": 0.10555581003427505, "20806": 0.25845035910606384, "20875": 0.12728634476661682, "20876": 0.22001366317272186, "21081": 0.9500881433486938, "21104": 0.05417001247406006, "21150": 0.07159364968538284, "21434": 0.10379679501056671, "21660": 0.1064341589808464, "21663": 0.08871890604496002, "21755": 0.16607704758644104, "21778": 0.02792670577764511, "21903": 0.009718249551951885, "21961": 0.4914994537830353, "21976": 0.2719337046146393, "22170": 0.18492233753204346, "22184": 0.11604541540145874, "22199": 0.01934296265244484, "22269": 0.040196798741817474, "22520": 0.8764448165893555, "22616": 0.06337817758321762, "22777": 0.40806588530540466, "22916": 0.18654440343379974, "23087": 0.2674594223499298, "23260": 0.04860413447022438, "23350": 0.9232974052429199, "23737": 0.15693697333335876, "23750": 0.151916041970253, "23760": 0.011650617234408855, "23852": 0.13157635927200317, "23900": 0.255429208278656, "24093": 0.18248429894447327, "24100": 0.32553088665008545, "24278": 0.3339579105377197, "24587": 0.8633513450622559, "24759": 0.5968599319458008, "24936": 0.00875066313892603, "24965": 0.2763880789279938, "25022": 0.8981585502624512, "25269": 1.031988263130188, "25338": 0.06154331564903259, "25354": 0.2223619967699051, "25409": 0.7086513638496399, "25952": 0.22704219818115234, "25971": 0.20818853378295898, "26013": 0.34922540187835693, "26236": 0.9886114001274109, "26305": 0.06520967930555344, "26520": 0.2637155055999756, "26572": 0.13755162060260773, "26601": 0.23710809648036957, "26721": 0.8161250352859497, "26835": 0.3177432417869568, "26874": 0.0752234235405922, "26886": 0.5324648022651672, "27222": 0.18167030811309814, "27354": 0.5174443125724792, "27711": 0.6872705817222595, "27881": 0.10818854719400406, "28207": 0.007782140281051397, "28297": 1.2873153686523438, "28389": 0.006812678650021553, "28436": 0.4487839937210083, "28472": 0.14518201351165771, "28648": 0.7463917136192322, "28711": 1.420846700668335, "28873": 0.38441169261932373, "28911": 0.5483922958374023, "29264": 0.1384023278951645, "29361": 0.04113444685935974, "29474": 0.4177590310573578, "29486": 0.8450632095336914} | 13857083 | Detection of persistent cervical carcinogenic human papillomavirus (HPV) DNA is used as a marker for cervical cancer risk in clinical trials. The authors performed a systematic review and meta-analysis of the association between persistent HPV DNA and high-grade cervical intraepithelial neoplasia (CIN2-3), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer (together designated CIN2-3/HSIL+) to evaluate the robustness of HPV persistence for clinical use. MEDLINE and Current Contents were searched through January 30, 2006. Relative risks (RRs) were stratified by HPV comparison group. Of 2,035 abstracts, 41 studies were eligible for inclusion in the meta-analysis. Over 22,500 women were included in calculation of RRs for persistent HPV DNA detection and cervical neoplasia. RRs ranged from 1.3 (95% confidence interval: 1.1, 1.5) to 813.0 (95% confidence interval: 168.2, 3,229.2) for CIN2-3/HSIL+ versus 12 months), wider testing intervals, CIN2-3/HSIL+, and use of an HPV-negative reference group were consistently associated with higher RRs. Thus, HPV persistence was consistently and strongly associated with CIN2-3/HSIL+, despite wide variation in definitions and study methods. The magnitude of association varied by duration of persistence and testing interval. Precise definition and standardization of HPV testing, sampling procedure, and test interval are needed for reliable clinical testing. These findings validate HPV persistence as a clinical marker and endpoint. | Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis. |
{"1011": 0.030771657824516296, "1057": 0.29109421372413635, "1059": 1.2802826166152954, "1061": 0.7610978484153748, "1156": 0.39893341064453125, "1996": 0.07431721687316895, "2011": 0.22001366317272186, "2029": 0.11517547070980072, "2044": 0.009718249551951885, "2061": 0.6128603219985962, "2066": 0.07159364968538284, "2079": 0.07612881064414978, "2088": 0.14179791510105133, "2092": 0.17759032547473907, "2102": 0.42225050926208496, "2109": 0.006812678650021553, "2135": 0.1913948506116867, "2188": 0.2674594223499298, "2207": 0.6296497583389282, "2243": 0.29109421372413635, "2273": 0.12642613053321838, "2339": 0.07159364968538284, "2349": 0.18492233753204346, "2378": 0.25088030099868774, "2389": 0.19862671196460724, "2458": 0.6892333030700684, "2470": 0.011650617234408855, "2487": 0.07793712615966797, "2509": 0.43434104323387146, "2511": 0.2516399025917053, "2515": 0.18816383183002472, "2524": 0.09050461649894714, "2535": 0.6853039860725403, "2565": 0.11691460013389587, "2566": 0.1889725625514984, "2590": 0.6064908504486084, "2695": 0.6512666940689087, "2713": 0.4580921530723572, "2764": 0.09406650811433792, "2765": 0.23015019297599792, "2799": 0.19220098853111267, "2817": 0.3949938118457794, "2860": 0.1808556467294693, "2891": 0.4203280806541443, "2913": 0.17267228662967682, "2920": 0.1930064558982849, "2981": 1.0285027027130127, "3081": 0.0842406153678894, "3160": 0.5800528526306152, "3231": 0.04487626627087593, "3251": 0.20977331697940826, "3273": 0.3027053773403168, "3278": 0.23092569410800934, "3287": 0.6075552701950073, "3348": 0.304147332906723, "3372": 1.4432357549667358, "3378": 0.03360854089260101, "3433": 0.5290185213088989, "3458": 0.6989894509315491, "3463": 0.36426326632499695, "3466": 0.11951763927936554, "3491": 0.28890204429626465, "3508": 0.38041436672210693, "3512": 0.07068414986133575, "3526": 0.5584990978240967, "3625": 0.1485546976327896, "3670": 0.28743788599967957, "3697": 0.7845434546470642, "3767": 0.2983669638633728, "3795": 0.5528968572616577, "3796": 0.17020416259765625, "3800": 0.14433705806732178, "3853": 0.24325250089168549, "3896": 0.03360854089260101, "3973": 0.3485364317893982, "3980": 0.28450319170951843, "4032": 0.8247235417366028, "4072": 0.14686977863311768, "4130": 0.3141832649707794, "4187": 0.036437395960092545, "4223": 0.40546512603759766, "4245": 0.04674193635582924, "4295": 0.4093637466430664, "4333": 1.0326838493347168, "4336": 0.09495500475168228, "4395": 0.5816917419433594, "4424": 0.2317005842924118, "4442": 0.6950984001159668, "4503": 0.1510767638683319, "4539": 0.08603433519601822, "4570": 0.05694137513637543, "4730": 0.09938567131757736, "4742": 0.7881022095680237, "4765": 0.27934664487838745, "4778": 0.2741633653640747, "4807": 0.011650617234408855, "4937": 0.5506471395492554, "4958": 0.6512666940689087, "4962": 0.5651806592941284, "4972": 0.11517547070980072, "4975": 0.43938836455345154, "5149": 0.8534175157546997, "5197": 0.6573580503463745, "5250": 0.6684301495552063, "5273": 0.11778303235769272, "5323": 0.4158279001712799, "5387": 0.08961215615272522, "5393": 0.2711893916130066, "5441": 0.3297532796859741, "5449": 0.11168810725212097, "5547": 0.036437395960092545, "5638": 0.5849615335464478, "5725": 0.9037119746208191, "5769": 0.40220460295677185, "5838": 0.306306391954422, "5991": 0.014542185701429844, "6003": 0.11951763927936554, "6032": 0.011650617234408855, "6190": 0.10291612148284912, "6388": 0.0019512200960889459, "6844": 0.966567873954773, "6869": 0.757441520690918, "6887": 0.4286321699619293, "6897": 0.22626367211341858, "7065": 0.7220231294631958, "7077": 0.0174254160374403, "7085": 0.35403475165367126, "7127": 0.11168810725212097, "7275": 0.02316705882549286, "7337": 0.4400174915790558, "7366": 0.17267228662967682, "7403": 0.2786078155040741, "7411": 0.037378571927547455, "7461": 0.10906458646059036, "7512": 0.21922965347766876, "7531": 0.06612417846918106, "7539": 0.058784693479537964, "7591": 0.07431721687316895, "7645": 0.29255300760269165, "7666": 0.8780695199966431, "7669": 0.38041436672210693, "7711": 0.12384103983640671, "7755": 0.8366385698318481, "7784": 0.3381449282169342, "7790": 0.2034190446138382, "7816": 0.4734157919883728, "7870": 0.1905880719423294, "7882": 0.762009859085083, "8000": 0.7445381283760071, "8153": 0.04207121208310127, "8161": 0.03925827145576477, "8171": 0.5220900774002075, "8190": 0.1873544454574585, "8247": 0.4673144817352295, "8361": 0.1710275560617447, "8394": 0.0317181795835495, "8458": 0.40285754203796387, "8468": 0.1384023278951645, "8498": 0.08603433519601822, "8601": 0.010684899985790253, "8781": 0.20102575421333313, "8803": 0.8813109993934631, "8814": 0.45623743534088135, "9007": 0.4158279001712799, "9070": 0.05694137513637543, "9099": 0.4824984669685364, "9165": 0.18329764902591705, "9174": 0.3423145115375519, "9319": 0.28963330388069153, "9330": 0.9256220459938049, "9350": 0.2026219218969345, "9455": 0.0354953333735466, "9463": 0.6410312056541443, "9513": 0.1011524572968483, "9587": 0.35813871026039124, "10047": 0.38905516266822815, "10111": 0.2576959431171417, "10253": 0.8057082891464233, "10368": 0.2478361576795578, "10509": 0.14518201351165771, "10595": 0.05417001247406006, "10610": 0.7818660736083984, "10738": 0.3519764244556427, "10744": 0.16524957120418549, "10769": 0.12642613053321838, "10804": 0.31489628553390503, "10847": 0.05694137513637543, "10960": 0.3304552733898163, "11333": 0.3662964701652527, "11417": 0.07068414986133575, "11432": 0.2918238639831543, "11674": 0.025073638185858727, "11734": 0.960606575012207, "11909": 0.10379679501056671, "12044": 0.9021284580230713, "12222": 0.47584590315818787, "12247": 0.03360854089260101, "12328": 1.0151457786560059, "12407": 0.05417001247406006, "12456": 0.0606246218085289, "12636": 1.036847710609436, "12644": 0.6744182109832764, "12732": 1.0894558429718018, "12987": 0.19220098853111267, "13070": 0.20421554148197174, "13248": 0.5903874635696411, "13260": 0.7248653769493103, "13490": 0.7755908370018005, "13500": 0.5596157908439636, "13512": 0.25995752215385437, "13523": 0.9317949414253235, "13770": 0.7592713832855225, "13776": 0.045809537172317505, "13791": 0.1229778528213501, "13833": 0.24631060659885406, "13908": 0.5925496220588684, "13909": 1.1917895078659058, "14008": 0.03360854089260101, "14053": 0.2822965085506439, "14120": 0.49923527240753174, "14127": 0.3070250153541565, "14192": 0.33115679025650024, "14193": 1.244919776916504, "14463": 0.013579257763922215, "14494": 0.5607312321662903, "14578": 0.21687394380569458, "14627": 0.5903874635696411, "14706": 0.27934664487838745, "14828": 1.1598494052886963, "15085": 0.12728634476661682, "15115": 0.022212404757738113, "15124": 0.14602625370025635, "15176": 0.30989447236061096, "15286": 0.29400965571403503, "15451": 0.42225050926208496, "15527": 0.8357921838760376, "15536": 0.7314660549163818, "15543": 0.23324857652187347, "15549": 0.7665573358535767, "15630": 0.4818955361843109, "15663": 0.21922965347766876, "15868": 0.6482070088386536, "16081": 0.18329764902591705, "16127": 0.3526630103588104, "16221": 0.7463917136192322, "16285": 0.06703783571720123, "16341": 0.058784693479537964, "16412": 0.4818955361843109, "16452": 0.083342544734478, "16690": 1.1537069082260132, "16771": 0.10555581003427505, "16778": 0.18654440343379974, "16910": 0.8813109993934631, "16984": 0.21687394380569458, "17376": 0.28670501708984375, "17379": 0.31560876965522766, "17417": 0.7565253376960754, "17419": 0.9500881433486938, "17441": 0.026976587250828743, "17448": 0.6011518239974976, "17666": 0.34023189544677734, "17785": 0.022212404757738113, "17820": 0.6317287683486938, "17890": 0.319873183965683, "18047": 1.4469189643859863, "18260": 0.9546096324920654, "18562": 1.3862943649291992, "18595": 0.7809720039367676, "18675": 0.5433003902435303, "18714": 0.4654768109321594, "18724": 1.0668635368347168, "18924": 0.7067264318466187, "18938": 0.8893690705299377, "19138": 0.22157983481884003, "19181": 0.09406650811433792, "19220": 0.05417001247406006, "19241": 0.8731874823570251, "19296": 0.35745587944984436, "19389": 0.7537717819213867, "19601": 0.13157635927200317, "19653": 0.27044451236724854, "19722": 0.015504186972975731, "19802": 0.0752234235405922, "19817": 0.10555581003427505, "19863": 0.32129061222076416, "19872": 0.8829278349876404, "20350": 0.04487626627087593, "20464": 0.7408206462860107, "20603": 0.5871354341506958, "20630": 0.31560876965522766, "20752": 0.34300774335861206, "20858": 0.0009760859538801014, "21009": 0.0842406153678894, "21376": 0.18167030811309814, "21575": 0.3269403576850891, "21618": 0.8264343738555908, "21709": 0.022212404757738113, "21890": 0.41840189695358276, "21903": 0.46486347913742065, "21919": 0.7898768186569214, "21923": 0.24248650670051575, "21925": 0.1011524572968483, "21975": 0.11343330889940262, "22047": 0.09406650811433792, "22248": 0.06337817758321762, "22281": 0.1718502640724182, "22330": 0.6207655072212219, "22422": 0.16690383851528168, "22694": 0.31204116344451904, "22731": 0.2160874605178833, "23150": 0.0770333781838417, "23277": 0.2089812457561493, "23339": 0.011650617234408855, "23498": 0.09495500475168228, "23586": 0.7510106563568115, "23892": 0.5427330136299133, "24051": 0.1677299439907074, "24054": 0.7473171949386597, "24360": 0.5957841277122498, "24541": 0.05139094591140747, "24933": 0.2089812457561493, "24972": 0.022212404757738113, "25389": 0.02316705882549286, "25403": 1.0030416250228882, "25456": 0.5909284353256226, "25502": 0.10291612148284912, "25610": 0.10906458646059036, "25644": 0.5197699069976807, "25714": 0.11168810725212097, "25937": 0.3956514894962311, "26083": 0.13499516248703003, "26151": 0.07612881064414978, "26243": 0.1693800985813141, "26288": 0.015504186972975731, "26402": 1.1109062433242798, "26530": 0.10555581003427505, "26534": 0.25239890813827515, "26572": 0.16442140936851501, "26601": 0.021256839856505394, "26616": 0.15442965924739838, "26651": 0.23710809648036957, "26773": 0.42353010177612305, "26775": 0.31204116344451904, "28086": 0.21293537318706512, "28156": 0.17922431230545044, "28173": 0.7286425232887268, "28177": 0.6512666940689087, "28696": 0.8740028142929077, "28835": 0.07884006202220917, "29021": 0.820433497428894, "29242": 0.07159364968538284} | 13867350 | The canonical Wnt signaling pathway is of paramount importance in development and disease. An emergent question is whether the upstream cascade of the canonical Wnt pathway has physiologically relevant roles beyond β-catenin-mediated transcription, which is difficult to study due to the pervasive role of this protein. Here, we show that transcriptionally silent spermatozoa respond to Wnt signals released from the epididymis and that mice mutant for the Wnt regulator Cyclin Y-like 1 are male sterile due to immotile and malformed spermatozoa. Post-transcriptional Wnt signaling impacts spermatozoa through GSK3 by (1) reducing global protein poly-ubiquitination to maintain protein homeostasis; (2) inhibiting septin 4 phosphorylation to establish a membrane diffusion barrier in the sperm tail; and (3) inhibiting protein phosphatase 1 to initiate sperm motility. The results indicate that Wnt signaling orchestrates a rich post-transcriptional sperm maturation program and invite revisiting transcription-independent Wnt signaling in somatic cells as well. | Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation |
{"1011": 0.2105647772550583, "1039": 0.3910386264324188, "1056": 0.997294545173645, "2005": 0.07341018319129944, "2006": 0.16442140936851501, "2008": 0.02792670577764511, "2011": 0.1994270235300064, "2029": 0.151916041970253, "2046": 0.1477125883102417, "2075": 0.11430477350950241, "2079": 0.10818854719400406, "2090": 0.009718249551951885, "2099": 0.6244332790374756, "2109": 0.11343330889940262, "2117": 0.6512666940689087, "2119": 0.20580662786960602, "2128": 0.19622190296649933, "2155": 0.841701865196228, "2188": 0.26146242022514343, "2209": 0.06154331564903259, "2266": 0.4177590310573578, "2339": 0.04113444685935974, "2362": 0.007782140281051397, "2372": 0.319873183965683, "2377": 0.41840189695358276, "2389": 0.06703783571720123, "2426": 0.04860413447022438, "2430": 0.5347557663917542, "2515": 0.23633737862110138, "2529": 0.41001203656196594, "2535": 0.755608320236206, "2537": 0.3381449282169342, "2550": 0.0019512200960889459, "2581": 0.42735910415649414, "2599": 0.3588210940361023, "2613": 0.23092569410800934, "2620": 0.47402387857437134, "2654": 0.7445381283760071, "2676": 0.347847044467926, "2695": 0.3019835948944092, "2750": 0.18816383183002472, "2756": 0.05046287178993225, "2765": 0.020300358533859253, "2828": 0.1619328260421753, "2832": 0.17759032547473907, "2892": 0.06977381557226181, "2920": 0.32270604372024536, "2945": 0.5021947622299194, "2953": 0.6471850275993347, "3012": 0.28082266449928284, "3064": 0.2674594223499298, "3073": 0.0317181795835495, "3112": 0.175953671336174, "3144": 0.19622190296649933, "3145": 0.5098485946655273, "3248": 0.3034266233444214, "3252": 0.7380234599113464, "3319": 0.21922965347766876, "3370": 0.3248254358768463, "3375": 0.755608320236206, "3378": 0.0842406153678894, "3416": 0.08961215615272522, "3431": 0.2470736801624298, "3436": 0.26296505331993103, "3463": 0.129004567861557, "3466": 0.4041621685028076, "3508": 0.932563841342926, "3526": 0.9147270321846008, "3563": 0.43434104323387146, "3625": 0.0842406153678894, "3640": 0.19541899859905243, "3670": 0.6000806093215942, "3674": 0.22859740257263184, "3729": 1.3998736143112183, "3796": 0.6312094330787659, "3800": 0.083342544734478, "3853": 0.7124901413917542, "3896": 0.03266380727291107, "3905": 0.11517547070980072, "3937": 0.4158279001712799, "3989": 0.025073638185858727, "4077": 0.6441128253936768, "4115": 0.08603433519601822, "4127": 0.07793712615966797, "4183": 0.15023678541183472, "4187": 0.7220231294631958, "4286": 0.3409265875816345, "4295": 0.2089812457561493, "4310": 0.41001203656196594, "4319": 0.23479416966438293, "4395": 0.6813592314720154, "4442": 0.9386941194534302, "4539": 0.21530038118362427, "4621": 0.24631060659885406, "4742": 0.8633513450622559, "4824": 0.23402166366577148, "4945": 0.3248254358768463, "4957": 0.08961215615272522, "4958": 0.304147332906723, "4962": 0.3777405619621277, "4972": 0.5033760666847229, "5072": 0.08603433519601822, "5079": 0.4002431631088257, "5090": 0.41195443272590637, "5228": 0.176772341132164, "5234": 0.15023678541183472, "5260": 0.27786844968795776, "5387": 0.3325583338737488, "5421": 0.29981520771980286, "5441": 0.07159364968538284, "5449": 1.0158531665802002, "5495": 0.33115679025650024, "5668": 0.4938860833644867, "5788": 0.3560888469219208, "5799": 0.05786345899105072, "5850": 0.4909018874168396, "5876": 0.46853771805763245, "5919": 0.4770587682723999, "5991": 0.40220460295677185, "6032": 0.28670501708984375, "6190": 0.3409265875816345, "6194": 0.3910386264324188, "6309": 0.03360854089260101, "6370": 0.08064348995685577, "6494": 0.22937409579753876, "6612": 0.5925496220588684, "6848": 0.19622190296649933, "6897": 0.3897167444229126, "6936": 0.15275461971759796, "7242": 0.4145384132862091, "7337": 0.41001203656196594, "7366": 0.732405424118042, "7461": 0.06612417846918106, "7591": 0.13925230503082275, "7691": 0.7482418417930603, "7755": 0.8917738795280457, "7814": 0.1994270235300064, "7816": 0.5092619061470032, "7872": 0.7086513638496399, "8000": 0.9005423784255981, "8018": 1.5490573644638062, "8031": 0.1751343309879303, "8246": 0.08154398202896118, "8290": 0.8357921838760376, "8332": 0.48068851232528687, "8360": 0.27934664487838745, "8525": 0.011650617234408855, "8552": 0.13071982562541962, "8566": 0.3784096837043762, "8878": 0.4938860833644867, "8898": 0.3526630103588104, "9007": 0.21530038118362427, "9099": 0.37640097737312317, "9247": 0.7028654217720032, "9285": 0.4425300657749176, "9319": 0.09850110858678818, "9331": 0.6212902665138245, "9350": 0.015504186972975731, "9358": 0.0029254043474793434, "9513": 0.08513788133859634, "9662": 0.21214580535888672, "9869": 0.3241194784641266, "10047": 0.43875885009765625, "10253": 0.5651806592941284, "10266": 1.0008903741836548, "10381": 0.19782574474811554, "10586": 0.17431432008743286, "10595": 0.12642613053321838, "10599": 0.5751199722290039, "10737": 0.06246116757392883, "10738": 0.9317949414253235, "10769": 1.1971133947372437, "10851": 0.306306391954422, "10924": 0.040196798741817474, "11211": 0.04674193635582924, "11244": 0.11081436276435852, "11311": 1.0628231763839722, "11403": 0.04207121208310127, "11626": 0.1064341589808464, "11705": 0.4574742913246155, "11835": 0.6950984001159668, "11896": 0.013579257763922215, "12222": 0.6931471824645996, "12226": 0.10731173306703568, "12248": 0.1602703034877777, "12328": 0.7881022095680237, "12353": 0.34577593207359314, "12402": 0.3005385100841522, "12562": 0.007782140281051397, "12928": 0.5232481360435486, "12987": 0.08871890604496002, "13070": 0.17922431230545044, "13122": 0.2674594223499298, "13490": 0.31845372915267944, "13791": 0.77198725938797, "13833": 1.1462857723236084, "13922": 0.21135559678077698, "14031": 0.37640097737312317, "14126": 0.00875066313892603, "14152": 0.20660123229026794, "14187": 0.02887592278420925, "14193": 0.7987030148506165, "14228": 0.22704219818115234, "14340": 0.6197150945663452, "14667": 0.2105647772550583, "14828": 0.8212929964065552, "15115": 0.04860413447022438, "15176": 0.32764431834220886, "15403": 0.3601844012737274, "15420": 0.015504186972975731, "15428": 0.42990362644195557, "15538": 0.18492233753204346, "15743": 1.0172666311264038, "15869": 0.03360854089260101, "16012": 0.26446542143821716, "16026": 0.3127557039260864, "16221": 0.014542185701429844, "16530": 0.32341301441192627, "16605": 0.00875066313892603, "16706": 0.15943801403045654, "16730": 0.0354953333735466, "16771": 0.11168810725212097, "16834": 0.013579257763922215, "17261": 0.4734157919883728, "17379": 0.3850763738155365, "17441": 0.2954642176628113, "17637": 0.16607704758644104, "17837": 0.6265231370925903, "18120": 0.4400174915790558, "18178": 0.22548456490039825, "18714": 0.24171993136405945, "18715": 0.9294845461845398, "18856": 0.034552380442619324, "18903": 0.03360854089260101, "18969": 0.07250232994556427, "19506": 0.7163142561912537, "19872": 0.26146242022514343, "19913": 0.09317722171545029, "20051": 0.7473171949386597, "20350": 0.13925230503082275, "20544": 0.46117570996284485, "20582": 0.7674643993377686, "20752": 0.12384103983640671, "20817": 0.2637155055999756, "20992": 0.10818854719400406, "21114": 0.004870930220931768, "21150": 0.7473171949386597, "21471": 0.06612417846918106, "21477": 0.13071982562541962, "21557": 0.0797421783208847, "21575": 0.28082266449928284, "21618": 0.2637155055999756, "21903": 0.7028654217720032, "21919": 0.6754127144813538, "21935": 0.37102460861206055, "22160": 0.02792670577764511, "22330": 0.6343214511871338, "22407": 1.5152989625930786, "22419": 0.6233867406845093, "22907": 0.7445381283760071, "22930": 0.029824240133166313, "22931": 0.28670501708984375, "22975": 1.0828639268875122, "23041": 0.6999598741531372, "23833": 0.18329764902591705, "24054": 0.022212404757738113, "24169": 0.3416208028793335, "24229": 0.12038381397724152, "24594": 0.5596157908439636, "25194": 0.10026945173740387, "26244": 0.07250232994556427, "26773": 0.3318578004837036, "27054": 0.4002431631088257, "27144": 0.05694137513637543, "27709": 0.1994270235300064, "27781": 0.29400965571403503, "27854": 1.2404102087020874, "28353": 0.15275461971759796, "28667": 0.40611594915390015, "28696": 0.8861536383628845, "28788": 0.10818854719400406, "28873": 0.27934664487838745, "29060": 0.07431721687316895, "29206": 0.7047978043556213, "29215": 0.05970508232712746, "29242": 0.053244512528181076, "29489": 0.03360854089260101} | 13868795 | Ligation of the CD28 receptor on T cells provides a critical second signal alongside T cell receptor (TCR) ligation for naive T cell activation. Here, we discuss the expression, structure, and biochemistry of CD28 and its ligands. CD28 signals play a key role in many T cell processes, including cytoskeletal remodeling, production of cytokines, survival, and differentiation. CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis. We outline the roles that CD28 and its family members play in human disease and we review the clinical efficacy of drugs that block CD28 ligands. Despite the centrality of CD28 and its family members and ligands to immune function, many aspects of CD28 biology remain unclear. Translation of a basic understanding of CD28 function into immunomodulatory therapeutics has been uneven, with both successes and failures. Such real-world results might stem from multiple factors, including complex receptor-ligand interactions among CD28 family members, differences between the mouse and human CD28 families, and cell-type specific roles of CD28 family members. | CD28 Costimulation: From Mechanism to Therapy. |
{"1041": 0.19381128251552582, "1045": 0.42225050926208496, "1048": 0.04674193635582924, "1049": 0.4974553883075714, "1054": 0.16442140936851501, "2003": 0.04207121208310127, "2005": 0.3084607720375061, "2006": 0.24325250089168549, "2007": 0.09850110858678818, "2009": 0.14179791510105133, "2012": 0.1930064558982849, "2051": 0.08154398202896118, "2054": 0.1011524572968483, "2065": 0.15693697333335876, "2075": 0.37102460861206055, "2094": 0.11778303235769272, "2109": 0.32905077934265137, "2128": 0.6348392367362976, "2224": 0.012615402229130268, "2248": 1.1610734462738037, "2302": 0.03266380727291107, "2421": 0.2576959431171417, "2443": 0.371698260307312, "2445": 0.009718249551951885, "2470": 0.09495500475168228, "2556": 0.15860503911972046, "2557": 0.29255300760269165, "2593": 0.23556606471538544, "2604": 0.026976587250828743, "2607": 0.5466978549957275, "2641": 0.12038381397724152, "2649": 0.026976587250828743, "2686": 0.5635144114494324, "2720": 0.6358738541603088, "2721": 0.6502478122711182, "2744": 0.3723714053630829, "2771": 0.15275461971759796, "2777": 0.0019512200960889459, "2817": 0.12986256182193756, "2825": 0.6634125709533691, "2837": 0.0317181795835495, "2864": 0.0752234235405922, "2886": 0.029824240133166313, "2904": 0.23556606471538544, "2936": 0.15943801403045654, "2950": 0.06977381557226181, "2966": 0.5021947622299194, "3130": 0.2478361576795578, "3154": 0.38308101892471313, "3231": 0.6317287683486938, "3233": 0.19862671196460724, "3251": 0.18004031479358673, "3319": 0.1477125883102417, "3350": 0.151916041970253, "3408": 0.3297532796859741, "3436": 0.18492233753204346, "3497": 0.0174254160374403, "3512": 0.37974658608436584, "3560": 0.2607102394104004, "3563": 0.007782140281051397, "3579": 0.7436100244522095, "3591": 0.6332852244377136, "3615": 0.176772341132164, "3659": 0.03266380727291107, "3674": 1.034073829650879, "3680": 0.12470348179340363, "3746": 0.3601844012737274, "3800": 0.11256109178066254, "3891": 0.4311734735965729, "3898": 0.11343330889940262, "3917": 0.8796916007995605, "3921": 0.18411032855510712, "3949": 0.2576959431171417, "4050": 0.08513788133859634, "4072": 0.04207121208310127, "4081": 0.41840189695358276, "4097": 0.5139457583427429, "4106": 0.02887592278420925, "4118": 0.4855078160762787, "4127": 0.04860413447022438, "4208": 0.37707099318504333, "4295": 0.8152611255645752, "4298": 0.12384103983640671, "4340": 0.1229778528213501, "4453": 0.2531573474407196, "4484": 0.04767346754670143, "4491": 0.25239890813827515, "4523": 0.38905516266822815, "4588": 0.47584590315818787, "4649": 0.7482418417930603, "4718": 0.46363574266433716, "4725": 0.5506471395492554, "4760": 0.0913962796330452, "4800": 0.2493593990802765, "4871": 0.1913948506116867, "4921": 0.1485546976327896, "5022": 0.3615458607673645, "5082": 0.2689530849456787, "5171": 0.35060185194015503, "5286": 0.1718502640724182, "5352": 0.22157983481884003, "5393": 0.24018502235412598, "5461": 0.29255300760269165, "5498": 0.5427330136299133, "5579": 0.09584271162748337, "5604": 0.46117570996284485, "5646": 0.014542185701429844, "5761": 0.058784693479537964, "5769": 0.17759032547473907, "5776": 0.38174858689308167, "5796": 1.5407240390777588, "5852": 0.6296497583389282, "5876": 0.04767346754670143, "5906": 0.05046287178993225, "5918": 0.0606246218085289, "5997": 1.3635773658752441, "6028": 0.3339579105377197, "6061": 0.3870677351951599, "6075": 0.06703783571720123, "6083": 0.5410289764404297, "6131": 0.6244332790374756, "6179": 0.016465263441205025, "6210": 0.020300358533859253, "6219": 0.0606246218085289, "6335": 0.03925827145576477, "6377": 0.9591107368469238, "6413": 0.026976587250828743, "6427": 0.14433705806732178, "6483": 0.15359249711036682, "6508": 0.5341835021972656, "6555": 0.09672962874174118, "6592": 0.846739649772644, "6602": 0.10731173306703568, "6612": 0.6970458030700684, "6709": 0.13414156436920166, "6749": 0.2786078155040741, "6767": 0.7987030148506165, "6845": 0.0317181795835495, "6878": 0.09495500475168228, "6936": 0.10906458646059036, "6970": 0.4974553883075714, "6994": 0.007782140281051397, "7065": 0.7445381283760071, "7242": 0.35745587944984436, "7355": 0.02887592278420925, "7356": 0.04674193635582924, "7438": 0.025073638185858727, "7476": 0.8567397594451904, "7515": 0.052318159490823746, "7534": 0.3141832649707794, "7587": 0.6759096384048462, "7645": 0.5295937061309814, "7667": 0.42225050926208496, "7679": 0.35745587944984436, "7709": 0.3910386264324188, "7749": 0.23015019297599792, "7863": 0.9857001900672913, "7870": 0.5729197263717651, "7902": 0.16276304423809052, "7995": 0.10379679501056671, "8001": 1.210009217262268, "8030": 0.2689530849456787, "8040": 0.7898768186569214, "8060": 1.1400591135025024, "8107": 0.11778303235769272, "8249": 0.025073638185858727, "8312": 0.8682814836502075, "8343": 0.22626367211341858, "8346": 0.6989894509315491, "8715": 0.15526613593101501, "8720": 0.07793712615966797, "8761": 0.08603433519601822, "8778": 0.0317181795835495, "8853": 0.20421554148197174, "9104": 0.5145297050476074, "9108": 0.1477125883102417, "9181": 1.1906025409698486, "9289": 0.8845420479774475, "9312": 0.997294545173645, "9320": 1.0641717910766602, "9398": 0.036437395960092545, "9447": 0.49982786178588867, "9556": 0.08871890604496002, "9560": 0.47584590315818787, "9626": 0.35060185194015503, "9888": 0.3547199070453644, "9897": 0.07159364968538284, "9932": 0.006812678650021553, "9938": 0.20501139760017395, "9986": 0.07431721687316895, "10047": 0.2317005842924118, "10091": 0.015504186972975731, "10147": 0.10379679501056671, "10467": 0.8459017872810364, "10521": 0.04767346754670143, "10580": 0.3676496744155884, "10788": 0.2763880789279938, "10840": 0.1889725625514984, "10886": 0.47584590315818787, "10956": 0.4531385898590088, "10976": 0.07341018319129944, "11100": 0.5220900774002075, "11156": 0.17922431230545044, "11207": 0.10467668622732162, "11211": 0.025073638185858727, "11268": 0.08064348995685577, "11326": 0.4311734735965729, "11338": 0.013579257763922215, "11360": 0.1229778528213501, "11433": 0.1229778528213501, "11441": 0.981317400932312, "11475": 0.46486347913742065, "11487": 0.27786844968795776, "11498": 0.7647408246994019, "11586": 1.1312761306762695, "11594": 0.3027053773403168, "11616": 1.256105661392212, "11709": 0.20022670924663544, "11980": 0.15023678541183472, "12020": 0.04207121208310127, "12126": 1.1115491390228271, "12207": 0.05786345899105072, "12374": 0.2247048318386078, "12407": 0.15860503911972046, "12650": 0.987156867980957, "12653": 0.13499516248703003, "12832": 0.23556606471538544, "12939": 0.020300358533859253, "12997": 0.29473719000816345, "13105": 0.34023189544677734, "13221": 0.02316705882549286, "13425": 0.18004031479358673, "13594": 0.9217445850372314, "13616": 0.1229778528213501, "13722": 0.46608972549438477, "13921": 0.7583568692207336, "13996": 0.010684899985790253, "14155": 0.3850763738155365, "14213": 0.13755162060260773, "14313": 0.3297532796859741, "14358": 0.41647201776504517, "14386": 0.22001366317272186, "14931": 0.2667117714881897, "14967": 0.6218147873878479, "14995": 0.06154331564903259, "15004": 0.29036402702331543, "15141": 0.09850110858678818, "15298": 0.7295845746994019, "15549": 0.7220231294631958, "15596": 1.02149498462677, "15644": 0.0019512200960889459, "15918": 0.2837681770324707, "16014": 0.12814582884311676, "16021": 0.554580807685852, "16134": 0.41195443272590637, "16157": 0.5701626539230347, "16206": 0.030771657824516296, "16330": 0.6317287683486938, "16461": 0.48850810527801514, "16474": 1.2471669912338257, "16670": 0.42225050926208496, "16691": 0.07159364968538284, "16755": 0.14349138736724854, "16853": 0.7124901413917542, "16914": 0.06703783571720123, "17011": 1.202995777130127, "17225": 0.40285754203796387, "17245": 0.0009760859538801014, "17261": 0.24171993136405945, "17409": 0.5618454217910767, "18075": 0.09406650811433792, "18216": 0.7473171949386597, "18349": 0.20739519596099854, "18444": 0.23324857652187347, "18725": 0.22392450273036957, "18809": 0.20580662786960602, "18847": 0.9363996982574463, "19229": 0.8057082891464233, "19269": 0.15442965924739838, "19601": 0.034552380442619324, "19842": 0.40285754203796387, "19862": 0.16442140936851501, "19875": 0.06977381557226181, "20077": 0.23015019297599792, "20166": 0.02887592278420925, "20464": 0.6989894509315491, "20589": 0.1734936386346817, "20692": 0.05417001247406006, "20794": 0.036437395960092545, "20868": 0.32129061222076416, "21045": 0.06246116757392883, "21307": 0.20421554148197174, "21339": 0.10203468054533005, "21391": 0.09406650811433792, "21628": 0.08871890604496002, "21792": 0.39762192964553833, "22380": 0.20421554148197174, "22520": 0.8306987881660461, "22564": 0.11343330889940262, "22930": 0.7925328612327576, "22939": 0.3034266233444214, "22945": 0.1619328260421753, "23086": 0.21765978634357452, "23208": 0.28082266449928284, "23302": 0.01934296265244484, "23683": 0.23324857652187347, "23969": 0.06795065850019455, "24098": 0.4286321699619293, "24413": 0.08154398202896118, "24491": 0.25467249751091003, "24501": 0.4356052577495575, "24582": 0.4568560719490051, "24668": 0.07884006202220917, "24699": 0.41065993905067444, "24940": 0.05694137513637543, "24978": 0.00875066313892603, "25284": 0.13157635927200317, "25458": 0.09672962874174118, "25481": 0.8965662121772766, "25891": 0.23556606471538544, "26419": 0.10026945173740387, "26535": 0.3127557039260864, "26745": 1.0172666311264038, "27011": 1.001607894897461, "27102": 0.1905880719423294, "27179": 0.259204238653183, "27312": 0.2447827309370041, "27354": 0.23633737862110138, "27404": 0.5930894017219543, "27673": 0.17840765416622162, "27718": 0.6400018334388733, "27777": 0.27712854743003845, "28170": 0.9769153594970703, "28173": 0.7898768186569214, "28346": 0.12470348179340363, "28667": 0.34922540187835693, "29215": 0.41065993905067444, "29251": 0.24018502235412598, "29264": 0.03831886500120163} | 13870943 | The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS. " | Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. |
{"1011": 0.05970508232712746, "1018": 0.09495500475168228, "1038": 0.24859806895256042, "1043": 0.9515975713729858, "1054": 1.185243844985962, "1996": 0.2637155055999756, "1999": 0.056018441915512085, "2005": 0.014542185701429844, "2008": 0.025073638185858727, "2011": 0.1970241367816925, "2012": 0.10906458646059036, "2015": 0.6699305176734924, "2024": 0.21530038118362427, "2029": 0.1751343309879303, "2073": 0.13670019805431366, "2079": 0.2786078155040741, "2109": 0.06429435312747955, "2112": 0.09672962874174118, "2128": 0.27044451236724854, "2135": 0.013579257763922215, "2140": 0.5838727951049805, "2179": 0.3560888469219208, "2193": 0.06337817758321762, "2213": 0.05786345899105072, "2265": 0.12986256182193756, "2273": 0.7105726003646851, "2290": 0.23633737862110138, "2331": 0.034552380442619324, "2389": 0.0842406153678894, "2402": 0.009718249551951885, "2458": 0.6389714479446411, "2475": 0.16276304423809052, "2487": 0.4537591338157654, "2491": 0.7610978484153748, "2501": 0.08513788133859634, "2515": 0.22626367211341858, "2522": 0.35334911942481995, "2535": 0.3949938118457794, "2549": 0.6714286804199219, "2550": 0.026976587250828743, "2590": 0.48430517315864563, "2665": 0.011650617234408855, "2678": 0.32199856638908386, "2680": 0.175953671336174, "2693": 0.016465263441205025, "2695": 0.1477125883102417, "2764": 0.2223619967699051, "2828": 0.07159364968538284, "2832": 0.5607312321662903, "2913": 0.053244512528181076, "2920": 0.09584271162748337, "2946": 0.45623743534088135, "3048": 0.13157635927200317, "3065": 0.04113444685935974, "3231": 0.03925827145576477, "3251": 0.04767346754670143, "3252": 0.20102575421333313, "3273": 0.0029254043474793434, "3278": 0.04207121208310127, "3350": 0.0317181795835495, "3378": 0.0009760859538801014, "3405": 0.33605360984802246, "3406": 0.4196864068508148, "3463": 0.004870930220931768, "3466": 0.020300358533859253, "3469": 0.10993985831737518, "3491": 0.2652147710323334, "3495": 0.5551415085792542, "3526": 0.9500881433486938, "3584": 0.22782009840011597, "3603": 0.151916041970253, "3616": 0.16359257698059082, "3622": 0.1229778528213501, "3625": 0.1946154683828354, "3652": 0.10555581003427505, "3654": 0.11256109178066254, "3665": 0.018384648486971855, "3669": 0.0019512200960889459, "3710": 0.40351006388664246, "3718": 0.24401791393756866, "3760": 0.10026945173740387, "3768": 0.472198486328125, "3800": 0.20580662786960602, "3853": 0.6563454270362854, "3930": 0.06977381557226181, "3965": 0.07884006202220917, "4013": 0.7105726003646851, "4072": 0.09761575609445572, "4127": 0.02412080205976963, "4146": 0.009718249551951885, "4167": 1.0492360591888428, "4176": 0.1384023278951645, "4195": 0.11691460013389587, "4240": 0.38041436672210693, "4359": 0.6270449161529541, "4394": 0.12642613053321838, "4442": 1.0775588750839233, "4503": 0.34508460760116577, "4531": 0.06154331564903259, "4758": 0.7201237678527832, "4877": 0.1221139207482338, "4962": 0.3601844012737274, "4972": 0.4267219603061676, "4975": 0.75193190574646, "4987": 0.678390383720398, "5009": 0.7610978484153748, "5013": 0.272677481174469, "5090": 0.08871890604496002, "5197": 0.25088030099868774, "5498": 0.6553317308425903, "5547": 0.4531385898590088, "5603": 0.07341018319129944, "5633": 0.31560876965522766, "5644": 0.2852376699447632, "5716": 0.025073638185858727, "5769": 0.03925827145576477, "5788": 0.4500300884246826, "5970": 0.052318159490823746, "6080": 0.1619328260421753, "6091": 0.3656192123889923, "6169": 0.06246116757392883, "6194": 0.6970458030700684, "6366": 0.05786345899105072, "6541": 0.5404602885246277, "6632": 1.1450434923171997, "6653": 0.06886265426874161, "6657": 0.5347557663917542, "6776": 0.6502478122711182, "6876": 0.32129061222076416, "6914": 0.6181373596191406, "7046": 0.053244512528181076, "7312": 0.7463917136192322, "7337": 0.22937409579753876, "7361": 0.7115318179130554, "7366": 0.15860503911972046, "7461": 0.016465263441205025, "7645": 0.46055975556373596, "7691": 0.6603899002075195, "7711": 0.755608320236206, "7784": 0.08064348995685577, "7872": 0.11951763927936554, "7885": 0.05694137513637543, "8000": 1.0023250579833984, "8102": 0.8861536383628845, "8153": 0.4831010699272156, "8161": 0.28743788599967957, "8208": 0.3409265875816345, "8247": 0.7978238463401794, "8346": 0.006812678650021553, "8360": 0.15860503911972046, "8361": 0.11256109178066254, "8469": 0.28082266449928284, "8546": 0.40351006388664246, "8606": 0.16110190749168396, "8694": 0.6420594453811646, "8713": 0.026976587250828743, "8745": 0.22157983481884003, "8878": 0.015504186972975731, "9007": 0.13414156436920166, "9113": 0.6970458030700684, "9165": 0.007782140281051397, "9230": 0.7258110046386719, "9289": 0.6228629946708679, "9307": 0.1710275560617447, "9350": 0.37102460861206055, "9412": 0.7201237678527832, "9556": 0.574020504951477, "9702": 0.43053874373435974, "9706": 0.524982750415802, "9756": 0.49864232540130615, "9885": 0.259204238653183, "9958": 0.22859740257263184, "10016": 0.26446542143821716, "10024": 0.026976587250828743, "10383": 0.04207121208310127, "10440": 0.26446542143821716, "10548": 0.26446542143821716, "10572": 0.6265231370925903, "10580": 0.4158279001712799, "10595": 0.045809537172317505, "10599": 0.3560888469219208, "10627": 0.3485364317893982, "10744": 0.04674193635582924, "10804": 0.3897167444229126, "10826": 0.24018502235412598, "10876": 1.02149498462677, "10958": 0.27934664487838745, "10976": 0.17431432008743286, "11009": 0.06246116757392883, "11158": 0.7454653382301331, "11236": 0.08244366943836212, "11265": 0.5500838756561279, "11432": 0.39367714524269104, "11486": 0.056018441915512085, "11598": 0.4196864068508148, "11707": 0.35950297117233276, "11791": 0.05694137513637543, "12177": 0.43434104323387146, "12222": 0.04674193635582924, "12230": 0.12556517124176025, "12313": 0.11778303235769272, "12328": 1.229617714881897, "12468": 0.5284429788589478, "12562": 0.026976587250828743, "12604": 0.10291612148284912, "12667": 0.02412080205976963, "12798": 0.5393219590187073, "13366": 0.1734936386346817, "13416": 0.26446542143821716, "13447": 0.5307431221008301, "13512": 0.3443928062915802, "13633": 0.09672962874174118, "13655": 0.11343330889940262, "13833": 0.27044451236724854, "13908": 0.48970574140548706, "13910": 0.6989894509315491, "13911": 0.040196798741817474, "13995": 0.16524957120418549, "14031": 0.14433705806732178, "14087": 0.3622259199619293, "14130": 0.176772341132164, "14313": 0.1332872211933136, "14332": 0.0770333781838417, "14449": 1.0312920808792114, "14520": 0.03925827145576477, "14669": 0.24631060659885406, "14874": 0.055094651877880096, "14988": 0.1734936386346817, "15074": 0.037378571927547455, "15176": 0.11778303235769272, "15255": 1.4578880071640015, "15395": 0.10906458646059036, "15544": 0.06429435312747955, "15660": 0.8534175157546997, "15698": 1.0423725843429565, "15756": 0.5540198087692261, "15757": 0.16690383851528168, "15924": 0.0019512200960889459, "15946": 0.05046287178993225, "16122": 0.043007105588912964, "16148": 0.35060185194015503, "16238": 0.030771657824516296, "16308": 0.11778303235769272, "16360": 0.11778303235769272, "16505": 0.3170322775840759, "16691": 0.35403475165367126, "16836": 0.03360854089260101, "16910": 0.037378571927547455, "16983": 0.7144040465354919, "17132": 1.1281205415725708, "17351": 0.13071982562541962, "17913": 0.1477125883102417, "18195": 1.4883290529251099, "18419": 0.7845434546470642, "18439": 1.0123108625411987, "18600": 0.034552380442619324, "18809": 0.1358480453491211, "18888": 0.5438674688339233, "18964": 0.3353555500507355, "19335": 0.09317722171545029, "19653": 0.5232481360435486, "19696": 0.15359249711036682, "19723": 0.10818854719400406, "19739": 0.22001366317272186, "19894": 1.024303913116455, "20010": 0.6573580503463745, "20011": 0.8013357520103455, "20014": 0.7258110046386719, "20063": 0.13670019805431366, "20132": 0.6348392367362976, "20350": 0.09317722171545029, "20368": 0.18004031479358673, "20582": 0.13414156436920166, "20731": 0.2317005842924118, "20884": 0.07884006202220917, "20996": 0.24325250089168549, "21017": 0.9583619832992554, "21046": 0.20660123229026794, "21101": 0.5968599319458008, "21144": 0.31204116344451904, "21257": 0.0009760859538801014, "21262": 0.6558387279510498, "21471": 0.25694093108177185, "21525": 0.30486753582954407, "21600": 0.1401015669107437, "21833": 0.11430477350950241, "22110": 0.18654440343379974, "22170": 0.1619328260421753, "22187": 0.015504186972975731, "22260": 0.11865071207284927, "22262": 0.4462870955467224, "22415": 0.2501201331615448, "22476": 0.7220231294631958, "22607": 0.0009760859538801014, "22694": 0.1384023278951645, "22802": 0.1332872211933136, "22806": 0.8649974465370178, "23277": 0.3897167444229126, "23296": 0.3750596046447754, "23496": 1.1561684608459473, "23737": 0.31560876965522766, "23767": 0.1477125883102417, "24269": 0.2786078155040741, "24501": 0.23092569410800934, "24972": 0.09672962874174118, "25006": 0.4400174915790558, "25269": 0.12038381397724152, "25708": 0.06886265426874161, "25950": 1.0815403461456299, "25957": 0.14095009863376617, "26033": 0.10731173306703568, "26394": 0.10555581003427505, "26773": 0.05786345899105072, "27094": 0.16524957120418549, "27108": 0.014542185701429844, "27287": 1.117955207824707, "27321": 0.20739519596099854, "27532": 0.306306391954422, "28086": 0.36494144797325134, "28105": 0.04674193635582924, "28156": 0.3930181860923767, "28177": 0.058784693479537964, "28227": 0.650757372379303, "28228": 0.9687942266464233, "28636": 0.7845434546470642, "28788": 0.15943801403045654, "28828": 0.13670019805431366, "28829": 0.04394211992621422, "29076": 0.17840765416622162, "29107": 0.09850110858678818, "29290": 0.0770333781838417, "29300": 0.17840765416622162, "29489": 0.6420594453811646, "29577": 0.175953671336174} | 13878124 | Radial glial cells (RGCs) in the developing cerebral cortex are progenitors for neurons and glia, and their processes serve as guideposts for migrating neurons. So far, it has remained unclear whether RGC processes also control the function of RGCs more directly. Here, we show that RGC numbers and cortical size are reduced in mice lacking beta1 integrins in RGCs. TUNEL stainings and time-lapse video recordings demonstrate that beta1-deficient RGCs processes detach from the meningeal basement membrane (BM) followed by apoptotic death of RGCs. Apoptosis is also induced by surgical removal of the meninges. Finally, mice lacking the BM components laminin alpha2 and alpha4 show defects in the attachment of RGC processes at the meninges, a reduction in cortical size, and enhanced apoptosis of RGC cells. Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size. | Regulation of radial glial survival by signals from the meninges. |
{"1007": 0.022212404757738113, "1009": 0.8349450826644897, "1011": 0.15943801403045654, "1022": 0.6202403903007507, "1039": 0.175953671336174, "1056": 0.8941729068756104, "2005": 0.12986256182193756, "2012": 0.1384023278951645, "2020": 0.07431721687316895, "2029": 0.10818854719400406, "2033": 0.2969166338443756, "2037": 0.2830325961112976, "2047": 0.175953671336174, "2063": 0.151916041970253, "2076": 0.5478278398513794, "2079": 0.2531573474407196, "2104": 0.176772341132164, "2109": 0.10203468054533005, "2128": 0.36086538434028625, "2182": 0.23015019297599792, "2188": 0.41001203656196594, "2302": 0.401551216840744, "2339": 0.1602703034877777, "2361": 0.66441810131073, "2470": 0.14349138736724854, "2497": 0.4580921530723572, "2515": 0.19782574474811554, "2535": 0.7583568692207336, "2583": 0.18978065252304077, "2590": 0.15359249711036682, "2618": 0.1384023278951645, "2620": 1.2152372598648071, "2709": 0.021256839856505394, "2734": 0.07793712615966797, "2750": 0.056018441915512085, "2765": 0.1994270235300064, "2777": 0.28743788599967957, "2809": 0.37974658608436584, "2817": 0.30989447236061096, "2864": 0.15943801403045654, "2865": 0.6228629946708679, "2913": 0.40806588530540466, "2920": 0.1873544454574585, "2953": 1.001607894897461, "3085": 0.3588210940361023, "3113": 0.5784112811088562, "3116": 0.45499902963638306, "3161": 0.23402166366577148, "3217": 0.8567397594451904, "3223": 0.45623743534088135, "3273": 0.16442140936851501, "3283": 0.19862671196460724, "3372": 0.28450319170951843, "3433": 0.7692760229110718, "3457": 0.1212492436170578, "3463": 0.18654440343379974, "3466": 0.7546905279159546, "3526": 0.9643365740776062, "3563": 0.22001366317272186, "3593": 0.15275461971759796, "3625": 0.21530038118362427, "3639": 0.00875066313892603, "3668": 0.056018441915512085, "3670": 0.14349138736724854, "3676": 0.09672962874174118, "3685": 0.010684899985790253, "3697": 0.08871890604496002, "3728": 0.07068414986133575, "3729": 1.2204381227493286, "3734": 0.3743882179260254, "3754": 0.11604541540145874, "3787": 0.5607312321662903, "3800": 0.2607102394104004, "3853": 0.3027053773403168, "3896": 0.0913962796330452, "4039": 0.6000806093215942, "4072": 0.4794800877571106, "4187": 0.040196798741817474, "4395": 0.603290855884552, "4397": 0.688742995262146, "4403": 0.09938567131757736, "4423": 0.32553088665008545, "4442": 1.1018621921539307, "4487": 0.13414156436920166, "4504": 0.15526613593101501, "4523": 0.8949713706970215, "4539": 0.11604541540145874, "4570": 0.04207121208310127, "4606": 0.2822965085506439, "4742": 0.7500885725021362, "4783": 0.045809537172317505, "4935": 1.1012130975723267, "4945": 0.18248429894447327, "4962": 0.22548456490039825, "5034": 1.0802149772644043, "5092": 0.1358480453491211, "5157": 0.2409527748823166, "5250": 0.7969439625740051, "5391": 0.02316705882549286, "5393": 0.5466978549957275, "5423": 0.6823468804359436, "5425": 0.10993985831737518, "5449": 0.19381128251552582, "5478": 0.23015019297599792, "5668": 0.8813109993934631, "5769": 0.2822965085506439, "5783": 0.7881022095680237, "5918": 0.47463157773017883, "5942": 0.20421554148197174, "5964": 0.13499516248703003, "6010": 0.14602625370025635, "6123": 0.4512746334075928, "6132": 0.7389566898345947, "6508": 0.4673144817352295, "6528": 0.6911921501159668, "6553": 0.603290855884552, "6562": 0.5734702348709106, "6633": 0.03831886500120163, "6653": 0.7845434546470642, "6827": 0.7445381283760071, "6869": 0.2954642176628113, "6897": 0.09761575609445572, "6942": 0.2822965085506439, "7012": 0.06703783571720123, "7065": 0.11168810725212097, "7127": 0.03925827145576477, "7337": 0.27712854743003845, "7366": 0.17759032547473907, "7461": 0.13071982562541962, "7568": 0.040196798741817474, "7591": 0.06612417846918106, "7645": 0.5528968572616577, "7654": 0.9271688461303711, "7670": 0.4812922179698944, "7711": 0.006812678650021553, "7738": 0.0019512200960889459, "7755": 0.7934166193008423, "7790": 0.11168810725212097, "7816": 0.6487176418304443, "7818": 0.684319257736206, "7865": 0.4248080551624298, "7885": 0.18573370575904846, "7949": 0.03831886500120163, "8010": 0.13670019805431366, "8031": 1.2677175998687744, "8153": 0.05970508232712746, "8171": 0.8608771562576294, "8382": 0.4462870955467224, "8479": 0.9162907600402832, "8590": 0.011650617234408855, "8751": 0.4568560719490051, "8878": 1.0382318496704102, "8980": 0.06154331564903259, "8985": 0.5506471395492554, "9007": 0.401551216840744, "9034": 0.007782140281051397, "9095": 0.36697331070899963, "9096": 0.1229778528213501, "9186": 0.2837681770324707, "9313": 0.5984715819358826, "9358": 0.10467668622732162, "9377": 0.043007105588912964, "9487": 0.06337817758321762, "9488": 0.05139094591140747, "9597": 0.04113444685935974, "9694": 0.22937409579753876, "9820": 0.015504186972975731, "9878": 0.22937409579753876, "9996": 0.05970508232712746, "10372": 0.09406650811433792, "10467": 0.06886265426874161, "10509": 0.14264501631259918, "10572": 0.11604541540145874, "10580": 0.39893341064453125, "10595": 0.016465263441205025, "10737": 0.05970508232712746, "10738": 1.0927356481552124, "10752": 0.35677260160446167, "10769": 0.3297532796859741, "10804": 0.23556606471538544, "10960": 0.4831010699272156, "11157": 0.21922965347766876, "11311": 0.3388410806655884, "11369": 0.053244512528181076, "11813": 0.09317722171545029, "11991": 0.10467668622732162, "12222": 0.6674286723136902, "12247": 0.11517547070980072, "12322": 0.0029254043474793434, "12369": 0.5215105414390564, "12407": 0.12728634476661682, "12562": 0.14939609169960022, "12732": 0.12384103983640671, "12879": 0.21372433006763458, "12987": 0.0770333781838417, "13102": 0.49030399322509766, "13113": 1.1756457090377808, "13153": 1.0920805931091309, "13225": 0.2034190446138382, "13434": 0.8152611255645752, "13595": 0.09406650811433792, "13685": 0.02316705882549286, "13720": 0.37102460861206055, "13791": 1.0506030321121216, "13833": 0.39367714524269104, "13868": 0.16110190749168396, "13883": 0.11865071207284927, "13910": 0.10379679501056671, "13922": 0.04953393340110779, "14120": 0.35060185194015503, "14187": 0.5596157908439636, "14262": 0.02887592278420925, "14313": 0.0797421783208847, "14340": 0.31204116344451904, "14505": 0.33953672647476196, "14772": 0.18329764902591705, "14828": 0.9485763907432556, "14856": 0.9240728616714478, "14905": 0.3241194784641266, "14956": 0.33675122261047363, "15176": 0.2830325961112976, "15185": 0.2852376699447632, "15245": 0.34370049834251404, "15527": 0.07884006202220917, "15543": 0.1011524572968483, "15663": 0.3409265875816345, "15878": 1.5005991458892822, "16012": 0.5947071313858032, "16026": 0.9440274834632874, "16360": 1.1506214141845703, "16389": 0.02412080205976963, "16429": 0.14433705806732178, "16453": 0.8143964409828186, "16514": 0.1970241367816925, "16558": 0.11081436276435852, "16691": 0.21372433006763458, "16840": 0.043007105588912964, "16882": 0.06429435312747955, "16984": 0.21922965347766876, "17441": 0.6553317308425903, "17459": 0.3743882179260254, "17914": 0.007782140281051397, "18089": 1.1798561811447144, "18120": 0.20580662786960602, "18191": 0.3963087201118469, "18259": 0.010684899985790253, "18410": 0.0797421783208847, "18461": 0.09317722171545029, "18647": 0.006812678650021553, "18714": 0.6218147873878479, "18715": 0.14349138736724854, "18804": 0.32553088665008545, "18856": 0.5244048833847046, "19009": 0.5827828645706177, "19220": 0.16359257698059082, "19293": 0.0752234235405922, "19335": 0.04113444685935974, "19359": 0.1685553640127182, "19389": 0.058784693479537964, "19530": 0.1677299439907074, "19601": 0.1384023278951645, "19653": 0.23556606471538544, "19723": 0.23864774405956268, "19736": 0.23633737862110138, "19872": 0.3443928062915802, "19892": 0.15943801403045654, "19907": 0.029824240133166313, "20062": 0.6522845029830933, "20086": 0.7248653769493103, "20250": 0.8109301924705505, "20350": 0.10731173306703568, "20544": 0.7201237678527832, "20598": 0.18816383183002472, "20752": 0.5903874635696411, "20755": 0.10026945173740387, "20770": 0.29981520771980286, "20817": 0.5612884759902954, "20850": 0.029824240133166313, "20858": 0.17759032547473907, "21106": 0.5887627601623535, "21453": 1.0960047245025635, "21466": 0.009718249551951885, "21575": 0.5398913025856018, "21618": 0.3870677351951599, "21709": 0.18411032855510712, "21864": 0.8117979168891907, "21903": 0.3995884954929352, "21919": 0.6176109313964844, "21967": 0.3012613356113434, "22166": 0.3547199070453644, "22170": 0.2659635543823242, "22312": 0.05786345899105072, "22975": 0.0606246218085289, "22991": 0.052318159490823746, "23041": 0.2652147710323334, "23150": 0.08603433519601822, "23586": 0.0058422754518687725, "23737": 0.25995752215385437, "23924": 0.6446255445480347, "23934": 0.026976587250828743, "24133": 0.11951763927936554, "24203": 0.11604541540145874, "24278": 0.0797421783208847, "24345": 0.0029254043474793434, "24501": 0.27786844968795776, "24545": 0.026025565341114998, "25117": 0.12556517124176025, "25145": 0.040196798741817474, "25194": 0.3588210940361023, "25344": 0.14433705806732178, "25416": 0.1930064558982849, "25644": 0.11517547070980072, "25761": 0.31560876965522766, "25808": 0.20102575421333313, "25829": 0.5313173532485962, "25969": 0.11517547070980072, "26239": 0.14433705806732178, "26243": 0.04860413447022438, "26261": 1.1834511756896973, "26402": 0.0009760859538801014, "26419": 0.029824240133166313, "26520": 0.05786345899105072, "26534": 0.0354953333735466, "26651": 0.06429435312747955, "26773": 0.25995752215385437, "26835": 0.1384023278951645, "27321": 0.037378571927547455, "27833": 0.13755162060260773, "27854": 0.2089812457561493, "28577": 0.15023678541183472, "28667": 0.12384103983640671, "28696": 1.0229004621505737, "28788": 0.38308101892471313, "28873": 0.13755162060260773, "28964": 1.0668635368347168} | 13878643 | Newly activated CD8(+) T cells reprogram their metabolism to meet the extraordinary biosynthetic demands of clonal expansion; however, the signals that mediate metabolic reprogramming remain poorly defined. Here we demonstrate an essential role for sterol regulatory element-binding proteins (SREBPs) in the acquisition of effector-cell metabolism. Without SREBP signaling, CD8(+) T cells were unable to blast, which resulted in attenuated clonal expansion during viral infection. Mechanistic studies indicated that SREBPs were essential for meeting the heightened lipid requirements of membrane synthesis during blastogenesis. SREBPs were dispensable for homeostatic proliferation, which indicated a context-specific requirement for SREBPs in effector responses. Our studies provide insights into the molecular signals that underlie the metabolic reprogramming of CD8(+) T cells during the transition from quiescence to activation. | The sterol regulatory element binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity |
{"2001": 0.5139457583427429, "2009": 0.259204238653183, "2011": 0.31560876965522766, "2013": 0.007782140281051397, "2018": 0.11778303235769272, "2020": 0.23402166366577148, "2038": 0.16276304423809052, "2042": 0.20739519596099854, "2043": 0.4487839937210083, "2052": 0.14349138736724854, "2058": 0.21765978634357452, "2062": 0.12814582884311676, "2071": 0.347847044467926, "2073": 0.23864774405956268, "2076": 0.11778303235769272, "2084": 0.22001366317272186, "2086": 0.10203468054533005, "2087": 0.175953671336174, "2088": 0.22937409579753876, "2095": 0.5579402446746826, "2106": 0.5215105414390564, "2107": 0.24171993136405945, "2111": 0.10906458646059036, "2129": 0.19622190296649933, "2138": 0.32905077934265137, "2144": 0.5267143249511719, "2152": 0.3409265875816345, "2158": 0.12038381397724152, "2172": 0.11430477350950241, "2200": 0.1619328260421753, "2211": 0.011650617234408855, "2250": 0.12384103983640671, "2251": 0.41195443272590637, "2257": 0.2501201331615448, "2263": 0.06886265426874161, "2301": 0.025073638185858727, "2312": 0.0029254043474793434, "2318": 0.1946154683828354, "2331": 0.5635144114494324, "2339": 0.5860490798950195, "2351": 0.45251765847206116, "2381": 0.39696553349494934, "2406": 0.11778303235769272, "2412": 0.025073638185858727, "2413": 0.4400174915790558, "2419": 0.04394211992621422, "2432": 0.7163142561912537, "2439": 0.07159364968538284, "2446": 0.49864232540130615, "2471": 0.02412080205976963, "2475": 0.13243216276168823, "2494": 1.2250384092330933, "2501": 0.5696102976799011, "2504": 0.27934664487838745, "2526": 0.46914875507354736, "2529": 0.7969439625740051, "2541": 0.4512746334075928, "2543": 0.1913948506116867, "2555": 0.4400174915790558, "2560": 0.3106105625629425, "2580": 0.0038986403960734606, "2584": 0.12038381397724152, "2599": 0.11951763927936554, "2605": 0.9060825705528259, "2621": 1.1369311809539795, "2636": 0.2034190446138382, "2639": 0.2026219218969345, "2647": 0.8965662121772766, "2648": 0.13414156436920166, "2680": 0.4337083101272583, "2682": 0.2969166338443756, "2707": 0.4203280806541443, "2718": 0.026976587250828743, "2724": 0.5925496220588684, "2730": 0.4311734735965729, "2742": 0.4158279001712799, "2757": 0.24018502235412598, "2762": 0.8567397594451904, "2763": 0.2786078155040741, "2765": 0.14518201351165771, "2812": 0.3622259199619293, "2824": 0.3916989266872406, "2825": 0.4132472574710846, "2885": 1.1166772842407227, "2919": 0.08244366943836212, "2922": 0.10203468054533005, "2927": 0.08603433519601822, "2980": 0.7665573358535767, "2988": 0.34370049834251404, "3000": 0.35403475165367126, "3011": 0.14179791510105133, "3032": 0.3982778787612915, "3047": 0.3127557039260864, "3058": 0.13157635927200317, "3059": 0.567397952079773, "3103": 0.28082266449928284, "3114": 0.15023678541183472, "3120": 0.05046287178993225, "3141": 0.42416930198669434, "3147": 0.22079704701900482, "3160": 0.6254787445068359, "3168": 0.10993985831737518, "3189": 0.09761575609445572, "3251": 0.23092569410800934, "3261": 0.0019512200960889459, "3278": 0.0174254160374403, "3280": 0.45623743534088135, "3283": 0.11517547070980072, "3284": 0.38905516266822815, "3303": 0.8715548515319824, "3304": 0.9500881433486938, "3313": 0.40741631388664246, "3378": 0.05970508232712746, "3382": 0.841701865196228, "3399": 0.08692999184131622, "3426": 0.7969439625740051, "3439": 0.23479416966438293, "3445": 0.48850810527801514, "3450": 0.49030399322509766, "3458": 0.1970241367816925, "3466": 0.42225050926208496, "3497": 0.7398891448974609, "3500": 0.2317005842924118, "3522": 0.21530038118362427, "3577": 0.08961215615272522, "3618": 0.12556517124176025, "3623": 0.45623743534088135, "3625": 0.04860413447022438, "3684": 1.1629066467285156, "3690": 0.055094651877880096, "3722": 0.2516399025917053, "3747": 0.7491656541824341, "3795": 0.2409527748823166, "3798": 0.06977381557226181, "3806": 0.21922965347766876, "3867": 0.11517547070980072, "3891": 0.8187123537063599, "3896": 0.1930064558982849, "3938": 0.3423145115375519, "3980": 0.06795065850019455, "4010": 0.4041621685028076, "4023": 0.5069117546081543, "4040": 0.013579257763922215, "4044": 0.4093637466430664, "4068": 0.20421554148197174, "4125": 0.05786345899105072, "4131": 0.10906458646059036, "4148": 0.01934296265244484, "4158": 0.3547199070453644, "4199": 0.23479416966438293, "4254": 0.3318578004837036, "4286": 0.6128603219985962, "4288": 0.034552380442619324, "4305": 0.57457035779953, "4358": 0.32553088665008545, "4400": 0.966567873954773, "4436": 0.07612881064414978, "4483": 0.1384023278951645, "4602": 0.011650617234408855, "4627": 0.010684899985790253, "4633": 0.9147270321846008, "4655": 0.3163207769393921, "4672": 0.1477125883102417, "4678": 0.022212404757738113, "4785": 1.068206787109375, "4786": 0.4624064862728119, "4795": 0.2969166338443756, "4797": 0.11168810725212097, "4803": 0.012615402229130268, "4852": 0.39762192964553833, "4860": 0.9256220459938049, "4894": 0.015504186972975731, "4895": 0.3676496744155884, "4973": 0.2089812457561493, "5043": 0.3191637098789215, "5105": 0.5696102976799011, "5158": 0.16359257698059082, "5186": 0.026025565341114998, "5201": 0.3269403576850891, "5255": 0.0029254043474793434, "5258": 0.5069117546081543, "5278": 0.026976587250828743, "5302": 0.5685047507286072, "5320": 0.7638313174247742, "5360": 0.2478361576795578, "5409": 0.04674193635582924, "5473": 0.13414156436920166, "5476": 0.06612417846918106, "5665": 0.472198486328125, "5706": 0.011650617234408855, "5787": 0.15023678541183472, "5857": 0.24859806895256042, "5866": 0.3676496744155884, "5876": 0.3374483287334442, "5975": 0.6358738541603088, "5981": 0.11256109178066254, "6011": 0.0009760859538801014, "6021": 0.16607704758644104, "6022": 0.06612417846918106, "6034": 0.17267228662967682, "6061": 0.011650617234408855, "6075": 0.0019512200960889459, "6086": 0.0842406153678894, "6150": 0.8022117614746094, "6214": 0.12556517124176025, "6230": 0.11343330889940262, "6310": 0.6233867406845093, "6327": 0.839173436164856, "6351": 0.19622190296649933, "6383": 0.21372433006763458, "6409": 0.08603433519601822, "6677": 0.7038320899009705, "6691": 0.520350456237793, "6693": 0.17267228662967682, "6698": 0.11691460013389587, "6803": 0.6578640341758728, "6932": 0.05970508232712746, "6976": 0.018384648486971855, "7017": 0.3127557039260864, "7023": 0.8764448165893555, "7064": 0.026025565341114998, "7074": 0.23092569410800934, "7108": 0.11430477350950241, "7224": 0.5827828645706177, "7327": 0.6902132034301758, "7457": 0.3615458607673645, "7461": 0.46055975556373596, "7469": 0.036437395960092545, "7595": 0.010684899985790253, "7666": 0.12470348179340363, "7695": 0.3777405619621277, "7705": 0.41195443272590637, "7715": 0.6064908504486084, "7810": 0.13670019805431366, "7914": 0.15526613593101501, "7915": 0.22392450273036957, "7973": 0.23402166366577148, "8020": 0.14686977863311768, "8092": 0.803087055683136, "8211": 0.09495500475168228, "8249": 0.28670501708984375, "8343": 0.03360854089260101, "8372": 0.1808556467294693, "8455": 0.10731173306703568, "8465": 0.09228714555501938, "8554": 0.7105726003646851, "8664": 0.23324857652187347, "8729": 0.11604541540145874, "8737": 0.2470736801624298, "8767": 0.1212492436170578, "8776": 0.11517547070980072, "8781": 0.2786078155040741, "8792": 0.7683706283569336, "8797": 0.09228714555501938, "8915": 0.21530038118362427, "9002": 0.3662964701652527, "9223": 0.036437395960092545, "9252": 0.1693800985813141, "9313": 0.0354953333735466, "9509": 0.04487626627087593, "9575": 0.10993985831737518, "9592": 0.11168810725212097, "9685": 0.42225050926208496, "9723": 0.23324857652187347, "9765": 0.06977381557226181, "9829": 0.35813871026039124, "9944": 0.3423145115375519, "9983": 0.4228905141353607, "9987": 0.053244512528181076, "10035": 0.27786844968795776, "10066": 0.44753631949424744, "10074": 0.6128603219985962, "10173": 0.07793712615966797, "10174": 0.11604541540145874, "10194": 0.562402069568634, "10197": 0.417115718126297, "10273": 0.037378571927547455, "10347": 0.6149744987487793, "10383": 0.055094651877880096, "10434": 0.10818854719400406, "10451": 0.9037119746208191, "10572": 0.7182208299636841, "10611": 0.09584271162748337, "10744": 0.06886265426874161, "10796": 0.46853771805763245, "10803": 0.4002431631088257, "10808": 0.5238267183303833, "10831": 0.5534584522247314, "10867": 0.09584271162748337, "10889": 0.011650617234408855, "10945": 0.6254787445068359, "11207": 1.1683861017227173, "11352": 0.053244512528181076, "11515": 0.5607312321662903, "11768": 0.36697331070899963, "12130": 0.22548456490039825, "12473": 0.12556517124176025, "12483": 0.5506471395492554, "12503": 0.14939609169960022, "12719": 0.436867892742157, "12890": 0.5860490798950195, "12959": 0.8780695199966431, "12972": 0.05417001247406006, "13210": 0.3949938118457794, "13330": 0.31560876965522766, "13352": 0.016465263441205025, "13356": 0.029824240133166313, "13382": 0.23402166366577148, "13467": 0.777387797832489, "13481": 0.5156965255737305, "13531": 0.14518201351165771, "13686": 0.777387797832489, "13977": 0.02412080205976963, "14061": 0.4450363218784332, "14080": 0.8666408061981201, "14153": 0.11430477350950241, "14384": 0.2026219218969345, "14386": 0.02316705882549286, "14404": 0.6233867406845093, "14670": 0.18411032855510712, "14872": 0.5220900774002075, "14883": 0.19541899859905243, "15194": 0.04113444685935974, "15330": 0.004870930220931768, "15356": 0.07884006202220917, "15559": 0.1905880719423294, "15596": 0.401551216840744, "15602": 0.3134697377681732, "15741": 0.2409527748823166, "15760": 0.009718249551951885, "15849": 0.02792670577764511, "15855": 0.20580662786960602, "15865": 0.5415972471237183, "16014": 0.08692999184131622, "16507": 0.22937409579753876, "16535": 1.2267581224441528, "16605": 0.15610189735889435, "16635": 1.024303913116455, "16655": 0.0606246218085289, "16676": 0.016465263441205025, "16773": 0.18978065252304077, "16884": 0.1889725625514984, "16913": 0.0009760859538801014, "17003": 0.8550800085067749, "17077": 0.3106105625629425, "17158": 0.25845035910606384, "17319": 0.040196798741817474, "17351": 0.034552380442619324, "17566": 0.04767346754670143, "17631": 0.15943801403045654, "17846": 0.17759032547473907, "18130": 0.1358480453491211, "18559": 0.347847044467926, "18665": 0.012615402229130268, "18949": 0.37907835841178894, "19188": 0.06154331564903259, "19199": 0.1693800985813141, "19209": 0.08782484382390976, "19352": 0.07250232994556427, "19383": 0.574020504951477, "19454": 0.021256839856505394, "19527": 0.21530038118362427, "19653": 0.5127768516540527, "19933": 0.1685553640127182, "20063": 0.045809537172317505, "20192": 0.24018502235412598, "20540": 0.20580662786960602, "20592": 0.27934664487838745, "20652": 0.19782574474811554, "20871": 0.2652147710323334, "20930": 0.981317400932312, "22302": 0.6043586730957031, "22374": 0.04113444685935974, "22382": 0.34922540187835693, "22552": 0.05786345899105072, "22835": 0.2184450328350067, "22924": 0.10906458646059036, "23651": 0.6882523894309998, "23879": 0.3070250153541565, "24413": 0.012615402229130268, "24734": 0.3850763738155365, "25121": 0.014542185701429844, "25300": 1.160461664199829, "25817": 0.10203468054533005, "25870": 0.22782009840011597, "26245": 0.176772341132164, "26888": 0.11517547070980072, "27097": 0.3750596046447754, "27223": 0.11951763927936554, "27247": 0.43875885009765625, "27301": 0.22001366317272186, "27965": 0.09761575609445572, "28102": 0.07341018319129944, "28171": 0.23479416966438293, "28283": 0.7809720039367676, "28362": 0.2447827309370041, "29226": 0.2918238639831543, "29290": 0.11691460013389587, "29494": 0.09050461649894714} | 13882658 | The summer of 2003 was probably the hottest in Europe since at latest ad 1500, and unusually large numbers of heat-related deaths were reported in France, Germany and Italy. It is an ill-posed question whether the 2003 heatwave was caused, in a simple deterministic sense, by a modification of the external influences on climate—for example, increasing concentrations of greenhouse gases in the atmosphere—because almost any such weather event might have occurred by chance in an unmodified climate. However, it is possible to estimate by how much human activities may have increased the risk of the occurrence of such a heatwave. Here we use this conceptual framework to estimate the contribution of human-induced increases in atmospheric concentrations of greenhouse gases and other pollutants to the risk of the occurrence of unusually high mean summer temperatures throughout a large region of continental Europe. Using a threshold for mean summer temperature that was exceeded in 2003, but in no other year since the start of the instrumental record in 1851, we estimate it is very likely (confidence level >90%) that human influence has at least doubled the risk of a heatwave exceeding this threshold magnitude. | Human contribution to the European heatwave of 2003 |
{"1037": 0.030771657824516296, "2003": 0.31489628553390503, "2024": 0.10467668622732162, "2046": 0.14939609169960022, "2052": 0.11865071207284927, "2054": 0.5261374711990356, "2064": 0.05694137513637543, "2070": 0.11517547070980072, "2071": 0.20739519596099854, "2079": 0.40546512603759766, "2089": 0.3615458607673645, "2094": 0.18816383183002472, "2108": 0.08064348995685577, "2109": 0.12470348179340363, "2110": 0.38441169261932373, "2128": 0.11778303235769272, "2129": 0.03266380727291107, "2138": 0.07884006202220917, "2139": 0.2026219218969345, "2163": 0.2659635543823242, "2170": 0.14349138736724854, "2217": 0.48670899868011475, "2236": 0.28963330388069153, "2241": 0.10291612148284912, "2339": 0.42225050926208496, "2358": 0.13414156436920166, "2364": 0.020300358533859253, "2368": 0.09495500475168228, "2370": 0.08064348995685577, "2393": 0.3325583338737488, "2401": 0.4462870955467224, "2415": 0.33953672647476196, "2421": 0.058784693479537964, "2453": 0.043007105588912964, "2460": 0.20739519596099854, "2470": 0.2830325961112976, "2488": 0.037378571927547455, "2507": 0.2018241584300995, "2515": 0.3910386264324188, "2535": 0.12728634476661682, "2550": 0.07341018319129944, "2554": 0.2478361576795578, "2556": 0.4145384132862091, "2571": 0.3750596046447754, "2591": 0.7389566898345947, "2625": 0.1064341589808464, "2649": 0.11168810725212097, "2711": 0.07793712615966797, "2744": 0.4818955361843109, "2795": 0.32129061222076416, "2803": 0.4318077862262726, "2812": 0.33953672647476196, "2817": 0.07884006202220917, "2850": 0.2470736801624298, "2869": 0.026976587250828743, "2885": 0.052318159490823746, "2895": 0.7201237678527832, "2944": 0.6754127144813538, "2965": 0.11430477350950241, "2966": 0.12814582884311676, "2993": 0.44566190242767334, "3012": 0.32553088665008545, "3086": 0.46302130818367004, "3207": 0.8981585502624512, "3209": 0.554580807685852, "3258": 0.3241194784641266, "3303": 0.0317181795835495, "3347": 0.1905880719423294, "3350": 0.0606246218085289, "3372": 0.4412745535373688, "3399": 0.18329764902591705, "3408": 0.083342544734478, "3424": 1.0298984050750732, "3426": 0.3070250153541565, "3449": 0.16524957120418549, "3466": 0.7500885725021362, "3491": 0.21135559678077698, "3563": 0.18248429894447327, "3571": 0.32129061222076416, "3574": 0.11604541540145874, "3663": 0.2711893916130066, "3671": 0.2231435477733612, "3695": 0.08513788133859634, "3772": 0.18329764902591705, "3785": 0.1913948506116867, "3800": 0.043007105588912964, "3818": 0.04674193635582924, "3853": 0.056018441915512085, "3896": 0.8666408061981201, "3957": 0.12038381397724152, "3965": 0.25995752215385437, "4048": 0.5021947622299194, "4081": 0.32553088665008545, "4094": 0.4512746334075928, "4125": 0.35745587944984436, "4200": 0.6466736793518066, "4275": 0.44753631949424744, "4295": 0.6950984001159668, "4319": 1.1205062866210938, "4355": 0.32129061222076416, "4456": 0.5127768516540527, "4487": 0.15693697333335876, "4489": 0.0797421783208847, "4503": 0.2160874605178833, "4506": 0.3949938118457794, "4522": 0.012615402229130268, "4541": 0.24401791393756866, "4588": 0.21530038118362427, "4630": 0.9162907600402832, "4650": 0.13499516248703003, "4654": 0.10993985831737518, "4863": 0.5232481360435486, "4928": 0.08692999184131622, "4973": 0.05139094591140747, "5022": 0.46853771805763245, "5072": 0.4679262638092041, "5159": 0.23092569410800934, "5177": 0.4855078160762787, "5218": 0.5472630262374878, "5301": 0.03360854089260101, "5320": 0.3262358605861664, "5335": 0.22782009840011597, "5360": 0.12038381397724152, "5547": 0.3416208028793335, "5577": 0.13414156436920166, "5714": 0.4709797203540802, "5769": 0.20022670924663544, "5776": 0.44753631949424744, "5790": 0.2018241584300995, "5834": 0.16110190749168396, "5850": 1.117316484451294, "6011": 0.4093637466430664, "6074": 0.2576959431171417, "6083": 0.7629209756851196, "6123": 0.4794800877571106, "6149": 0.3416208028793335, "6155": 0.4673144817352295, "6179": 0.39762192964553833, "6210": 0.35060185194015503, "6235": 0.09584271162748337, "6245": 1.1211429834365845, "6370": 0.21214580535888672, "6455": 0.3777405619621277, "6459": 0.09228714555501938, "6483": 0.10379679501056671, "6517": 0.10026945173740387, "6523": 0.2561853528022766, "6525": 0.5278670787811279, "6544": 0.5584990978240967, "6592": 0.5860490798950195, "6633": 0.43434104323387146, "6666": 0.016465263441205025, "6678": 0.681853175163269, "6693": 0.5080875158309937, "6699": 0.4286321699619293, "6728": 0.1602703034877777, "6779": 0.49982786178588867, "6825": 0.6048921346664429, "6832": 0.7201237678527832, "6887": 0.5957841277122498, "6888": 0.9021284580230713, "6897": 0.846739649772644, "6911": 0.1734936386346817, "7068": 0.5540198087692261, "7126": 0.2516399025917053, "7137": 0.23092569410800934, "7242": 0.2969166338443756, "7251": 0.02887592278420925, "7327": 0.981317400932312, "7355": 0.014542185701429844, "7366": 0.4914994537830353, "7367": 0.7239188551902771, "7403": 0.11168810725212097, "7438": 0.018384648486971855, "7461": 0.5174443125724792, "7512": 0.35334911942481995, "7526": 0.11604541540145874, "7603": 0.319873183965683, "7607": 0.20818853378295898, "7620": 0.03925827145576477, "7644": 0.0029254043474793434, "7666": 0.5336109399795532, "7667": 0.20739519596099854, "7741": 0.05417001247406006, "7870": 0.23092569410800934, "7951": 0.026025565341114998, "8030": 0.48670899868011475, "8146": 0.2837681770324707, "8237": 0.7500885725021362, "8317": 0.5629584193229675, "8319": 0.2837681770324707, "8458": 0.8074519634246826, "8599": 0.11081436276435852, "8751": 0.6170841455459595, "8757": 0.037378571927547455, "8761": 0.25694093108177185, "8776": 0.06429435312747955, "8857": 0.9546096324920654, "8920": 0.19622190296649933, "8941": 0.0058422754518687725, "9031": 0.2501201331615448, "9048": 0.5947071313858032, "9104": 0.28670501708984375, "9113": 0.22001366317272186, "9239": 0.5893046259880066, "9375": 0.129004567861557, "9415": 0.09761575609445572, "9491": 0.2659635543823242, "9539": 0.4770587682723999, "9718": 0.034552380442619324, "9905": 0.6793810129165649, "9966": 0.37707099318504333, "9990": 0.004870930220931768, "9998": 0.18248429894447327, "10047": 0.11778303235769272, "10089": 0.4431571960449219, "10091": 0.1905880719423294, "10318": 0.5506471395492554, "10521": 0.030771657824516296, "10572": 0.4248080551624298, "10597": 0.08513788133859634, "10719": 0.7096124291419983, "10744": 0.27934664487838745, "10782": 0.1477125883102417, "10840": 0.15610189735889435, "10847": 0.0038986403960734606, "10976": 0.48068851232528687, "11031": 0.6441128253936768, "11069": 1.0285027027130127, "11213": 0.22392450273036957, "11265": 0.2659635543823242, "11325": 0.6471850275993347, "11390": 0.9531047344207764, "11493": 0.3883931338787079, "11507": 0.2018241584300995, "11514": 0.06795065850019455, "11643": 0.3877306580543518, "11791": 0.1229778528213501, "12070": 0.41065993905067444, "12269": 0.2105647772550583, "12285": 0.2478361576795578, "12452": 0.011650617234408855, "12748": 0.3141832649707794, "12893": 0.4337083101272583, "13004": 0.1710275560617447, "13143": 0.7710843086242676, "13181": 0.9209672808647156, "13331": 0.6000806093215942, "13339": 0.29400965571403503, "13371": 0.04487626627087593, "13449": 0.12384103983640671, "13494": 0.009718249551951885, "13531": 0.26146242022514343, "13691": 0.8796916007995605, "13701": 0.3374483287334442, "13749": 0.034552380442619324, "13859": 0.14939609169960022, "13946": 0.0038986403960734606, "13986": 0.8534175157546997, "14061": 0.0317181795835495, "14144": 0.48068851232528687, "14155": 0.16690383851528168, "14286": 0.37974658608436584, "14358": 0.3077431619167328, "14440": 0.28670501708984375, "14609": 0.3464667797088623, "14667": 0.8450632095336914, "14671": 0.5045560002326965, "14777": 0.6950984001159668, "14813": 0.1401015669107437, "14868": 0.5301685929298401, "15034": 0.17759032547473907, "15069": 0.8315495252609253, "15316": 0.0770333781838417, "15345": 0.3850763738155365, "15804": 0.3464667797088623, "15869": 0.5186077356338501, "15872": 0.0797421783208847, "15911": 0.5110208988189697, "16012": 0.8161250352859497, "16020": 0.06977381557226181, "16127": 0.1930064558982849, "16313": 0.6921701431274414, "16429": 0.7333439588546753, "16441": 1.0094679594039917, "16487": 0.09050461649894714, "16507": 0.01934296265244484, "16514": 0.21214580535888672, "16599": 0.2696990668773651, "17261": 0.18978065252304077, "17522": 0.39762192964553833, "17568": 0.4673144817352295, "17629": 0.31204116344451904, "17770": 0.06795065850019455, "17959": 0.23864774405956268, "17994": 0.1510767638683319, "18075": 0.5612884759902954, "18146": 0.5773153901100159, "18178": 0.5010119676589966, "18224": 0.9783848524093628, "18391": 0.5110208988189697, "18420": 0.8383291959762573, "18447": 0.1751343309879303, "18905": 0.8247235417366028, "19338": 0.03925827145576477, "19389": 0.7286425232887268, "19470": 0.49923527240753174, "19515": 0.6400018334388733, "19518": 0.3949938118457794, "19653": 0.6492279767990112, "19676": 0.40220460295677185, "19690": 0.09761575609445572, "19811": 0.20022670924663544, "19824": 0.05970508232712746, "19915": 0.021256839856505394, "19960": 0.48670899868011475, "20110": 1.241539478302002, "20166": 0.3248254358768463, "20207": 1.02149498462677, "20228": 0.37371641397476196, "20233": 0.4400174915790558, "20242": 0.10291612148284912, "20624": 0.07884006202220917, "20640": 0.3683255612850189, "20680": 0.755608320236206, "20714": 0.736154317855835, "20738": 0.14179791510105133, "20746": 0.5381823778152466, "20858": 0.472198486328125, "20896": 0.33605360984802246, "20906": 0.10731173306703568, "20915": 0.13925230503082275, "20992": 0.6296497583389282, "21252": 0.07159364968538284, "21685": 0.0317181795835495, "21970": 0.5729197263717651, "22461": 0.052318159490823746, "22597": 0.5816917419433594, "22851": 0.10026945173740387, "22930": 0.1685553640127182, "23130": 0.0058422754518687725, "23216": 0.02887592278420925, "23364": 0.2852376699447632, "23683": 0.4311734735965729, "23691": 0.2317005842924118, "24054": 0.0317181795835495, "24128": 0.255429208278656, "24305": 0.0058422754518687725, "24330": 1.034073829650879, "24436": 0.6989894509315491, "24479": 0.6048921346664429, "24491": 0.7276995778083801, "24710": 0.045809537172317505, "24759": 0.4196864068508148, "24797": 0.11778303235769272, "24846": 0.10555581003427505, "24906": 0.15610189735889435, "24920": 0.2689530849456787, "25194": 0.1685553640127182, "25323": 0.06612417846918106, "25344": 0.36086538434028625, "25353": 0.39367714524269104, "25428": 0.018384648486971855, "25519": 0.37035053968429565, "25613": 0.7028654217720032, "25920": 0.7987030148506165, "25940": 0.09317722171545029, "26452": 0.29981520771980286, "26591": 0.4002431631088257, "26657": 0.574020504951477, "27144": 0.567397952079773, "27290": 0.3163207769393921, "27295": 0.2447827309370041, "27343": 0.09672962874174118, "27351": 0.7500885725021362, "27484": 0.7115318179130554, "27542": 0.4248080551624298, "27718": 0.22157983481884003, "27756": 0.7845434546470642, "27824": 0.21214580535888672, "28297": 0.22157983481884003, "28667": 0.4487839937210083, "28828": 0.5174443125724792, "29171": 0.07884006202220917, "29180": 0.0842406153678894, "29290": 0.27712854743003845, "29486": 0.469759464263916} | 13883546 | The term antidepressant refers to a drug that helps to rectify specific biological abnormalities that give rise to the symptoms of depression. This exemplifies what we have called the “disease-centred” model of psychotropic drug action [ 1]. Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms. In contrast, we propose in this Essay that an alternative “drug-centred” model can better explain observed drug effects in psychiatric conditions. This drug-centred model suggests that instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms ( Table 1). Alcohol's disinhibiting effects may relieve symptoms of social phobia, but that does not imply that alcohol corrects a chemical imbalance underlying social phobia. Sedation may lessen high arousal, present in many acute psychiatric situations. Drugs that induce indifference, such as neuroleptics or opiates, may help reduce the distress of acute psychotic symptoms. Low-dose stimulants may help improve attention and concentration in the short term. Table 1 Main Assumptions of Two Models of Psychotropic Drug Action The disease-centred model in psychiatry leads researchers to infer antidepressant effects from patients' scores on symptom rating scales presumed to assess the manifestations of the disease. The drug-centred model, on the other hand, suggests that physiological and subjective effects of drugs should be examined in their own right. These effects include various forms of sedation, stimulation, and a plethora of biopsychological states. Depending on individual inclination and context (including a person's emotional state upon drug ingestion), intoxication with some drugs produces euphoria or mood elevation. Because tolerance develops, however, euphoriant effects do not persist with long-term use. If antidepressants or any other psychotropic drugs could be shown to have mood-elevating effects that were long-term and not diminished by being in a depressed emotional state, this would distinguish them from psychotropic drugs that cause euphoria and might prove uniquely useful in depressed patients (see Sidebar). | Do Antidepressants Cure or Create Abnormal Brain States? |
{"1011": 0.1710275560617447, "1041": 0.272677481174469, "1042": 0.7445381283760071, "1043": 0.011650617234408855, "1056": 0.9052929878234863, "1155": 0.5278670787811279, "1156": 0.6553317308425903, "1996": 0.03925827145576477, "2007": 0.03831886500120163, "2011": 0.45870962738990784, "2012": 0.2969166338443756, "2026": 0.5844172835350037, "2029": 0.10993985831737518, "2046": 0.29400965571403503, "2050": 0.2749055027961731, "2052": 0.13157635927200317, "2064": 0.2105647772550583, "2071": 0.5778634548187256, "2073": 0.05417001247406006, "2076": 0.07250232994556427, "2079": 0.12470348179340363, "2098": 0.5784112811088562, "2110": 0.07612881064414978, "2170": 0.30917787551879883, "2179": 0.23402166366577148, "2207": 0.0797421783208847, "2290": 0.2447827309370041, "2310": 0.7258110046386719, "2339": 0.015504186972975731, "2350": 0.4400174915790558, "2358": 0.5723689198493958, "2378": 0.5590575933456421, "2389": 0.4425300657749176, "2397": 0.7482418417930603, "2453": 0.04113444685935974, "2470": 0.09850110858678818, "2475": 0.6160298585891724, "2515": 0.2990913391113281, "2523": 0.3824150264263153, "2535": 0.7009293437004089, "2537": 0.5849615335464478, "2550": 0.7426811456680298, "2552": 0.9776504039764404, "2571": 0.27712854743003845, "2590": 0.29109421372413635, "2592": 0.4450363218784332, "2714": 0.4337083101272583, "2718": 0.6064908504486084, "2799": 0.5151132941246033, "2817": 0.3170322775840759, "2825": 0.22859740257263184, "2832": 0.11951763927936554, "2865": 0.06886265426874161, "2913": 0.2516399025917053, "2920": 0.24631060659885406, "3037": 0.22079704701900482, "3081": 0.0354953333735466, "3217": 0.5756692886352539, "3251": 0.18329764902591705, "3273": 0.1685553640127182, "3278": 0.6301699280738831, "3302": 0.5573811531066895, "3351": 0.1011524572968483, "3367": 0.4709797203540802, "3372": 0.4518963396549225, "3375": 0.5092619061470032, "3378": 0.34023189544677734, "3406": 0.40611594915390015, "3426": 0.21372433006763458, "3431": 0.2034190446138382, "3433": 1.005902886390686, "3445": 0.2637155055999756, "3452": 0.20739519596099854, "3466": 0.21372433006763458, "3491": 0.17267228662967682, "3526": 0.8433839678764343, "3595": 0.8957691192626953, "3603": 0.18978065252304077, "3623": 0.1401015669107437, "3625": 0.16690383851528168, "3652": 0.27044451236724854, "3670": 0.8893690705299377, "3671": 0.4132472574710846, "3775": 0.5376120805740356, "3853": 0.22937409579753876, "3893": 0.10291612148284912, "3896": 0.06977381557226181, "3929": 0.27564704418182373, "3930": 0.11865071207284927, "3965": 0.47584590315818787, "4013": 0.2539152204990387, "4022": 0.08064348995685577, "4072": 0.040196798741817474, "4125": 0.016465263441205025, "4146": 0.0029254043474793434, "4168": 0.684319257736206, "4215": 0.680370569229126, "4242": 0.6435998678207397, "4244": 0.5562619566917419, "4254": 0.037378571927547455, "4287": 0.12038381397724152, "4295": 0.28670501708984375, "4310": 0.5898461937904358, "4395": 0.6228629946708679, "4442": 0.9005423784255981, "4453": 0.2674594223499298, "4456": 1.3300546407699585, "4490": 0.3554046154022217, "4493": 0.1332872211933136, "4588": 0.48008447885513306, "4604": 0.03831886500120163, "4649": 0.05786345899105072, "4651": 0.034552380442619324, "4654": 1.299638032913208, "4668": 0.35060185194015503, "4671": 0.045809537172317505, "4719": 0.3464667797088623, "4742": 0.5347557663917542, "4806": 0.8925741910934448, "4807": 1.117955207824707, "4812": 0.02316705882549286, "4962": 0.31132611632347107, "4972": 0.04953393340110779, "5155": 0.1718502640724182, "5173": 0.6911921501159668, "5228": 0.7086513638496399, "5250": 0.10291612148284912, "5320": 0.05046287178993225, "5333": 0.06337817758321762, "5359": 0.45499902963638306, "5387": 0.2837681770324707, "5450": 0.37640097737312317, "5456": 0.0038986403960734606, "5603": 0.1619328260421753, "5744": 1.1512393951416016, "5838": 0.11256109178066254, "5847": 0.4788752794265747, "5867": 0.02887592278420925, "5886": 0.8004589080810547, "6022": 0.20818853378295898, "6061": 0.022212404757738113, "6162": 0.16690383851528168, "6357": 0.9754437208175659, "6388": 0.10291612148284912, "6528": 0.8941729068756104, "6529": 0.018384648486971855, "6541": 0.4574742913246155, "6650": 0.5098485946655273, "6678": 0.7610978484153748, "6726": 0.5685047507286072, "6740": 0.7408206462860107, "6761": 0.04207121208310127, "6792": 0.1212492436170578, "6869": 0.5849615335464478, "6959": 0.6941232681274414, "6970": 0.1011524572968483, "7013": 0.2089812457561493, "7137": 0.3750596046447754, "7327": 0.34370049834251404, "7337": 0.7105726003646851, "7366": 0.20102575421333313, "7461": 0.11081436276435852, "7551": 0.052318159490823746, "7591": 0.020300358533859253, "7645": 0.3027053773403168, "7696": 0.014542185701429844, "7711": 0.03360854089260101, "7755": 0.45623743534088135, "7784": 0.1946154683828354, "7790": 0.5016035437583923, "7816": 0.043007105588912964, "7834": 0.7951818704605103, "7870": 0.20660123229026794, "7883": 0.14264501631259918, "7885": 0.1677299439907074, "8116": 0.19862671196460724, "8153": 0.34508460760116577, "8171": 0.03360854089260101, "8200": 0.4709797203540802, "8247": 0.6833335757255554, "8281": 0.029824240133166313, "8290": 0.22937409579753876, "8319": 0.6482070088386536, "8335": 0.41195443272590637, "8360": 0.6634125709533691, "8449": 0.0317181795835495, "8462": 0.021256839856505394, "8556": 0.004870930220931768, "8710": 0.8057082891464233, "8733": 0.7755908370018005, "8803": 0.018384648486971855, "8878": 0.12728634476661682, "8885": 0.02792670577764511, "8907": 0.8400169610977173, "8920": 0.2976420819759369, "8924": 0.14264501631259918, "9007": 0.306306391954422, "9099": 0.3850763738155365, "9153": 0.07884006202220917, "9165": 0.10026945173740387, "9253": 0.35403475165367126, "9280": 0.13414156436920166, "9336": 0.6921701431274414, "9413": 0.029824240133166313, "9495": 1.0116009712219238, "9597": 0.2954642176628113, "9626": 0.053244512528181076, "9686": 0.00875066313892603, "9699": 0.007782140281051397, "9972": 0.2719337046146393, "10194": 0.36697331070899963, "10210": 0.0029254043474793434, "10253": 0.11778303235769272, "10266": 0.36086538434028625, "10318": 0.6332852244377136, "10509": 0.31489628553390503, "10572": 0.17267228662967682, "10595": 0.6911921501159668, "10639": 0.9302552938461304, "10744": 0.3262358605861664, "10769": 0.13499516248703003, "10847": 0.28963330388069153, "10882": 0.8091925978660583, "10956": 0.040196798741817474, "10960": 0.7960633039474487, "11005": 0.4831010699272156, "11228": 0.1930064558982849, "11253": 0.8366385698318481, "11423": 0.4132472574710846, "11475": 0.36358460783958435, "11628": 0.10993985831737518, "11644": 0.21135559678077698, "11659": 0.10906458646059036, "11835": 0.13670019805431366, "11860": 0.6989894509315491, "11981": 0.32199856638908386, "12005": 0.6254787445068359, "12061": 0.27342069149017334, "12222": 0.00875066313892603, "12322": 0.7258110046386719, "12328": 0.129004567861557, "12540": 0.40741631388664246, "12562": 0.6764062643051147, "12618": 1.0601204633712769, "12732": 0.3127557039260864, "12771": 0.04767346754670143, "12837": 0.57457035779953, "13024": 0.6669275164604187, "13330": 0.8091925978660583, "13331": 0.2561853528022766, "13472": 0.004870930220931768, "13494": 0.7791815400123596, "13521": 0.18329764902591705, "13656": 0.7665573358535767, "13791": 0.2983669638633728, "13833": 0.304147332906723, "13871": 0.016465263441205025, "13977": 0.15359249711036682, "14031": 0.2018241584300995, "14120": 0.6588751673698425, "14193": 0.04953393340110779, "14357": 0.5347557663917542, "14402": 0.02792670577764511, "14505": 0.5186077356338501, "14511": 0.12814582884311676, "14774": 0.524982750415802, "14828": 0.9805850982666016, "14905": 0.3409265875816345, "15024": 0.25239890813827515, "15027": 0.16359257698059082, "15370": 0.0038986403960734606, "15420": 0.11256109178066254, "15488": 0.5197699069976807, "15680": 0.6202403903007507, "16007": 0.4311734735965729, "16021": 0.755608320236206, "16412": 0.2105647772550583, "16453": 0.9598589539527893, "16636": 0.1930064558982849, "16677": 0.129004567861557, "16706": 0.5209306478500366, "16882": 0.09584271162748337, "16910": 0.21214580535888672, "16961": 0.7105726003646851, "17379": 0.10555581003427505, "17441": 0.11081436276435852, "17847": 0.052318159490823746, "18053": 0.09050461649894714, "18058": 0.17759032547473907, "18166": 0.35128939151763916, "18178": 0.3554046154022217, "18195": 0.12728634476661682, "18547": 0.034552380442619324, "18700": 0.08154398202896118, "18714": 0.23633737862110138, "18715": 0.02412080205976963, "18804": 0.07612881064414978, "18903": 0.021256839856505394, "19137": 1.3274686336517334, "19220": 0.07431721687316895, "19293": 0.0019512200960889459, "19570": 1.1524739265441895, "19601": 0.3897167444229126, "19653": 0.4041621685028076, "19818": 0.8917738795280457, "19824": 0.5381823778152466, "19872": 1.034073829650879, "20155": 0.28597161173820496, "20350": 0.21687394380569458, "20360": 0.34370049834251404, "20504": 0.7942996621131897, "20544": 0.1685553640127182, "20582": 1.2330384254455566, "20598": 0.40220460295677185, "20679": 0.04487626627087593, "20752": 0.18978065252304077, "20888": 0.5162794589996338, "21032": 0.4926934838294983, "21081": 0.5483922958374023, "21434": 0.6296497583389282, "21471": 0.18167030811309814, "21618": 0.07068414986133575, "21670": 0.0797421783208847, "21716": 1.060796856880188, "21903": 0.26146242022514343, "21919": 0.6332852244377136, "22330": 0.175953671336174, "22869": 0.5284429788589478, "22930": 0.11430477350950241, "23041": 0.42926809191703796, "23150": 0.20739519596099854, "23216": 0.28670501708984375, "23586": 0.40220460295677185, "23736": 0.04953393340110779, "23746": 0.03831886500120163, "23820": 0.47827014327049255, "23833": 0.04394211992621422, "23900": 0.03925827145576477, "24054": 0.4041621685028076, "24133": 0.1485546976327896, "24162": 0.07884006202220917, "24209": 0.26146242022514343, "24345": 0.8004589080810547, "24374": 0.5215105414390564, "24529": 0.03360854089260101, "24587": 0.1332872211933136, "24759": 0.05046287178993225, "24848": 0.0029254043474793434, "24873": 0.05694137513637543, "25100": 0.03831886500120163, "25194": 0.12814582884311676, "25323": 0.40285754203796387, "25409": 0.9394577741622925, "25456": 0.09938567131757736, "25468": 0.1677299439907074, "25643": 0.9583619832992554, "25708": 1.3233171701431274, "25714": 0.08244366943836212, "25778": 0.08692999184131622, "25808": 0.09228714555501938, "26243": 0.7276995778083801, "26288": 0.23864774405956268, "26402": 0.7647408246994019, "26642": 0.2470736801624298, "26651": 0.3346569836139679, "26773": 0.022212404757738113, "26874": 0.08871890604496002, "27045": 0.12384103983640671, "27099": 0.7537717819213867, "27144": 0.3381449282169342, "27453": 0.47827014327049255, "27642": 0.7755908370018005, "27792": 0.09850110858678818, "27854": 0.17840765416622162, "27881": 0.319873183965683, "27895": 0.05786345899105072, "28086": 0.0770333781838417, "28522": 1.0775588750839233, "28593": 0.7370892763137817, "28696": 0.058784693479537964, "28938": 0.1384023278951645, "29170": 0.42096930742263794, "29290": 0.13071982562541962, "29720": 0.2317005842924118} | 13889430 | There is a growing interest in the cell-cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated α-smooth muscle actin expression and other changes consistent with the process of fibroblast differentiation into myofibroblasts. We show that TGF-β is expressed at the exosome surface in association with the transmembrane proteoglycan betaglycan. Although existing in a latent state, this complex was fully functional in eliciting SMAD-dependent signaling. Inhibiting either signaling or betaglycan expression attenuated differentiation. While the kinetics and overall magnitude of the response were similar to that achieved with soluble TGF-β, we identified important qualitative differences unique to the exosomal route of TGF-β delivery, as exemplified by a significant elevation in fibroblast FGF2 production. This hitherto unknown trigger for instigating cellular differentiation in a distinctive manner has major implications for mechanisms underlying cancer-recruited stroma, fibrotic diseases, and wound-healing responses. | Cancer exosomes trigger fibroblast to myofibroblast differentiation. |
{"1011": 0.06886265426874161, "1019": 0.8925741910934448, "1039": 0.5255602598190308, "1045": 0.49864232540130615, "1049": 0.4151833653450012, "1056": 0.3034266233444214, "1060": 0.5968599319458008, "1999": 0.1808556467294693, "2003": 0.22157983481884003, "2020": 0.018384648486971855, "2026": 1.0641717910766602, "2033": 0.22782009840011597, "2042": 0.16442140936851501, "2043": 0.0058422754518687725, "2044": 0.1011524572968483, "2051": 0.255429208278656, "2102": 0.8281423449516296, "2116": 0.2830325961112976, "2140": 0.3750596046447754, "2146": 0.5010119676589966, "2166": 0.151916041970253, "2179": 0.417115718126297, "2184": 0.3622259199619293, "2186": 0.5952457785606384, "2220": 0.4228905141353607, "2235": 0.14602625370025635, "2240": 0.8383291959762573, "2261": 0.1889725625514984, "2274": 0.817850649356842, "2278": 0.0606246218085289, "2309": 0.319873183965683, "2331": 0.3877306580543518, "2358": 0.20421554148197174, "2389": 0.1946154683828354, "2420": 0.03360854089260101, "2458": 0.5092619061470032, "2470": 0.23556606471538544, "2475": 0.7047978043556213, "2497": 0.3588210940361023, "2506": 0.11168810725212097, "2509": 0.5324648022651672, "2511": 0.37974658608436584, "2581": 0.27712854743003845, "2629": 0.47766464948654175, "2649": 0.16276304423809052, "2695": 0.49864232540130615, "2702": 0.19381128251552582, "2706": 0.09938567131757736, "2720": 0.3676496744155884, "2754": 0.1685553640127182, "2764": 0.2561853528022766, "2771": 0.02316705882549286, "2777": 0.034552380442619324, "2817": 0.6075552701950073, "2828": 0.22937409579753876, "2839": 0.04860413447022438, "2863": 0.9310253858566284, "2913": 0.4831010699272156, "2944": 0.2689530849456787, "3067": 0.18978065252304077, "3085": 0.8022117614746094, "3134": 0.29981520771980286, "3144": 0.10467668622732162, "3155": 0.21687394380569458, "3156": 0.35950297117233276, "3210": 0.6497380137443542, "3215": 0.4938860833644867, "3226": 0.9754437208175659, "3273": 0.38041436672210693, "3313": 0.18978065252304077, "3372": 0.39367714524269104, "3393": 0.0354953333735466, "3406": 0.010684899985790253, "3408": 0.040196798741817474, "3435": 0.0038986403960734606, "3446": 0.401551216840744, "3468": 0.2145126610994339, "3526": 0.9005423784255981, "3560": 0.40546512603759766, "3587": 0.650757372379303, "3652": 0.2184450328350067, "3670": 0.5318912267684937, "3674": 1.2953691482543945, "3811": 0.6729245185852051, "3930": 0.7124901413917542, "3938": 0.6902132034301758, "3943": 0.7546905279159546, "3979": 0.10731173306703568, "3989": 0.09228714555501938, "4029": 0.5551415085792542, "4090": 0.14433705806732178, "4098": 0.29036402702331543, "4111": 0.5104349255561829, "4127": 0.2247048318386078, "4176": 0.5784112811088562, "4179": 0.1693800985813141, "4195": 0.24325250089168549, "4245": 0.05694137513637543, "4266": 0.004870930220931768, "4340": 0.25694093108177185, "4403": 0.0038986403960734606, "4442": 1.060796856880188, "4453": 0.4709797203540802, "4456": 1.0087559223175049, "4503": 0.32129061222076416, "4555": 0.6249561905860901, "4642": 0.06246116757392883, "4649": 0.3283478021621704, "4651": 0.15275461971759796, "4671": 0.26446542143821716, "4719": 0.17267228662967682, "4800": 0.7647408246994019, "4833": 0.57457035779953, "4961": 0.0913962796330452, "4962": 0.07068414986133575, "4975": 0.255429208278656, "4982": 0.5021947622299194, "5069": 0.4568560719490051, "5084": 0.27044451236724854, "5228": 0.20421554148197174, "5244": 0.16276304423809052, "5250": 0.25845035910606384, "5302": 0.04953393340110779, "5323": 0.1970241367816925, "5377": 0.1808556467294693, "5401": 0.3034266233444214, "5577": 0.05970508232712746, "5646": 0.17759032547473907, "5700": 0.22937409579753876, "5709": 0.2184450328350067, "5711": 0.01934296265244484, "5719": 0.129004567861557, "5796": 0.9546096324920654, "5923": 0.6410312056541443, "5944": 0.058784693479537964, "6019": 0.66441810131073, "6131": 0.7314660549163818, "6162": 0.13670019805431366, "6165": 0.1946154683828354, "6212": 0.11604541540145874, "6388": 0.06337817758321762, "6459": 0.006812678650021553, "6460": 0.3622259199619293, "6640": 0.0913962796330452, "6648": 0.5601736903190613, "6709": 0.011650617234408855, "6721": 0.23324857652187347, "6741": 0.5607312321662903, "6761": 0.23710809648036957, "6914": 0.777387797832489, "7012": 0.1946154683828354, "7017": 0.15442965924739838, "7065": 0.04767346754670143, "7142": 0.8625272512435913, "7242": 0.3409265875816345, "7245": 0.3353555500507355, "7356": 0.30558720231056213, "7368": 0.3019835948944092, "7371": 0.25694093108177185, "7382": 0.18654440343379974, "7411": 0.0019512200960889459, "7416": 0.7683706283569336, "7502": 0.3241194784641266, "7551": 0.03925827145576477, "7591": 0.6980181336402893, "7642": 0.07884006202220917, "7712": 0.2918238639831543, "7790": 0.757441520690918, "7885": 0.23324857652187347, "8000": 1.013020396232605, "8010": 0.10203468054533005, "8029": 0.04953393340110779, "8153": 0.6553317308425903, "8159": 0.4855078160762787, "8335": 0.10203468054533005, "8361": 0.0019512200960889459, "8469": 0.3241194784641266, "8523": 0.8323994874954224, "8578": 0.7629209756851196, "8754": 0.32553088665008545, "8898": 0.4267219603061676, "8902": 0.1358480453491211, "9014": 0.5092619061470032, "9253": 0.4126010537147522, "9324": 0.4938860833644867, "9335": 0.5174443125724792, "9350": 0.5139457583427429, "9355": 0.0842406153678894, "9367": 0.2026219218969345, "9513": 1.02149498462677, "9587": 0.1889725625514984, "9589": 1.0668635368347168, "9626": 0.567951500415802, "9677": 0.013579257763922215, "9869": 0.4512746334075928, "9998": 0.19220098853111267, "10085": 0.6338034868240356, "10375": 0.1384023278951645, "10556": 0.9178520441055298, "10572": 0.5568217039108276, "10610": 0.10203468054533005, "10722": 0.4286321699619293, "10788": 0.5767669677734375, "10843": 0.4831010699272156, "10924": 0.37974658608436584, "11047": 0.19541899859905243, "11156": 0.3949938118457794, "11231": 0.1619328260421753, "11263": 0.02412080205976963, "11338": 0.3077431619167328, "11432": 0.5438674688339233, "11467": 0.6862877607345581, "11475": 0.5415972471237183, "11487": 0.34370049834251404, "11498": 0.9348671436309814, "11791": 0.07250232994556427, "11853": 0.6538092494010925, "12123": 0.009718249551951885, "12192": 0.2689530849456787, "12228": 0.015504186972975731, "12256": 0.09761575609445572, "12326": 0.040196798741817474, "12328": 1.2358801364898682, "12395": 0.14095009863376617, "12530": 0.11256109178066254, "12906": 0.6348392367362976, "13004": 0.3084607720375061, "13070": 0.18167030811309814, "13088": 1.1744394302368164, "13164": 0.3897167444229126, "13368": 0.5376120805740356, "13369": 0.13670019805431366, "13595": 0.004870930220931768, "13656": 0.9225212931632996, "13717": 0.04113444685935974, "13871": 0.7028654217720032, "13908": 0.14602625370025635, "14095": 0.5033760666847229, "14128": 0.0354953333735466, "14142": 0.09850110858678818, "14163": 0.8957691192626953, "14399": 0.7163142561912537, "14408": 0.016465263441205025, "14561": 0.23402166366577148, "14639": 0.8550800085067749, "15527": 0.1905880719423294, "15946": 0.20739519596099854, "16001": 0.05694137513637543, "16007": 0.47827014327049255, "16026": 0.09495500475168228, "16221": 0.5057345628738403, "16453": 0.06154331564903259, "16463": 0.09317722171545029, "16483": 0.3141832649707794, "16505": 0.14686977863311768, "16558": 1.0382318496704102, "16670": 0.23247487843036652, "16703": 0.1994270235300064, "16706": 0.02316705882549286, "16913": 0.7314660549163818, "17261": 0.42608439922332764, "17404": 0.030771657824516296, "17598": 0.33605360984802246, "17630": 0.8731874823570251, "17707": 0.684319257736206, "17710": 0.0354953333735466, "17815": 0.055094651877880096, "18154": 0.2160874605178833, "18178": 0.1510767638683319, "18349": 1.4487555027008057, "18595": 0.052318159490823746, "18653": 0.45251765847206116, "18845": 0.021256839856505394, "19317": 0.06977381557226181, "19383": 0.688742995262146, "19476": 0.8143964409828186, "19481": 0.0317181795835495, "19653": 0.7105726003646851, "19734": 0.06246116757392883, "19761": 0.41195443272590637, "19842": 0.4831010699272156, "19875": 0.4450363218784332, "19962": 0.9147270321846008, "20250": 0.15693697333335876, "20350": 0.21687394380569458, "20360": 0.8074519634246826, "20389": 0.0317181795835495, "20504": 0.981317400932312, "20582": 0.04113444685935974, "20806": 0.13157635927200317, "21009": 0.04674193635582924, "21150": 0.05694137513637543, "21211": 0.010684899985790253, "21230": 0.11343330889940262, "21246": 0.06795065850019455, "21376": 0.06154331564903259, "21434": 0.7809720039367676, "21486": 0.38374659419059753, "21572": 0.6249561905860901, "21716": 0.803087055683136, "21926": 0.07612881064414978, "22022": 0.5723689198493958, "22025": 0.026976587250828743, "22160": 0.3346569836139679, "22275": 0.20022670924663544, "22291": 1.036847710609436, "22330": 0.5080875158309937, "22348": 0.7333439588546753, "22394": 1.458796739578247, "22520": 0.004870930220931768, "22578": 0.3897167444229126, "22694": 0.01934296265244484, "22907": 0.535327672958374, "23191": 0.2800849378108978, "23732": 0.07250232994556427, "23737": 0.06429435312747955, "23924": 0.06246116757392883, "24012": 0.43875885009765625, "24098": 0.35060185194015503, "24188": 0.09761575609445572, "24269": 0.4818955361843109, "24759": 0.4654768109321594, "24960": 0.9052929878234863, "25276": 0.7370892763137817, "25409": 0.43244171142578125, "25468": 0.6823468804359436, "25714": 1.0887986421585083, "25971": 0.058784693479537964, "26287": 0.8989537954330444, "26305": 0.06429435312747955, "26419": 0.2447827309370041, "26462": 0.07793712615966797, "26524": 0.14179791510105133, "26721": 0.6296497583389282, "27144": 0.083342544734478, "27159": 0.26296505331993103, "27491": 0.9929623603820801, "27528": 0.1485546976327896, "27814": 0.0174254160374403, "28024": 0.06703783571720123, "28086": 0.33953672647476196, "28156": 0.46363574266433716, "28311": 1.013020396232605, "28418": 1.1369311809539795, "28424": 0.06703783571720123, "28775": 0.5495203733444214, "28788": 0.09938567131757736, "29109": 0.020300358533859253, "29160": 0.14939609169960022, "29206": 0.9470623731613159, "29215": 0.12642613053321838, "29235": 0.3723714053630829, "29290": 0.77198725938797} | 13889962 | The 5T33 multiple myeloma is one of a series of transplantable murine myelomas arising spontaneously in C57BL/KaLwRij mice. This study describes the establishment and characterisation of the 5T33 murine myeloma in vitro as a cultured cell line in terms of its morphology, growth rate, expression of paraprotein (IgG2b) and tumorigenicity in syngeneic animals. The 5T33 cell line has been in continuous culture for over 10 months and has achieved more than passage 34. In culture, 5T33 myeloma grows as single cells or in small clusters of loosely adherent cells on an adherent stromal cell layer. Maximum doubling time is approximately 25 h, and over 90% of the cells express cytoplasmic IgG2b paraprotein. The cultured 5T33 myeloma cells are highly tumorigenic in C57BL/KaLwRij mice with as few as 500 cells inducing paralysis and death as early as day 36 post-tumour inoculation. Kinetics of tumour development and detection of IgG2b paraprotein are dose dependent. Two weeks following intravenous inoculation of 5 x 10(5) cultured 5T33 myeloma cells, tumour cells were readily identified in the bone marrow. By 3 weeks post-tumour inoculation, 5T33 myeloma cells were found in various tissues throughout the animal. Studies are now underway to determine the sensitivity of this cell line to various therapeutic modalities. | A model of multiple myeloma: culture of 5T33 murine myeloma cells and evaluation of tumorigenicity in the C57BL/KaLwRij mouse. |
{"1003": 0.17267228662967682, "1018": 0.02316705882549286, "1021": 0.20421554148197174, "1022": 0.22704219818115234, "1061": 0.7510106563568115, "1085": 0.44753631949424744, "1997": 0.21765978634357452, "2039": 0.07884006202220917, "2042": 0.04113444685935974, "2044": 0.3241194784641266, "2045": 0.11691460013389587, "2047": 0.5729197263717651, "2052": 0.28963330388069153, "2053": 0.06612417846918106, "2058": 0.2719337046146393, "2062": 0.31132611632347107, "2064": 0.20660123229026794, "2071": 0.3995884954929352, "2084": 0.0354953333735466, "2085": 0.1212492436170578, "2086": 0.4512746334075928, "2090": 0.034552380442619324, "2095": 0.1358480453491211, "2106": 0.14433705806732178, "2109": 0.07612881064414978, "2111": 0.23402166366577148, "2116": 0.07431721687316895, "2129": 0.10291612148284912, "2140": 0.37035053968429565, "2146": 0.3127557039260864, "2148": 0.5849615335464478, "2152": 0.09495500475168228, "2172": 0.14518201351165771, "2176": 0.0019512200960889459, "2193": 0.40089741349220276, "2229": 0.26146242022514343, "2241": 0.037378571927547455, "2260": 0.27712854743003845, "2263": 0.10026945173740387, "2275": 0.13157635927200317, "2279": 0.1221139207482338, "2289": 0.014542185701429844, "2313": 0.7881022095680237, "2324": 0.055094651877880096, "2339": 0.37102460861206055, "2358": 0.3903779089450836, "2367": 0.4374985992908478, "2396": 1.202409029006958, "2408": 0.8813109993934631, "2421": 0.00875066313892603, "2443": 0.016465263441205025, "2460": 0.7389566898345947, "2470": 0.49030399322509766, "2478": 0.3084607720375061, "2504": 0.43623676896095276, "2527": 0.05417001247406006, "2549": 0.8973627090454102, "2565": 0.36900100111961365, "2566": 0.5139457583427429, "2585": 0.04953393340110779, "2607": 0.4311734735965729, "2615": 0.20501139760017395, "2622": 0.0019512200960889459, "2691": 0.2470736801624298, "2698": 0.0038986403960734606, "2707": 0.1485546976327896, "2711": 0.11604541540145874, "2744": 0.7408206462860107, "2747": 0.27712854743003845, "2765": 0.469759464263916, "2779": 0.45932671427726746, "2783": 0.6608943343162537, "2802": 0.0752234235405922, "2815": 0.05970508232712746, "2817": 0.755608320236206, "2825": 0.16690383851528168, "2840": 0.7537717819213867, "2846": 0.24859806895256042, "2894": 0.3777405619621277, "2896": 0.3141832649707794, "2913": 0.5871354341506958, "2933": 0.09317722171545029, "2936": 0.006812678650021553, "2944": 1.1005635261535645, "2951": 0.3318578004837036, "2981": 0.7898768186569214, "2988": 0.48430517315864563, "3032": 0.05046287178993225, "3060": 0.848413348197937, "3063": 0.08692999184131622, "3088": 1.057410478591919, "3107": 0.1913948506116867, "3112": 0.21135559678077698, "3115": 0.5816917419433594, "3160": 0.5336109399795532, "3189": 0.4145384132862091, "3202": 0.19862671196460724, "3225": 0.02887592278420925, "3229": 0.8869584798812866, "3247": 0.10203468054533005, "3252": 0.7267557382583618, "3273": 0.42353010177612305, "3278": 0.16524957120418549, "3305": 0.07884006202220917, "3333": 0.08603433519601822, "3375": 0.3662964701652527, "3399": 0.3443928062915802, "3424": 0.7809720039367676, "3446": 0.24018502235412598, "3454": 0.2749055027961731, "3463": 0.7463917136192322, "3464": 0.10467668622732162, "3466": 0.40806588530540466, "3486": 0.24248650670051575, "3517": 0.14939609169960022, "3526": 0.06612417846918106, "3528": 0.05694137513637543, "3530": 0.23710809648036957, "3550": 0.5450005531311035, "3572": 0.03831886500120163, "3590": 0.46486347913742065, "3616": 0.004870930220931768, "3621": 0.3676496744155884, "3633": 0.2576959431171417, "3659": 0.02792670577764511, "3668": 0.2852376699447632, "3676": 0.05694137513637543, "3697": 0.45870962738990784, "3729": 0.6543170213699341, "3747": 0.12038381397724152, "3770": 0.47402387857437134, "3798": 0.5640701055526733, "3815": 0.3615458607673645, "3818": 0.09850110858678818, "3820": 0.7500885725021362, "3867": 0.31132611632347107, "3891": 0.2447827309370041, "3896": 0.33953672647476196, "3949": 0.7436100244522095, "3961": 0.23402166366577148, "3980": 0.48430517315864563, "3989": 0.6301699280738831, "4022": 0.7201237678527832, "4045": 0.1332872211933136, "4081": 0.20022670924663544, "4094": 0.9591107368469238, "4102": 0.5528968572616577, "4106": 0.5238267183303833, "4118": 0.4002431631088257, "4119": 0.3077431619167328, "4146": 0.06520967930555344, "4175": 0.5651806592941284, "4229": 0.5489565134048462, "4235": 0.22157983481884003, "4254": 1.1205062866210938, "4275": 0.9621002674102783, "4281": 0.8109301924705505, "4295": 0.1401015669107437, "4300": 0.1477125883102417, "4319": 0.11778303235769272, "4328": 0.5506471395492554, "4340": 0.3170322775840759, "4358": 0.7463917136192322, "4359": 0.15275461971759796, "4376": 0.36358460783958435, "4397": 0.21372433006763458, "4423": 0.7701805830001831, "4442": 0.347847044467926, "4481": 0.06429435312747955, "4489": 0.11168810725212097, "4492": 0.25088030099868774, "4530": 0.09495500475168228, "4531": 0.1229778528213501, "4541": 0.650757372379303, "4598": 0.18573370575904846, "4621": 0.15943801403045654, "4675": 0.6941232681274414, "4697": 0.09584271162748337, "4725": 0.5562619566917419, "4730": 0.11604541540145874, "4746": 0.5573811531066895, "4769": 0.07250232994556427, "4776": 0.1485546976327896, "4812": 0.41840189695358276, "4824": 0.058784693479537964, "4839": 0.4770587682723999, "4863": 0.6054253578186035, "4935": 0.4462870955467224, "4953": 0.13157635927200317, "4955": 0.7352184057235718, "4958": 0.8500841856002808, "5012": 0.14939609169960022, "5025": 0.3963087201118469, "5041": 0.42353010177612305, "5043": 0.3409265875816345, "5084": 0.7105726003646851, "5090": 0.31204116344451904, "5109": 0.41065993905067444, "5139": 0.5232481360435486, "5178": 0.7934166193008423, "5224": 0.03266380727291107, "5352": 0.052318159490823746, "5360": 0.3012613356113434, "5441": 0.14433705806732178, "5476": 0.12986256182193756, "5490": 0.17840765416622162, "5531": 0.2561853528022766, "5547": 0.7115318179130554, "5562": 0.03925827145576477, "5594": 0.35403475165367126, "5597": 1.0437490940093994, "5646": 0.3777405619621277, "5675": 0.052318159490823746, "5761": 0.025073638185858727, "5839": 0.5495203733444214, "5845": 0.14349138736724854, "5850": 0.010684899985790253, "5892": 0.4374985992908478, "5966": 0.37974658608436584, "5993": 0.33675122261047363, "6011": 0.23864774405956268, "6013": 0.13071982562541962, "6018": 0.32553088665008545, "6022": 0.6970458030700684, "6025": 0.32270604372024536, "6026": 0.18167030811309814, "6083": 0.1485546976327896, "6162": 0.0317181795835495, "6165": 0.18004031479358673, "6195": 0.16276304423809052, "6234": 0.574020504951477, "6388": 0.2969166338443756, "6434": 0.23402166366577148, "6438": 0.4419025182723999, "6526": 0.08154398202896118, "6551": 0.19622190296649933, "6592": 0.4709797203540802, "6593": 0.11256109178066254, "6612": 0.025073638185858727, "6648": 0.4812922179698944, "6689": 0.5701626539230347, "6698": 0.8805016279220581, "6721": 0.03831886500120163, "6743": 0.18573370575904846, "6745": 0.16524957120418549, "6747": 0.32199856638908386, "6779": 0.2696990668773651, "6882": 0.03831886500120163, "6936": 0.043007105588912964, "6937": 0.8187123537063599, "6939": 0.03360854089260101, "7011": 0.6517757177352905, "7012": 0.04394211992621422, "7017": 0.5718178153038025, "7023": 0.255429208278656, "7080": 0.3757305145263672, "7091": 0.5789587497711182, "7103": 0.16524957120418549, "7242": 0.7491656541824341, "7312": 0.5579402446746826, "7316": 0.02316705882549286, "7320": 0.31132611632347107, "7375": 0.17840765416622162, "7438": 0.30989447236061096, "7461": 0.5930894017219543, "7526": 0.2447827309370041, "7528": 0.05694137513637543, "7531": 0.1401015669107437, "7551": 0.36697331070899963, "7607": 0.15943801403045654, "7645": 0.1889725625514984, "7667": 0.22782009840011597, "7691": 0.02792670577764511, "7778": 0.5116065740585327, "7801": 0.21135559678077698, "7818": 0.6773988008499146, "7831": 0.7239188551902771, "7842": 0.4537591338157654, "7860": 0.37907835841178894, "7865": 0.2470736801624298, "7868": 0.04953393340110779, "7870": 0.27934664487838745, "7885": 0.30917787551879883, "7895": 0.6999598741531372, "7913": 0.0842406153678894, "7949": 0.22937409579753876, "8023": 0.19622190296649933, "8045": 1.1858406066894531, "8114": 0.6212902665138245, "8122": 0.9348671436309814, "8137": 0.5936289429664612, "8161": 0.1889725625514984, "8185": 0.16110190749168396, "8266": 0.5162794589996338, "8280": 0.3750596046447754, "8293": 0.23247487843036652, "8315": 0.16276304423809052, "8332": 0.32199856638908386, "8335": 0.16442140936851501, "8339": 0.20660123229026794, "8349": 0.3381449282169342, "8358": 0.7482418417930603, "8386": 1.1102628707885742, "8387": 1.0628231763839722, "8402": 0.18248429894447327, "8445": 0.16690383851528168, "8465": 0.1229778528213501, "8497": 0.7537717819213867, "8498": 0.23633737862110138, "8552": 0.036437395960092545, "8556": 0.5301685929298401, "8621": 0.08064348995685577, "8698": 0.6038249135017395, "8781": 0.10026945173740387, "8785": 1.0116009712219238, "8787": 0.7124901413917542, "8830": 1.02149498462677, "8849": 0.03925827145576477, "8898": 0.08513788133859634, "8920": 0.06886265426874161, "8970": 0.05139094591140747, "8985": 1.0108904838562012, "9010": 0.1930064558982849, "9099": 0.35060185194015503, "9104": 0.04767346754670143, "9132": 0.020300358533859253, "9174": 0.176772341132164, "9186": 0.7845434546470642, "9279": 0.32553088665008545, "9280": 0.03925827145576477, "9312": 0.5186077356338501, "9319": 0.045809537172317505, "9355": 0.1693800985813141, "9367": 0.009718249551951885, "9373": 0.6654226183891296, "9420": 0.18329764902591705, "9426": 0.7314660549163818, "9539": 0.6265231370925903, "9556": 0.5979346632957458, "9560": 0.8780695199966431, "9581": 0.12986256182193756, "9614": 0.8567397594451904, "9662": 0.7737906575202942, "9671": 0.14686977863311768, "9723": 0.33675122261047363, "9765": 0.0913962796330452, "9783": 0.2223619967699051, "9804": 0.034552380442619324, "9820": 1.4358283281326294, "9824": 0.7951818704605103, "9839": 0.6139179468154907, "9869": 0.2034190446138382, "9896": 0.3070250153541565, "9932": 0.06612417846918106, "9962": 0.05694137513637543, "9990": 0.3163207769393921, "10015": 0.05694137513637543, "10035": 0.5174443125724792, "10091": 0.5074998140335083, "10173": 0.7881022095680237, "10174": 0.401551216840744, "10197": 0.5849615335464478, "10368": 0.7229714393615723, "10372": 0.6327666640281677, "10374": 0.020300358533859253, "10449": 0.175953671336174, "10465": 0.151916041970253, "10521": 0.151916041970253, "10640": 0.15442965924739838, "10641": 0.3883931338787079, "10744": 0.30558720231056213, "10754": 0.6649205088615417, "10847": 0.7258110046386719, "10857": 0.04767346754670143, "10859": 0.034552380442619324, "10908": 0.23015019297599792, "10924": 0.472198486328125, "11027": 0.17840765416622162, "11207": 0.6389714479446411, "11208": 0.39762192964553833, "11213": 0.6654226183891296, "11234": 0.38905516266822815, "11310": 0.8740028142929077, "11380": 0.05139094591140747, "11436": 0.20580662786960602, "11538": 0.3547199070453644, "11543": 0.0174254160374403, "11581": 0.02412080205976963, "11619": 1.0179725885391235, "11628": 0.03831886500120163, "11643": 0.996573805809021, "11709": 0.7863243818283081, "11778": 0.10026945173740387, "11806": 0.09761575609445572, "11967": 0.812664806842804, "12046": 0.5995445251464844, "12107": 0.12642613053321838, "12298": 0.9417452812194824, "12318": 0.02792670577764511, "12353": 0.47584590315818787, "12381": 0.9493325352668762, "12435": 0.3547199070453644, "12479": 0.9005423784255981, "12503": 1.0695481300354004, "12504": 0.7009293437004089, "12515": 0.053244512528181076, "12596": 0.347847044467926, "12646": 0.08782484382390976, "12654": 0.0019512200960889459, "12702": 0.013579257763922215, "12823": 0.23864774405956268, "12826": 0.5427330136299133, "12863": 0.6430866718292236, "12898": 0.7370892763137817, "12928": 0.2247048318386078, "13070": 0.12728634476661682, "13105": 0.8195732831954956, "13235": 0.4568560719490051, "13356": 0.020300358533859253, "13416": 0.09850110858678818, "13434": 0.11430477350950241, "13441": 0.4752389192581177, "13464": 0.0038986403960734606, "13465": 0.8169882297515869, "13494": 0.47827014327049255, "13523": 0.013579257763922215, "13599": 0.7086513638496399, "13642": 0.5404602885246277, "13792": 0.3077431619167328, "13912": 0.18492233753204346, "13993": 0.15693697333335876, "13996": 0.7638313174247742, "14037": 0.12814582884311676, "14155": 0.21293537318706512, "14301": 0.016465263441205025, "14336": 0.3615458607673645, "14358": 0.23633737862110138, "14386": 0.29619070887565613, "14440": 0.4818955361843109, "14573": 0.6064908504486084, "14667": 0.1808556467294693, "14670": 0.6902132034301758, "14965": 0.16442140936851501, "15078": 0.08961215615272522, "15245": 0.9929623603820801, "15258": 0.0317181795835495, "15306": 0.8764448165893555, "15349": 0.05046287178993225, "15596": 0.11081436276435852, "15630": 0.4500300884246826, "15844": 0.4145384132862091, "15873": 0.14264501631259918, "15877": 0.14939609169960022, "15973": 0.4537591338157654, "16014": 0.9857001900672913, "16095": 0.0606246218085289, "16134": 0.5849615335464478, "16157": 0.27564704418182373, "16185": 0.42990362644195557, "16268": 0.3325583338737488, "16290": 0.31132611632347107, "16311": 0.2881702482700348, "16330": 0.49626702070236206, "16367": 0.3423145115375519, "16381": 0.8845420479774475, "16463": 0.058784693479537964, "16478": 0.02316705882549286, "16514": 0.7028654217720032, "16599": 0.10555581003427505, "16670": 0.2493593990802765, "16746": 0.45251765847206116, "16820": 0.7845434546470642, "17174": 0.2990913391113281, "17208": 0.567397952079773, "17261": 0.18573370575904846, "17390": 0.2969166338443756, "17431": 0.08871890604496002, "17503": 0.30917787551879883, "17537": 0.058784693479537964, "17547": 1.117955207824707, "17568": 0.823009729385376, "17626": 0.004870930220931768, "17678": 0.05046287178993225, "17680": 0.03925827145576477, "17724": 0.6202403903007507, "17727": 0.009718249551951885, "17820": 0.1693800985813141, "17830": 0.06337817758321762, "17839": 0.04860413447022438, "17862": 0.06520967930555344, "17890": 0.66441810131073, "17908": 0.2493593990802765, "17959": 0.3916989266872406, "18076": 0.25088030099868774, "18398": 0.3318578004837036, "18422": 0.22626367211341858, "18539": 0.3877306580543518, "18609": 0.03360854089260101, "18700": 0.2478361576795578, "18750": 0.17267228662967682, "18793": 0.13499516248703003, "18949": 1.3264323472976685, "18953": 0.38308101892471313, "18963": 0.043007105588912964, "19064": 0.32341301441192627, "19132": 0.006812678650021553, "19141": 0.2830325961112976, "19209": 0.6543170213699341, "19276": 0.058784693479537964, "19335": 0.05786345899105072, "19388": 0.8780695199966431, "19518": 0.8492490649223328, "19879": 0.13071982562541962, "19939": 0.7592713832855225, "20047": 0.19622190296649933, "20080": 0.20580662786960602, "20125": 0.8748174905776978, "20155": 0.10203468054533005, "20177": 0.42990362644195557, "20272": 0.5324648022651672, "20437": 0.026025565341114998, "20792": 0.13243216276168823, "20900": 0.23710809648036957, "20932": 1.0257055759429932, "21150": 0.4914994537830353, "21425": 0.3423145115375519, "21446": 0.036437395960092545, "21647": 0.14433705806732178, "21663": 0.2105647772550583, "21758": 0.0317181795835495, "21796": 0.803087055683136, "21931": 0.8152611255645752, "21934": 0.5963221788406372, "22022": 0.04953393340110779, "22025": 0.1384023278951645, "22318": 0.3084607720375061, "22571": 0.5156965255737305, "22634": 0.36358460783958435, "22658": 0.0174254160374403, "22835": 0.42225050926208496, "22963": 0.5968599319458008, "23041": 0.24248650670051575, "23087": 0.5290185213088989, "23208": 0.4374985992908478, "23274": 0.08961215615272522, "23284": 0.4794800877571106, "23364": 0.2881702482700348, "23599": 0.2089812457561493, "23624": 0.006812678650021553, "23661": 0.20580662786960602, "23671": 0.07250232994556427, "23889": 0.24171993136405945, "24010": 0.09761575609445572, "24093": 0.2954642176628113, "24094": 0.31560876965522766, "24155": 0.46670228242874146, "24286": 0.0019512200960889459, "24290": 0.1718502640724182, "24353": 0.48068851232528687, "24497": 0.040196798741817474, "24545": 0.011650617234408855, "24710": 0.6941232681274414, "24821": 0.11691460013389587, "24899": 0.0752234235405922, "24970": 0.32129061222076416, "25006": 0.6558387279510498, "25027": 0.16607704758644104, "25095": 0.12814582884311676, "25169": 0.5255602598190308, "25276": 0.46486347913742065, "25613": 0.2501201331615448, "25969": 0.6202403903007507, "26163": 0.06703783571720123, "26237": 0.5180262327194214, "26319": 0.1718502640724182, "26616": 0.13157635927200317, "26633": 0.2852376699447632, "26835": 0.04113444685935974, "27144": 0.18492233753204346, "27258": 0.09672962874174118, "27354": 0.09761575609445572, "27451": 0.5415972471237183, "27637": 0.36358460783958435, "27794": 0.29328158497810364, "27852": 0.2749055027961731, "28093": 0.09050461649894714, "28145": 0.04207121208310127, "28252": 0.07068414986133575, "28255": 0.5517725944519043, "28297": 0.10026945173740387, "28436": 0.8492490649223328, "28488": 0.19622190296649933, "28648": 0.25995752215385437, "29235": 0.9769153594970703, "29295": 0.10203468054533005, "29336": 0.04113444685935974, "29374": 0.567397952079773, "29458": 0.9531047344207764, "29490": 0.03831886500120163} | 13899137 | BACKGROUND Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. METHODS AND FINDINGS Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. CONCLUSIONS Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact. | HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa |
{"1003": 0.025073638185858727, "1998": 0.42735910415649414, "1999": 0.09761575609445572, "2001": 0.15275461971759796, "2004": 0.06429435312747955, "2011": 0.11517547070980072, "2012": 0.2976420819759369, "2015": 0.00875066313892603, "2020": 0.24401791393756866, "2037": 0.0842406153678894, "2042": 0.09850110858678818, "2044": 0.35677260160446167, "2057": 0.30989447236061096, "2058": 0.0797421783208847, "2062": 0.4450363218784332, "2075": 0.3897167444229126, "2084": 0.3723714053630829, "2086": 0.043007105588912964, "2087": 0.036437395960092545, "2095": 0.4794800877571106, "2106": 0.37371641397476196, "2108": 0.16359257698059082, "2109": 0.1477125883102417, "2111": 0.6027565002441406, "2114": 0.1229778528213501, "2116": 0.4349733293056488, "2144": 0.011650617234408855, "2158": 0.22937409579753876, "2166": 0.47158926725387573, "2179": 0.1677299439907074, "2193": 0.18816383183002472, "2216": 0.09495500475168228, "2236": 0.37371641397476196, "2246": 0.2696990668773651, "2254": 0.10906458646059036, "2263": 0.28963330388069153, "2268": 0.6492279767990112, "2273": 0.47584590315818787, "2287": 0.5568217039108276, "2294": 0.4891071021556854, "2296": 0.20421554148197174, "2298": 0.12038381397724152, "2306": 0.33605360984802246, "2308": 0.7153595685958862, "2313": 0.7863243818283081, "2317": 0.49982786178588867, "2329": 0.02792670577764511, "2331": 0.5827828645706177, "2339": 0.24631060659885406, "2351": 0.5925496220588684, "2358": 0.04674193635582924, "2370": 0.24859806895256042, "2381": 0.6064908504486084, "2394": 0.08154398202896118, "2411": 0.5540198087692261, "2414": 0.4132472574710846, "2426": 0.20739519596099854, "2431": 0.47036975622177124, "2432": 0.5662899017333984, "2439": 0.03266380727291107, "2450": 0.4512746334075928, "2465": 0.2447827309370041, "2470": 0.09938567131757736, "2491": 0.6249561905860901, "2501": 0.2531573474407196, "2523": 0.0038986403960734606, "2529": 0.11778303235769272, "2553": 0.6054253578186035, "2563": 0.7305257320404053, "2590": 0.1913948506116867, "2592": 0.11168810725212097, "2611": 0.13499516248703003, "2619": 0.11343330889940262, "2628": 0.4709797203540802, "2636": 0.28597161173820496, "2660": 0.2409527748823166, "2680": 0.5701626539230347, "2691": 0.8658194541931152, "2711": 0.15693697333335876, "2714": 0.04674193635582924, "2730": 0.3956514894962311, "2779": 0.058784693479537964, "2817": 0.3346569836139679, "2827": 0.0842406153678894, "2866": 0.6882523894309998, "2870": 0.25995752215385437, "2913": 0.21135559678077698, "2919": 0.025073638185858727, "2926": 0.007782140281051397, "2931": 0.6512666940689087, "2969": 1.1971133947372437, "2988": 0.5433003902435303, "3012": 0.3141832649707794, "3016": 0.6270449161529541, "3020": 0.4568560719490051, "3025": 0.32905077934265137, "3057": 0.4318077862262726, "3080": 0.3416208028793335, "3163": 0.23864774405956268, "3167": 0.15359249711036682, "3189": 0.2696990668773651, "3204": 0.2881702482700348, "3209": 0.7009293437004089, "3262": 0.03925827145576477, "3264": 0.12814582884311676, "3265": 0.6548244953155518, "3273": 0.19782574474811554, "3276": 0.11865071207284927, "3278": 0.3757305145263672, "3280": 0.5528968572616577, "3287": 0.6244332790374756, "3305": 0.13414156436920166, "3337": 0.09050461649894714, "3350": 0.4132472574710846, "3378": 0.8004589080810547, "3382": 0.04207121208310127, "3391": 0.5410289764404297, "3439": 0.5584990978240967, "3445": 0.20022670924663544, "3446": 0.5500838756561279, "3466": 0.30558720231056213, "3480": 0.5827828645706177, "3493": 0.15023678541183472, "3497": 0.7755908370018005, "3525": 0.3526630103588104, "3572": 0.4770587682723999, "3575": 0.9463045597076416, "3582": 0.18492233753204346, "3618": 0.23633737862110138, "3623": 0.015504186972975731, "3633": 0.43623676896095276, "3647": 0.14518201351165771, "3725": 0.4412745535373688, "3745": 0.0752234235405922, "3767": 0.5272908806800842, "3801": 0.5255602598190308, "3808": 0.01934296265244484, "3827": 1.3028278350830078, "3867": 0.5162794589996338, "3885": 0.176772341132164, "3891": 0.8748174905776978, "3896": 0.46363574266433716, "3920": 0.2822965085506439, "3921": 0.26296505331993103, "3949": 0.3318578004837036, "4053": 0.24859806895256042, "4102": 0.6160298585891724, "4126": 0.27044451236724854, "4141": 0.42225050926208496, "4148": 0.36086538434028625, "4158": 0.2719337046146393, "4178": 0.4512746334075928, "4235": 0.03831886500120163, "4254": 0.09050461649894714, "4281": 0.846739649772644, "4286": 0.08154398202896118, "4292": 0.16442140936851501, "4311": 0.020300358533859253, "4426": 0.2018241584300995, "4531": 0.0913962796330452, "4544": 0.4487839937210083, "4652": 0.2223619967699051, "4678": 0.14264501631259918, "4703": 0.6553317308425903, "4725": 0.18329764902591705, "4735": 0.2105647772550583, "4745": 0.6011518239974976, "4758": 0.25845035910606384, "4761": 0.18816383183002472, "4795": 0.35677260160446167, "4808": 0.4248080551624298, "4824": 0.42735910415649414, "4852": 0.026025565341114998, "5043": 0.7096124291419983, "5054": 0.680370569229126, "5082": 0.19622190296649933, "5145": 0.08064348995685577, "5177": 0.1889725625514984, "5197": 0.12986256182193756, "5229": 0.10467668622732162, "5258": 0.3170322775840759, "5264": 0.08782484382390976, "5281": 0.020300358533859253, "5303": 0.1619328260421753, "5345": 0.15442965924739838, "5360": 0.15860503911972046, "5387": 0.27786844968795776, "5462": 0.1994270235300064, "5570": 0.06612417846918106, "5591": 0.09495500475168228, "5636": 0.7201237678527832, "5637": 0.06246116757392883, "5665": 0.30486753582954407, "5694": 0.16276304423809052, "5776": 0.00875066313892603, "5799": 0.16359257698059082, "5816": 0.016465263441205025, "5842": 0.007782140281051397, "5845": 0.11691460013389587, "5876": 0.4914994537830353, "5895": 1.2666174173355103, "5907": 0.26820653676986694, "5920": 1.304418921470642, "5996": 0.10026945173740387, "6022": 0.3923587501049042, "6075": 0.3443928062915802, "6124": 0.4926934838294983, "6165": 0.5063233375549316, "6230": 0.02412080205976963, "6245": 0.17020416259765625, "6251": 0.3070250153541565, "6355": 0.6573580503463745, "6431": 0.12038381397724152, "6459": 0.6118015646934509, "6480": 0.09495500475168228, "6517": 0.09495500475168228, "6528": 0.5685047507286072, "6677": 0.4950772523880005, "6698": 0.5347557663917542, "6747": 0.6202403903007507, "6778": 0.27044451236724854, "6905": 0.306306391954422, "6923": 0.17020416259765625, "6937": 0.7463917136192322, "6976": 0.3995884954929352, "6997": 0.2247048318386078, "7017": 0.7370892763137817, "7018": 0.052318159490823746, "7058": 0.20580662786960602, "7080": 0.3262358605861664, "7145": 0.20660123229026794, "7173": 0.9256220459938049, "7267": 0.9987343549728394, "7297": 0.16607704758644104, "7331": 0.3106105625629425, "7386": 1.2488490343093872, "7461": 0.27934664487838745, "7613": 0.1602703034877777, "7711": 0.09584271162748337, "7778": 0.24554696679115295, "7831": 0.5607312321662903, "8107": 0.004870930220931768, "8152": 0.06520967930555344, "8211": 0.10731173306703568, "8281": 0.5151132941246033, "8317": 0.19622190296649933, "8392": 0.012615402229130268, "8580": 0.43244171142578125, "8664": 0.11256109178066254, "8729": 0.2741633653640747, "8740": 0.034552380442619324, "8777": 0.21214580535888672, "8832": 0.129004567861557, "9164": 0.14179791510105133, "9324": 0.8917738795280457, "9377": 0.053244512528181076, "9454": 0.5640701055526733, "9458": 0.15860503911972046, "9467": 0.15023678541183472, "9556": 0.5723689198493958, "9723": 0.41001203656196594, "9740": 0.5151132941246033, "9750": 0.22782009840011597, "9756": 0.1751343309879303, "9874": 0.1710275560617447, "9940": 0.09317722171545029, "9968": 0.1685553640127182, "10048": 0.009718249551951885, "10066": 0.02887592278420925, "10149": 0.3134697377681732, "10219": 0.30917787551879883, "10311": 0.37640097737312317, "10426": 0.4450363218784332, "10444": 0.7258110046386719, "10563": 0.13071982562541962, "10611": 0.23710809648036957, "10662": 0.0913962796330452, "10817": 0.0009760859538801014, "10831": 0.5767669677734375, "10857": 0.040196798741817474, "10859": 0.7389566898345947, "11165": 0.02887592278420925, "11331": 0.2531573474407196, "11524": 0.03266380727291107, "11746": 0.011650617234408855, "11788": 0.6960725784301758, "11878": 0.34508460760116577, "12010": 0.18329764902591705, "12107": 0.12986256182193756, "12290": 0.3676496744155884, "12345": 0.40089741349220276, "12381": 0.23556606471538544, "12435": 0.3297532796859741, "12461": 0.28670501708984375, "12491": 0.018384648486971855, "12596": 0.11517547070980072, "12654": 0.01934296265244484, "12765": 0.6128603219985962, "12826": 0.2145126610994339, "12893": 0.17267228662967682, "12906": 0.6212902665138245, "12908": 0.3283478021621704, "12955": 0.06429435312747955, "13047": 0.01934296265244484, "13105": 0.1693800985813141, "13187": 1.0828639268875122, "13191": 0.21135559678077698, "13356": 0.2247048318386078, "13436": 0.0038986403960734606, "13496": 0.29328158497810364, "13531": 0.09938567131757736, "13594": 0.5762182474136353, "13599": 0.28963330388069153, "13745": 0.09761575609445572, "13789": 0.0354953333735466, "14258": 0.33605360984802246, "14343": 0.31845372915267944, "14398": 0.03266380727291107, "14729": 0.41840189695358276, "14967": 0.6000806093215942, "14974": 0.01934296265244484, "15069": 0.0029254043474793434, "15157": 0.4914994537830353, "15170": 0.09672962874174118, "15192": 0.18329764902591705, "15226": 0.4196864068508148, "15451": 0.05139094591140747, "15596": 0.1477125883102417, "15873": 0.5941681861877441, "15982": 0.029824240133166313, "15996": 0.9857001900672913, "16085": 0.04487626627087593, "16134": 0.040196798741817474, "16187": 0.20977331697940826, "16211": 0.15777134895324707, "16593": 0.151916041970253, "16621": 0.14686977863311768, "16796": 0.016465263441205025, "16873": 0.06795065850019455, "16902": 0.8500841856002808, "16908": 0.055094651877880096, "16999": 0.10467668622732162, "17052": 0.0019512200960889459, "17062": 0.006812678650021553, "17119": 0.4228905141353607, "17216": 0.04207121208310127, "17393": 0.1710275560617447, "17631": 0.495672345161438, "17841": 0.03360854089260101, "18130": 0.10379679501056671, "18175": 0.04113444685935974, "18240": 0.4818955361843109, "18249": 0.1994270235300064, "18421": 0.4891071021556854, "18539": 0.05786345899105072, "18917": 0.2711893916130066, "18949": 0.4770587682723999, "19064": 0.0317181795835495, "19157": 0.04394211992621422, "19170": 0.417115718126297, "19188": 0.31204116344451904, "19591": 0.6223390698432922, "20070": 0.055094651877880096, "20272": 0.9394577741622925, "20274": 0.021256839856505394, "20334": 0.04394211992621422, "20390": 0.03266380727291107, "20462": 0.1229778528213501, "20572": 0.06429435312747955, "20576": 0.5057345628738403, "20676": 0.055094651877880096, "20873": 0.8433839678764343, "20983": 0.4437839686870575, "21024": 0.35813871026039124, "21551": 0.10555581003427505, "21604": 0.05417001247406006, "21754": 0.004870930220931768, "22963": 0.29473719000816345, "23094": 0.07159364968538284, "23277": 0.04207121208310127, "23280": 0.06703783571720123, "23318": 0.09584271162748337, "23368": 0.33953672647476196, "23900": 0.7426811456680298, "23995": 0.23787821829319, "24363": 0.21372433006763458, "24467": 0.7755908370018005, "24904": 0.05046287178993225, "24948": 0.6502478122711182, "25042": 0.3416208028793335, "25121": 0.44691193103790283, "25135": 0.22001366317272186, "25221": 0.5990082025527954, "25243": 0.0174254160374403, "25253": 0.684319257736206, "25394": 0.045809537172317505, "25406": 0.06612417846918106, "25596": 0.9005423784255981, "25763": 0.35677260160446167, "25947": 0.1510767638683319, "26094": 1.0668635368347168, "26319": 0.12642613053321838, "26453": 0.0058422754518687725, "26485": 0.5197699069976807, "26721": 0.36697331070899963, "26728": 0.1401015669107437, "27247": 0.10906458646059036, "27285": 0.1332872211933136, "27550": 0.18167030811309814, "27794": 0.034552380442619324, "28093": 0.10993985831737518, "29101": 0.09228714555501938} | 13900610 | BACKGROUND Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant. Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important. We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm. METHODS Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009. We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009. We also used a Bayesian approach to look at clustering of people who self-harmed. Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed. FINDINGS 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year. Self-harm rates were more than ten times higher in female prisoners than in male inmates. Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes. In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor. Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11-0·18). 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm. Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide. INTERPRETATION The burden of self-harm in prisoners is substantial, particularly in women. Self-harm in prison is associated with subsequent suicide in this setting. Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons. FUNDING Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health. | Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide |
{"1014": 0.40089741349220276, "1021": 0.2607102394104004, "1056": 0.11343330889940262, "1057": 0.15943801403045654, "1061": 0.38574060797691345, "1085": 0.026976587250828743, "1998": 0.4487839937210083, "2000": 0.1384023278951645, "2001": 0.07612881064414978, "2003": 0.13414156436920166, "2012": 0.05417001247406006, "2035": 0.34922540187835693, "2041": 0.004870930220931768, "2042": 0.07612881064414978, "2043": 0.13755162060260773, "2051": 0.42096930742263794, "2052": 0.11081436276435852, "2062": 0.052318159490823746, "2064": 0.08064348995685577, "2071": 0.3241194784641266, "2084": 0.056018441915512085, "2086": 0.3864043951034546, "2087": 0.10467668622732162, "2094": 0.029824240133166313, "2097": 0.016465263441205025, "2101": 0.49686139822006226, "2102": 1.1481462717056274, "2106": 0.14433705806732178, "2109": 0.040196798741817474, "2138": 0.16276304423809052, "2140": 0.3346569836139679, "2146": 0.24018502235412598, "2148": 0.8788808584213257, "2166": 0.5336109399795532, "2179": 0.02887592278420925, "2184": 0.06795065850019455, "2190": 0.16524957120418549, "2203": 0.1401015669107437, "2241": 0.3012613356113434, "2254": 0.1011524572968483, "2262": 0.5393219590187073, "2265": 0.00875066313892603, "2322": 0.1873544454574585, "2339": 0.40806588530540466, "2348": 0.018384648486971855, "2350": 0.27342069149017334, "2358": 0.5914691090583801, "2367": 0.3027053773403168, "2391": 0.46363574266433716, "2396": 1.222740888595581, "2421": 0.32199856638908386, "2423": 0.09406650811433792, "2443": 0.2539152204990387, "2470": 0.46670228242874146, "2478": 0.19782574474811554, "2488": 0.11778303235769272, "2525": 0.025073638185858727, "2527": 0.016465263441205025, "2549": 0.47766464948654175, "2560": 0.15275461971759796, "2565": 0.036437395960092545, "2582": 0.16442140936851501, "2599": 0.23710809648036957, "2615": 0.14518201351165771, "2625": 0.26446542143821716, "2644": 0.14939609169960022, "2664": 0.1384023278951645, "2670": 0.19782574474811554, "2692": 0.011650617234408855, "2707": 0.05046287178993225, "2744": 0.5324648022651672, "2747": 0.04207121208310127, "2750": 0.037378571927547455, "2754": 0.42225050926208496, "2764": 0.11430477350950241, "2765": 0.09850110858678818, "2783": 0.4228905141353607, "2791": 0.3262358605861664, "2817": 0.7276995778083801, "2825": 0.6170841455459595, "2832": 0.176772341132164, "2840": 0.7086513638496399, "2894": 0.2409527748823166, "2897": 0.3416208028793335, "2913": 0.5495203733444214, "2917": 0.040196798741817474, "2933": 0.2223619967699051, "2944": 1.0668635368347168, "2950": 0.07431721687316895, "2951": 0.1212492436170578, "3060": 1.1816552877426147, "3088": 1.2533208131790161, "3102": 0.151916041970253, "3104": 0.14518201351165771, "3107": 0.15860503911972046, "3112": 0.13243216276168823, "3125": 0.09317722171545029, "3130": 0.13157635927200317, "3132": 0.15860503911972046, "3139": 0.29036402702331543, "3144": 0.3850763738155365, "3176": 0.3241194784641266, "3202": 0.5838727951049805, "3215": 0.6265231370925903, "3225": 0.0317181795835495, "3229": 0.6867793202400208, "3231": 0.6410312056541443, "3252": 0.30558720231056213, "3258": 0.09495500475168228, "3273": 0.28890204429626465, "3289": 0.026976587250828743, "3296": 0.09050461649894714, "3298": 0.37102460861206055, "3305": 0.25239890813827515, "3322": 0.46117570996284485, "3343": 0.5489565134048462, "3348": 0.2394166737794876, "3357": 0.4926934838294983, "3372": 0.14602625370025635, "3375": 0.16607704758644104, "3399": 0.2652147710323334, "3424": 0.9131608605384827, "3463": 0.3269403576850891, "3464": 0.10203468054533005, "3465": 0.7482418417930603, "3466": 0.32199856638908386, "3491": 0.17759032547473907, "3497": 0.5180262327194214, "3517": 0.18492233753204346, "3526": 0.24018502235412598, "3559": 0.06703783571720123, "3659": 0.347847044467926, "3668": 0.34577593207359314, "3690": 0.31204116344451904, "3718": 0.07341018319129944, "3720": 0.3949938118457794, "3722": 0.2837681770324707, "3729": 0.40220460295677185, "3747": 0.04113444685935974, "3800": 0.04394211992621422, "3818": 0.22626367211341858, "3828": 0.1677299439907074, "3896": 0.04767346754670143, "3898": 0.4487839937210083, "3921": 0.5789587497711182, "3938": 0.8989537954330444, "3949": 0.66441810131073, "3979": 0.15860503911972046, "3988": 0.8247235417366028, "4081": 0.7028654217720032, "4084": 0.34023189544677734, "4094": 0.5244048833847046, "4102": 0.19381128251552582, "4106": 0.2089812457561493, "4118": 0.38905516266822815, "4140": 0.04113444685935974, "4146": 0.04394211992621422, "4175": 0.15023678541183472, "4225": 0.029824240133166313, "4235": 0.056018441915512085, "4254": 0.7144040465354919, "4275": 0.7629209756851196, "4281": 0.8682814836502075, "4288": 0.0317181795835495, "4295": 0.20580662786960602, "4319": 0.5795059204101562, "4423": 0.7845434546470642, "4424": 0.500420093536377, "4442": 0.4267219603061676, "4484": 0.13499516248703003, "4492": 0.16359257698059082, "4531": 0.2493593990802765, "4621": 1.005902886390686, "4639": 0.18573370575904846, "4652": 0.0029254043474793434, "4725": 0.45251765847206116, "4760": 0.034552380442619324, "4790": 0.026025565341114998, "4824": 0.20818853378295898, "4852": 0.2409527748823166, "4935": 0.3241194784641266, "5012": 0.7115318179130554, "5082": 0.08961215615272522, "5090": 0.20739519596099854, "5104": 0.524982750415802, "5258": 0.0317181795835495, "5332": 0.2561853528022766, "5366": 0.23015019297599792, "5415": 1.0992631912231445, "5425": 0.5244048833847046, "5531": 0.18573370575904846, "5533": 0.3170322775840759, "5552": 0.4824984669685364, "5597": 0.6502478122711182, "5604": 0.6699305176734924, "5656": 0.9842413663864136, "5711": 0.469759464263916, "5714": 0.7872136831283569, "5717": 0.3443928062915802, "5787": 0.2622140049934387, "5833": 0.2018241584300995, "5845": 0.23787821829319, "5850": 0.37974658608436584, "5852": 0.3353555500507355, "5892": 1.0735615491867065, "6001": 0.38308101892471313, "6018": 0.17020416259765625, "6028": 0.09406650811433792, "6033": 0.13925230503082275, "6043": 0.3005385100841522, "6061": 0.43244171142578125, "6083": 0.5601736903190613, "6125": 0.36358460783958435, "6143": 0.34577593207359314, "6164": 0.007782140281051397, "6179": 0.026976587250828743, "6194": 0.1229778528213501, "6210": 0.02316705882549286, "6234": 0.9340999722480774, "6256": 0.40611594915390015, "6325": 0.8374842405319214, "6366": 0.34715715050697327, "6367": 0.48670899868011475, "6383": 0.8281423449516296, "6388": 0.1718502640724182, "6450": 0.06977381557226181, "6464": 0.42990362644195557, "6537": 0.13414156436920166, "6592": 0.5640701055526733, "6646": 0.46486347913742065, "6721": 0.034552380442619324, "6726": 0.7491656541824341, "6749": 0.0019512200960889459, "6880": 0.15442965924739838, "6939": 0.10818854719400406, "7012": 0.10203468054533005, "7017": 0.03925827145576477, "7028": 0.18816383183002472, "7091": 0.3883931338787079, "7180": 0.1229778528213501, "7242": 0.981317400932312, "7320": 0.33605360984802246, "7337": 0.0038986403960734606, "7375": 0.1212492436170578, "7420": 0.010684899985790253, "7438": 0.7210738658905029, "7461": 0.1619328260421753, "7494": 0.02887592278420925, "7528": 0.03360854089260101, "7551": 0.28450319170951843, "7691": 0.14433705806732178, "7705": 0.0029254043474793434, "7718": 0.259204238653183, "7721": 0.9263957738876343, "7778": 0.015504186972975731, "7801": 0.06795065850019455, "7818": 0.5827828645706177, "7831": 0.08064348995685577, "7842": 0.8074519634246826, "7863": 0.8433839678764343, "7865": 0.2034190446138382, "7868": 0.022212404757738113, "7870": 0.036437395960092545, "7885": 0.16110190749168396, "7895": 0.7710843086242676, "7913": 0.04113444685935974, "8045": 0.8500841856002808, "8107": 0.2976420819759369, "8114": 0.2689530849456787, "8122": 0.08692999184131622, "8208": 0.14518201351165771, "8266": 0.1889725625514984, "8293": 0.272677481174469, "8321": 0.04767346754670143, "8332": 0.021256839856505394, "8361": 0.037378571927547455, "8387": 1.1300151348114014, "8778": 0.13755162060260773, "8785": 0.6139179468154907, "8790": 0.1401015669107437, "8830": 0.8057082891464233, "8961": 0.11951763927936554, "8985": 0.5562619566917419, "9104": 0.4126010537147522, "9186": 0.417115718126297, "9297": 0.20660123229026794, "9367": 0.053244512528181076, "9373": 0.007782140281051397, "9398": 0.23787821829319, "9412": 0.16110190749168396, "9436": 0.36697331070899963, "9462": 0.056018441915512085, "9513": 0.2763880789279938, "9526": 0.037378571927547455, "9539": 0.030771657824516296, "9556": 0.2749055027961731, "9608": 0.08064348995685577, "9614": 1.309177041053772, "9723": 0.10467668622732162, "9740": 0.08513788133859634, "9820": 1.4505887031555176, "9867": 0.2026219218969345, "9896": 0.15693697333335876, "9920": 0.1477125883102417, "9942": 0.7500885725021362, "10003": 0.029824240133166313, "10074": 0.6902132034301758, "10173": 0.8306987881660461, "10174": 0.05417001247406006, "10195": 0.35745587944984436, "10293": 0.06612417846918106, "10318": 0.854249119758606, "10372": 0.4041621685028076, "10408": 0.07250232994556427, "10436": 0.06886265426874161, "10476": 0.0770333781838417, "10648": 0.23092569410800934, "10744": 0.2409527748823166, "10788": 0.10555581003427505, "10949": 0.6862877607345581, "11027": 1.0960047245025635, "11100": 0.5033760666847229, "11213": 0.5936289429664612, "11310": 0.3864043951034546, "11326": 0.9021284580230713, "11436": 0.29400965571403503, "11619": 0.7881022095680237, "11643": 0.9186317324638367, "11663": 0.46608972549438477, "11847": 0.2493593990802765, "11860": 0.4855078160762787, "12020": 0.010684899985790253, "12167": 0.2247048318386078, "12210": 0.5450005531311035, "12238": 0.5191890001296997, "12274": 0.5483922958374023, "12298": 1.0437490940093994, "12318": 0.2954642176628113, "12353": 0.8281423449516296, "12477": 0.07793712615966797, "12504": 0.603290855884552, "12546": 0.7818660736083984, "12581": 0.3777405619621277, "12654": 0.43875885009765625, "12689": 0.5936289429664612, "12702": 0.43812891840934753, "12832": 0.037378571927547455, "12870": 0.29255300760269165, "12950": 0.3870677351951599, "12987": 0.06337817758321762, "13014": 0.5074998140335083, "13046": 0.2247048318386078, "13070": 0.5849615335464478, "13434": 0.16524957120418549, "13441": 0.34370049834251404, "13465": 0.8715548515319824, "13490": 0.7124901413917542, "13494": 0.6808650493621826, "13776": 0.020300358533859253, "13792": 0.0913962796330452, "13996": 0.176772341132164, "14244": 0.6527929902076721, "14301": 0.04860413447022438, "14336": 0.11951763927936554, "14440": 0.7665573358535767, "14446": 0.19622190296649933, "14667": 0.15777134895324707, "14670": 0.2983669638633728, "14679": 0.03266380727291107, "14780": 0.3297532796859741, "15157": 0.08154398202896118, "15245": 0.347847044467926, "15306": 0.48970574140548706, "15308": 0.1332872211933136, "15349": 0.8877626657485962, "15525": 0.2659635543823242, "15596": 0.19381128251552582, "15650": 0.5590575933456421, "15877": 0.07250232994556427, "15881": 0.13670019805431366, "15945": 0.2674594223499298, "15976": 0.4462870955467224, "16014": 0.9958525896072388, "16134": 0.5290185213088989, "16185": 0.40611594915390015, "16311": 0.7172679901123047, "16325": 0.3547199070453644, "16514": 0.804835319519043, "16599": 0.010684899985790253, "16670": 0.38308101892471313, "17047": 0.16276304423809052, "17060": 0.036437395960092545, "17208": 0.2786078155040741, "17261": 0.3353555500507355, "17404": 0.08513788133859634, "17503": 0.1693800985813141, "17547": 1.034767985343933, "17566": 0.2501201331615448, "17568": 0.7047978043556213, "17678": 0.151916041970253, "17839": 0.3409265875816345, "17862": 0.15943801403045654, "18076": 0.5596157908439636, "18272": 0.1602703034877777, "18452": 0.11517547070980072, "18949": 0.8534175157546997, "18953": 0.8117979168891907, "18963": 0.025073638185858727, "19195": 0.0317181795835495, "19209": 0.26146242022514343, "19269": 0.47584590315818787, "19294": 0.1693800985813141, "19335": 0.03831886500120163, "19388": 0.5540198087692261, "19481": 0.4728073179721832, "19518": 0.6233867406845093, "19566": 0.09850110858678818, "19628": 0.27342069149017334, "19717": 0.0317181795835495, "19763": 0.04113444685935974, "19939": 0.6980181336402893, "20272": 0.7124901413917542, "20694": 0.2822965085506439, "20792": 0.026976587250828743, "20872": 0.1913948506116867, "20875": 0.7201237678527832, "20900": 0.32058215141296387, "20932": 0.9271688461303711, "21150": 0.5370414853096008, "21183": 1.475906491279602, "21186": 0.49864232540130615, "21304": 0.5947071313858032, "21425": 0.25239890813827515, "21647": 0.24171993136405945, "21663": 0.26446542143821716, "21670": 0.14264501631259918, "21718": 0.06520967930555344, "21796": 0.0058422754518687725, "22248": 0.037378571927547455, "22505": 0.16607704758644104, "22718": 0.8349450826644897, "22793": 0.029824240133166313, "22945": 0.304147332906723, "23041": 0.22079704701900482, "23068": 0.05786345899105072, "23150": 0.2539152204990387, "23329": 0.12728634476661682, "23364": 0.2689530849456787, "24010": 0.06429435312747955, "24093": 0.29619070887565613, "24286": 0.18004031479358673, "24290": 0.1212492436170578, "24471": 0.823009729385376, "24479": 0.14433705806732178, "24710": 0.4574742913246155, "25027": 0.6512666940689087, "25040": 0.21530038118362427, "25095": 0.1212492436170578, "25169": 0.5685047507286072, "25300": 1.0030416250228882, "25323": 0.3077431619167328, "25366": 0.11517547070980072, "25430": 0.2881702482700348, "25437": 0.23324857652187347, "25613": 0.06429435312747955, "25927": 0.0058422754518687725, "25969": 0.1221139207482338, "26022": 0.30989447236061096, "26163": 0.04860413447022438, "26237": 0.23092569410800934, "26462": 0.06977381557226181, "26633": 0.02792670577764511, "26835": 0.00875066313892603, "26887": 0.10203468054533005, "26972": 0.0797421783208847, "27065": 0.11604541540145874, "27144": 0.06154331564903259, "28283": 0.9348671436309814, "28673": 0.26296505331993103, "28981": 0.20501139760017395, "29003": 0.07341018319129944, "29094": 0.06154331564903259, "29300": 0.03831886500120163, "29458": 0.9131608605384827} | 13901073 | BACKGROUND Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV. METHODS AND FINDINGS We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled. CONCLUSIONS Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination. Please see later in the article for the Editors' Summary. | Elimination of HIV in South Africa through Expanded Access to Antiretroviral Therapy: A Model Comparison Study |
{"1009": 0.22157983481884003, "1011": 0.1011524572968483, "1019": 0.5712664127349854, "1043": 0.6613984704017639, "1056": 1.0080435276031494, "1155": 0.42353010177612305, "1164": 0.2478361576795578, "2003": 0.006812678650021553, "2011": 0.23015019297599792, "2029": 0.23864774405956268, "2033": 0.4891071021556854, "2050": 0.5990082025527954, "2053": 0.8772575259208679, "2099": 0.052318159490823746, "2102": 0.4487839937210083, "2109": 0.07612881064414978, "2203": 0.8567397594451904, "2235": 0.17020416259765625, "2274": 0.2576959431171417, "2290": 0.07884006202220917, "2302": 0.03831886500120163, "2310": 0.15610189735889435, "2509": 0.47827014327049255, "2512": 0.34577593207359314, "2515": 0.2034190446138382, "2529": 0.5404602885246277, "2535": 0.15359249711036682, "2537": 0.7258110046386719, "2550": 0.4196864068508148, "2581": 0.4093637466430664, "2618": 0.32270604372024536, "2629": 1.2510874271392822, "2765": 0.401551216840744, "2891": 0.4837033152580261, "2920": 0.13925230503082275, "2953": 0.13925230503082275, "3022": 0.03266380727291107, "3081": 0.1602703034877777, "3161": 0.016465263441205025, "3278": 0.0770333781838417, "3283": 0.3588210940361023, "3334": 0.5016035437583923, "3433": 0.8633513450622559, "3445": 0.5607312321662903, "3463": 0.48610860109329224, "3466": 0.6461620330810547, "3508": 0.12814582884311676, "3526": 0.6709295511245728, "3587": 0.29109421372413635, "3595": 0.030771657824516296, "3623": 0.5968599319458008, "3670": 0.5618454217910767, "3853": 0.7987030148506165, "3893": 0.037378571927547455, "3896": 0.5579402446746826, "3904": 0.17759032547473907, "3921": 0.3883931338787079, "3949": 0.5466978549957275, "3965": 0.28597161173820496, "4244": 0.08782484382390976, "4286": 0.4067663550376892, "4313": 0.1477125883102417, "4359": 0.28963330388069153, "4442": 0.8740028142929077, "4456": 0.18329764902591705, "4496": 0.259204238653183, "4517": 0.6043586730957031, "4539": 0.32764431834220886, "4668": 0.2637155055999756, "4700": 0.5238267183303833, "4742": 0.4831010699272156, "4747": 0.48430517315864563, "4748": 0.5186077356338501, "4834": 0.026025565341114998, "4852": 0.0009760859538801014, "4921": 0.013579257763922215, "4957": 0.11081436276435852, "4962": 0.1229778528213501, "4972": 0.5057345628738403, "5054": 0.817850649356842, "5155": 0.06520967930555344, "5159": 0.14518201351165771, "5228": 0.08692999184131622, "5250": 0.8091925978660583, "5333": 0.020300358533859253, "5360": 0.4158279001712799, "5387": 0.4950772523880005, "5423": 0.7314660549163818, "5449": 0.01934296265244484, "5547": 0.13670019805431366, "5603": 0.13499516248703003, "5642": 0.33605360984802246, "5648": 0.7482418417930603, "5666": 0.6926587820053101, "5668": 0.04207121208310127, "5799": 0.14264501631259918, "5845": 0.20580662786960602, "5850": 0.13755162060260773, "5876": 0.20660123229026794, "6022": 0.791648268699646, "6187": 0.3141832649707794, "6258": 0.07793712615966797, "6305": 0.28082266449928284, "6377": 0.1889725625514984, "6470": 0.29473719000816345, "6541": 0.37907835841178894, "6551": 0.2749055027961731, "6843": 0.03360854089260101, "6869": 0.319873183965683, "6887": 0.46117570996284485, "6914": 0.083342544734478, "7137": 0.11168810725212097, "7242": 0.22157983481884003, "7274": 0.5562619566917419, "7337": 0.3084607720375061, "7361": 0.36494144797325134, "7438": 0.2719337046146393, "7457": 0.4487839937210083, "7461": 0.6343214511871338, "7476": 0.6207655072212219, "7507": 0.49864232540130615, "7591": 0.16690383851528168, "7755": 0.4709797203540802, "7863": 1.1450434923171997, "7889": 0.07431721687316895, "8031": 0.083342544734478, "8107": 0.1485546976327896, "8153": 0.40089741349220276, "8171": 0.5139457583427429, "8319": 0.08154398202896118, "8360": 0.2881702482700348, "8458": 0.4145384132862091, "8529": 0.7067264318466187, "8878": 0.6286086440086365, "8939": 0.6374238729476929, "8945": 0.5855054259300232, "8961": 0.417115718126297, "9007": 0.6734226942062378, "9416": 0.052318159490823746, "9513": 0.11778303235769272, "9597": 0.2184450328350067, "9607": 0.997294545173645, "9839": 0.16607704758644104, "9885": 0.5261374711990356, "10124": 0.4093637466430664, "10253": 0.7258110046386719, "10509": 0.129004567861557, "10548": 0.681853175163269, "10572": 0.981317400932312, "10722": 0.07341018319129944, "10737": 0.26446542143821716, "10752": 0.5191890001296997, "10769": 1.005902886390686, "10814": 0.8666408061981201, "10960": 0.6286086440086365, "11022": 0.7827593088150024, "11099": 0.42990362644195557, "11100": 0.7295845746994019, "11113": 0.15526613593101501, "11211": 1.162295937538147, "11231": 0.7028654217720032, "11290": 0.14349138736724854, "11311": 0.09584271162748337, "11663": 0.6451379656791687, "11921": 0.016465263441205025, "12099": 0.020300358533859253, "12381": 0.011650617234408855, "12473": 0.10555581003427505, "12541": 0.1808556467294693, "12737": 0.5865923762321472, "12818": 1.1834511756896973, "12987": 0.8083226680755615, "13143": 0.043007105588912964, "13153": 0.6867793202400208, "13341": 0.011650617234408855, "13416": 0.02412080205976963, "13441": 0.3084607720375061, "13490": 0.817850649356842, "13512": 0.17840765416622162, "13531": 0.5010119676589966, "13656": 0.6080870032310486, "13791": 0.9493325352668762, "13833": 1.0101795196533203, "13922": 0.29109421372413635, "14074": 0.151916041970253, "14095": 0.06977381557226181, "14120": 0.3034266233444214, "14262": 0.4444103240966797, "14449": 0.05786345899105072, "14454": 0.8901712894439697, "14526": 0.7220231294631958, "14573": 0.8517522215843201, "14828": 0.272677481174469, "14841": 0.21922965347766876, "15115": 0.5629584193229675, "15306": 0.029824240133166313, "15431": 0.03925827145576477, "15472": 1.149384617805481, "15637": 0.6664261221885681, "15663": 0.10379679501056671, "15946": 0.1970241367816925, "16000": 0.055094651877880096, "16026": 0.06612417846918106, "16081": 0.007782140281051397, "16185": 0.14518201351165771, "16285": 0.4512746334075928, "16341": 0.12728634476661682, "16523": 1.4450790882110596, "16730": 0.9783848524093628, "16882": 0.8748174905776978, "17076": 0.08603433519601822, "17379": 0.29036402702331543, "17441": 0.5495203733444214, "17603": 0.4412745535373688, "17643": 0.15442965924739838, "17712": 0.75193190574646, "17788": 0.2696990668773651, "17913": 0.38574060797691345, "18089": 0.052318159490823746, "18139": 0.0009760859538801014, "18231": 0.08961215615272522, "18260": 0.4203280806541443, "18674": 0.1510767638683319, "18688": 0.06886265426874161, "18714": 0.4431571960449219, "18847": 0.7546905279159546, "19220": 0.6223390698432922, "19481": 0.22001366317272186, "19653": 0.7898768186569214, "19780": 0.7463917136192322, "19872": 1.0855059623718262, "19961": 0.3910386264324188, "19982": 0.890972912311554, "20118": 0.7038320899009705, "20187": 1.0901126861572266, "20299": 0.4412745535373688, "20350": 0.12728634476661682, "20534": 0.8658194541931152, "20544": 0.672426164150238, "20752": 0.2478361576795578, "20766": 0.03266380727291107, "20806": 0.4113073945045471, "20817": 0.15023678541183472, "20858": 0.3824150264263153, "20868": 0.15860503911972046, "21040": 0.011650617234408855, "21338": 0.009718249551951885, "21434": 0.37974658608436584, "21449": 1.1929750442504883, "21466": 0.10291612148284912, "21471": 1.1726272106170654, "21472": 0.24325250089168549, "21486": 0.02792670577764511, "21579": 0.4093637466430664, "21693": 0.5495203733444214, "21733": 0.7907629609107971, "21799": 0.09495500475168228, "21903": 0.4286321699619293, "21919": 0.06520967930555344, "22239": 0.7144040465354919, "22595": 0.3883931338787079, "22610": 0.8550800085067749, "22930": 0.1602703034877777, "22935": 0.08064348995685577, "23079": 0.04953393340110779, "23216": 0.2531573474407196, "23296": 0.26446542143821716, "23352": 0.34023189544677734, "23518": 0.4709797203540802, "23572": 0.29400965571403503, "23586": 0.9485763907432556, "23746": 0.1619328260421753, "23777": 0.03831886500120163, "23797": 0.04207121208310127, "23974": 1.54988694190979, "24054": 0.8400169610977173, "24171": 0.42353010177612305, "24203": 0.9317949414253235, "24269": 0.8608771562576294, "24324": 0.6654226183891296, "24529": 0.39367714524269104, "24587": 1.0526502132415771, "24665": 0.12470348179340363, "24848": 0.24554696679115295, "25117": 0.05786345899105072, "25194": 0.3005385100841522, "25276": 0.03925827145576477, "25456": 0.5646255612373352, "25714": 0.44691193103790283, "25761": 0.030771657824516296, "26033": 0.3084607720375061, "26187": 0.2822965085506439, "26224": 0.1930064558982849, "26402": 0.9531047344207764, "26419": 0.09406650811433792, "26494": 0.17431432008743286, "26565": 0.6848117709159851, "26651": 0.23787821829319, "26721": 0.7978238463401794, "26773": 0.02316705882549286, "26785": 0.630689799785614, "27295": 0.05139094591140747, "27321": 0.5010119676589966, "27833": 0.09228714555501938, "27854": 0.40351006388664246, "27989": 0.07431721687316895, "28113": 0.3443928062915802, "28228": 0.8366385698318481, "28696": 0.10379679501056671, "28788": 0.02887592278420925, "29166": 0.8091925978660583, "29290": 0.3339579105377197} | 13902570 | OBJECTIVE TGR5 is a G-protein-coupled receptor for bile acids. So far, little is known about the function of TGR5 in vascular endothelial cells. APPROACH AND RESULTS In bovine aortic endothelial cells, treatment with a bile acid having a high affinity to TGR5, taurolithocholic acid (TLCA), significantly increased NO production. This effect was abolished by small interfering RNA-mediated depletion of TGR5. TLCA-induced NO production was also observed in human umbilical vein endothelial cells measured via intracellular cGMP accumulation. TLCA increased endothelial NO synthase(ser1177) phosphorylation in human umbilical vein endothelial cells. This response was accompanied by increased Akt(ser473) phosphorylation and intracellular Ca(2+). Inhibition of these signals significantly decreased TLCA-induced NO production. We next examined whether TGR5-mediated NO production affects inflammatory responses of endothelial cells. In human umbilical vein endothelial cells, TLCA significantly reduced tumor necrosis factor-α-induced adhesion of monocytes, vascular cell adhesion molecule-1 expression, and activation of nuclear factor-κB. TLCA also inhibited lipopolysaccharide-induced monocyte adhesion to mesenteric venules in vivo. These inhibitory effects of TLCA were abrogated by NO synthase inhibition. CONCLUSIONS TGR5 agonism induces NO production via Akt activation and intracellular Ca(2+) increase in vascular endothelial cells, and this function inhibits monocyte adhesion in response to inflammatory stimuli. | Bile acid receptor TGR5 agonism induces NO production and reduces monocyte adhesion in vascular endothelial cells. |
{"1011": 0.10203468054533005, "1042": 0.6260011196136475, "1052": 0.5795059204101562, "1998": 0.0317181795835495, "2003": 0.08154398202896118, "2007": 0.13670019805431366, "2024": 0.1485546976327896, "2029": 0.07612881064414978, "2072": 0.14349138736724854, "2075": 0.176772341132164, "2155": 1.0748957395553589, "2159": 0.04487626627087593, "2171": 0.004870930220931768, "2177": 0.4349733293056488, "2179": 0.12728634476661682, "2213": 0.10555581003427505, "2227": 0.7239188551902771, "2229": 0.11168810725212097, "2266": 0.4374985992908478, "2291": 0.18004031479358673, "2310": 0.777387797832489, "2350": 0.49864232540130615, "2358": 0.4002431631088257, "2362": 0.08513788133859634, "2364": 0.0058422754518687725, "2372": 0.17840765416622162, "2389": 0.052318159490823746, "2427": 0.34023189544677734, "2465": 0.23015019297599792, "2470": 0.05046287178993225, "2483": 0.05786345899105072, "2487": 0.28670501708984375, "2529": 0.5324648022651672, "2594": 0.06795065850019455, "2615": 1.2238903045654297, "2649": 0.06154331564903259, "2662": 0.4437839686870575, "2817": 0.36967599391937256, "2828": 0.1229778528213501, "2913": 0.272677481174469, "2944": 0.5612884759902954, "2945": 0.680370569229126, "2950": 0.08244366943836212, "2953": 0.24401791393756866, "2966": 0.5127768516540527, "3001": 0.38574060797691345, "3085": 0.500420093536377, "3128": 0.6512666940689087, "3132": 0.34922540187835693, "3141": 0.12986256182193756, "3168": 0.619189441204071, "3193": 0.0797421783208847, "3226": 0.6244332790374756, "3239": 0.2969166338443756, "3252": 0.6233867406845093, "3273": 0.31489628553390503, "3278": 0.29036402702331543, "3303": 0.28670501708984375, "3370": 0.2918238639831543, "3375": 0.8492490649223328, "3378": 0.2231435477733612, "3397": 0.18492233753204346, "3426": 0.5427330136299133, "3431": 0.176772341132164, "3451": 0.12556517124176025, "3491": 0.0354953333735466, "3526": 0.3870677351951599, "3562": 0.7827593088150024, "3563": 0.06977381557226181, "3593": 0.7086513638496399, "3603": 0.0029254043474793434, "3605": 0.12038381397724152, "3625": 0.14686977863311768, "3677": 0.8195732831954956, "3768": 0.1510767638683319, "3775": 0.49982786178588867, "3806": 0.4145384132862091, "3893": 0.8682814836502075, "3896": 0.09495500475168228, "3900": 1.072225570678711, "4045": 0.23864774405956268, "4111": 0.6970458030700684, "4117": 0.1332872211933136, "4127": 0.11343330889940262, "4176": 0.8238670229911804, "4179": 0.7305257320404053, "4275": 0.3956514894962311, "4286": 0.7610978484153748, "4295": 0.6112717390060425, "4308": 0.3656192123889923, "4320": 0.009718249551951885, "4429": 1.4199029207229614, "4442": 0.15693697333335876, "4453": 0.48970574140548706, "4492": 0.29036402702331543, "4696": 0.11778303235769272, "4786": 0.013579257763922215, "4812": 0.7276995778083801, "4895": 0.43053874373435974, "4937": 0.4158279001712799, "4987": 0.33675122261047363, "5090": 0.39893341064453125, "5098": 0.4770587682723999, "5250": 0.9021284580230713, "5320": 0.6583697199821472, "5332": 0.7305257320404053, "5344": 0.22079704701900482, "5383": 0.11343330889940262, "5390": 0.6059582233428955, "5435": 0.2852376699447632, "5555": 0.24631060659885406, "5579": 0.37035053968429565, "5813": 0.42544642090797424, "5884": 0.6704301834106445, "6077": 0.05694137513637543, "6096": 0.8731874823570251, "6178": 0.6275664567947388, "6184": 0.6202403903007507, "6187": 0.4177590310573578, "6219": 0.08513788133859634, "6338": 0.12556517124176025, "6459": 0.11081436276435852, "6483": 0.5191890001296997, "6537": 0.0174254160374403, "6598": 0.0797421783208847, "6612": 0.13071982562541962, "6709": 0.0770333781838417, "6767": 0.38174858689308167, "6819": 0.13925230503082275, "6858": 0.2954642176628113, "6895": 0.28890204429626465, "6904": 0.14602625370025635, "7141": 0.34922540187835693, "7315": 0.6202403903007507, "7337": 0.6659244894981384, "7355": 0.5261374711990356, "7356": 0.11168810725212097, "7366": 0.20580662786960602, "7784": 0.5404602885246277, "7865": 1.2846163511276245, "7870": 0.5882205963134766, "8031": 0.16359257698059082, "8171": 0.7863243818283081, "8278": 0.037378571927547455, "8290": 0.7510106563568115, "8332": 0.8161250352859497, "8360": 0.6054253578186035, "8382": 0.0752234235405922, "8516": 0.07250232994556427, "8552": 0.15610189735889435, "8556": 0.2409527748823166, "8578": 0.46853771805763245, "8676": 0.18816383183002472, "8681": 0.4431571960449219, "8735": 0.15359249711036682, "8789": 0.46117570996284485, "8832": 0.2990913391113281, "8870": 0.5662899017333984, "8985": 0.3141832649707794, "9064": 0.151916041970253, "9071": 0.35813871026039124, "9201": 0.17922431230545044, "9207": 0.18816383183002472, "9289": 0.3381449282169342, "9456": 0.07068414986133575, "9530": 0.10731173306703568, "9626": 0.5069117546081543, "9700": 1.102510929107666, "9751": 0.37102460861206055, "9820": 0.2689530849456787, "9821": 0.48068851232528687, "10178": 0.06520967930555344, "10250": 1.3911652565002441, "10266": 0.8731874823570251, "10327": 0.45251765847206116, "10374": 0.10203468054533005, "10496": 0.4673144817352295, "10572": 0.29981520771980286, "10595": 0.6482070088386536, "10639": 0.007782140281051397, "10737": 0.2637155055999756, "10768": 0.7827593088150024, "10769": 1.1211429834365845, "10840": 0.08244366943836212, "10847": 0.47463157773017883, "10946": 0.11517547070980072, "11325": 0.6244332790374756, "11338": 0.040196798741817474, "11416": 0.3903779089450836, "11538": 0.255429208278656, "11643": 0.17431432008743286, "11767": 0.24325250089168549, "11829": 0.12384103983640671, "11835": 0.6348392367362976, "11993": 0.08692999184131622, "12093": 0.42608439922332764, "12171": 0.2105647772550583, "12346": 0.018384648486971855, "12369": 0.3656192123889923, "12546": 0.09317722171545029, "12702": 0.34508460760116577, "12735": 0.32270604372024536, "12848": 0.6054253578186035, "12859": 0.5421652793884277, "12935": 0.03266380727291107, "12987": 1.2791962623596191, "13100": 0.5069117546081543, "13181": 0.6897233724594116, "13268": 0.0842406153678894, "13348": 0.04394211992621422, "13434": 1.1005635261535645, "13458": 0.13925230503082275, "13706": 0.5668440461158752, "13833": 1.108330488204956, "13851": 0.2539152204990387, "13880": 0.04767346754670143, "13922": 0.35060185194015503, "14064": 0.21372433006763458, "14187": 0.1332872211933136, "14440": 0.25995752215385437, "14449": 0.7791815400123596, "14766": 0.2145126610994339, "15026": 0.23710809648036957, "15088": 0.46608972549438477, "15245": 0.11865071207284927, "15420": 0.34023189544677734, "15431": 0.06154331564903259, "15451": 0.0354953333735466, "15651": 0.8691008687019348, "15695": 0.29400965571403503, "15821": 0.23402166366577148, "15923": 0.5010119676589966, "16098": 0.7163142561912537, "16146": 0.1384023278951645, "16464": 0.8298473954200745, "16514": 0.04860413447022438, "16531": 0.8861536383628845, "16567": 0.05417001247406006, "16781": 0.0842406153678894, "16792": 0.02412080205976963, "17341": 0.11517547070980072, "17404": 0.28963330388069153, "17668": 0.03360854089260101, "17678": 0.058784693479537964, "17886": 0.3723714053630829, "18191": 1.3060075044631958, "18401": 0.034552380442619324, "18859": 0.08782484382390976, "18898": 0.2105647772550583, "19019": 0.15359249711036682, "19126": 0.04674193635582924, "19476": 0.23247487843036652, "19610": 0.4374985992908478, "19653": 0.46853771805763245, "19792": 0.9915141463279724, "19857": 0.18573370575904846, "19872": 0.05139094591140747, "20014": 0.02792670577764511, "20062": 0.4950772523880005, "20569": 0.015504186972975731, "20594": 0.5238267183303833, "20763": 0.08064348995685577, "20817": 0.4879087805747986, "20906": 0.020300358533859253, "21025": 0.28963330388069153, "21162": 0.1685553640127182, "21210": 0.7124901413917542, "21471": 0.5827828645706177, "21595": 0.08244366943836212, "21663": 1.0768938064575195, "21685": 0.10731173306703568, "21770": 0.012615402229130268, "21861": 0.06154331564903259, "21935": 0.23247487843036652, "22167": 0.26296505331993103, "22476": 0.3588210940361023, "22718": 0.07159364968538284, "22974": 0.8298473954200745, "23192": 0.10555581003427505, "23350": 1.2175520658493042, "23758": 0.9425065517425537, "24004": 0.8022117614746094, "24012": 0.09228714555501938, "24093": 0.5696102976799011, "24169": 0.3824150264263153, "24635": 0.5551415085792542, "24757": 0.40220460295677185, "25032": 0.839173436164856, "25090": 0.2493593990802765, "25274": 0.21214580535888672, "25476": 0.020300358533859253, "25700": 0.13157635927200317, "26013": 0.8957691192626953, "26052": 0.2184450328350067, "26396": 0.05970508232712746, "26524": 0.10993985831737518, "26835": 0.6704301834106445, "27169": 0.29619070887565613, "27263": 0.056018441915512085, "28389": 0.09761575609445572, "28735": 0.22079704701900482, "28775": 1.1911962032318115, "28848": 0.46608972549438477, "28873": 0.23402166366577148, "28896": 0.17020416259765625, "29060": 0.3897167444229126, "29105": 0.4145384132862091, "29110": 0.8780695199966431, "29135": 0.15526613593101501, "29290": 0.6921701431274414, "29489": 0.23556606471538544, "29525": 0.7028654217720032} | 13903052 | The Caliciviridae family comprises positive-sense RNA viruses of medical and veterinary significance. In humans, caliciviruses are a major cause of acute gastroenteritis, while in animals respiratory illness, conjunctivitis, stomatitis, and hemorrhagic disease are documented. Investigation of virus-host interactions is limited by a lack of culture systems for many viruses in this family. Feline calicivirus (FCV), a member of the Vesivirus genus, provides a tractable model, since it may be propagated in cell culture. Feline junctional adhesion molecule 1 (fJAM-1) was recently identified as a functional receptor for FCV. We have analyzed the structure of this virus-receptor complex by cryo-electron microscopy and three-dimensional image reconstruction, combined with fitting of homology modeled high-resolution coordinates. We show that domain 1 of fJAM-1 binds to the outer face of the P2 domain of the FCV capsid protein VP1, inducing conformational changes in the viral capsid. This study provides the first structural view of a native calicivirus-protein receptor complex and insights into the mechanisms of virus attachment and uncoating. | Structural insights into calicivirus attachment and uncoating. |
{"1011": 0.18492233753204346, "1017": 0.4041621685028076, "1028": 0.2689530849456787, "1042": 0.06977381557226181, "1043": 0.5472630262374878, "1054": 0.37707099318504333, "1056": 0.6000806093215942, "1997": 0.12814582884311676, "2025": 0.0029254043474793434, "2029": 0.19782574474811554, "2035": 0.32553088665008545, "2050": 0.38441169261932373, "2078": 0.0317181795835495, "2080": 0.9005423784255981, "2083": 0.18573370575904846, "2093": 0.06977381557226181, "2166": 0.4568560719490051, "2182": 0.1718502640724182, "2184": 0.22548456490039825, "2200": 0.03831886500120163, "2290": 0.1332872211933136, "2339": 0.0606246218085289, "2353": 0.09406650811433792, "2378": 0.3019835948944092, "2396": 0.3353555500507355, "2421": 0.11604541540145874, "2426": 0.045809537172317505, "2443": 0.045809537172317505, "2470": 0.175953671336174, "2487": 0.6181373596191406, "2509": 0.9139442443847656, "2512": 0.6926587820053101, "2515": 0.2317005842924118, "2523": 0.6941232681274414, "2535": 0.7445381283760071, "2537": 0.5898461937904358, "2546": 0.6353566646575928, "2550": 0.3723714053630829, "2575": 0.11168810725212097, "2581": 0.04207121208310127, "2607": 1.0229004621505737, "2633": 0.09050461649894714, "2750": 0.15023678541183472, "2765": 0.31845372915267944, "2776": 0.3077431619167328, "2817": 0.37974658608436584, "2864": 0.034552380442619324, "2891": 0.4873090982437134, "2898": 0.6704301834106445, "2913": 0.3353555500507355, "2920": 0.2409527748823166, "2947": 0.21135559678077698, "2951": 0.4855078160762787, "2966": 0.05694137513637543, "3081": 0.5893046259880066, "3169": 0.1808556467294693, "3170": 0.06612417846918106, "3255": 0.016465263441205025, "3265": 0.176772341132164, "3273": 0.22079704701900482, "3286": 0.4349733293056488, "3298": 0.2478361576795578, "3375": 1.0567318201065063, "3378": 0.6877616047859192, "3399": 0.022212404757738113, "3406": 0.39762192964553833, "3424": 0.6543170213699341, "3426": 0.06337817758321762, "3433": 0.9147270321846008, "3445": 0.32553088665008545, "3463": 0.23710809648036957, "3466": 0.259204238653183, "3491": 0.31845372915267944, "3498": 0.20421554148197174, "3525": 0.03925827145576477, "3563": 0.045809537172317505, "3576": 1.17624831199646, "3593": 0.32270604372024536, "3597": 0.5833279490470886, "3603": 0.10555581003427505, "3623": 0.21765978634357452, "3625": 0.18248429894447327, "3633": 0.29981520771980286, "3670": 0.2749055027961731, "3745": 0.2918238639831543, "3747": 0.06429435312747955, "3802": 0.08064348995685577, "3853": 0.0770333781838417, "3891": 0.46055975556373596, "3896": 0.21293537318706512, "3965": 0.24859806895256042, "4013": 0.9849710464477539, "4130": 0.5324648022651672, "4187": 0.822151780128479, "4207": 0.5324648022651672, "4235": 0.08961215615272522, "4254": 0.7510106563568115, "4295": 1.0285027027130127, "4307": 0.272677481174469, "4340": 0.3519764244556427, "4395": 0.5751199722290039, "4419": 1.3759875297546387, "4453": 0.3656192123889923, "4456": 0.2674594223499298, "4667": 0.87237149477005, "4668": 0.2674594223499298, "4821": 0.37907835841178894, "4962": 1.0001721382141113, "5012": 0.17759032547473907, "5022": 0.43053874373435974, "5155": 0.11430477350950241, "5158": 0.011650617234408855, "5201": 0.28890204429626465, "5250": 0.255429208278656, "5298": 0.2247048318386078, "5319": 0.2478361576795578, "5320": 0.10291612148284912, "5352": 0.6451379656791687, "5360": 0.4374985992908478, "5369": 0.6064908504486084, "5387": 0.3134697377681732, "5452": 0.5220900774002075, "5533": 1.0158531665802002, "5547": 0.0058422754518687725, "5646": 0.2231435477733612, "5664": 0.4145384132862091, "5666": 0.31132611632347107, "5729": 0.45623743534088135, "5748": 0.5795059204101562, "5776": 0.5421652793884277, "5787": 0.24171993136405945, "5857": 0.684319257736206, "5876": 0.11865071207284927, "6022": 0.2034190446138382, "6064": 0.6000806093215942, "6190": 0.8400169610977173, "6335": 1.1363043785095215, "6459": 0.03360854089260101, "6473": 0.015504186972975731, "6529": 0.013579257763922215, "6537": 0.11691460013389587, "6541": 0.010684899985790253, "6612": 0.8796916007995605, "6631": 0.10906458646059036, "6691": 0.9340999722480774, "6709": 0.23324857652187347, "6779": 0.23247487843036652, "6869": 0.47766464948654175, "6872": 0.04860413447022438, "6873": 0.011650617234408855, "6897": 0.1930064558982849, "7028": 0.10467668622732162, "7137": 0.20102575421333313, "7242": 0.11517547070980072, "7337": 0.21214580535888672, "7355": 0.3877306580543518, "7356": 0.08871890604496002, "7366": 0.28450319170951843, "7400": 0.00875066313892603, "7403": 1.2627575397491455, "7457": 0.36697331070899963, "7461": 0.37907835841178894, "7578": 0.17840765416622162, "7645": 0.11865071207284927, "7691": 0.20022670924663544, "7870": 0.8796916007995605, "7883": 0.17020416259765625, "7885": 0.015504186972975731, "7900": 0.401551216840744, "8020": 0.21293537318706512, "8023": 0.2983669638633728, "8031": 0.17267228662967682, "8092": 0.13755162060260773, "8119": 0.05139094591140747, "8137": 0.35677260160446167, "8197": 0.0317181795835495, "8247": 0.1946154683828354, "8349": 0.1011524572968483, "8358": 0.0174254160374403, "8386": 0.5393219590187073, "8465": 0.04394211992621422, "8552": 0.48068851232528687, "8715": 0.2034190446138382, "8761": 0.32199856638908386, "8821": 0.12038381397724152, "8898": 0.3485364317893982, "8924": 0.5517725944519043, "8985": 0.15275461971759796, "8991": 0.5033760666847229, "9002": 0.5133614540100098, "9007": 0.39762192964553833, "9096": 0.07341018319129944, "9118": 1.0546929836273193, "9128": 0.026976587250828743, "9165": 0.9194108247756958, "9297": 0.2852376699447632, "9319": 0.07431721687316895, "9349": 0.1229778528213501, "9426": 0.19782574474811554, "9513": 0.2741633653640747, "9523": 0.8022117614746094, "9560": 0.8682814836502075, "9597": 0.27342069149017334, "9671": 0.0842406153678894, "9783": 0.43244171142578125, "9820": 0.012615402229130268, "9869": 0.472198486328125, "9932": 0.1734936386346817, "9996": 0.1384023278951645, "10074": 0.0770333781838417, "10091": 0.0019512200960889459, "10253": 0.7352184057235718, "10256": 0.5336109399795532, "10258": 0.5952457785606384, "10509": 0.21135559678077698, "10514": 0.38574060797691345, "10572": 0.3241194784641266, "10586": 0.4891071021556854, "10744": 0.16276304423809052, "10790": 0.012615402229130268, "10840": 0.3676496744155884, "10857": 0.06795065850019455, "10924": 0.7370892763137817, "10960": 0.7755908370018005, "11020": 0.3163207769393921, "11156": 0.03925827145576477, "11229": 0.12986256182193756, "11311": 0.3910386264324188, "11321": 0.8845420479774475, "11363": 0.02412080205976963, "11387": 0.1693800985813141, "11441": 0.4938860833644867, "11553": 0.05970508232712746, "11616": 0.6999598741531372, "11619": 0.41065993905067444, "11631": 0.9531047344207764, "11909": 0.07159364968538284, "12115": 0.3241194784641266, "12130": 0.3248254358768463, "12207": 0.014542185701429844, "12248": 0.7629209756851196, "12260": 0.9348671436309814, "12359": 0.24325250089168549, "12369": 0.812664806842804, "12521": 0.20739519596099854, "12530": 0.09228714555501938, "12667": 0.5696102976799011, "12732": 1.181056022644043, "12763": 0.014542185701429844, "12839": 0.21765978634357452, "12987": 0.1873544454574585, "13070": 0.49030399322509766, "13091": 0.007782140281051397, "13105": 0.7827593088150024, "13181": 0.012615402229130268, "13416": 0.11951763927936554, "13418": 0.17431432008743286, "13458": 0.9798521995544434, "13464": 0.6960725784301758, "13494": 0.16276304423809052, "13531": 0.02316705882549286, "13675": 0.5612884759902954, "13874": 0.029824240133166313, "13938": 0.011650617234408855, "14074": 0.29981520771980286, "14080": 0.3318578004837036, "14120": 0.3982778787612915, "14142": 0.0029254043474793434, "14163": 0.13499516248703003, "14193": 0.14264501631259918, "14228": 0.2607102394104004, "14427": 0.3297532796859741, "14471": 1.0788878202438354, "14486": 0.25845035910606384, "14494": 0.5495203733444214, "14608": 0.3656192123889923, "14670": 0.472198486328125, "14786": 0.037378571927547455, "14800": 0.7482418417930603, "14828": 0.2247048318386078, "15112": 0.052318159490823746, "15361": 0.0797421783208847, "15420": 0.4002431631088257, "15527": 0.4400174915790558, "15543": 0.16524957120418549, "15801": 0.020300358533859253, "15877": 0.12556517124176025, "16014": 0.20660123229026794, "16206": 0.175953671336174, "16221": 0.7683706283569336, "16238": 0.03360854089260101, "16275": 0.1685553640127182, "16281": 0.013579257763922215, "16387": 0.151916041970253, "16412": 0.2637155055999756, "16463": 0.567397952079773, "16474": 0.4400174915790558, "16505": 0.2247048318386078, "16514": 0.08871890604496002, "16515": 0.4145384132862091, "16530": 0.22079704701900482, "16605": 0.28963330388069153, "16690": 0.04953393340110779, "16706": 0.4412745535373688, "16771": 0.12470348179340363, "16884": 0.43875885009765625, "16910": 1.0648454427719116, "16913": 0.9115922451019287, "17651": 0.004870930220931768, "17782": 0.0174254160374403, "18002": 0.1384023278951645, "18077": 0.8057082891464233, "18078": 0.2800849378108978, "18260": 0.02316705882549286, "18275": 0.10906458646059036, "18464": 0.5483922958374023, "18516": 0.49982786178588867, "18549": 0.0770333781838417, "18700": 0.004870930220931768, "18715": 1.1994705200195312, "18847": 0.5461324453353882, "18900": 0.7592713832855225, "18969": 0.2231435477733612, "18976": 0.15275461971759796, "19009": 0.1734936386346817, "19132": 1.439538836479187, "19137": 0.12642613053321838, "19209": 0.36426326632499695, "19293": 0.036437395960092545, "19314": 0.28963330388069153, "19345": 0.672426164150238, "19500": 0.2160874605178833, "19539": 1.1941591501235962, "19601": 0.10203468054533005, "19653": 0.19381128251552582, "19676": 0.11256109178066254, "19872": 0.2516399025917053, "20062": 0.5381823778152466, "20117": 0.18329764902591705, "20187": 1.2549926042556763, "20350": 0.23556606471538544, "20353": 0.1734936386346817, "20397": 0.1064341589808464, "20467": 0.14518201351165771, "20567": 0.034552380442619324, "20569": 0.26296505331993103, "20582": 0.2478361576795578, "21155": 0.19541899859905243, "21198": 0.22079704701900482, "21262": 0.06337817758321762, "21268": 0.24325250089168549, "21425": 0.006812678650021553, "21446": 0.0797421783208847, "21486": 0.014542185701429844, "21557": 0.07884006202220917, "21733": 0.9591107368469238, "21903": 0.39893341064453125, "22026": 0.1677299439907074, "22330": 0.8740028142929077, "22529": 0.06246116757392883, "22643": 0.0038986403960734606, "22901": 0.029824240133166313, "22930": 0.06520967930555344, "22931": 0.018384648486971855, "23041": 0.2026219218969345, "23205": 0.013579257763922215, "23284": 0.3127557039260864, "23606": 0.8933739066123962, "23737": 0.1685553640127182, "23833": 0.12384103983640671, "23892": 0.006812678650021553, "23900": 0.2983669638633728, "23971": 0.17759032547473907, "24004": 0.056018441915512085, "24054": 0.010684899985790253, "24186": 0.17840765416622162, "24229": 0.3297532796859741, "24353": 0.26146242022514343, "24558": 0.07612881064414978, "24623": 0.8600510358810425, "24670": 0.03360854089260101, "24757": 0.11951763927936554, "25117": 0.06429435312747955, "25206": 0.38905516266822815, "25360": 0.20102575421333313, "25469": 0.24018502235412598, "25502": 0.6254787445068359, "25524": 0.2983669638633728, "25605": 0.026976587250828743, "25686": 0.04860413447022438, "25708": 1.175042748451233, "26180": 0.06246116757392883, "26305": 0.7352184057235718, "26378": 0.1510767638683319, "26462": 0.004870930220931768, "26534": 0.2667117714881897, "26572": 0.8475768566131592, "26601": 0.19782574474811554, "26651": 0.24018502235412598, "26741": 0.9194108247756958, "26745": 1.094698429107666, "26835": 0.31845372915267944, "26874": 0.17020416259765625, "26944": 0.6872705817222595, "27321": 0.7314660549163818, "27641": 1.0986123085021973, "27642": 0.037378571927547455, "27717": 0.15777134895324707, "28286": 1.076228141784668, "28290": 0.3416208028793335, "28389": 0.004870930220931768, "28436": 1.0835250616073608, "28788": 0.22001366317272186, "28873": 0.4248080551624298, "28935": 0.07884006202220917, "29107": 0.0354953333735466, "29206": 0.14349138736724854, "29458": 0.3034266233444214, "29720": 0.669430673122406} | 13905670 | The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn's disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. | Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway |
{"1011": 0.037378571927547455, "1014": 0.37907835841178894, "1998": 0.13499516248703003, "2012": 0.058784693479537964, "2021": 0.06429435312747955, "2049": 0.19541899859905243, "2053": 0.2160874605178833, "2060": 0.4462870955467224, "2062": 0.06246116757392883, "2066": 0.12728634476661682, "2082": 0.016465263441205025, "2084": 0.6369074583053589, "2090": 0.34370049834251404, "2109": 0.1011524572968483, "2119": 0.4286321699619293, "2166": 0.23787821829319, "2168": 0.3870677351951599, "2169": 0.2394166737794876, "2174": 0.006812678650021553, "2177": 0.151916041970253, "2219": 0.1384023278951645, "2235": 0.17759032547473907, "2241": 0.029824240133166313, "2331": 0.40546512603759766, "2339": 0.013579257763922215, "2348": 0.0174254160374403, "2364": 0.4067663550376892, "2367": 0.35950297117233276, "2403": 0.11778303235769272, "2415": 0.08064348995685577, "2421": 0.05417001247406006, "2443": 0.036437395960092545, "2451": 0.36290550231933594, "2464": 0.5197699069976807, "2470": 0.5925496220588684, "2475": 0.42353010177612305, "2478": 0.31132611632347107, "2488": 0.7969439625740051, "2495": 0.3416208028793335, "2512": 1.0601204633712769, "2515": 0.19541899859905243, "2522": 0.18978065252304077, "2571": 0.5267143249511719, "2625": 0.07250232994556427, "2640": 0.4400174915790558, "2674": 0.24248650670051575, "2714": 0.8707374930381775, "2729": 0.812664806842804, "2731": 0.36426326632499695, "2740": 0.8500841856002808, "2750": 0.31845372915267944, "2765": 0.33953672647476196, "2800": 0.49982786178588867, "2817": 0.7426811456680298, "2818": 0.6249561905860901, "2836": 0.029824240133166313, "2866": 0.23479416966438293, "2890": 0.20501139760017395, "2892": 0.3883931338787079, "2902": 1.0641717910766602, "2913": 0.7827593088150024, "2934": 0.2184450328350067, "2951": 0.7629209756851196, "2966": 0.7827593088150024, "2967": 0.15023678541183472, "3001": 0.04767346754670143, "3112": 0.13071982562541962, "3125": 0.2689530849456787, "3131": 0.46608972549438477, "3132": 0.16607704758644104, "3141": 0.09050461649894714, "3160": 0.4425300657749176, "3197": 0.4487839937210083, "3218": 0.08961215615272522, "3227": 0.04860413447022438, "3251": 0.3012613356113434, "3252": 0.9500881433486938, "3273": 0.319873183965683, "3278": 0.29036402702331543, "3289": 0.20580662786960602, "3319": 0.42096930742263794, "3325": 0.5139457583427429, "3350": 0.8357921838760376, "3375": 0.06703783571720123, "3446": 0.11691460013389587, "3447": 0.4574742913246155, "3452": 0.5607312321662903, "3460": 0.15023678541183472, "3463": 0.6016870141029358, "3465": 0.04394211992621422, "3466": 0.4462870955467224, "3469": 0.0009760859538801014, "3497": 0.3134697377681732, "3556": 0.17020416259765625, "3563": 0.49030399322509766, "3570": 0.77198725938797, "3576": 0.6000806093215942, "3618": 0.03360854089260101, "3619": 0.3106105625629425, "3643": 0.10291612148284912, "3647": 0.1358480453491211, "3723": 0.40285754203796387, "3737": 0.10026945173740387, "3760": 0.18573370575904846, "3785": 0.1751343309879303, "3808": 0.11951763927936554, "3831": 0.935633659362793, "3836": 0.9131608605384827, "3867": 0.09584271162748337, "3872": 0.5415972471237183, "3891": 0.8796916007995605, "3896": 0.33325836062431335, "3904": 0.06154331564903259, "3906": 0.6070231795310974, "3929": 0.3656192123889923, "3979": 0.2501201331615448, "3980": 0.06703783571720123, "4036": 0.38574060797691345, "4050": 0.2637155055999756, "4082": 0.014542185701429844, "4083": 0.175953671336174, "4094": 0.23324857652187347, "4102": 0.757441520690918, "4106": 0.7105726003646851, "4118": 0.2501201331615448, "4127": 0.04207121208310127, "4128": 0.7229714393615723, "4146": 0.09850110858678818, "4200": 0.11865071207284927, "4252": 1.300702452659607, "4254": 0.11430477350950241, "4279": 0.013579257763922215, "4281": 0.6420594453811646, "4292": 0.35813871026039124, "4295": 0.6317287683486938, "4322": 0.757441520690918, "4328": 0.13157635927200317, "4358": 0.015504186972975731, "4431": 0.3656192123889923, "4453": 0.14518201351165771, "4456": 0.7295845746994019, "4489": 0.619189441204071, "4513": 0.1693800985813141, "4547": 0.09584271162748337, "4621": 0.0038986403960734606, "4650": 0.22782009840011597, "4725": 0.4412745535373688, "4788": 0.75193190574646, "4795": 0.11778303235769272, "4818": 0.08244366943836212, "4839": 0.16524957120418549, "4866": 0.05139094591140747, "4895": 0.2447827309370041, "4896": 0.1229778528213501, "4926": 0.1873544454574585, "4953": 0.0913962796330452, "5022": 0.6118015646934509, "5089": 0.6813592314720154, "5090": 0.9783848524093628, "5140": 0.40741631388664246, "5145": 0.28450319170951843, "5281": 0.25088030099868774, "5301": 0.23864774405956268, "5335": 0.42735910415649414, "5345": 0.9225212931632996, "5422": 0.2674594223499298, "5427": 0.11343330889940262, "5443": 0.6808650493621826, "5531": 0.12986256182193756, "5546": 0.06429435312747955, "5585": 0.40741631388664246, "5617": 0.0842406153678894, "5666": 0.5696102976799011, "5729": 0.0606246218085289, "5769": 0.05970508232712746, "5770": 0.12470348179340363, "5776": 0.8869584798812866, "5788": 0.06886265426874161, "5816": 0.9084475636482239, "5966": 0.6813592314720154, "5970": 0.28082266449928284, "5981": 0.6828403472900391, "5986": 0.3810817003250122, "5989": 0.022212404757738113, "6020": 0.11430477350950241, "6022": 0.8238670229911804, "6083": 0.05786345899105072, "6109": 0.2223619967699051, "6196": 0.15693697333335876, "6210": 0.013579257763922215, "6365": 0.034552380442619324, "6388": 0.22937409579753876, "6428": 0.053244512528181076, "6431": 0.8349450826644897, "6463": 0.04674193635582924, "6526": 0.020300358533859253, "6540": 0.1064341589808464, "6551": 0.06795065850019455, "6563": 0.21765978634357452, "6570": 0.7144040465354919, "6592": 0.42353010177612305, "6593": 0.176772341132164, "6612": 0.9754437208175659, "6660": 0.23787821829319, "6666": 0.0317181795835495, "6685": 0.05139094591140747, "6702": 0.22704219818115234, "6704": 0.2160874605178833, "6739": 0.2026219218969345, "6747": 0.3949938118457794, "6801": 0.17922431230545044, "6821": 0.1619328260421753, "6914": 0.6862877607345581, "6937": 0.08513788133859634, "7012": 0.4158279001712799, "7017": 0.36494144797325134, "7023": 0.8699195384979248, "7091": 0.4113073945045471, "7175": 0.009718249551951885, "7242": 0.20421554148197174, "7355": 0.0029254043474793434, "7388": 0.6897233724594116, "7435": 0.11691460013389587, "7461": 0.3163207769393921, "7522": 0.23556606471538544, "7539": 0.7398891448974609, "7551": 0.23092569410800934, "7578": 0.6022219061851501, "7583": 0.5860490798950195, "7593": 0.06429435312747955, "7604": 0.4462870955467224, "7620": 0.11691460013389587, "7644": 0.03266380727291107, "7690": 0.417115718126297, "7691": 0.7163142561912537, "7705": 0.10026945173740387, "7748": 0.16359257698059082, "7778": 0.23092569410800934, "7792": 0.1384023278951645, "7809": 0.8366385698318481, "7831": 0.839173436164856, "7870": 0.45870962738990784, "7882": 0.07250232994556427, "7885": 0.1808556467294693, "7899": 0.272677481174469, "7972": 0.05046287178993225, "8023": 0.02792670577764511, "8029": 0.007782140281051397, "8182": 0.3262358605861664, "8220": 0.025073638185858727, "8280": 0.2160874605178833, "8292": 0.41065993905067444, "8323": 0.952351450920105, "8329": 0.45251765847206116, "8332": 0.736154317855835, "8335": 0.01934296265244484, "8357": 0.026976587250828743, "8376": 0.30558720231056213, "8377": 0.03831886500120163, "8386": 0.034552380442619324, "8450": 0.8550800085067749, "8519": 0.4196864068508148, "8583": 0.0913962796330452, "8781": 0.026976587250828743, "8835": 0.23402166366577148, "8882": 0.16359257698059082, "8906": 0.2954642176628113, "8911": 0.4974553883075714, "8951": 0.10818854719400406, "9047": 0.6862877607345581, "9162": 0.04487626627087593, "9229": 0.06795065850019455, "9312": 0.3077431619167328, "9349": 0.6911921501159668, "9450": 0.5186077356338501, "9556": 0.6471850275993347, "9560": 0.9386941194534302, "9608": 0.0317181795835495, "9823": 0.42096930742263794, "9839": 0.26446542143821716, "9871": 1.0641717910766602, "9905": 0.07159364968538284, "9967": 0.1970241367816925, "10020": 0.24018502235412598, "10035": 0.34300774335861206, "10194": 0.5685047507286072, "10197": 0.23247487843036652, "10365": 0.0317181795835495, "10426": 0.5092619061470032, "10539": 0.05417001247406006, "10611": 0.38441169261932373, "10618": 0.02412080205976963, "10624": 0.29109421372413635, "10640": 0.23864774405956268, "10750": 0.2184450328350067, "10752": 0.8152611255645752, "10755": 0.38041436672210693, "10800": 0.06886265426874161, "10802": 0.09406650811433792, "10831": 0.5098485946655273, "10857": 0.015504186972975731, "11091": 0.10555581003427505, "11119": 0.14518201351165771, "11157": 0.025073638185858727, "11234": 0.7987030148506165, "11314": 0.0770333781838417, "11343": 0.2837681770324707, "11441": 0.35128939151763916, "11455": 0.0842406153678894, "11490": 0.16442140936851501, "11500": 0.1619328260421753, "11616": 0.36358460783958435, "11656": 0.03360854089260101, "11707": 0.1751343309879303, "11714": 0.021256839856505394, "11778": 0.2837681770324707, "11806": 0.10203468054533005, "11922": 0.4419025182723999, "12044": 0.5461324453353882, "12148": 0.11430477350950241, "12319": 0.5882205963134766, "12353": 0.3353555500507355, "12381": 0.16690383851528168, "12421": 0.5629584193229675, "12435": 0.681853175163269, "12546": 0.06246116757392883, "12596": 0.45932671427726746, "12618": 0.5607312321662903, "12637": 0.07250232994556427, "12654": 0.6492279767990112, "12682": 0.06886265426874161, "12763": 0.08692999184131622, "12826": 0.672426164150238, "12912": 0.22937409579753876, "12941": 0.0797421783208847, "12980": 0.0752234235405922, "13014": 0.2160874605178833, "13033": 0.6862877607345581, "13105": 1.0748957395553589, "13143": 0.5930894017219543, "13356": 0.9739698171615601, "13436": 0.39433568716049194, "13473": 0.7647408246994019, "13483": 0.7482418417930603, "13494": 0.06429435312747955, "13599": 0.7389566898345947, "13691": 0.00875066313892603, "13827": 0.02412080205976963, "14025": 0.3683255612850189, "14171": 0.25088030099868774, "14336": 0.5220900774002075, "14379": 0.15359249711036682, "14386": 0.06612417846918106, "14402": 0.7782850861549377, "14621": 0.09050461649894714, "14667": 0.0354953333735466, "14817": 0.18329764902591705, "14964": 0.3127557039260864, "15087": 0.011650617234408855, "15185": 0.503966212272644, "15189": 0.00875066313892603, "15258": 0.11517547070980072, "15268": 0.17020416259765625, "15306": 0.6911921501159668, "15316": 0.10026945173740387, "15431": 0.5010119676589966, "15525": 0.02887592278420925, "15559": 0.03360854089260101, "15631": 0.32553088665008545, "15901": 0.1332872211933136, "15945": 0.31204116344451904, "16134": 0.46486347913742065, "16157": 0.31560876965522766, "16302": 0.472198486328125, "16330": 0.35677260160446167, "16474": 0.14179791510105133, "16478": 0.1401015669107437, "16480": 0.66441810131073, "16505": 0.1889725625514984, "16902": 0.10203468054533005, "16940": 0.7096124291419983, "16965": 0.01934296265244484, "17208": 0.05046287178993225, "17237": 0.469759464263916, "17261": 0.05786345899105072, "17537": 0.012615402229130268, "17544": 0.5433003902435303, "17631": 0.05417001247406006, "17826": 0.08154398202896118, "17865": 0.20421554148197174, "17881": 0.6043586730957031, "17908": 0.3499138653278351, "17982": 0.11951763927936554, "18100": 0.18248429894447327, "18185": 0.2034190446138382, "18420": 0.12814582884311676, "18539": 0.4512746334075928, "18609": 0.9302552938461304, "18700": 0.03831886500120163, "18976": 0.7426811456680298, "19037": 0.4145384132862091, "19064": 0.3381449282169342, "19158": 0.3034266233444214, "19159": 0.052318159490823746, "19160": 0.11081436276435852, "19188": 0.2969166338443756, "19476": 0.08154398202896118, "19515": 0.08871890604496002, "19541": 0.16524957120418549, "19824": 0.1718502640724182, "19922": 0.306306391954422, "19960": 0.3241194784641266, "20175": 0.5186077356338501, "20246": 0.19381128251552582, "20389": 0.31845372915267944, "20502": 0.14433705806732178, "20767": 0.18654440343379974, "20936": 0.347847044467926, "21090": 0.3723714053630829, "21150": 0.36290550231933594, "21230": 0.19862671196460724, "21557": 0.08154398202896118, "21770": 0.7737906575202942, "21893": 0.3560888469219208, "22799": 0.01934296265244484, "22939": 0.27044451236724854, "22963": 0.5822374224662781, "23087": 0.4926934838294983, "23208": 0.11343330889940262, "23219": 0.259204238653183, "23260": 0.09406650811433792, "23284": 0.12986256182193756, "23329": 0.151916041970253, "23572": 0.04860413447022438, "23614": 0.09584271162748337, "23710": 0.03360854089260101, "23900": 0.16110190749168396, "24004": 0.06612417846918106, "24081": 0.1873544454574585, "24155": 0.007782140281051397, "24203": 0.5174443125724792, "24343": 0.20739519596099854, "24658": 0.12728634476661682, "24735": 0.3304552733898163, "24840": 0.18654440343379974, "24854": 0.04953393340110779, "25022": 0.7038320899009705, "25095": 0.15610189735889435, "25409": 0.12038381397724152, "25835": 0.18573370575904846, "25934": 0.04113444685935974, "26206": 0.0354953333735466, "26319": 0.18004031479358673, "26745": 0.7105726003646851, "27058": 0.9598589539527893, "27204": 0.17431432008743286, "27615": 0.05970508232712746, "28093": 0.3464667797088623, "28173": 0.5871354341506958, "28436": 0.08692999184131622, "28789": 0.40285754203796387, "29060": 0.12986256182193756, "29277": 0.02887592278420925, "29295": 0.6471850275993347, "29392": 0.1332872211933136} | 13906581 | Background Extensive debate exists in the healthcare community over whether outcomes of medical care at teaching hospitals and other healthcare units are better or worse than those at the respective nonteaching ones. Thus, our goal was to systematically evaluate the evidence pertaining to this question. Methods and Findings We reviewed all studies that compared teaching versus nonteaching healthcare structures for mortality or any other patient outcome, regardless of health condition. Studies were retrieved from PubMed, contact with experts, and literature cross-referencing. Data were extracted on setting, patients, data sources, author affiliations, definition of compared groups, types of diagnoses considered, adjusting covariates, and estimates of effect for mortality and for each other outcome. Overall, 132 eligible studies were identified, including 93 on mortality and 61 on other eligible outcomes (22 addressed both). Synthesis of the available adjusted estimates on mortality yielded a summary relative risk of 0.96 (95% confidence interval [CI], 0.93–1.00) for teaching versus nonteaching healthcare structures and 1.04 (95% CI, 0.99–1.10) for minor teaching versus nonteaching ones. There was considerable heterogeneity between studies (I2 = 72% for the main analysis). Results were similar in studies using clinical and those using administrative databases. No differences were seen in the 14 studies fully adjusting for volume/experience, severity, and comorbidity (relative risk 1.01). Smaller studies did not differ in their results from larger studies. Differences were seen for some diagnoses (e.g., significantly better survival for breast cancer and cerebrovascular accidents in teaching hospitals and significantly better survival from cholecystectomy in nonteaching hospitals), but these were small in magnitude. Other outcomes were diverse, but typically teaching healthcare structures did not do better than nonteaching ones. Conclusions The available data are limited by their nonrandomized design, but overall they do not suggest that a healthcare facility's teaching status on its own markedly improves or worsens patient outcomes. Differences for specific diseases cannot be excluded, but are likely to be small. | Patient Outcomes with Teaching Versus Nonteaching Healthcare: A Systematic Review |
{"1011": 0.07612881064414978, "1019": 0.17759032547473907, "1044": 0.5612884759902954, "1998": 0.14433705806732178, "1999": 0.009718249551951885, "2002": 0.01934296265244484, "2010": 0.75193190574646, "2011": 0.3824150264263153, "2029": 0.1358480453491211, "2043": 0.2689530849456787, "2044": 0.679875910282135, "2051": 0.03831886500120163, "2057": 0.07612881064414978, "2061": 0.5186077356338501, "2075": 0.37907835841178894, "2076": 0.6260011196136475, "2079": 0.16276304423809052, "2089": 0.009718249551951885, "2099": 0.16690383851528168, "2128": 0.6862877607345581, "2129": 0.15693697333335876, "2146": 0.5784112811088562, "2169": 0.1384023278951645, "2179": 0.14349138736724854, "2203": 0.16276304423809052, "2206": 0.19541899859905243, "2274": 0.040196798741817474, "2320": 0.10555581003427505, "2334": 0.637939989566803, "2339": 0.07612881064414978, "2417": 0.006812678650021553, "2424": 0.11778303235769272, "2504": 0.010684899985790253, "2509": 0.619189441204071, "2515": 0.2689530849456787, "2529": 0.2247048318386078, "2558": 0.3601844012737274, "2582": 0.31132611632347107, "2689": 0.6176109313964844, "2695": 0.1510767638683319, "2733": 0.1718502640724182, "2754": 0.05694137513637543, "2765": 0.0770333781838417, "2777": 0.28670501708984375, "2832": 0.39367714524269104, "2839": 0.32341301441192627, "2864": 0.1619328260421753, "2904": 0.44566190242767334, "2918": 0.6512666940689087, "2920": 0.20580662786960602, "2951": 0.20421554148197174, "3120": 0.15359249711036682, "3134": 0.27786844968795776, "3252": 0.8247235417366028, "3370": 0.960606575012207, "3378": 0.7987030148506165, "3431": 0.820433497428894, "3433": 0.05694137513637543, "3463": 0.09495500475168228, "3466": 0.40220460295677185, "3508": 0.6734226942062378, "3525": 0.1710275560617447, "3526": 0.3248254358768463, "3550": 0.14179791510105133, "3560": 0.3353555500507355, "3603": 0.1970241367816925, "3670": 0.7827593088150024, "3714": 0.2696990668773651, "3755": 0.5729197263717651, "3798": 0.2394166737794876, "3853": 0.09850110858678818, "3896": 0.24631060659885406, "3989": 0.12038381397724152, "4195": 0.0842406153678894, "4198": 0.2881702482700348, "4383": 0.3027053773403168, "4397": 0.045809537172317505, "4403": 0.15359249711036682, "4442": 0.42544642090797424, "4515": 0.6476961374282837, "4531": 0.015504186972975731, "4568": 0.8649974465370178, "4654": 0.49626702070236206, "4668": 0.16359257698059082, "4685": 0.09761575609445572, "4697": 0.42990362644195557, "4712": 0.0317181795835495, "4962": 1.0519683361053467, "4964": 0.16110190749168396, "5090": 0.5990082025527954, "5158": 0.24018502235412598, "5219": 0.15943801403045654, "5228": 0.17840765416622162, "5258": 0.08603433519601822, "5278": 0.37974658608436584, "5290": 0.09406650811433792, "5302": 0.3662964701652527, "5320": 0.010684899985790253, "5402": 0.2105647772550583, "5418": 0.7537717819213867, "5449": 0.30558720231056213, "5456": 0.09761575609445572, "5524": 0.8091925978660583, "5591": 0.3163207769393921, "5616": 0.00875066313892603, "5728": 0.0354953333735466, "5845": 0.11951763927936554, "5854": 0.09317722171545029, "6022": 0.11081436276435852, "6026": 0.32058215141296387, "6064": 1.325395107269287, "6149": 0.04674193635582924, "6194": 0.2105647772550583, "6310": 0.6405166387557983, "6337": 0.520350456237793, "6418": 0.3949938118457794, "6433": 0.2837681770324707, "6540": 0.46363574266433716, "6903": 0.8500841856002808, "6971": 0.09672962874174118, "6993": 0.13499516248703003, "7060": 0.6744182109832764, "7065": 0.37974658608436584, "7077": 0.8682814836502075, "7176": 0.472198486328125, "7178": 0.29400965571403503, "7183": 0.20818853378295898, "7192": 1.2610986232757568, "7233": 0.35060185194015503, "7246": 0.3127557039260864, "7264": 0.1905880719423294, "7336": 0.1221139207482338, "7337": 0.3353555500507355, "7356": 0.39696553349494934, "7366": 0.35813871026039124, "7403": 0.8550800085067749, "7461": 0.23247487843036652, "7523": 0.07159364968538284, "7532": 0.28450319170951843, "7578": 0.25088030099868774, "7673": 0.014542185701429844, "7709": 0.0038986403960734606, "7810": 0.09406650811433792, "7885": 0.05694137513637543, "7888": 0.319873183965683, "7901": 0.14686977863311768, "8081": 0.3923587501049042, "8093": 0.4770587682723999, "8117": 0.04860413447022438, "8171": 0.04487626627087593, "8332": 0.5596157908439636, "8358": 0.33953672647476196, "8360": 0.0009760859538801014, "8386": 0.5573811531066895, "8539": 0.3526630103588104, "8642": 0.4412745535373688, "8735": 0.44753631949424744, "8757": 0.41065993905067444, "8776": 0.6739205718040466, "8980": 0.1401015669107437, "8991": 0.2786078155040741, "9007": 0.8764448165893555, "9031": 0.40220460295677185, "9096": 0.06612417846918106, "9099": 0.469759464263916, "9165": 0.9893379211425781, "9211": 0.2990913391113281, "9214": 0.669430673122406, "9239": 0.10026945173740387, "9247": 0.47463157773017883, "9276": 0.11168810725212097, "9285": 0.15359249711036682, "9355": 0.06337817758321762, "9367": 0.02887592278420925, "9412": 0.20102575421333313, "9556": 0.016465263441205025, "9597": 0.18248429894447327, "9601": 0.10906458646059036, "9879": 0.1710275560617447, "10057": 0.12814582884311676, "10086": 0.11168810725212097, "10109": 0.12556517124176025, "10315": 0.7370892763137817, "10341": 0.11865071207284927, "10381": 0.7854343056678772, "10426": 0.012615402229130268, "10438": 0.08603433519601822, "10525": 0.05417001247406006, "10572": 0.9147270321846008, "10595": 0.2105647772550583, "10708": 0.5551415085792542, "10744": 0.0770333781838417, "10799": 0.05694137513637543, "11019": 0.12986256182193756, "11022": 0.1913948506116867, "11031": 0.9958525896072388, "11115": 0.5696102976799011, "11233": 0.20102575421333313, "11383": 0.07431721687316895, "11423": 0.35813871026039124, "11477": 0.8550800085067749, "11598": 0.31489628553390503, "11674": 0.22859740257263184, "11703": 0.026025565341114998, "11787": 0.28450319170951843, "12335": 0.009718249551951885, "12644": 0.7398891448974609, "12662": 1.2204381227493286, "12709": 0.007782140281051397, "12719": 0.5584990978240967, "12987": 0.22626367211341858, "13330": 0.009718249551951885, "13369": 0.8057082891464233, "13371": 0.17020416259765625, "13442": 0.24554696679115295, "13458": 0.40871503949165344, "13483": 0.18329764902591705, "13557": 0.05139094591140747, "13595": 0.2607102394104004, "13671": 1.3505052328109741, "13685": 0.0174254160374403, "14080": 0.7800771594047546, "14144": 0.7782850861549377, "14171": 0.2105647772550583, "14193": 1.244919776916504, "14336": 0.06246116757392883, "14409": 0.016465263441205025, "14471": 0.5232481360435486, "14494": 0.16524957120418549, "14584": 0.1685553640127182, "14591": 0.3191637098789215, "14800": 0.04767346754670143, "15176": 0.058784693479537964, "15359": 0.1332872211933136, "15527": 0.12728634476661682, "15543": 0.056018441915512085, "15581": 0.045809537172317505, "15729": 0.06154331564903259, "15757": 0.03266380727291107, "15778": 0.1619328260421753, "15826": 0.09317722171545029, "15887": 0.2749055027961731, "15932": 0.9271688461303711, "15946": 0.18329764902591705, "16221": 0.30917787551879883, "16285": 0.9432673454284668, "16487": 0.026025565341114998, "16705": 0.43938836455345154, "16706": 0.5573811531066895, "16771": 0.06337817758321762, "16913": 1.1205062866210938, "17183": 0.9021284580230713, "17241": 0.011650617234408855, "17574": 0.15526613593101501, "17598": 0.9084475636482239, "17629": 0.04487626627087593, "17708": 0.10026945173740387, "17820": 0.010684899985790253, "17850": 1.6447447538375854, "17879": 0.7537717819213867, "17993": 0.05139094591140747, "18322": 0.07793712615966797, "18340": 0.22782009840011597, "18856": 0.13243216276168823, "19037": 0.25088030099868774, "19293": 0.026976587250828743, "19476": 0.1212492436170578, "19653": 0.8152611255645752, "19723": 0.28082266449928284, "19817": 0.23092569410800934, "19933": 0.5789587497711182, "20045": 0.40741631388664246, "20063": 0.32341301441192627, "20363": 1.0986123085021973, "20449": 0.00875066313892603, "20870": 0.013579257763922215, "20983": 0.022212404757738113, "21114": 0.08154398202896118, "21197": 0.7889899015426636, "21208": 0.2786078155040741, "21647": 0.469759464263916, "21716": 0.9348671436309814, "21770": 0.05139094591140747, "22415": 0.10379679501056671, "22552": 0.47463157773017883, "22574": 0.037378571927547455, "23150": 0.06429435312747955, "23191": 0.176772341132164, "23216": 0.07793712615966797, "23217": 0.13499516248703003, "23797": 0.052318159490823746, "23943": 0.8004589080810547, "24004": 1.0101795196533203, "24051": 0.4067663550376892, "24081": 0.2026219218969345, "24388": 0.011650617234408855, "24418": 0.4926934838294983, "24473": 0.025073638185858727, "24490": 0.05046287178993225, "24501": 0.3615458607673645, "24731": 0.045809537172317505, "24854": 0.015504186972975731, "25003": 1.426491141319275, "25269": 0.23710809648036957, "25336": 0.11168810725212097, "25502": 0.66441810131073, "26014": 0.3409265875816345, "26296": 1.0471819639205933, "26520": 0.22001366317272186, "26773": 0.07612881064414978, "26775": 0.5990082025527954, "26874": 0.2969166338443756, "27642": 0.014542185701429844, "28024": 0.20739519596099854, "28295": 0.22859740257263184, "28424": 0.0797421783208847, "28436": 0.22157983481884003, "28472": 0.9621002674102783, "28527": 0.029824240133166313, "29060": 0.25694093108177185, "29129": 0.18573370575904846, "29206": 0.22079704701900482, "29226": 0.5010119676589966, "29290": 0.6853039860725403, "29455": 0.036437395960092545, "29598": 0.12728634476661682} | 13906892 | We characterize the changes in chromatin structure, DNA methylation and transcription during and after homologous DNA repair (HR). We find that HR modifies the DNA methylation pattern of the repaired segment. HR also alters local histone H3 methylation as well chromatin structure by inducing DNA-chromatin loops connecting the 5' and 3' ends of the repaired gene. During a two-week period after repair, transcription-associated demethylation promoted by Base Excision Repair enzymes further modifies methylation of the repaired DNA. Subsequently, the repaired genes display stable but diverse methylation profiles. These profiles govern the levels of expression in each clone. Our data argue that DNA methylation and chromatin remodelling induced by HR may be a source of permanent variation of gene expression in somatic cells. | DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism |
{"1011": 0.4537591338157654, "1044": 0.13755162060260773, "1052": 0.2637155055999756, "1997": 0.12038381397724152, "1999": 0.151916041970253, "2004": 0.14349138736724854, "2005": 0.0317181795835495, "2008": 0.037378571927547455, "2010": 0.9371650815010071, "2011": 0.3963087201118469, "2012": 0.8641747236251831, "2029": 0.2711893916130066, "2049": 0.1734936386346817, "2076": 0.22548456490039825, "2079": 0.22782009840011597, "2080": 0.27044451236724854, "2140": 0.4400174915790558, "2155": 0.35060185194015503, "2239": 0.2470736801624298, "2334": 0.6223390698432922, "2339": 0.018384648486971855, "2350": 0.5601736903190613, "2361": 0.9139442443847656, "2377": 0.272677481174469, "2487": 0.27934664487838745, "2509": 0.33325836062431335, "2515": 0.25694093108177185, "2535": 0.7182208299636841, "2546": 0.15943801403045654, "2549": 0.29981520771980286, "2572": 0.20501139760017395, "2583": 0.03925827145576477, "2590": 0.030771657824516296, "2609": 0.3034266233444214, "2724": 0.1710275560617447, "2824": 0.35403475165367126, "2832": 0.21687394380569458, "2891": 0.8281423449516296, "2896": 0.3757305145263672, "2920": 0.5110208988189697, "3081": 0.034552380442619324, "3248": 0.4132472574710846, "3252": 0.6358738541603088, "3258": 1.133164644241333, "3378": 0.13499516248703003, "3450": 0.23247487843036652, "3457": 0.006812678650021553, "3550": 0.11951763927936554, "3563": 0.5729197263717651, "3625": 0.2954642176628113, "3754": 0.5844172835350037, "3800": 0.08064348995685577, "3853": 0.32764431834220886, "3977": 0.3903779089450836, "4023": 0.2447827309370041, "4053": 0.981317400932312, "4187": 0.757441520690918, "4395": 0.53589928150177, "4453": 0.37035053968429565, "4523": 0.25845035910606384, "4544": 0.14602625370025635, "4573": 0.5330380201339722, "4668": 0.4624064862728119, "4697": 0.13755162060260773, "4748": 1.2975058555603027, "4758": 0.25845035910606384, "4842": 0.9621002674102783, "4962": 0.5330380201339722, "4972": 0.07341018319129944, "5012": 0.11081436276435852, "5017": 0.839173436164856, "5072": 0.2145126610994339, "5090": 0.2800849378108978, "5158": 0.030771657824516296, "5214": 0.07159364968538284, "5250": 0.8715548515319824, "5258": 0.025073638185858727, "5319": 0.02792670577764511, "5391": 0.3601844012737274, "5416": 0.28743788599967957, "5449": 0.5104349255561829, "5524": 0.8517522215843201, "5531": 0.007782140281051397, "5536": 0.8247235417366028, "5587": 0.1905880719423294, "5591": 0.7426811456680298, "5643": 0.7629209756851196, "5648": 0.42225050926208496, "5884": 0.49626702070236206, "6032": 0.04394211992621422, "6064": 1.2856967449188232, "6215": 0.15359249711036682, "6370": 0.0770333781838417, "6418": 0.25845035910606384, "6494": 0.5387523174285889, "6624": 0.5607312321662903, "6673": 0.4770587682723999, "6709": 0.2637155055999756, "6871": 0.34370049834251404, "6980": 0.12986256182193756, "7077": 0.0009760859538801014, "7096": 0.06977381557226181, "7160": 0.16276304423809052, "7192": 1.2797396183013916, "7233": 0.1332872211933136, "7246": 0.4145384132862091, "7327": 0.8829278349876404, "7336": 0.07341018319129944, "7337": 0.9576126337051392, "7342": 0.10026945173740387, "7347": 0.3443928062915802, "7366": 0.2749055027961731, "7403": 0.4450363218784332, "7461": 0.01934296265244484, "7590": 0.16524957120418549, "7645": 0.10993985831737518, "7677": 0.1751343309879303, "7711": 0.42608439922332764, "7790": 0.6027565002441406, "7816": 0.6466736793518066, "8031": 0.8989537954330444, "8081": 0.3019835948944092, "8109": 0.011650617234408855, "8171": 0.8004589080810547, "8327": 0.06612417846918106, "8332": 0.6999598741531372, "8360": 0.2089812457561493, "8382": 0.5455666780471802, "8496": 0.7220231294631958, "8516": 0.8780695199966431, "8735": 0.22392450273036957, "8898": 0.04674193635582924, "8915": 0.42225050926208496, "9007": 0.7038320899009705, "9078": 0.07250232994556427, "9125": 0.053244512528181076, "9165": 0.19862671196460724, "9232": 1.0172666311264038, "9483": 0.6989894509315491, "9544": 0.4812922179698944, "9547": 0.2954642176628113, "9556": 0.4938860833644867, "9568": 0.026025565341114998, "9597": 0.5162794589996338, "9706": 1.1274882555007935, "9869": 0.5244048833847046, "9996": 0.10026945173740387, "10057": 0.07159364968538284, "10253": 0.04487626627087593, "10270": 1.5833184719085693, "10315": 0.7314660549163818, "10335": 0.5186077356338501, "10354": 0.21922965347766876, "10381": 0.6980181336402893, "10483": 0.07884006202220917, "10509": 0.03360854089260101, "10572": 0.9029204845428467, "10595": 0.7370892763137817, "10637": 0.0317181795835495, "10737": 0.2145126610994339, "10738": 0.5016035437583923, "10924": 0.30989447236061096, "11022": 0.16276304423809052, "11115": 0.5696102976799011, "11253": 0.08871890604496002, "11439": 0.06520967930555344, "11598": 0.151916041970253, "11698": 0.5278670787811279, "12157": 0.018384648486971855, "12222": 0.9798521995544434, "12394": 0.3519764244556427, "12530": 0.08513788133859634, "12649": 0.1477125883102417, "12719": 0.034552380442619324, "12737": 0.07612881064414978, "12879": 0.06795065850019455, "12987": 0.5033760666847229, "13100": 0.40089741349220276, "13153": 0.29328158497810364, "13458": 0.037378571927547455, "13671": 1.0695481300354004, "13833": 0.13925230503082275, "13922": 0.3381449282169342, "14080": 0.22937409579753876, "14187": 0.9724938273429871, "14193": 0.3963087201118469, "14405": 0.31845372915267944, "14471": 0.1710275560617447, "14997": 0.2501201331615448, "15011": 0.23479416966438293, "15115": 0.08064348995685577, "15176": 0.6254787445068359, "15262": 0.3269403576850891, "15530": 0.037378571927547455, "15543": 0.14433705806732178, "15669": 0.018384648486971855, "15775": 1.020087480545044, "15887": 0.034552380442619324, "15946": 0.22626367211341858, "16221": 0.018384648486971855, "16226": 0.9769153594970703, "16285": 0.2822965085506439, "16298": 0.31132611632347107, "16305": 0.1913948506116867, "16627": 0.011650617234408855, "16706": 0.4818955361843109, "16840": 0.05417001247406006, "16862": 0.4437839686870575, "16913": 0.7258110046386719, "17366": 0.7537717819213867, "17379": 0.025073638185858727, "17703": 0.2749055027961731, "17782": 0.41195443272590637, "18861": 0.006812678650021553, "18969": 0.5920094847679138, "18996": 0.9922385215759277, "19395": 1.2341761589050293, "19425": 0.0058422754518687725, "19613": 0.4537591338157654, "19653": 0.7295845746994019, "19798": 0.22937409579753876, "19872": 0.18573370575904846, "19882": 0.011650617234408855, "19995": 0.19862671196460724, "20045": 0.029824240133166313, "20228": 0.272677481174469, "20350": 0.15693697333335876, "20363": 1.022197961807251, "20817": 0.9037119746208191, "21197": 0.15359249711036682, "21316": 0.40806588530540466, "21471": 0.09584271162748337, "21575": 0.41001203656196594, "21618": 0.3757305145263672, "21647": 0.40871503949165344, "21716": 0.9447870850563049, "21800": 0.5244048833847046, "21821": 1.0423725843429565, "21903": 0.21687394380569458, "21967": 0.0019512200960889459, "22282": 0.0606246218085289, "22476": 0.10818854719400406, "22574": 0.22626367211341858, "23370": 1.0001721382141113, "23381": 0.1212492436170578, "23943": 0.2231435477733612, "24004": 0.27712854743003845, "24054": 0.16110190749168396, "24171": 0.757441520690918, "24269": 0.6059582233428955, "24271": 0.7105726003646851, "24312": 0.13755162060260773, "24879": 0.15777134895324707, "25117": 0.004870930220931768, "25502": 0.3723714053630829, "25644": 0.11951763927936554, "25761": 0.04487626627087593, "26296": 1.0250049829483032, "26402": 0.18411032855510712, "26534": 0.28890204429626465, "26572": 1.2948341369628906, "26601": 0.22079704701900482, "26773": 0.8517522215843201, "26874": 0.2160874605178833, "27216": 0.2659635543823242, "27642": 0.12384103983640671, "27777": 0.02887592278420925, "27790": 0.040196798741817474, "27854": 0.24631060659885406, "28163": 0.2969166338443756, "29060": 0.1510767638683319, "29290": 0.34715715050697327, "29598": 0.0019512200960889459} | 13907427 | Poly(ADP-ribosyl)ation plays a major role in DNA repair, where it regulates chromatin relaxation as one of the critical events in the repair process. However, the molecular mechanism by which poly(ADP-ribose) modulates chromatin remains poorly understood. Here we identify the poly(ADP-ribose)-regulated protein APLF as a DNA-damage-specific histone chaperone. APLF preferentially binds to the histone H3/H4 tetramer via its C-terminal acidic motif, which is homologous to the motif conserved in the histone chaperones of the NAP1L family (NAP1L motif). We further demonstrate that APLF exhibits histone chaperone activities in a manner that is dependent on its acidic domain and that the NAP1L motif is critical for the repair capacity of APLF in vivo. Finally, we identify structural analogs of APLF in lower eukaryotes with the ability to bind histones and localize to the sites of DNA-damage-induced poly(ADP-ribosyl)ation. Collectively, these findings define the involvement of histone chaperones in poly(ADP-ribose)-regulated DNA repair reactions. | DNA repair factor APLF is a histone chaperone. |
{"1014": 0.4093637466430664, "1017": 0.1384023278951645, "1018": 0.12814582884311676, "1020": 0.16690383851528168, "1021": 0.01934296265244484, "1023": 0.10818854719400406, "1026": 0.08244366943836212, "1044": 0.259204238653183, "1048": 0.24631060659885406, "1052": 0.47827014327049255, "1081": 0.1718502640724182, "2043": 0.1229778528213501, "2051": 0.12728634476661682, "2052": 0.012615402229130268, "2076": 0.6970458030700684, "2084": 0.3877306580543518, "2090": 0.41840189695358276, "2093": 0.13071982562541962, "2102": 0.10203468054533005, "2116": 0.02792670577764511, "2119": 0.35677260160446167, "2146": 0.0174254160374403, "2168": 0.083342544734478, "2174": 0.10555581003427505, "2290": 0.36290550231933594, "2308": 0.8143964409828186, "2340": 0.13499516248703003, "2348": 0.24248650670051575, "2349": 0.04953393340110779, "2353": 0.7342816591262817, "2367": 0.41065993905067444, "2385": 0.28155985474586487, "2388": 0.151916041970253, "2403": 0.6275664567947388, "2408": 0.6096806526184082, "2410": 0.10906458646059036, "2423": 0.12986256182193756, "2450": 0.6563454270362854, "2459": 0.4752389192581177, "2491": 0.5551415085792542, "2504": 0.053244512528181076, "2509": 0.48068851232528687, "2512": 0.7500885725021362, "2515": 0.016465263441205025, "2531": 0.5729197263717651, "2538": 0.05139094591140747, "2540": 0.0770333781838417, "2549": 0.24859806895256042, "2558": 0.5629584193229675, "2561": 0.7086513638496399, "2575": 0.4974553883075714, "2595": 0.3346569836139679, "2615": 0.05694137513637543, "2617": 0.004870930220931768, "2620": 0.4500300884246826, "2638": 0.5191890001296997, "2683": 0.30917787551879883, "2689": 0.3982778787612915, "2714": 0.5370414853096008, "2750": 0.6543170213699341, "2765": 0.5209306478500366, "2781": 0.5444341897964478, "2811": 1.1337933540344238, "2812": 0.3910386264324188, "2815": 0.176772341132164, "2846": 0.23710809648036957, "2895": 0.007782140281051397, "2896": 0.045809537172317505, "2904": 0.10993985831737518, "2931": 0.472198486328125, "2951": 0.5301685929298401, "2953": 0.6970458030700684, "3064": 0.3353555500507355, "3131": 0.5751199722290039, "3147": 0.9340999722480774, "3161": 0.38374659419059753, "3177": 0.15526613593101501, "3197": 0.688742995262146, "3231": 0.436867892742157, "3251": 0.037378571927547455, "3273": 0.0317181795835495, "3276": 0.05970508232712746, "3278": 0.16359257698059082, "3279": 0.10026945173740387, "3336": 0.30917787551879883, "3370": 0.5232481360435486, "3371": 0.3982778787612915, "3378": 0.6754127144813538, "3399": 0.13414156436920166, "3405": 0.1808556467294693, "3429": 0.36426326632499695, "3431": 0.5151132941246033, "3433": 0.8731874823570251, "3435": 0.18978065252304077, "3445": 0.1485546976327896, "3446": 0.3910386264324188, "3450": 0.33953672647476196, "3452": 0.38041436672210693, "3461": 0.42416930198669434, "3463": 0.5174443125724792, "3466": 0.36426326632499695, "3467": 0.20102575421333313, "3491": 0.05786345899105072, "3512": 0.25239890813827515, "3517": 0.11256109178066254, "3556": 0.016465263441205025, "3567": 0.31132611632347107, "3590": 0.21687394380569458, "3618": 0.613389253616333, "3619": 0.48850810527801514, "3623": 0.04113444685935974, "3630": 0.401551216840744, "3643": 0.2983669638633728, "3653": 0.3297532796859741, "3670": 0.3464667797088623, "3671": 0.3923587501049042, "3684": 0.12642613053321838, "3778": 0.9798521995544434, "3798": 0.06795065850019455, "3801": 0.3588210940361023, "3822": 0.3353555500507355, "3893": 0.007782140281051397, "3896": 0.25845035910606384, "4002": 0.3070250153541565, "4010": 0.007782140281051397, "4023": 0.8788808584213257, "4029": 0.27342069149017334, "4094": 0.0317181795835495, "4102": 0.16690383851528168, "4106": 0.11778303235769272, "4146": 0.02792670577764511, "4167": 0.23556606471538544, "4182": 0.24631060659885406, "4281": 0.040196798741817474, "4359": 0.6862877607345581, "4403": 0.034552380442619324, "4456": 0.1946154683828354, "4489": 0.22704219818115234, "4504": 0.23633737862110138, "4508": 0.5284429788589478, "4525": 0.0038986403960734606, "4555": 0.39696553349494934, "4602": 0.05970508232712746, "4651": 0.021256839856505394, "4654": 0.5512100458145142, "4668": 0.20739519596099854, "4672": 0.9842413663864136, "4703": 0.022212404757738113, "4742": 0.0770333781838417, "4758": 0.5197699069976807, "4834": 0.19541899859905243, "4860": 0.35813871026039124, "4950": 0.015504186972975731, "4984": 0.08154398202896118, "5012": 1.156782865524292, "5013": 0.058784693479537964, "5043": 0.21922965347766876, "5213": 0.01934296265244484, "5228": 0.6543170213699341, "5300": 0.05417001247406006, "5376": 0.02887592278420925, "5387": 0.10203468054533005, "5388": 0.5021947622299194, "5393": 0.33953672647476196, "5402": 0.1212492436170578, "5443": 0.3656192123889923, "5468": 0.17020416259765625, "5511": 0.19381128251552582, "5531": 0.026025565341114998, "5547": 0.39762192964553833, "5585": 0.401551216840744, "5604": 0.3485364317893982, "5662": 0.14602625370025635, "5668": 0.43875885009765625, "5717": 0.21214580535888672, "5718": 0.037378571927547455, "5769": 0.5438674688339233, "5809": 0.12728634476661682, "5816": 0.6598852276802063, "5840": 0.2983669638633728, "5852": 0.11430477350950241, "5956": 0.1994270235300064, "5966": 0.12642613053321838, "6020": 0.09317722171545029, "6022": 0.29328158497810364, "6075": 1.1274882555007935, "6091": 0.4734157919883728, "6109": 0.35950297117233276, "6258": 0.006812678650021553, "6388": 0.1889725625514984, "6400": 0.23710809648036957, "6420": 0.13157635927200317, "6431": 0.7163142561912537, "6463": 0.176772341132164, "6470": 0.29036402702331543, "6522": 0.15023678541183472, "6532": 1.0641717910766602, "6601": 0.32270604372024536, "6650": 0.4531385898590088, "6726": 0.28082266449928284, "6740": 0.6415454745292664, "6869": 0.33325836062431335, "6875": 1.2353124618530273, "6909": 0.04860413447022438, "6911": 0.175953671336174, "6976": 0.2637155055999756, "6993": 0.4980490207672119, "7103": 0.026025565341114998, "7127": 0.13499516248703003, "7312": 0.5767669677734375, "7367": 0.004870930220931768, "7388": 0.11256109178066254, "7461": 0.25694093108177185, "7493": 0.04860413447022438, "7505": 0.07159364968538284, "7539": 0.10379679501056671, "7551": 0.26146242022514343, "7591": 0.19622190296649933, "7594": 0.16276304423809052, "7633": 0.1677299439907074, "7645": 0.08513788133859634, "7685": 0.06886265426874161, "7706": 0.030771657824516296, "7708": 0.175953671336174, "7711": 0.6118015646934509, "7718": 0.44566190242767334, "7730": 0.18411032855510712, "7778": 0.0038986403960734606, "7827": 0.3777405619621277, "7831": 0.15860503911972046, "7885": 0.058784693479537964, "7959": 0.09850110858678818, "7978": 0.10906458646059036, "8015": 0.4431571960449219, "8023": 0.022212404757738113, "8117": 0.7009293437004089, "8122": 0.15777134895324707, "8131": 0.016465263441205025, "8161": 0.0752234235405922, "8187": 0.022212404757738113, "8303": 0.11778303235769272, "8319": 0.06246116757392883, "8329": 0.18492233753204346, "8449": 0.0058422754518687725, "8479": 0.23402166366577148, "8566": 0.15023678541183472, "8737": 0.562402069568634, "8803": 0.09406650811433792, "8822": 0.15442965924739838, "8878": 0.6543170213699341, "8913": 0.732405424118042, "8988": 0.684319257736206, "9099": 0.9717550277709961, "9113": 0.9131608605384827, "9141": 0.19381128251552582, "9211": 0.040196798741817474, "9367": 0.5284429788589478, "9495": 0.034552380442619324, "9507": 0.7210738658905029, "9515": 0.38441169261932373, "9556": 0.030771657824516296, "9560": 0.13157635927200317, "9597": 0.02316705882549286, "9765": 0.09938567131757736, "9885": 0.22001366317272186, "9888": 0.1905880719423294, "9997": 0.055094651877880096, "10032": 1.3341783285140991, "10194": 0.08244366943836212, "10225": 0.06429435312747955, "10318": 0.0174254160374403, "10346": 1.0250049829483032, "10391": 0.015504186972975731, "10509": 0.07793712615966797, "10548": 0.35128939151763916, "10572": 0.8534175157546997, "10627": 0.680370569229126, "10708": 0.1358480453491211, "10720": 0.043007105588912964, "10732": 0.5629584193229675, "10744": 1.1134753227233887, "10755": 0.014542185701429844, "10756": 0.22079704701900482, "10768": 0.17020416259765625, "10847": 0.08961215615272522, "10960": 0.34922540187835693, "10976": 0.6149744987487793, "11062": 0.06612417846918106, "11146": 0.0058422754518687725, "11207": 0.36494144797325134, "11234": 0.37371641397476196, "11265": 0.5489565134048462, "11324": 0.2763880789279938, "11326": 0.015504186972975731, "11373": 0.4734157919883728, "11709": 0.09938567131757736, "11941": 0.056018441915512085, "12044": 1.0848461389541626, "12126": 0.29981520771980286, "12184": 0.9279413223266602, "12241": 0.8039615154266357, "12306": 0.35334911942481995, "12353": 0.03831886500120163, "12380": 0.15359249711036682, "12435": 0.5139457583427429, "12436": 0.12814582884311676, "12503": 0.03266380727291107, "12516": 0.11168810725212097, "12565": 0.5045560002326965, "12702": 0.6853039860725403, "12709": 0.15442965924739838, "12809": 0.2622140049934387, "12884": 0.00875066313892603, "13015": 0.4574742913246155, "13026": 1.2175520658493042, "13070": 0.7333439588546753, "13105": 0.02316705882549286, "13113": 0.3297532796859741, "13120": 0.07159364968538284, "13139": 0.7389566898345947, "13184": 0.27934664487838745, "13221": 0.38308101892471313, "13316": 0.12556517124176025, "13330": 0.00875066313892603, "13331": 0.21293537318706512, "13373": 0.7755908370018005, "13416": 0.15860503911972046, "13472": 0.04394211992621422, "13483": 0.15023678541183472, "13490": 0.37371641397476196, "13594": 0.0058422754518687725, "13791": 1.0540125370025635, "13892": 0.12642613053321838, "14120": 0.40285754203796387, "14267": 0.22001366317272186, "14413": 0.31560876965522766, "14446": 0.0317181795835495, "14505": 0.1212492436170578, "14526": 0.37907835841178894, "14613": 0.025073638185858727, "14616": 0.7076893448829651, "14639": 0.25845035910606384, "14963": 0.10203468054533005, "14969": 1.160461664199829, "15044": 0.15610189735889435, "15258": 0.055094651877880096, "15275": 0.6363908052444458, "15276": 0.10026945173740387, "15330": 0.12728634476661682, "15399": 0.2763880789279938, "15403": 0.1510767638683319, "15431": 0.6931471824645996, "15698": 0.3084607720375061, "15756": 0.32341301441192627, "15758": 0.3409265875816345, "15946": 0.5284429788589478, "15965": 0.7436100244522095, "16014": 0.02316705882549286, "16118": 0.22001366317272186, "16121": 0.13670019805431366, "16185": 0.22782009840011597, "16256": 1.167778730392456, "16330": 0.19622190296649933, "16341": 0.013579257763922215, "16535": 0.05417001247406006, "16705": 0.04394211992621422, "16749": 0.35128939151763916, "16824": 0.03831886500120163, "16834": 0.09761575609445572, "16902": 0.15693697333335876, "16952": 0.129004567861557, "16989": 0.42735910415649414, "17076": 0.1229778528213501, "17134": 0.6358738541603088, "17191": 0.056018441915512085, "17376": 0.03266380727291107, "17441": 0.4950772523880005, "17465": 0.4400174915790558, "17503": 0.09584271162748337, "17531": 0.52266925573349, "17547": 0.06246116757392883, "17606": 0.39893341064453125, "17748": 0.03831886500120163, "17816": 0.08154398202896118, "17819": 0.040196798741817474, "17847": 0.11168810725212097, "17850": 0.13925230503082275, "17890": 0.043007105588912964, "17913": 0.0058422754518687725, "18133": 0.036437395960092545, "18155": 0.013579257763922215, "18279": 0.1970241367816925, "18564": 0.19622190296649933, "18714": 0.1994270235300064, "18721": 0.6950984001159668, "18749": 0.030771657824516296, "18772": 0.02887592278420925, "18861": 0.04953393340110779, "18949": 1.1128336191177368, "19037": 0.23864774405956268, "19064": 0.603290855884552, "19220": 0.44753631949424744, "19239": 0.9084475636482239, "19319": 0.03266380727291107, "19389": 0.1221139207482338, "19547": 0.11256109178066254, "19653": 0.7191727757453918, "19701": 0.0174254160374403, "19761": 0.09495500475168228, "19817": 0.04953393340110779, "19833": 0.058784693479537964, "20100": 0.6823468804359436, "20116": 0.04767346754670143, "20317": 0.6420594453811646, "20350": 0.14939609169960022, "20367": 1.0193830728530884, "20382": 0.08603433519601822, "20523": 0.09672962874174118, "20544": 0.7047978043556213, "20614": 0.21687394380569458, "20617": 0.004870930220931768, "20692": 0.40220460295677185, "20704": 0.04860413447022438, "20752": 0.1011524572968483, "20858": 0.8731874823570251, "21017": 0.08154398202896118, "21106": 0.9147270321846008, "21150": 0.3656192123889923, "21305": 0.8135309815406799, "21358": 0.06154331564903259, "21371": 0.0009760859538801014, "21374": 0.11778303235769272, "21399": 0.05970508232712746, "21449": 0.9037119746208191, "21539": 0.4512746334075928, "21608": 0.14349138736724854, "21700": 0.0019512200960889459, "21766": 0.1477125883102417, "21963": 0.083342544734478, "21967": 0.03925827145576477, "22035": 0.4337083101272583, "22239": 0.08064348995685577, "22259": 0.02792670577764511, "22261": 0.3601844012737274, "22828": 0.24018502235412598, "22930": 0.04207121208310127, "22935": 0.17759032547473907, "23072": 0.2018241584300995, "23130": 0.2145126610994339, "23216": 0.48430517315864563, "23284": 0.17840765416622162, "23362": 0.053244512528181076, "23586": 0.2409527748823166, "23632": 0.4500300884246826, "23676": 0.37907835841178894, "23900": 0.3916989266872406, "24081": 0.03925827145576477, "24278": 0.06795065850019455, "24327": 0.2607102394104004, "24501": 0.09850110858678818, "24624": 0.06246116757392883, "24848": 0.1602703034877777, "24887": 0.14264501631259918, "25006": 0.6327666640281677, "25194": 0.5033760666847229, "25292": 0.06612417846918106, "25344": 0.12986256182193756, "25353": 0.7105726003646851, "25458": 0.11081436276435852, "25543": 0.7389566898345947, "25604": 0.7907629609107971, "25714": 0.19381128251552582, "25761": 0.21214580535888672, "25972": 0.4512746334075928, "26163": 1.0868242979049683, "26206": 0.2493593990802765, "26237": 0.03925827145576477, "26243": 0.8074519634246826, "26402": 0.007782140281051397, "26651": 0.3560888469219208, "27159": 0.12470348179340363, "27166": 0.4145384132862091, "27295": 0.4158279001712799, "27312": 0.20022670924663544, "27354": 0.09050461649894714, "27678": 0.13755162060260773, "27881": 0.762009859085083, "28086": 0.02316705882549286, "28093": 0.08782484382390976, "28139": 0.9194108247756958, "28207": 0.3325583338737488, "28215": 0.043007105588912964, "28228": 0.4126010537147522, "28436": 0.3027053773403168, "28483": 0.8281423449516296, "28696": 0.2607102394104004, "28756": 0.5080875158309937, "28901": 0.12038381397724152, "29048": 0.3141832649707794, "29160": 0.07612881064414978, "29290": 0.37102460861206055, "29441": 0.02412080205976963, "29510": 0.19782574474811554, "29657": 0.1970241367816925} | 13907928 | Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation. | Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women. |
{"1011": 0.21293537318706512, "1015": 0.574020504951477, "1038": 0.9958525896072388, "1052": 0.029824240133166313, "2005": 0.11865071207284927, "2007": 0.25995752215385437, "2008": 0.10818854719400406, "2028": 0.42608439922332764, "2029": 0.3810817003250122, "2034": 0.036437395960092545, "2044": 0.06246116757392883, "2061": 0.6043586730957031, "2064": 0.07068414986133575, "2066": 0.20501139760017395, "2076": 0.2089812457561493, "2089": 0.04767346754670143, "2110": 0.36494144797325134, "2128": 0.20102575421333313, "2163": 0.22079704701900482, "2220": 0.4752389192581177, "2278": 0.8074519634246826, "2309": 0.08513788133859634, "2361": 0.7314660549163818, "2362": 0.23324857652187347, "2377": 0.009718249551951885, "2403": 0.15860503911972046, "2415": 0.04860413447022438, "2483": 0.8748174905776978, "2487": 1.0051883459091187, "2515": 0.05139094591140747, "2535": 0.5086748600006104, "2540": 0.12470348179340363, "2545": 0.23556606471538544, "2590": 0.42225050926208496, "2646": 0.2160874605178833, "2695": 0.7028654217720032, "2714": 0.23864774405956268, "2734": 0.13670019805431366, "2799": 0.5215105414390564, "2817": 0.34715715050697327, "2832": 0.09850110858678818, "2875": 0.1619328260421753, "2894": 0.5472630262374878, "2913": 0.22548456490039825, "2920": 0.5186077356338501, "2944": 0.23092569410800934, "2947": 0.07159364968538284, "2993": 0.08154398202896118, "3041": 0.2231435477733612, "3085": 0.6583697199821472, "3145": 0.6823468804359436, "3217": 0.7665573358535767, "3223": 0.5528968572616577, "3248": 0.1221139207482338, "3258": 0.4311734735965729, "3273": 0.129004567861557, "3278": 0.02792670577764511, "3372": 0.4462870955467224, "3378": 0.14602625370025635, "3433": 0.052318159490823746, "3468": 0.14095009863376617, "3508": 0.5573811531066895, "3526": 0.9379299283027649, "3563": 0.11604541540145874, "3625": 0.13499516248703003, "3670": 0.034552380442619324, "3755": 0.1946154683828354, "3853": 0.13071982562541962, "3893": 0.7454653382301331, "3921": 0.26146242022514343, "3930": 0.0019512200960889459, "4013": 0.0058422754518687725, "4072": 0.3027053773403168, "4081": 0.05139094591140747, "4130": 0.02887592278420925, "4167": 0.36358460783958435, "4195": 0.052318159490823746, "4245": 0.3723714053630829, "4340": 0.06612417846918106, "4372": 0.14939609169960022, "4395": 0.29109421372413635, "4403": 0.018384648486971855, "4442": 1.1005635261535645, "4487": 0.306306391954422, "4517": 0.04207121208310127, "4523": 0.20818853378295898, "4765": 0.6149744987487793, "4818": 0.5963221788406372, "4958": 0.9225212931632996, "4962": 0.678390383720398, "5020": 0.007782140281051397, "5173": 0.3318578004837036, "5197": 0.09495500475168228, "5214": 0.03266380727291107, "5224": 0.29109421372413635, "5244": 0.15860503911972046, "5250": 0.026025565341114998, "5302": 0.5033760666847229, "5326": 0.5404602885246277, "5387": 0.13755162060260773, "5393": 0.06795065850019455, "5441": 0.38441169261932373, "5478": 0.27564704418182373, "5537": 0.009718249551951885, "5546": 0.5364705324172974, "5662": 0.7907629609107971, "5700": 0.29619070887565613, "5714": 0.777387797832489, "5769": 0.12814582884311676, "5831": 0.1685553640127182, "5847": 0.4824984669685364, "5918": 0.13925230503082275, "5942": 0.2837681770324707, "6032": 0.7463917136192322, "6064": 0.37640097737312317, "6083": 0.2741633653640747, "6132": 0.7889899015426636, "6169": 0.9178520441055298, "6309": 0.18816383183002472, "6562": 0.5646255612373352, "6592": 0.14264501631259918, "6622": 0.11604541540145874, "6920": 0.1212492436170578, "6942": 0.045809537172317505, "7028": 0.05046287178993225, "7065": 0.8780695199966431, "7127": 0.022212404757738113, "7235": 0.0842406153678894, "7337": 0.18978065252304077, "7366": 0.28670501708984375, "7403": 0.8100618124008179, "7531": 0.3910386264324188, "7645": 0.4067663550376892, "7666": 0.37974658608436584, "7694": 0.2231435477733612, "7816": 0.19541899859905243, "7872": 1.1689931154251099, "7885": 0.01934296265244484, "7901": 0.12470348179340363, "8010": 0.15943801403045654, "8107": 0.16690383851528168, "8153": 0.29473719000816345, "8360": 0.0058422754518687725, "8498": 0.2674594223499298, "8523": 1.0382318496704102, "8713": 0.8212929964065552, "8878": 0.10731173306703568, "9007": 0.4330752193927765, "9095": 0.04113444685935974, "9125": 0.053244512528181076, "9128": 0.04860413447022438, "9165": 0.5244048833847046, "9319": 0.38441169261932373, "9496": 0.6543170213699341, "9563": 0.009718249551951885, "9675": 0.2231435477733612, "9686": 0.966567873954773, "10278": 0.28082266449928284, "10318": 0.7389566898345947, "10572": 0.0842406153678894, "10580": 0.1485546976327896, "10744": 0.1751343309879303, "10867": 1.0748957395553589, "10915": 0.12986256182193756, "10956": 0.1602703034877777, "10975": 1.104454517364502, "11008": 0.7881022095680237, "11067": 0.03266380727291107, "11601": 0.22079704701900482, "11674": 0.32129061222076416, "11698": 0.02887592278420925, "11835": 0.025073638185858727, "11892": 0.016465263441205025, "12115": 0.0913962796330452, "12322": 0.8315495252609253, "12402": 0.2881702482700348, "12435": 0.30989447236061096, "12562": 0.08244366943836212, "12644": 0.6451379656791687, "12732": 0.48068851232528687, "12827": 0.812664806842804, "12987": 0.15023678541183472, "13102": 0.6420594453811646, "13113": 1.0444365739822388, "13418": 0.04860413447022438, "13458": 0.04394211992621422, "13502": 0.15860503911972046, "13595": 0.16276304423809052, "13637": 0.03925827145576477, "13711": 0.06612417846918106, "13791": 0.14433705806732178, "13833": 0.09406650811433792, "13908": 0.020300358533859253, "13922": 0.03266380727291107, "14067": 0.3723714053630829, "14083": 0.04487626627087593, "14162": 0.5963221788406372, "14193": 0.14602625370025635, "14471": 0.3409265875816345, "14482": 0.045809537172317505, "14499": 0.025073638185858727, "14627": 0.052318159490823746, "14800": 0.3374483287334442, "14828": 0.12814582884311676, "14988": 0.08871890604496002, "15480": 0.32905077934265137, "15527": 0.24325250089168549, "15543": 0.09228714555501938, "15698": 0.17759032547473907, "15946": 0.06429435312747955, "16048": 0.11168810725212097, "16098": 0.6233867406845093, "16216": 0.9162907600402832, "16221": 0.18329764902591705, "16360": 1.0828639268875122, "16463": 0.21765978634357452, "16530": 0.6769026517868042, "16691": 0.03266380727291107, "16706": 0.21372433006763458, "16910": 0.32764431834220886, "16932": 0.8813109993934631, "16984": 0.043007105588912964, "17289": 0.2018241584300995, "17598": 0.055094651877880096, "17820": 0.7934166193008423, "17824": 0.015504186972975731, "17890": 0.49030399322509766, "17960": 1.4900912046432495, "18047": 0.1212492436170578, "18547": 0.11778303235769272, "18714": 0.0019512200960889459, "18720": 1.248288631439209, "19160": 0.025073638185858727, "19220": 0.045809537172317505, "19269": 0.4425300657749176, "19345": 0.2983669638633728, "19601": 0.14179791510105133, "19639": 0.3615458607673645, "19653": 0.3318578004837036, "19723": 0.37371641397476196, "20228": 0.7009293437004089, "20544": 0.036437395960092545, "20582": 0.2719337046146393, "20594": 1.0144377946853638, "20648": 0.09050461649894714, "21017": 0.034552380442619324, "21800": 0.32270604372024536, "21903": 0.06337817758321762, "22081": 0.26446542143821716, "22117": 1.4142210483551025, "22311": 1.1109062433242798, "22863": 0.8525851964950562, "23150": 0.13925230503082275, "23163": 0.1384023278951645, "23207": 0.9386941194534302, "23216": 0.04394211992621422, "23323": 0.021256839856505394, "23737": 0.13243216276168823, "23758": 0.09050461649894714, "23767": 0.2184450328350067, "24269": 0.10993985831737518, "24759": 0.49030399322509766, "25070": 1.3222765922546387, "25416": 0.053244512528181076, "25714": 0.14095009863376617, "25761": 0.014542185701429844, "26305": 0.034552380442619324, "26471": 1.1211429834365845, "26616": 0.4318077862262726, "26802": 0.8517522215843201, "26927": 1.0271050930023193, "27528": 0.15943801403045654, "27777": 0.1064341589808464, "27841": 0.015504186972975731, "28086": 1.154322862625122, "28283": 0.8699195384979248, "28405": 0.10291612148284912, "28498": 0.11168810725212097, "28516": 0.020300358533859253, "28667": 0.013579257763922215, "28699": 0.1485546976327896, "28788": 0.13071982562541962, "29129": 0.015504186972975731, "29206": 1.0601204633712769, "29280": 0.4891071021556854, "29290": 0.04860413447022438} | 13910150 | Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells. They together initiate epigenetic reprogramming in early germ cells toward an underlying pluripotent state, which is equivalent to embryonic stem cells (ESCs). Whereas Prdm14 alone can promote reprogramming and is important for the propagation of the pluripotent state, it is not known whether Blimp1 is similarly involved. By using a genetic approach, we demonstrate that Blimp1 is dispensable for the derivation and maintenance of ESCs and postimplantation epiblast stem cells (epiSCs). Notably, Blimp1 is also dispensable for reprogramming epiSCs to ESCs. Thus, although Blimp1 is obligatory for PGC specification, it is not required for the reversion of epiSCs to ESCs and for their maintenance thereafter. This study suggests that reprogramming, including that of somatic cells to ESCs, may not entail an obligatory route through a Blimp1-positive PGC-like state. | The Germ Cell Determinant Blimp1 Is Not Required for Derivation of Pluripotent Stem Cells |
{"1011": 0.034552380442619324, "1017": 0.09938567131757736, "1019": 0.08961215615272522, "1052": 0.23015019297599792, "2004": 0.006812678650021553, "2005": 0.08603433519601822, "2008": 0.10906458646059036, "2011": 0.07884006202220917, "2015": 0.2160874605178833, "2024": 0.07431721687316895, "2028": 0.2018241584300995, "2029": 0.3262358605861664, "2035": 0.36494144797325134, "2036": 0.45251765847206116, "2053": 0.16524957120418549, "2060": 0.14095009863376617, "2069": 0.15275461971759796, "2076": 0.603290855884552, "2079": 0.29473719000816345, "2093": 0.4374985992908478, "2102": 0.9005423784255981, "2109": 0.07793712615966797, "2124": 0.2719337046146393, "2166": 0.3810817003250122, "2178": 0.0019512200960889459, "2179": 0.05694137513637543, "2274": 0.0029254043474793434, "2361": 1.1738357543945312, "2515": 0.2184450328350067, "2532": 0.30558720231056213, "2535": 0.34370049834251404, "2542": 0.6254787445068359, "2592": 0.3388410806655884, "2629": 0.9857001900672913, "2691": 0.1619328260421753, "2832": 0.15275461971759796, "2865": 0.014542185701429844, "2920": 0.11517547070980072, "3141": 0.7809720039367676, "3215": 0.49626702070236206, "3265": 0.06337817758321762, "3283": 0.04113444685935974, "3313": 0.20022670924663544, "3319": 0.23710809648036957, "3338": 0.1358480453491211, "3366": 0.3297532796859741, "3378": 0.7683706283569336, "3490": 0.623910129070282, "3522": 0.06520967930555344, "3526": 0.5707147121429443, "3563": 0.512191891670227, "3603": 0.4330752193927765, "3625": 0.6186635494232178, "3670": 0.755608320236206, "3674": 0.32553088665008545, "3690": 0.006812678650021553, "3698": 0.1734936386346817, "3728": 0.036437395960092545, "3800": 0.11951763927936554, "3853": 0.3177432417869568, "3935": 0.11081436276435852, "4013": 0.16524957120418549, "4015": 0.22157983481884003, "4047": 0.46608972549438477, "4162": 0.06246116757392883, "4235": 0.04113444685935974, "4442": 0.3676496744155884, "4453": 0.18248429894447327, "4502": 0.20022670924663544, "4523": 1.3123366832733154, "4563": 0.7380234599113464, "4651": 0.08154398202896118, "4681": 0.5191890001296997, "4758": 0.020300358533859253, "4800": 0.9302552938461304, "4957": 0.04487626627087593, "4962": 0.9386941194534302, "4972": 0.12986256182193756, "5123": 0.11081436276435852, "5134": 0.3070250153541565, "5228": 0.013579257763922215, "5258": 0.08782484382390976, "5387": 0.9455460906028748, "5402": 0.7389566898345947, "5415": 0.25239890813827515, "5449": 0.8475768566131592, "5456": 0.38441169261932373, "5537": 0.15023678541183472, "5680": 0.25845035910606384, "5876": 0.8161250352859497, "5884": 0.9515975713729858, "6064": 0.9515975713729858, "6129": 0.25694093108177185, "6342": 0.8161250352859497, "6364": 0.613389253616333, "6499": 0.016465263441205025, "6509": 0.22392450273036957, "6560": 0.15359249711036682, "6622": 1.0519683361053467, "6673": 0.4770587682723999, "6679": 0.09228714555501938, "6709": 0.14433705806732178, "6789": 0.2026219218969345, "6873": 0.1889725625514984, "6897": 0.1384023278951645, "6934": 0.6027565002441406, "6936": 0.10818854719400406, "7126": 0.025073638185858727, "7197": 0.41065993905067444, "7327": 0.5941681861877441, "7337": 0.13925230503082275, "7361": 0.1710275560617447, "7366": 0.4537591338157654, "7403": 0.6170841455459595, "7677": 0.08782484382390976, "7711": 0.3177432417869568, "7730": 0.07250232994556427, "7770": 0.5232481360435486, "7807": 0.401551216840744, "7816": 0.5718178153038025, "7882": 0.052318159490823746, "7905": 0.6729245185852051, "7964": 0.5784112811088562, "8004": 0.21214580535888672, "8091": 0.2786078155040741, "8171": 0.07250232994556427, "8197": 0.055094651877880096, "8387": 0.15442965924739838, "8456": 0.27934664487838745, "8516": 0.00875066313892603, "8569": 0.8731874823570251, "8650": 0.15610189735889435, "8991": 0.3325583338737488, "9007": 0.890972912311554, "9033": 0.33675122261047363, "9048": 0.16607704758644104, "9099": 0.9209672808647156, "9152": 0.29400965571403503, "9165": 0.8057082891464233, "9287": 0.27786844968795776, "9397": 0.0354953333735466, "9585": 0.18167030811309814, "9670": 0.13499516248703003, "9894": 0.034552380442619324, "10327": 1.0257055759429932, "10737": 0.16110190749168396, "10738": 0.3547199070453644, "10752": 0.09228714555501938, "10857": 0.02316705882549286, "10924": 0.0009760859538801014, "10956": 0.13157635927200317, "11022": 1.0788878202438354, "11211": 0.47827014327049255, "11403": 0.010684899985790253, "11423": 0.24554696679115295, "11457": 0.674915611743927, "11469": 0.04953393340110779, "11534": 0.18411032855510712, "11553": 0.4126010537147522, "11598": 0.09672962874174118, "11767": 0.619189441204071, "11867": 1.0802149772644043, "11981": 0.08782484382390976, "12016": 0.8195732831954956, "12033": 0.04767346754670143, "12067": 0.05417001247406006, "12222": 0.6223390698432922, "12322": 0.08064348995685577, "12527": 0.034552380442619324, "12562": 0.15693697333335876, "12636": 0.19782574474811554, "12667": 0.16359257698059082, "12681": 0.17922431230545044, "12702": 0.5871354341506958, "12709": 0.4248080551624298, "12711": 0.05139094591140747, "12761": 1.1249549388885498, "12789": 0.4974553883075714, "12939": 0.12384103983640671, "12987": 1.6394517421722412, "13024": 0.37640097737312317, "13032": 0.08961215615272522, "13100": 0.9340999722480774, "13458": 0.9371650815010071, "13530": 0.11951763927936554, "13876": 0.010684899985790253, "13922": 0.04207121208310127, "13995": 0.25845035910606384, "14193": 1.4900912046432495, "14206": 0.46914875507354736, "14357": 0.45437926054000854, "14471": 0.2659635543823242, "14828": 0.06154331564903259, "14895": 0.1718502640724182, "14947": 0.08064348995685577, "15176": 0.7827593088150024, "15543": 0.7124901413917542, "15577": 0.31845372915267944, "15636": 0.3519764244556427, "15680": 0.47036975622177124, "15841": 0.18816383183002472, "15923": 0.5080875158309937, "16012": 0.08154398202896118, "16221": 0.1930064558982849, "16285": 0.8100618124008179, "16371": 1.0506030321121216, "16913": 0.3656192123889923, "17341": 0.8366385698318481, "17637": 0.10818854719400406, "17782": 1.0151457786560059, "18227": 0.3615458607673645, "18231": 0.0174254160374403, "18260": 0.08064348995685577, "18287": 0.5336109399795532, "18855": 0.3241194784641266, "19293": 0.3547199070453644, "19601": 0.20660123229026794, "19623": 0.006812678650021553, "19723": 0.04394211992621422, "19780": 0.7389566898345947, "19795": 0.28082266449928284, "19852": 0.6769026517868042, "19995": 1.0116009712219238, "20320": 0.15275461971759796, "20490": 0.619189441204071, "20607": 0.18167030811309814, "20755": 0.7463917136192322, "21162": 0.3269403576850891, "21186": 0.7482418417930603, "21197": 0.026976587250828743, "21575": 0.4113073945045471, "21618": 0.23864774405956268, "21647": 0.23633737862110138, "21685": 0.10906458646059036, "21906": 0.026025565341114998, "21996": 0.8666408061981201, "22026": 0.09406650811433792, "22422": 0.006812678650021553, "22806": 0.08692999184131622, "23192": 0.35677260160446167, "23797": 0.13243216276168823, "23915": 0.010684899985790253, "24004": 0.5968599319458008, "24024": 0.2470736801624298, "24051": 0.4624064862728119, "24137": 0.006812678650021553, "24277": 0.7182208299636841, "24312": 0.9994535446166992, "24668": 0.5729197263717651, "24791": 0.37371641397476196, "24978": 0.06246116757392883, "25502": 0.13499516248703003, "25562": 0.0317181795835495, "25644": 0.07884006202220917, "25856": 0.2493593990802765, "26041": 0.8981585502624512, "26223": 0.2531573474407196, "26282": 0.16276304423809052, "26512": 0.47827014327049255, "26534": 0.15275461971759796, "26773": 0.7809720039367676, "26775": 0.9635916948318481, "27216": 0.306306391954422, "27617": 0.022212404757738113, "27777": 0.10203468054533005, "28086": 0.15275461971759796, "28498": 0.24631060659885406, "28745": 1.4321038722991943, "28790": 0.043007105588912964, "28848": 0.688742995262146} | 13912224 | Evolutionary related multisubunit RNA polymerases (RNAPs) transcribe the genomes of all living organisms. Whereas the core subunits of RNAPs are universally conserved in all three domains of life-indicative of a common evolutionary descent-this only applies to one RNAP-associated transcription factor-Spt5, also known as NusG in bacteria. All other factors that aid RNAP during the transcription cycle are specific for the individual domain or only conserved between archaea and eukaryotes. Spt5 and its bacterial homologue NusG regulate gene expression in several ways by (i) modulating transcription processivity and promoter proximal pausing, (ii) coupling transcription and RNA processing or translation, and (iii) recruiting termination factors and thereby silencing laterally transferred DNA and protecting the genome against double-stranded DNA breaks. This review discusses recent discoveries that identify Spt5-like factors as evolutionary conserved nexus for the regulation and coordination of the machineries responsible for information processing in the cell. | A Nexus for Gene Expression—Molecular Mechanisms of Spt5 and NusG in the Three Domains of Life |
{"1011": 0.175953671336174, "1018": 0.0797421783208847, "1019": 0.0913962796330452, "1020": 0.05046287178993225, "1044": 0.3416208028793335, "1060": 0.6911921501159668, "2000": 0.1710275560617447, "2002": 0.07431721687316895, "2003": 0.08154398202896118, "2005": 0.1994270235300064, "2011": 0.09050461649894714, "2012": 0.12556517124176025, "2015": 0.16607704758644104, "2048": 0.36290550231933594, "2057": 0.12384103983640671, "2062": 0.38308101892471313, "2064": 0.34715715050697327, "2075": 0.2105647772550583, "2079": 0.0770333781838417, "2083": 0.8349450826644897, "2090": 0.4337083101272583, "2102": 0.034552380442619324, "2109": 0.4950772523880005, "2116": 0.3297532796859741, "2129": 0.24171993136405945, "2146": 0.48670899868011475, "2152": 0.9084475636482239, "2158": 0.21135559678077698, "2169": 0.1384023278951645, "2172": 0.10555581003427505, "2179": 0.37035053968429565, "2190": 0.46117570996284485, "2193": 0.02412080205976963, "2203": 0.7047978043556213, "2224": 0.45870962738990784, "2256": 0.052318159490823746, "2269": 0.6634125709533691, "2273": 0.36967599391937256, "2275": 0.36426326632499695, "2290": 0.2026219218969345, "2291": 0.04487626627087593, "2312": 0.09317722171545029, "2321": 0.24554696679115295, "2322": 0.3388410806655884, "2336": 0.4318077862262726, "2339": 0.22626367211341858, "2362": 0.04953393340110779, "2388": 0.5197699069976807, "2421": 0.11430477350950241, "2460": 1.104454517364502, "2470": 0.09406650811433792, "2475": 0.7426811456680298, "2478": 0.417115718126297, "2488": 0.08692999184131622, "2502": 0.11865071207284927, "2515": 0.1930064558982849, "2521": 0.5762182474136353, "2525": 0.28082266449928284, "2531": 0.6338034868240356, "2532": 0.6654226183891296, "2537": 0.2160874605178833, "2550": 0.3526630103588104, "2566": 0.6400018334388733, "2570": 0.29981520771980286, "2592": 0.7610978484153748, "2595": 0.21372433006763458, "2622": 0.6543170213699341, "2640": 0.30989447236061096, "2659": 0.23787821829319, "2682": 0.026976587250828743, "2765": 0.29473719000816345, "2775": 0.5393219590187073, "2779": 0.036437395960092545, "2783": 0.4126010537147522, "2812": 0.3877306580543518, "2817": 0.11517547070980072, "2825": 0.05417001247406006, "2832": 0.15023678541183472, "2836": 0.8877626657485962, "2844": 0.04674193635582924, "2846": 0.27564704418182373, "2879": 0.16442140936851501, "2881": 0.5232481360435486, "2898": 0.13243216276168823, "2913": 0.24018502235412598, "2918": 0.7537717819213867, "2936": 0.5324648022651672, "2944": 0.6155022978782654, "2946": 0.7728893756866455, "2951": 0.9005423784255981, "2966": 0.43244171142578125, "2974": 0.7592713832855225, "3008": 0.06795065850019455, "3020": 0.4932899475097656, "3070": 0.6394867897033691, "3075": 0.0797421783208847, "3091": 0.8349450826644897, "3104": 0.23710809648036957, "3112": 0.08064348995685577, "3130": 0.04113444685935974, "3139": 0.44753631949424744, "3144": 0.0174254160374403, "3177": 0.2478361576795578, "3191": 0.9842413663864136, "3231": 0.48670899868011475, "3284": 0.5069117546081543, "3287": 0.8941729068756104, "3292": 0.8567397594451904, "3337": 0.022212404757738113, "3397": 0.33953672647476196, "3435": 0.20739519596099854, "3445": 0.23402166366577148, "3446": 0.7389566898345947, "3463": 0.5635144114494324, "3469": 0.0029254043474793434, "3556": 0.5069117546081543, "3563": 0.129004567861557, "3566": 0.18248429894447327, "3594": 0.304147332906723, "3611": 0.3870677351951599, "3623": 0.469759464263916, "3634": 0.12986256182193756, "3638": 0.24018502235412598, "3668": 0.630689799785614, "3674": 0.2696990668773651, "3676": 0.5784112811088562, "3701": 0.15023678541183472, "3737": 0.6086184978485107, "3752": 0.9052929878234863, "3767": 0.5301685929298401, "3778": 0.0174254160374403, "3800": 0.19381128251552582, "3811": 0.40285754203796387, "3816": 0.3588210940361023, "3832": 0.0019512200960889459, "3867": 0.18004031479358673, "3934": 0.2852376699447632, "3940": 0.46608972549438477, "3952": 0.4873090982437134, "3965": 0.6107416749000549, "3977": 0.02887592278420925, "3995": 0.5116065740585327, "4013": 0.6828403472900391, "4098": 0.04860413447022438, "4106": 0.3723714053630829, "4118": 0.8161250352859497, "4160": 0.2711893916130066, "4183": 1.0755622386932373, "4245": 0.16524957120418549, "4275": 0.35128939151763916, "4295": 0.3170322775840759, "4328": 0.00875066313892603, "4338": 0.9515975713729858, "4403": 1.020087480545044, "4423": 0.21922965347766876, "4431": 0.29981520771980286, "4454": 0.013579257763922215, "4456": 0.0058422754518687725, "4488": 0.24018502235412598, "4493": 0.16359257698059082, "4515": 0.21687394380569458, "4520": 0.5232481360435486, "4531": 0.04487626627087593, "4539": 0.013579257763922215, "4555": 0.26820653676986694, "4566": 0.1905880719423294, "4588": 0.18167030811309814, "4595": 0.6634125709533691, "4616": 0.1401015669107437, "4621": 0.04487626627087593, "4646": 0.1602703034877777, "4666": 0.055094651877880096, "4677": 0.04207121208310127, "4678": 0.7389566898345947, "4685": 0.27564704418182373, "4691": 0.03266380727291107, "4710": 0.013579257763922215, "4725": 0.7665573358535767, "4766": 0.052318159490823746, "4820": 0.29473719000816345, "4838": 0.24325250089168549, "4867": 0.010684899985790253, "4919": 0.036437395960092545, "4962": 0.7463917136192322, "5056": 0.19622190296649933, "5097": 0.1946154683828354, "5155": 0.08603433519601822, "5266": 0.04860413447022438, "5292": 0.969535231590271, "5301": 0.5027855634689331, "5331": 0.20421554148197174, "5335": 0.6613984704017639, "5383": 0.6218147873878479, "5461": 0.4818955361843109, "5514": 0.009718249551951885, "5537": 1.190008521080017, "5593": 0.2447827309370041, "5604": 0.4831010699272156, "5665": 0.8238670229911804, "5787": 0.1485546976327896, "5799": 0.08244366943836212, "5813": 0.10291612148284912, "5852": 0.2622140049934387, "5907": 0.29255300760269165, "5997": 0.512191891670227, "6022": 0.3615458607673645, "6028": 0.6011518239974976, "6064": 0.9225212931632996, "6075": 0.3297532796859741, "6129": 0.16359257698059082, "6162": 0.13071982562541962, "6165": 0.5903874635696411, "6179": 0.2539152204990387, "6325": 1.070887804031372, "6364": 0.3877306580543518, "6415": 0.030771657824516296, "6434": 0.09938567131757736, "6493": 0.35334911942481995, "6522": 0.2786078155040741, "6551": 0.0606246218085289, "6578": 0.1011524572968483, "6627": 0.25088030099868774, "6687": 0.13414156436920166, "6694": 0.846739649772644, "6727": 0.4818955361843109, "6747": 0.19862671196460724, "6786": 0.7692760229110718, "6790": 0.04207121208310127, "6809": 0.28963330388069153, "6829": 0.09495500475168228, "6887": 0.7408206462860107, "6903": 0.011650617234408855, "6942": 0.8756314516067505, "6945": 0.22626367211341858, "7017": 0.41195443272590637, "7023": 0.0058422754518687725, "7077": 0.0317181795835495, "7099": 0.5232481360435486, "7137": 0.34577593207359314, "7146": 1.004473328590393, "7237": 0.2674594223499298, "7366": 0.3499138653278351, "7403": 0.7746911644935608, "7457": 0.4067663550376892, "7512": 0.6813592314720154, "7561": 0.987156867980957, "7620": 0.12038381397724152, "7644": 0.4891071021556854, "7645": 0.08692999184131622, "7689": 0.4145384132862091, "7709": 0.09495500475168228, "7718": 0.5116065740585327, "7809": 0.35060185194015503, "7820": 0.4926934838294983, "7870": 0.35334911942481995, "7885": 0.016465263441205025, "7888": 0.36426326632499695, "7908": 0.25694093108177185, "7949": 0.45499902963638306, "8068": 0.40806588530540466, "8082": 0.5495203733444214, "8114": 0.2539152204990387, "8122": 0.3554046154022217, "8141": 0.24859806895256042, "8150": 0.7352184057235718, "8168": 0.6793810129165649, "8192": 0.06703783571720123, "8319": 0.02316705882549286, "8321": 0.6907027959823608, "8377": 0.1619328260421753, "8402": 0.371698260307312, "8462": 0.12384103983640671, "8487": 0.5472630262374878, "8553": 0.11604541540145874, "8599": 0.09317722171545029, "8893": 0.026976587250828743, "8991": 0.8433839678764343, "9096": 0.7342816591262817, "9099": 0.03360854089260101, "9132": 0.4158279001712799, "9165": 0.5925496220588684, "9229": 0.15693697333335876, "9320": 0.6118015646934509, "9381": 0.26296505331993103, "9407": 0.1229778528213501, "9412": 0.319873183965683, "9447": 0.175953671336174, "9546": 0.04674193635582924, "9631": 1.04512357711792, "9646": 0.20580662786960602, "9671": 0.23092569410800934, "9699": 0.12986256182193756, "9737": 0.0009760859538801014, "9839": 0.1619328260421753, "9896": 0.23787821829319, "10032": 0.18978065252304077, "10071": 0.8509185314178467, "10381": 0.28670501708984375, "10415": 0.1946154683828354, "10438": 0.058784693479537964, "10466": 0.4914994537830353, "10624": 0.319873183965683, "10640": 0.9857001900672913, "10660": 0.28597161173820496, "10697": 0.8829278349876404, "10742": 0.3877306580543518, "10750": 0.12556517124176025, "10756": 0.2026219218969345, "10826": 0.6338034868240356, "10898": 0.18816383183002472, "10910": 0.04487626627087593, "10924": 0.037378571927547455, "11062": 0.36290550231933594, "11211": 0.3963087201118469, "11244": 0.11517547070980072, "11326": 0.09938567131757736, "11397": 0.35745587944984436, "11598": 0.1212492436170578, "11619": 0.1913948506116867, "11643": 0.38308101892471313, "11649": 0.016465263441205025, "11709": 0.1212492436170578, "11718": 0.4286321699619293, "11927": 0.010684899985790253, "11991": 0.42225050926208496, "12103": 0.5313173532485962, "12260": 0.07341018319129944, "12335": 0.7144040465354919, "12353": 0.0317181795835495, "12367": 1.0298984050750732, "12374": 0.3949938118457794, "12381": 0.5156965255737305, "12490": 0.15860503911972046, "12504": 0.5272908806800842, "12637": 0.2394166737794876, "12641": 0.3077431619167328, "12717": 0.8400169610977173, "12739": 0.6877616047859192, "12762": 0.272677481174469, "12789": 0.09672962874174118, "12889": 0.4624064862728119, "12987": 0.3560888469219208, "13265": 0.08154398202896118, "13369": 0.33675122261047363, "13458": 1.1121915578842163, "13462": 0.2223619967699051, "13512": 0.3409265875816345, "13685": 0.05970508232712746, "13792": 0.17431432008743286, "13874": 0.16524957120418549, "13912": 0.3339579105377197, "13938": 0.22157983481884003, "14125": 0.19541899859905243, "14193": 0.10906458646059036, "14246": 0.19541899859905243, "14471": 0.5116065740585327, "14494": 0.058784693479537964, "14536": 0.16524957120418549, "14644": 0.11604541540145874, "14798": 0.5855054259300232, "15007": 0.22937409579753876, "15058": 0.04767346754670143, "15258": 0.2493593990802765, "15502": 0.18492233753204346, "15670": 0.014542185701429844, "15873": 0.10379679501056671, "15924": 0.8298473954200745, "16012": 0.06154331564903259, "16014": 0.08513788133859634, "16134": 0.5947071313858032, "16216": 0.17267228662967682, "16221": 0.30486753582954407, "16227": 0.1619328260421753, "16275": 0.11865071207284927, "16281": 0.21687394380569458, "16416": 0.13499516248703003, "16515": 0.25845035910606384, "16706": 1.1249549388885498, "16731": 0.20739519596099854, "16840": 0.02316705882549286, "16861": 0.30989447236061096, "16914": 0.25239890813827515, "17208": 0.0029254043474793434, "17287": 0.018384648486971855, "17531": 0.7009293437004089, "17547": 0.040196798741817474, "17592": 0.45994341373443604, "17598": 0.1685553640127182, "17702": 0.04487626627087593, "17904": 0.0174254160374403, "18195": 0.2990913391113281, "18212": 0.3956514894962311, "18231": 0.23787821829319, "18422": 0.018384648486971855, "18780": 1.2900071144104004, "18925": 0.02887592278420925, "19274": 0.7333439588546753, "19518": 0.03925827145576477, "19610": 0.02792670577764511, "19780": 0.29400965571403503, "19974": 0.3381449282169342, "20047": 0.4568560719490051, "20300": 0.2247048318386078, "20353": 0.06795065850019455, "20600": 0.029824240133166313, "20906": 0.1808556467294693, "21369": 1.1121915578842163, "21557": 0.034552380442619324, "21600": 1.3720329999923706, "21672": 0.43434104323387146, "21677": 0.8247235417366028, "21716": 0.20421554148197174, "21718": 0.5116065740585327, "21770": 0.7086513638496399, "22026": 0.34715715050697327, "22269": 0.17267228662967682, "22415": 0.0842406153678894, "22778": 0.3077431619167328, "23599": 0.4980490207672119, "23676": 0.04394211992621422, "23760": 0.29328158497810364, "23767": 0.015504186972975731, "23851": 0.33953672647476196, "24004": 0.06703783571720123, "24110": 0.013579257763922215, "24353": 0.22548456490039825, "24396": 0.3547199070453644, "24558": 1.5058120489120483, "24710": 0.637939989566803, "24759": 0.630689799785614, "24840": 0.16359257698059082, "25086": 0.056018441915512085, "25206": 0.2800849378108978, "25256": 0.27934664487838745, "25291": 0.04487626627087593, "25426": 0.04674193635582924, "25524": 0.5729197263717651, "25586": 0.6441128253936768, "25708": 0.08244366943836212, "25837": 0.04394211992621422, "25845": 0.025073638185858727, "25937": 0.1946154683828354, "26236": 0.28082266449928284, "26305": 1.0560526847839355, "26319": 0.0174254160374403, "26601": 0.2145126610994339, "26633": 0.6872705817222595, "26702": 0.2478361576795578, "26741": 0.10993985831737518, "26802": 0.04487626627087593, "26836": 0.1229778528213501, "26874": 0.9115922451019287, "26952": 0.0029254043474793434, "27046": 0.35128939151763916, "27507": 0.1946154683828354, "27605": 0.09495500475168228, "27642": 0.6950984001159668, "27965": 0.7665573358535767, "28024": 0.08961215615272522, "28177": 0.08154398202896118, "28436": 0.28082266449928284, "29458": 0.029824240133166313} | 13914198 | High-throughput sequencing technologies produce short sequence reads that can contain phase information if they span two or more heterozygote genotypes. This information is not routinely used by current methods that infer haplotypes from genotype data. We have extended the SHAPEIT2 method to use phase-informative sequencing reads to improve phasing accuracy. Our model incorporates the read information in a probabilistic model through base quality scores within each read. The method is primarily designed for high-coverage sequence data or data sets that already have genotypes called. One important application is phasing of single samples sequenced at high coverage for use in medical sequencing and studies of rare diseases. Our method can also use existing panels of reference haplotypes. We tested the method by using a mother-father-child trio sequenced at high-coverage by Illumina together with the low-coverage sequence data from the 1000 Genomes Project (1000GP). We found that use of phase-informative reads increases the mean distance between switch errors by 22% from 274.4 kb to 328.6 kb. We also used male chromosome X haplotypes from the 1000GP samples to simulate sequencing reads with varying insert size, read length, and base error rate. When using short 100 bp paired-end reads, we found that using mixtures of insert sizes produced the best results. When using longer reads with high error rates (5-20 kb read with 4%-15% error per base), phasing performance was substantially improved. | Haplotype estimation using sequencing reads. |
{"1013": 0.175953671336174, "1062": 0.3824150264263153, "1997": 0.2539152204990387, "1998": 0.175953671336174, "2005": 0.0019512200960889459, "2051": 0.4425300657749176, "2053": 0.24631060659885406, "2062": 0.06154331564903259, "2071": 0.02316705882549286, "2073": 0.17431432008743286, "2084": 0.17759032547473907, "2099": 0.3353555500507355, "2104": 0.0009760859538801014, "2116": 0.19782574474811554, "2145": 0.176772341132164, "2146": 0.02412080205976963, "2148": 0.7445381283760071, "2169": 0.2501201331615448, "2172": 0.33953672647476196, "2177": 0.052318159490823746, "2188": 0.22079704701900482, "2227": 0.11081436276435852, "2302": 0.24325250089168549, "2312": 0.2576959431171417, "2326": 0.5033760666847229, "2335": 0.08513788133859634, "2339": 0.0606246218085289, "2358": 0.4431571960449219, "2363": 0.030771657824516296, "2391": 0.23402166366577148, "2396": 1.0808777809143066, "2406": 0.3084607720375061, "2408": 0.3170322775840759, "2426": 0.2184450328350067, "2470": 0.0038986403960734606, "2489": 0.8247235417366028, "2527": 0.025073638185858727, "2561": 0.5116065740585327, "2565": 0.5762182474136353, "2566": 0.018384648486971855, "2578": 0.6502478122711182, "2634": 0.1677299439907074, "2660": 0.11256109178066254, "2670": 0.0913962796330452, "2685": 0.43244171142578125, "2714": 0.40351006388664246, "2729": 0.7610978484153748, "2740": 0.6714286804199219, "2769": 0.42926809191703796, "2779": 0.5816917419433594, "2797": 0.6461620330810547, "2840": 0.5080875158309937, "2847": 0.46608972549438477, "2853": 0.33325836062431335, "2902": 0.5903874635696411, "2911": 0.08603433519601822, "2944": 0.2763880789279938, "2966": 0.3723714053630829, "2985": 0.6011518239974976, "3024": 0.5381823778152466, "3032": 0.6212902665138245, "3060": 1.1512393951416016, "3073": 0.4286321699619293, "3078": 0.7782850861549377, "3088": 1.2082605361938477, "3104": 0.23247487843036652, "3126": 0.9052929878234863, "3151": 0.5696102976799011, "3188": 0.04674193635582924, "3204": 0.3499138653278351, "3263": 0.13755162060260773, "3343": 0.46670228242874146, "3344": 0.11691460013389587, "3361": 0.7286425232887268, "3424": 0.5816917419433594, "3446": 0.083342544734478, "3452": 0.29981520771980286, "3454": 0.37035053968429565, "3460": 0.36290550231933594, "3463": 0.25694093108177185, "3465": 1.1524739265441895, "3477": 0.11430477350950241, "3541": 0.8264343738555908, "3604": 0.43623676896095276, "3623": 0.18167030811309814, "3640": 0.21687394380569458, "3653": 0.8039615154266357, "3665": 0.9108069539070129, "3715": 0.7370892763137817, "3825": 0.17840765416622162, "3856": 0.259204238653183, "3867": 0.12986256182193756, "3942": 0.5145297050476074, "3949": 0.5404602885246277, "3976": 0.4444103240966797, "3998": 0.29473719000816345, "4015": 0.10026945173740387, "4060": 0.49864232540130615, "4090": 0.2990913391113281, "4102": 0.18411032855510712, "4106": 0.010684899985790253, "4118": 0.3903779089450836, "4128": 0.1808556467294693, "4146": 0.259204238653183, "4228": 0.2493593990802765, "4281": 1.0519683361053467, "4295": 0.2501201331615448, "4297": 0.30989447236061096, "4305": 0.46117570996284485, "4319": 0.3423145115375519, "4322": 0.08961215615272522, "4346": 0.34300774335861206, "4357": 0.16359257698059082, "4358": 0.12986256182193756, "4380": 0.0029254043474793434, "4387": 0.6583697199821472, "4505": 0.36086538434028625, "4522": 0.5762182474136353, "4651": 0.1930064558982849, "4725": 0.49686139822006226, "4746": 0.18573370575904846, "4804": 0.23324857652187347, "4855": 0.06337817758321762, "4909": 0.19782574474811554, "4942": 0.8074519634246826, "5022": 0.6118015646934509, "5150": 0.025073638185858727, "5166": 0.3897167444229126, "5171": 0.006812678650021553, "5193": 0.6327666640281677, "5247": 0.6502478122711182, "5271": 0.129004567861557, "5332": 0.6186635494232178, "5338": 0.16607704758644104, "5345": 0.638455867767334, "5356": 0.040196798741817474, "5366": 0.8109301924705505, "5422": 0.3423145115375519, "5427": 0.4412745535373688, "5443": 0.04953393340110779, "5446": 0.6734226942062378, "5543": 0.11081436276435852, "5547": 0.14518201351165771, "5571": 0.35745587944984436, "5776": 0.7182208299636841, "5845": 0.03266380727291107, "5850": 0.2576959431171417, "5938": 0.5979346632957458, "6018": 0.04113444685935974, "6022": 0.2034190446138382, "6025": 0.17922431230545044, "6043": 0.40871503949165344, "6083": 0.037378571927547455, "6164": 0.6950984001159668, "6165": 0.05139094591140747, "6325": 0.08513788133859634, "6363": 0.12728634476661682, "6370": 0.10731173306703568, "6431": 0.2160874605178833, "6450": 0.5139457583427429, "6463": 0.026025565341114998, "6599": 0.22937409579753876, "6612": 0.20102575421333313, "6653": 0.6086184978485107, "6787": 0.4624064862728119, "6959": 0.18167030811309814, "7017": 0.2852376699447632, "7023": 0.4624064862728119, "7045": 0.5069117546081543, "7058": 0.6123310327529907, "7079": 0.05786345899105072, "7099": 0.2983669638633728, "7118": 0.5174443125724792, "7140": 0.24859806895256042, "7242": 0.13499516248703003, "7320": 0.4914994537830353, "7408": 0.31132611632347107, "7435": 0.3743882179260254, "7438": 0.129004567861557, "7597": 0.20660123229026794, "7636": 0.48670899868011475, "7667": 0.06246116757392883, "7829": 0.1677299439907074, "7831": 0.2659635543823242, "7842": 0.777387797832489, "7870": 0.151916041970253, "7879": 0.6902132034301758, "7895": 0.6941232681274414, "7909": 0.0058422754518687725, "7938": 0.2763880789279938, "8127": 0.1930064558982849, "8130": 0.3883931338787079, "8168": 0.43434104323387146, "8266": 0.14602625370025635, "8302": 0.6038249135017395, "8323": 0.34577593207359314, "8387": 0.9409833550453186, "8445": 0.25239890813827515, "8497": 0.06795065850019455, "8566": 0.20660123229026794, "8569": 0.025073638185858727, "8622": 0.0029254043474793434, "8630": 0.009718249551951885, "8746": 0.38574060797691345, "8907": 0.24018502235412598, "8932": 0.41195443272590637, "8984": 0.06886265426874161, "8985": 0.42096930742263794, "9030": 0.13670019805431366, "9139": 0.34370049834251404, "9236": 0.5347557663917542, "9279": 0.2800849378108978, "9347": 0.10026945173740387, "9349": 0.8332487344741821, "9687": 0.5651806592941284, "9701": 0.27564704418182373, "9740": 0.3163207769393921, "9820": 1.2381477355957031, "9835": 0.16359257698059082, "9839": 0.0009760859538801014, "9871": 0.6244332790374756, "9883": 0.25694093108177185, "9983": 0.2881702482700348, "10031": 0.2659635543823242, "10035": 0.08692999184131622, "10174": 0.5573811531066895, "10197": 0.018384648486971855, "10316": 0.3683255612850189, "10372": 0.19782574474811554, "10411": 0.07341018319129944, "10426": 0.036437395960092545, "10521": 0.19381128251552582, "10613": 0.255429208278656, "10802": 0.2247048318386078, "10807": 0.02792670577764511, "10859": 0.956112265586853, "10961": 0.5098485946655273, "11005": 0.14349138736724854, "11095": 0.11691460013389587, "11154": 0.08871890604496002, "11399": 0.06612417846918106, "11412": 0.1994270235300064, "11670": 0.10379679501056671, "11727": 0.5662899017333984, "11735": 0.010684899985790253, "11780": 0.347847044467926, "11806": 0.0019512200960889459, "11959": 0.1677299439907074, "12135": 0.44753631949424744, "12298": 0.6823468804359436, "12381": 0.33953672647476196, "12435": 0.3241194784641266, "12823": 0.07341018319129944, "12867": 0.3012613356113434, "12893": 0.35060185194015503, "12928": 0.06886265426874161, "13003": 0.2317005842924118, "13092": 0.1477125883102417, "13143": 0.43875885009765625, "13441": 0.31204116344451904, "13445": 0.0770333781838417, "13465": 0.6739205718040466, "13483": 0.4879087805747986, "13491": 0.09050461649894714, "13732": 0.28082266449928284, "13751": 0.3588210940361023, "13790": 0.7701805830001831, "13859": 0.1946154683828354, "14084": 0.0752234235405922, "14155": 0.38374659419059753, "14358": 0.04860413447022438, "14506": 0.0842406153678894, "14566": 1.151856780052185, "14667": 0.31132611632347107, "15053": 0.0029254043474793434, "15087": 0.6043586730957031, "15170": 0.5472630262374878, "15245": 0.2983669638633728, "15265": 0.11256109178066254, "15306": 0.31132611632347107, "15373": 0.06977381557226181, "15406": 0.17020416259765625, "15408": 0.08064348995685577, "15471": 0.07431721687316895, "15535": 0.3757305145263672, "15877": 1.2753846645355225, "15970": 0.1693800985813141, "15976": 0.3034266233444214, "16095": 0.09761575609445572, "16134": 0.5398913025856018, "16185": 0.010684899985790253, "16268": 0.029824240133166313, "16269": 0.15526613593101501, "16302": 0.5232481360435486, "16514": 0.27712854743003845, "16671": 0.07431721687316895, "17047": 0.29981520771980286, "17208": 0.6027565002441406, "17459": 0.38041436672210693, "17463": 0.21214580535888672, "17591": 0.28670501708984375, "17865": 0.7809720039367676, "17867": 0.09050461649894714, "17943": 0.7067264318466187, "18004": 0.20580662786960602, "18076": 0.5979346632957458, "18137": 0.23556606471538544, "18276": 0.47463157773017883, "18313": 0.05786345899105072, "18422": 0.38174858689308167, "18512": 0.11865071207284927, "19003": 0.47036975622177124, "19132": 0.09672962874174118, "19414": 0.0354953333735466, "19446": 0.03831886500120163, "19783": 0.5295937061309814, "19817": 0.040196798741817474, "19843": 0.29400965571403503, "19851": 0.2105647772550583, "20125": 0.6980181336402893, "20177": 0.33675122261047363, "20272": 0.36494144797325134, "20391": 0.10467668622732162, "20700": 0.7782850861549377, "21124": 0.02316705882549286, "21150": 0.0317181795835495, "21462": 0.016465263441205025, "21762": 0.0029254043474793434, "22173": 0.2711893916130066, "22371": 0.19220098853111267, "22667": 0.35677260160446167, "22697": 0.5718178153038025, "23041": 0.20102575421333313, "23564": 1.1128336191177368, "23733": 0.1619328260421753, "23734": 0.12556517124176025, "23778": 0.0009760859538801014, "24093": 0.0317181795835495, "24207": 0.8117979168891907, "24229": 0.08603433519601822, "24290": 0.018384648486971855, "24343": 0.010684899985790253, "24479": 0.016465263441205025, "24505": 0.9317949414253235, "25022": 0.3374483287334442, "25040": 0.07341018319129944, "25219": 0.02792670577764511, "25276": 0.19220098853111267, "25366": 0.053244512528181076, "25430": 0.10993985831737518, "25612": 0.05786345899105072, "25640": 0.045809537172317505, "26163": 0.23710809648036957, "26237": 0.7067264318466187, "26419": 1.207676887512207, "26563": 0.18167030811309814, "26728": 0.15023678541183472, "26887": 0.07612881064414978, "27615": 0.0842406153678894, "28393": 0.2983669638633728, "28673": 0.09938567131757736, "28768": 0.08064348995685577, "28836": 0.23864774405956268, "28849": 0.1477125883102417, "29235": 0.6679295301437378, "29288": 0.28890204429626465} | 13914633 | BACKGROUND HIV and tuberculosis (TB) services are provided free of charge in many sub-Saharan African countries, but patients still incur costs. METHODS Patient-exit interviews were conducted in primary health care clinics in rural South Africa with representative samples of 200 HIV-infected patients enrolled in a pre-antiretroviral treatment (pre-ART) program, 300 patients receiving antiretroviral treatment (ART), and 300 patients receiving TB treatment. For each group, we calculated health expenditures across different spending categories, time spent traveling to and using services, and how patients financed their spending. Associations between patient group and costs were assessed in multivariate regression models. RESULTS Total monthly health expenditures [1 USD = 7.3 South African Rand (ZAR)] were ZAR 171 [95% confidence interval (CI): 134 to 207] for pre-ART, ZAR 164 (95% CI: 141 to 187) for ART, and ZAR 122 (95% CI: 105 to 140) for TB patients (P = 0.01). Total monthly time costs (in hours) were 3.4 (95% CI: 3.3 to 3.5) for pre-ART, 5.0 (95% CI: 4.7 to 5.3) for ART, and 3.2 (95% CI: 2.9 to 3.4) for TB patients (P < 0.01). Although overall patient costs were similar across groups, pre-ART patients spent on average ZAR 29.2 more on traditional healers and ZAR 25.9 more on chemists and private doctors than ART patients, whereas ART patients spent ZAR 34.0 more than pre-ART patients on transport to clinics (P < 0.05 for all results). Thirty-one percent of pre-ART, 39% of ART, and 41% of TB patients borrowed money or sold assets to finance health care. CONCLUSIONS Patients receiving nominally free care for HIV/TB face large private costs, commonly leading to financial distress. Subsidized transport, fewer clinic visits, and drug pick-up points closer to home could reduce costs for ART patients, potentially improving retention and adherence. Large expenditure on alternative care among pre-ART patients suggests that transitioning patients to ART earlier, as under HIV treatment-as-prevention policies, may not substantially increase patients' financial burden. | Time and Money: The True Costs of Health Care Utilization for Patients Receiving "Free" HIV/Tuberculosis Care and Treatment in Rural KwaZulu-Natal. |
{"1037": 0.13925230503082275, "2003": 0.07431721687316895, "2013": 0.0752234235405922, "2047": 0.25088030099868774, "2054": 0.0038986403960734606, "2109": 0.18329764902591705, "2126": 0.036437395960092545, "2129": 0.23402166366577148, "2155": 0.33675122261047363, "2168": 0.9248477816581726, "2170": 0.45623743534088135, "2171": 0.8821197748184204, "2182": 0.31489628553390503, "2214": 0.2026219218969345, "2224": 0.02887592278420925, "2291": 0.8298473954200745, "2315": 0.7683706283569336, "2339": 0.34508460760116577, "2344": 0.15943801403045654, "2362": 0.0317181795835495, "2367": 0.5805994272232056, "2408": 0.10026945173740387, "2427": 0.6950984001159668, "2445": 0.09672962874174118, "2517": 0.39696553349494934, "2536": 0.07068414986133575, "2580": 0.1401015669107437, "2640": 0.18248429894447327, "2649": 0.440646231174469, "2674": 0.13670019805431366, "2689": 0.25995752215385437, "2714": 0.672426164150238, "2750": 0.3810817003250122, "2795": 0.014542185701429844, "2801": 0.04767346754670143, "2832": 0.020300358533859253, "2881": 0.4349733293056488, "2904": 0.09495500475168228, "2925": 0.04394211992621422, "3001": 0.5393219590187073, "3015": 0.1510767638683319, "3025": 0.08961215615272522, "3080": 0.1485546976327896, "3115": 0.08961215615272522, "3125": 0.4412745535373688, "3130": 0.05139094591140747, "3141": 0.4311734735965729, "3252": 0.4400174915790558, "3289": 0.20102575421333313, "3399": 0.13499516248703003, "3415": 0.8780695199966431, "3513": 0.10906458646059036, "3560": 0.3304552733898163, "3562": 0.034552380442619324, "3584": 0.1693800985813141, "3674": 0.13755162060260773, "3800": 0.35060185194015503, "3818": 0.5662899017333984, "3830": 0.06154331564903259, "3832": 0.05046287178993225, "3853": 0.3077431619167328, "3858": 0.4267219603061676, "3975": 0.03266380727291107, "3978": 0.025073638185858727, "4045": 0.0797421783208847, "4081": 0.1685553640127182, "4089": 0.1221139207482338, "4096": 0.4679262638092041, "4118": 0.29328158497810364, "4137": 0.7934166193008423, "4233": 0.4764525294303894, "4289": 0.6016870141029358, "4339": 0.2539152204990387, "4351": 0.1873544454574585, "4453": 0.2317005842924118, "4493": 0.24171993136405945, "4541": 0.04207121208310127, "4680": 0.14179791510105133, "4874": 0.1930064558982849, "4962": 0.3723714053630829, "4972": 0.19381128251552582, "5038": 0.304147332906723, "5071": 0.05694137513637543, "5090": 0.1011524572968483, "5250": 1.1573970317840576, "5278": 0.22157983481884003, "5320": 0.09584271162748337, "5412": 0.030771657824516296, "5449": 0.21530038118362427, "5457": 0.6270449161529541, "5537": 0.18248429894447327, "5577": 0.13157635927200317, "5579": 0.272677481174469, "5679": 0.5461324453353882, "5816": 0.058784693479537964, "5892": 0.022212404757738113, "6048": 0.21765978634357452, "6064": 0.4673144817352295, "6083": 0.0058422754518687725, "6100": 0.006812678650021553, "6235": 0.053244512528181076, "6378": 0.3012613356113434, "6415": 0.037378571927547455, "6512": 0.32553088665008545, "6614": 0.040196798741817474, "6635": 0.0029254043474793434, "6673": 0.07159364968538284, "6709": 0.41647201776504517, "6721": 0.09050461649894714, "6724": 0.9470623731613159, "6807": 0.2837681770324707, "6936": 0.03266380727291107, "7141": 0.15023678541183472, "7235": 1.036847710609436, "7337": 0.3077431619167328, "7366": 0.4419025182723999, "7403": 0.11081436276435852, "7539": 0.9635916948318481, "7809": 0.18978065252304077, "7843": 0.0174254160374403, "7848": 0.22157983481884003, "7863": 1.022197961807251, "7900": 0.06795065850019455, "8053": 0.009718249551951885, "8171": 1.2129170894622803, "8259": 0.13499516248703003, "8332": 0.20501139760017395, "8335": 0.07068414986133575, "8360": 0.11081436276435852, "8382": 0.03266380727291107, "8516": 0.03925827145576477, "8720": 0.16524957120418549, "8775": 0.9827804565429688, "9075": 0.14095009863376617, "9504": 0.026025565341114998, "9614": 0.14686977863311768, "9886": 0.0913962796330452, "9896": 0.2830325961112976, "10324": 1.0326838493347168, "10335": 0.777387797832489, "10340": 0.09317722171545029, "10737": 0.23556606471538544, "10744": 0.2394166737794876, "10782": 0.05139094591140747, "10958": 0.18492233753204346, "11027": 0.2954642176628113, "11038": 0.21530038118362427, "11092": 0.48670899868011475, "11095": 0.13243216276168823, "11100": 0.6941232681274414, "11234": 0.25995752215385437, "11455": 0.1710275560617447, "11630": 0.3283478021621704, "11683": 0.12556517124176025, "11778": 0.35745587944984436, "12151": 0.016465263441205025, "12319": 0.37304413318634033, "12440": 0.3949938118457794, "12571": 0.045809537172317505, "12599": 0.16690383851528168, "12649": 0.006812678650021553, "12987": 0.5651806592941284, "13014": 0.0797421783208847, "13096": 0.20580662786960602, "13534": 0.043007105588912964, "13578": 0.25088030099868774, "13792": 0.04767346754670143, "13922": 0.3283478021621704, "14062": 0.03925827145576477, "14402": 0.6233867406845093, "14477": 0.6446255445480347, "14570": 0.08064348995685577, "14593": 0.010684899985790253, "14600": 0.3141832649707794, "14622": 0.28743788599967957, "14799": 0.5607312321662903, "14847": 0.4311734735965729, "14869": 0.22782009840011597, "14905": 0.3141832649707794, "14916": 0.3034266233444214, "15142": 0.9739698171615601, "15200": 0.25239890813827515, "16134": 0.06154331564903259, "16151": 0.09761575609445572, "16261": 0.00875066313892603, "16367": 0.06795065850019455, "16599": 0.5483922958374023, "16706": 0.8349450826644897, "16801": 0.6254787445068359, "16861": 0.1946154683828354, "16965": 0.04113444685935974, "17146": 0.39893341064453125, "17592": 0.08064348995685577, "18026": 0.1710275560617447, "18425": 0.03360854089260101, "18442": 0.31132611632347107, "18444": 0.05786345899105072, "18513": 0.255429208278656, "18847": 0.23092569410800934, "19137": 0.37907835841178894, "19395": 1.3998736143112183, "19639": 0.2223619967699051, "20080": 0.11951763927936554, "20123": 0.0317181795835495, "20363": 0.04860413447022438, "20381": 0.14264501631259918, "21197": 0.823009729385376, "21770": 0.20102575421333313, "21937": 0.06703783571720123, "21991": 0.23402166366577148, "22026": 0.026976587250828743, "22369": 0.058784693479537964, "23079": 0.27934664487838745, "23148": 0.009718249551951885, "23718": 0.9515975713729858, "23911": 0.7951818704605103, "24004": 1.0702182054519653, "24022": 0.5347557663917542, "24216": 0.18654440343379974, "24312": 0.31560876965522766, "24414": 0.07884006202220917, "24473": 0.22548456490039825, "24854": 0.33675122261047363, "24944": 0.5489565134048462, "25117": 0.009718249551951885, "25269": 0.2800849378108978, "25274": 0.21372433006763458, "25426": 0.06154331564903259, "25835": 0.1994270235300064, "25876": 0.37907835841178894, "25963": 0.12384103983640671, "26206": 0.1229778528213501, "26268": 0.0058422754518687725, "26874": 0.4770587682723999, "27343": 0.020300358533859253, "27637": 0.13071982562541962, "27642": 1.2198615074157715, "28078": 0.28670501708984375, "28295": 0.09317722171545029, "28353": 0.015504186972975731, "28616": 0.06612417846918106, "28679": 0.5903874635696411, "28847": 0.37640097737312317, "29060": 0.058784693479537964, "29446": 0.01934296265244484} | 13915464 | A system for naming ribosomal proteins is described that the authors intend to use in the future. They urge others to adopt it. The objective is to eliminate the confusion caused by the assignment of identical names to ribosomal proteins from different species that are unrelated in structure and function. In the system proposed here, homologous ribosomal proteins are assigned the same name, regardless of species. It is designed so that new names are similar enough to old names to be easily recognized, but are written in a format that unambiguously identifies them as 'new system' names. | A new system for naming ribosomal proteins. |
{"1013": 0.1677299439907074, "1039": 0.37907835841178894, "1052": 0.42990362644195557, "1056": 0.5284429788589478, "2003": 0.3339579105377197, "2006": 0.04674193635582924, "2013": 0.15442965924739838, "2023": 0.06612417846918106, "2038": 0.20977331697940826, "2042": 0.04860413447022438, "2043": 0.20501139760017395, "2047": 0.46853771805763245, "2054": 0.13414156436920166, "2061": 0.7105726003646851, "2062": 0.04674193635582924, "2073": 0.02792670577764511, "2085": 0.45251765847206116, "2095": 0.10555581003427505, "2116": 0.7352184057235718, "2121": 0.7124901413917542, "2140": 0.20102575421333313, "2179": 0.18167030811309814, "2193": 0.6960725784301758, "2207": 0.603290855884552, "2230": 0.2749055027961731, "2312": 0.23710809648036957, "2350": 0.5816917419433594, "2361": 0.29473719000816345, "2364": 0.04674193635582924, "2405": 0.2674594223499298, "2424": 0.10906458646059036, "2426": 0.009718249551951885, "2440": 0.42608439922332764, "2470": 0.3012613356113434, "2515": 0.00875066313892603, "2529": 0.6270449161529541, "2545": 0.2160874605178833, "2563": 0.18411032855510712, "2565": 0.010684899985790253, "2592": 0.7737906575202942, "2609": 0.7380234599113464, "2622": 0.6112717390060425, "2671": 0.09850110858678818, "2686": 0.11081436276435852, "2713": 0.7610978484153748, "2739": 0.2531573474407196, "2747": 0.08961215615272522, "2800": 0.6394867897033691, "2806": 0.12470348179340363, "2818": 0.7067264318466187, "2820": 0.4067663550376892, "2828": 0.14349138736724854, "2838": 0.32199856638908386, "2862": 0.17267228662967682, "2866": 0.822151780128479, "2922": 0.2918238639831543, "2951": 1.0229004621505737, "2983": 0.2561853528022766, "2988": 0.02316705882549286, "3067": 0.5618454217910767, "3075": 0.40546512603759766, "3085": 0.5069117546081543, "3120": 0.2160874605178833, "3145": 0.3241194784641266, "3193": 0.06246116757392883, "3278": 0.5968599319458008, "3340": 0.10906458646059036, "3366": 0.5307431221008301, "3444": 0.14264501631259918, "3508": 0.44691193103790283, "3522": 0.13071982562541962, "3572": 0.08871890604496002, "3579": 0.669430673122406, "3603": 0.09761575609445572, "3616": 0.4568560719490051, "3642": 0.46853771805763245, "3652": 0.14095009863376617, "3654": 0.861702561378479, "3725": 0.15023678541183472, "3728": 0.37707099318504333, "3784": 0.1946154683828354, "3898": 0.007782140281051397, "3906": 0.5936289429664612, "3931": 0.2659635543823242, "3934": 0.38374659419059753, "3940": 0.6950984001159668, "3945": 0.151916041970253, "4007": 0.16276304423809052, "4037": 0.890972912311554, "4045": 0.6212902665138245, "4106": 0.06246116757392883, "4127": 0.48610860109329224, "4160": 0.09317722171545029, "4208": 0.3824150264263153, "4219": 0.7295845746994019, "4226": 0.848413348197937, "4286": 0.4673144817352295, "4289": 0.5021947622299194, "4295": 0.2741633653640747, "4352": 0.056018441915512085, "4372": 0.4537591338157654, "4397": 0.02316705882549286, "4456": 1.3331490755081177, "4466": 0.05786345899105072, "4473": 0.04674193635582924, "4520": 0.045809537172317505, "4573": 0.5080875158309937, "4751": 0.058784693479537964, "4772": 0.15023678541183472, "4773": 0.6207655072212219, "4852": 0.20022670924663544, "4957": 0.2719337046146393, "4962": 1.004473328590393, "4975": 0.10993985831737518, "4989": 0.4248080551624298, "5139": 0.029824240133166313, "5187": 0.24554696679115295, "5304": 0.5762182474136353, "5383": 0.007782140281051397, "5471": 0.6181373596191406, "5530": 0.5562619566917419, "5537": 0.06520967930555344, "5577": 0.22782009840011597, "5754": 0.6265231370925903, "5799": 0.12986256182193756, "5884": 0.3923587501049042, "5921": 0.06703783571720123, "6064": 0.7482418417930603, "6079": 0.12728634476661682, "6369": 1.1798561811447144, "6377": 0.4794800877571106, "6388": 0.11604541540145874, "6412": 0.10291612148284912, "6529": 0.11691460013389587, "6640": 0.18573370575904846, "6745": 0.25845035910606384, "6747": 0.3241194784641266, "6761": 0.0019512200960889459, "6782": 0.4818955361843109, "6845": 0.06977381557226181, "6846": 0.2689530849456787, "6882": 0.2231435477733612, "6897": 0.6291293501853943, "6971": 0.4349733293056488, "7017": 0.026976587250828743, "7085": 0.4673144817352295, "7099": 0.3777405619621277, "7134": 0.2576959431171417, "7155": 0.12470348179340363, "7172": 0.5618454217910767, "7366": 0.4831010699272156, "7403": 0.8917738795280457, "7479": 0.5646255612373352, "7551": 0.08782484382390976, "7552": 0.09938567131757736, "7578": 0.6853039860725403, "7679": 0.3757305145263672, "7689": 0.9710156321525574, "7692": 0.6139179468154907, "7721": 0.9287132620811462, "7784": 0.07159364968538284, "7801": 0.0354953333735466, "7809": 1.1205062866210938, "7870": 0.18167030811309814, "7885": 0.535327672958374, "7887": 0.04113444685935974, "7900": 0.07159364968538284, "7957": 0.05046287178993225, "7995": 0.08692999184131622, "8153": 0.013579257763922215, "8156": 0.637939989566803, "8168": 0.7333439588546753, "8171": 0.012615402229130268, "8299": 0.3910386264324188, "8346": 0.5573811531066895, "8376": 0.14179791510105133, "8382": 0.04487626627087593, "8389": 0.6828403472900391, "8425": 0.41840189695358276, "8756": 0.26146242022514343, "8780": 0.03266380727291107, "8832": 0.7295845746994019, "8860": 0.04207121208310127, "8906": 0.33325836062431335, "8917": 0.503966212272644, "8991": 0.7314660549163818, "9165": 1.0688776969909668, "9167": 0.6471850275993347, "9227": 0.1930064558982849, "9233": 0.021256839856505394, "9247": 0.05139094591140747, "9250": 0.01934296265244484, "9253": 0.38308101892471313, "9285": 0.1889725625514984, "9336": 0.10467668622732162, "9445": 0.012615402229130268, "9537": 0.40806588530540466, "9626": 0.20818853378295898, "9725": 0.2394166737794876, "10071": 0.020300358533859253, "10077": 1.034073829650879, "10161": 0.083342544734478, "10176": 0.18329764902591705, "10461": 0.0842406153678894, "10651": 0.2026219218969345, "10722": 0.27786844968795776, "10843": 0.28963330388069153, "10955": 0.011650617234408855, "10997": 0.0770333781838417, "11307": 0.4909018874168396, "11343": 0.35403475165367126, "11346": 0.1332872211933136, "11568": 0.9553611874580383, "11630": 0.6254787445068359, "11657": 0.4349733293056488, "11744": 0.5795059204101562, "11778": 0.5979346632957458, "11890": 0.7333439588546753, "12105": 0.2478361576795578, "12117": 0.1930064558982849, "12200": 0.3784096837043762, "12273": 0.49864232540130615, "12359": 0.043007105588912964, "12374": 0.2696990668773651, "12644": 0.9060825705528259, "12731": 0.7239188551902771, "12739": 0.03831886500120163, "12978": 0.732405424118042, "13023": 0.4624064862728119, "13458": 1.1444218158721924, "13625": 0.05694137513637543, "13656": 0.920189380645752, "14163": 0.5517725944519043, "14176": 0.05046287178993225, "14338": 0.40741631388664246, "14409": 0.31132611632347107, "14448": 1.7660409212112427, "14471": 0.4914994537830353, "14494": 1.244919776916504, "14660": 0.08244366943836212, "14678": 0.3241194784641266, "14751": 0.25088030099868774, "14800": 0.16359257698059082, "14905": 0.77198725938797, "14930": 0.1011524572968483, "15058": 0.040196798741817474, "15172": 0.3850763738155365, "15527": 0.8057082891464233, "15584": 0.037378571927547455, "15612": 0.43938836455345154, "15850": 0.09317722171545029, "16007": 0.4374985992908478, "16012": 0.6970458030700684, "16044": 0.1384023278951645, "16186": 0.11604541540145874, "16221": 1.2358801364898682, "16227": 0.026025565341114998, "16238": 0.469759464263916, "16602": 0.05694137513637543, "16706": 0.3346569836139679, "16770": 0.2145126610994339, "16861": 0.7898768186569214, "16948": 0.09495500475168228, "17287": 0.9739698171615601, "17409": 0.6139179468154907, "17592": 0.2674594223499298, "17736": 0.66441810131073, "17881": 0.8583967685699463, "17940": 0.7601850032806396, "18139": 0.8306987881660461, "18419": 0.1229778528213501, "18558": 0.2689530849456787, "18594": 0.14349138736724854, "18739": 0.5871354341506958, "18804": 0.09761575609445572, "18925": 0.1889725625514984, "18939": 0.3034266233444214, "19309": 0.4425300657749176, "19660": 0.18492233753204346, "19824": 0.6043586730957031, "19913": 0.010684899985790253, "20353": 0.35403475165367126, "20360": 0.8450632095336914, "20370": 0.1873544454574585, "20481": 0.11256109178066254, "20906": 0.28597161173820496, "21011": 0.2470736801624298, "21081": 0.3916989266872406, "21182": 0.9987343549728394, "21434": 0.7863243818283081, "21472": 0.037378571927547455, "21600": 0.7239188551902771, "21839": 0.06246116757392883, "21846": 0.3084607720375061, "22025": 0.1229778528213501, "22026": 0.7239188551902771, "22047": 0.0058422754518687725, "22203": 0.19782574474811554, "22272": 0.011650617234408855, "22275": 1.1659544706344604, "22345": 1.2840756177902222, "22402": 0.35745587944984436, "22409": 0.29255300760269165, "22778": 0.28155985474586487, "22910": 0.175953671336174, "22932": 0.11168810725212097, "22956": 0.04487626627087593, "22975": 0.6980181336402893, "23087": 0.3388410806655884, "23138": 0.06703783571720123, "23237": 0.009718249551951885, "23777": 0.1485546976327896, "23892": 0.15693697333335876, "24264": 0.14179791510105133, "24434": 0.7755908370018005, "24501": 0.4337083101272583, "24558": 0.4974553883075714, "24665": 0.5718178153038025, "24759": 0.06154331564903259, "25206": 0.2223619967699051, "25331": 0.015504186972975731, "25409": 1.001607894897461, "25468": 0.319873183965683, "25524": 0.5723689198493958, "25677": 0.12986256182193756, "25746": 0.18654440343379974, "25855": 0.4500300884246826, "25925": 0.04113444685935974, "26083": 0.022212404757738113, "26224": 0.0038986403960734606, "26305": 0.22548456490039825, "26319": 0.1477125883102417, "26601": 0.17759032547473907, "26702": 0.2034190446138382, "26741": 0.24859806895256042, "26874": 0.12814582884311676, "27009": 0.2976420819759369, "27144": 0.0752234235405922, "27425": 0.27934664487838745, "27530": 0.8917738795280457, "27531": 0.08692999184131622, "27642": 0.14939609169960022, "27881": 0.1946154683828354, "28207": 0.04487626627087593, "28893": 0.736154317855835, "29206": 0.040196798741817474} | 13916484 | COSMIC (http://www.sanger.ac.uk/cosmic) curates comprehensive information on somatic mutations in human cancer. Release v48 (July 2010) describes over 136,000 coding mutations in almost 542,000 tumour samples; of the 18,490 genes documented, 4803 (26%) have one or more mutations. Full scientific literature curations are available on 83 major cancer genes and 49 fusion gene pairs (19 new cancer genes and 30 new fusion pairs this year) and this number is continually increasing. Key amongst these is TP53, now available through a collaboration with the IARC p53 database. In addition to data from the Cancer Genome Project (CGP) at the Sanger Institute, UK, and The Cancer Genome Atlas project (TCGA), large systematic screens are also now curated. Major website upgrades now make these data much more mineable, with many new selection filters and graphics. A Biomart is now available allowing more automated data mining and integration with other biological databases. Annotation of genomic features has become a significant focus; COSMIC has begun curating full-genome resequencing experiments, developing new web pages, export formats and graphics styles. With all genomic information recently updated to GRCh37, COSMIC integrates many diverse types of mutation information and is making much closer links with Ensembl and other data resources. | COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer |
{"1011": 0.41389304399490356, "1038": 0.2881702482700348, "1042": 0.16524957120418549, "1047": 0.812664806842804, "1050": 1.1363043785095215, "1053": 0.371698260307312, "1056": 0.0317181795835495, "1164": 0.9310253858566284, "2000": 0.11343330889940262, "2003": 0.35745587944984436, "2005": 0.04394211992621422, "2053": 0.14433705806732178, "2064": 0.23092569410800934, "2078": 0.2667117714881897, "2079": 0.012615402229130268, "2102": 0.007782140281051397, "2109": 0.5010119676589966, "2120": 0.1212492436170578, "2128": 0.3443928062915802, "2129": 0.22937409579753876, "2140": 0.49982786178588867, "2167": 0.13071982562541962, "2179": 0.01934296265244484, "2182": 0.3930181860923767, "2224": 0.2105647772550583, "2240": 0.4891071021556854, "2243": 0.9271688461303711, "2270": 0.151916041970253, "2302": 0.19541899859905243, "2339": 0.06246116757392883, "2342": 0.0606246218085289, "2378": 0.013579257763922215, "2470": 0.7987030148506165, "2475": 0.0019512200960889459, "2478": 0.1221139207482338, "2497": 0.935633659362793, "2511": 0.5139457583427429, "2512": 0.04767346754670143, "2515": 0.1510767638683319, "2529": 0.37102460861206055, "2535": 0.0029254043474793434, "2546": 0.8901712894439697, "2557": 0.09495500475168228, "2589": 0.1808556467294693, "2590": 0.4400174915790558, "2615": 0.04860413447022438, "2629": 0.05786345899105072, "2671": 0.05046287178993225, "2734": 0.0606246218085289, "2817": 0.20501139760017395, "2832": 0.03925827145576477, "2864": 0.04860413447022438, "2892": 0.11081436276435852, "2912": 0.4920966327190399, "2913": 0.18978065252304077, "2951": 0.03360854089260101, "2974": 0.021256839856505394, "3078": 0.31132611632347107, "3117": 0.5707147121429443, "3132": 0.40285754203796387, "3145": 0.013579257763922215, "3161": 0.7220231294631958, "3210": 0.37707099318504333, "3211": 0.13499516248703003, "3231": 0.5110208988189697, "3273": 0.014542185701429844, "3293": 0.41195443272590637, "3351": 0.28082266449928284, "3406": 0.09495500475168228, "3433": 0.554580807685852, "3465": 0.417115718126297, "3489": 0.20022670924663544, "3501": 0.5551415085792542, "3526": 0.8152611255645752, "3594": 0.12038381397724152, "3597": 0.32270604372024536, "3670": 0.018384648486971855, "3683": 0.25088030099868774, "3698": 0.04674193635582924, "3746": 0.43244171142578125, "3779": 0.3170322775840759, "3800": 0.1718502640724182, "3898": 0.0058422754518687725, "3941": 0.5584990978240967, "3973": 0.3777405619621277, "4007": 0.49923527240753174, "4045": 0.13670019805431366, "4072": 0.05046287178993225, "4094": 0.004870930220931768, "4106": 0.6619023680686951, "4115": 0.17431432008743286, "4118": 0.7380234599113464, "4135": 0.7942996621131897, "4146": 0.07341018319129944, "4160": 0.1994270235300064, "4179": 0.1212492436170578, "4246": 0.27786844968795776, "4286": 0.06795065850019455, "4340": 0.029824240133166313, "4442": 0.6176109313964844, "4453": 0.029824240133166313, "4456": 0.09850110858678818, "4517": 1.3464484214782715, "4539": 0.03266380727291107, "4632": 0.1384023278951645, "4651": 0.026976587250828743, "4710": 0.11778303235769272, "4725": 0.7737906575202942, "4783": 0.043007105588912964, "4801": 0.304147332906723, "4812": 0.052318159490823746, "4871": 0.16442140936851501, "4939": 0.18411032855510712, "4948": 0.018384648486971855, "4950": 0.0317181795835495, "4962": 0.3723714053630829, "5197": 0.20977331697940826, "5250": 0.45994341373443604, "5283": 0.5506471395492554, "5387": 0.15442965924739838, "5390": 0.02887592278420925, "5425": 0.11343330889940262, "5449": 0.5404602885246277, "5456": 0.022212404757738113, "5461": 0.4462870955467224, "5468": 0.9084475636482239, "5488": 0.09850110858678818, "5553": 0.14939609169960022, "5604": 0.35060185194015503, "5646": 0.06429435312747955, "5693": 0.03360854089260101, "5705": 0.34922540187835693, "5761": 0.6118015646934509, "5787": 0.1693800985813141, "5852": 0.18329764902591705, "5867": 0.20739519596099854, "5884": 0.48670899868011475, "5906": 0.5551415085792542, "5910": 0.06154331564903259, "5911": 0.22157983481884003, "6028": 0.5347557663917542, "6064": 0.3283478021621704, "6177": 0.35745587944984436, "6179": 0.23092569410800934, "6216": 0.0009760859538801014, "6388": 0.040196798741817474, "6398": 0.8306987881660461, "6450": 0.026976587250828743, "6537": 0.2674594223499298, "6583": 0.2983669638633728, "6602": 0.06337817758321762, "6709": 0.10291612148284912, "6726": 0.2394166737794876, "6779": 0.603290855884552, "6786": 0.015504186972975731, "6845": 0.2501201331615448, "6846": 0.12556517124176025, "6897": 0.021256839856505394, "6922": 0.23864774405956268, "6948": 0.2607102394104004, "6950": 0.03360854089260101, "6968": 0.043007105588912964, "6994": 0.7333439588546753, "7097": 0.16110190749168396, "7275": 0.007782140281051397, "7316": 0.09050461649894714, "7366": 0.2317005842924118, "7551": 0.175953671336174, "7591": 0.6769026517868042, "7594": 0.7009293437004089, "7630": 0.3903779089450836, "7633": 0.347847044467926, "7645": 0.13755162060260773, "7709": 0.2394166737794876, "7718": 0.20022670924663544, "7724": 0.2105647772550583, "7756": 0.013579257763922215, "7778": 0.09228714555501938, "7790": 0.34508460760116577, "7831": 0.052318159490823746, "7860": 0.0770333781838417, "7875": 0.3374483287334442, "7885": 0.31132611632347107, "8080": 0.06703783571720123, "8153": 0.10818854719400406, "8171": 0.05046287178993225, "8247": 0.23556606471538544, "8325": 0.3622259199619293, "8428": 0.2763880789279938, "8449": 0.7398891448974609, "8569": 0.2983669638633728, "8629": 0.006812678650021553, "8674": 0.0029254043474793434, "8720": 0.10026945173740387, "8778": 0.06154331564903259, "8822": 0.3304552733898163, "8878": 0.3163207769393921, "9099": 1.0668635368347168, "9152": 0.5925496220588684, "9312": 0.02887592278420925, "9398": 0.4337083101272583, "9447": 0.2763880789279938, "9593": 0.07159364968538284, "9854": 0.46853771805763245, "9888": 0.11691460013389587, "9896": 0.08871890604496002, "10047": 0.469759464263916, "10091": 0.14264501631259918, "10210": 0.13499516248703003, "10322": 0.26446542143821716, "10327": 0.23247487843036652, "10556": 0.2652147710323334, "10645": 0.05417001247406006, "10719": 1.1406835317611694, "10753": 0.24248650670051575, "10788": 0.8715548515319824, "10847": 0.13755162060260773, "10903": 0.8332487344741821, "10905": 0.08244366943836212, "11088": 0.36494144797325134, "11151": 0.08154398202896118, "11156": 0.6000806093215942, "11160": 0.16359257698059082, "11231": 0.2822965085506439, "11253": 0.49982786178588867, "11265": 0.4818955361843109, "11311": 0.35950297117233276, "11326": 0.13925230503082275, "11329": 0.1808556467294693, "11382": 0.2983669638633728, "11487": 0.7163142561912537, "11532": 0.12986256182193756, "11702": 0.3283478021621704, "11705": 0.06246116757392883, "12060": 0.2983669638633728, "12115": 0.1808556467294693, "12126": 0.9680526852607727, "12248": 0.2749055027961731, "12322": 0.20102575421333313, "12326": 0.22704219818115234, "12352": 0.31132611632347107, "12376": 0.21135559678077698, "12395": 0.5336109399795532, "12477": 0.1384023278951645, "12530": 0.2969166338443756, "12540": 0.09495500475168228, "12546": 0.8973627090454102, "12562": 0.6862877607345581, "12835": 0.06246116757392883, "12849": 0.5139457583427429, "12902": 0.18004031479358673, "12921": 0.5936289429664612, "12935": 0.3870677351951599, "12941": 0.06703783571720123, "12987": 0.46302130818367004, "13004": 0.22782009840011597, "13091": 0.3170322775840759, "13221": 0.6348392367362976, "13316": 0.47463157773017883, "13490": 0.06337817758321762, "13502": 0.6487176418304443, "13538": 0.012615402229130268, "13594": 0.637939989566803, "13722": 0.35950297117233276, "13776": 0.07793712615966797, "13791": 0.7692760229110718, "13806": 0.2749055027961731, "13808": 0.18329764902591705, "13871": 0.13243216276168823, "13970": 0.2830325961112976, "14114": 0.33115679025650024, "14120": 0.1401015669107437, "14161": 0.30486753582954407, "14193": 1.0073304176330566, "14228": 0.043007105588912964, "14639": 0.7854343056678772, "14679": 0.2317005842924118, "15113": 0.35334911942481995, "15125": 0.2105647772550583, "15141": 0.12728634476661682, "15403": 0.05694137513637543, "15527": 0.18573370575904846, "15737": 0.04394211992621422, "15764": 0.020300358533859253, "15851": 0.04860413447022438, "15877": 0.4286321699619293, "15922": 0.08961215615272522, "16000": 1.5589666366577148, "16026": 0.058784693479537964, "16107": 0.0606246218085289, "16134": 0.6425731778144836, "16221": 0.4580921530723572, "16280": 0.47158926725387573, "16371": 0.6714286804199219, "16429": 0.3588210940361023, "16578": 0.05046287178993225, "16660": 0.040196798741817474, "16706": 0.2223619967699051, "16803": 0.04860413447022438, "16824": 0.1221139207482338, "17009": 0.2231435477733612, "17212": 0.5168620347976685, "17404": 0.3339579105377197, "17669": 0.5151132941246033, "17710": 0.3676496744155884, "17785": 0.14602625370025635, "17788": 0.07159364968538284, "17823": 0.16442140936851501, "17826": 0.17840765416622162, "17908": 0.5186077356338501, "17953": 0.44753631949424744, "17975": 0.07159364968538284, "18259": 0.3662964701652527, "18411": 0.03925827145576477, "18422": 0.05417001247406006, "18554": 0.0770333781838417, "18639": 0.2969166338443756, "18642": 0.1710275560617447, "18699": 0.5116065740585327, "18715": 0.0009760859538801014, "18856": 0.01934296265244484, "19034": 0.6441128253936768, "19648": 0.0029254043474793434, "19658": 0.41001203656196594, "19761": 0.026025565341114998, "19817": 0.129004567861557, "20030": 0.8731874823570251, "20155": 1.2605451345443726, "20253": 0.11951763927936554, "20348": 0.29255300760269165, "20393": 0.18329764902591705, "20502": 0.08244366943836212, "20544": 0.2160874605178833, "20686": 0.045809537172317505, "20792": 0.6244332790374756, "21114": 0.24401791393756866, "21117": 0.10026945173740387, "21677": 0.6921701431274414, "21685": 0.2749055027961731, "21890": 0.6415454745292664, "21903": 0.7881022095680237, "22153": 0.04860413447022438, "22184": 0.49864232540130615, "22248": 0.29036402702331543, "22330": 0.17267228662967682, "22426": 0.016465263441205025, "22499": 0.020300358533859253, "22684": 0.16690383851528168, "22718": 0.8212929964065552, "22828": 0.0009760859538801014, "22907": 0.011650617234408855, "22931": 0.40806588530540466, "23041": 0.8649974465370178, "23191": 0.1718502640724182, "23216": 0.10993985831737518, "23330": 0.10467668622732162, "23375": 0.3034266233444214, "23616": 0.6096806526184082, "23767": 0.45994341373443604, "23923": 0.3241194784641266, "23961": 0.5370414853096008, "24051": 0.16110190749168396, "24098": 0.23633737862110138, "24110": 1.013020396232605, "24209": 0.6420594453811646, "24316": 0.12038381397724152, "24635": 0.6502478122711182, "24838": 0.11778303235769272, "24869": 0.1011524572968483, "24978": 0.46853771805763245, "25194": 0.48068851232528687, "25458": 0.26820653676986694, "25509": 0.15442965924739838, "25526": 0.20580662786960602, "25608": 0.04207121208310127, "25708": 0.21214580535888672, "25714": 0.14602625370025635, "25930": 0.5162794589996338, "25952": 0.34922540187835693, "25971": 0.3903779089450836, "26419": 0.28743788599967957, "26632": 0.7305257320404053, "26646": 0.10906458646059036, "26661": 0.009718249551951885, "26835": 0.2539152204990387, "27011": 0.4425300657749176, "27354": 0.35128939151763916, "27404": 0.3423145115375519, "27453": 0.4580921530723572, "27544": 0.14518201351165771, "27781": 0.42096930742263794, "27937": 0.17267228662967682, "28038": 0.08154398202896118, "28282": 0.06612417846918106, "28286": 0.15860503911972046, "28329": 0.21135559678077698, "28518": 0.11604541540145874, "28788": 0.16690383851528168, "28846": 0.11604541540145874, "28873": 0.40089741349220276, "28991": 0.1970241367816925, "29017": 0.13925230503082275, "29105": 0.7047978043556213, "29123": 0.0019512200960889459, "29175": 0.2026219218969345, "29237": 0.02887592278420925, "29490": 0.12384103983640671, "29535": 0.2516399025917053, "29726": 0.45251765847206116} | 13916951 | Quantitative measurement of NF-kappaB nuclear translocation is an important research tool in cellular immunology. Established methodologies have a number of limitations, such as poor sensitivity, high cost or dependence on cell lines. Novel imaging methods to measure nuclear translocation of transcriptionally active components of NF-kappaB are being used but are also partly limited by the need for specialist imaging equipment or image analysis software. Herein we present a method for quantitative detection of NF-kappaB rel A nuclear translocation, using immunofluorescence microscopy and the public domain image analysis software ImageJ that can be easily adopted for cellular immunology research without the need for specialist image analysis expertise and at low cost. The method presented here is validated by demonstrating the time course and dose response of NF-kappaB nuclear translocation in primary human macrophages stimulated with LPS, and by comparison with a commercial NF-kappaB activation reporter cell line. | Quantitative imaging assay for NF-κB nuclear translocation in primary human macrophages |
{"1022": 0.3683255612850189, "1043": 0.5461324453353882, "1052": 0.5410289764404297, "1996": 0.012615402229130268, "1997": 0.09584271162748337, "1998": 0.28082266449928284, "2005": 0.0058422754518687725, "2012": 0.18492233753204346, "2013": 0.09495500475168228, "2015": 0.053244512528181076, "2024": 0.19541899859905243, "2026": 0.5174443125724792, "2029": 0.09850110858678818, "2037": 0.2539152204990387, "2047": 0.07431721687316895, "2075": 0.4926934838294983, "2079": 0.025073638185858727, "2116": 0.09584271162748337, "2122": 0.026025565341114998, "2129": 0.03925827145576477, "2135": 0.3381449282169342, "2169": 0.27342069149017334, "2176": 0.1358480453491211, "2177": 0.5618454217910767, "2179": 0.04394211992621422, "2203": 0.6533012986183167, "2226": 0.5718178153038025, "2306": 0.0009760859538801014, "2313": 0.34922540187835693, "2350": 0.5685047507286072, "2364": 0.14518201351165771, "2367": 0.5186077356338501, "2416": 0.09584271162748337, "2427": 0.11343330889940262, "2458": 0.4926934838294983, "2463": 0.037378571927547455, "2465": 1.049919843673706, "2475": 0.6813592314720154, "2515": 0.0354953333735466, "2536": 0.2501201331615448, "2566": 0.5324648022651672, "2583": 0.11865071207284927, "2594": 0.4311734735965729, "2612": 0.06520967930555344, "2618": 0.12642613053321838, "2698": 0.2576959431171417, "2719": 0.23710809648036957, "2742": 0.2786078155040741, "2764": 0.11081436276435852, "2785": 0.175953671336174, "2809": 0.5762182474136353, "2828": 0.681853175163269, "2832": 0.1751343309879303, "2944": 0.06154331564903259, "2951": 0.8100618124008179, "2967": 0.35813871026039124, "3252": 0.03831886500120163, "3305": 0.2622140049934387, "3366": 0.6410312056541443, "3526": 1.175042748451233, "3605": 0.12038381397724152, "3669": 0.0606246218085289, "3754": 0.4891071021556854, "3853": 0.6202403903007507, "3928": 0.175953671336174, "4037": 0.18816383183002472, "4106": 0.3127557039260864, "4127": 0.7942996621131897, "4132": 0.42990362644195557, "4160": 0.6181373596191406, "4167": 1.292155385017395, "4181": 0.7258110046386719, "4195": 0.006812678650021553, "4219": 0.1718502640724182, "4245": 0.5191890001296997, "4280": 0.9907892942428589, "4310": 0.5393219590187073, "4353": 0.6202403903007507, "4387": 0.7057625651359558, "4397": 0.22001366317272186, "4442": 1.1147572994232178, "4453": 0.33605360984802246, "4503": 0.14686977863311768, "4505": 0.40089741349220276, "4522": 0.7683706283569336, "4696": 0.14939609169960022, "4773": 0.3464667797088623, "4824": 0.2696990668773651, "4962": 0.7863243818283081, "4972": 0.6038249135017395, "4973": 0.3134697377681732, "5214": 0.036437395960092545, "5379": 0.46608972549438477, "5500": 0.29109421372413635, "5537": 0.6348392367362976, "5579": 0.6931471824645996, "5666": 0.8534175157546997, "5844": 0.2983669638633728, "5906": 0.2800849378108978, "5911": 0.2800849378108978, "5966": 0.3283478021621704, "6064": 0.2447827309370041, "6091": 0.20421554148197174, "6194": 0.4093637466430664, "6219": 0.22548456490039825, "6337": 0.5822374224662781, "6459": 0.19381128251552582, "6585": 0.19782574474811554, "6632": 0.16690383851528168, "6709": 0.4374985992908478, "6845": 0.619189441204071, "6895": 0.5301685929298401, "6897": 0.2689530849456787, "6923": 0.33115679025650024, "6994": 0.05417001247406006, "7013": 0.2516399025917053, "7080": 0.5057345628738403, "7141": 0.2184450328350067, "7236": 0.014542185701429844, "7248": 0.34577593207359314, "7366": 0.5568217039108276, "7403": 0.5483922958374023, "7578": 0.08871890604496002, "7590": 0.21922965347766876, "7591": 0.436867892742157, "7692": 0.2667117714881897, "7809": 0.6764062643051147, "7816": 0.25088030099868774, "7831": 0.1913948506116867, "7957": 0.16359257698059082, "8000": 0.9021284580230713, "8137": 0.12038381397724152, "8153": 0.31560876965522766, "8213": 0.3019835948944092, "8290": 0.4950772523880005, "8360": 0.2719337046146393, "8422": 0.9317949414253235, "8462": 0.5410289764404297, "8569": 0.7934166193008423, "8676": 0.1011524572968483, "8681": 0.36426326632499695, "8720": 0.5410289764404297, "8790": 0.45932671427726746, "9007": 0.6629094481468201, "9099": 0.5925496220588684, "9113": 0.4926934838294983, "9165": 0.6773988008499146, "9605": 0.040196798741817474, "9699": 0.20739519596099854, "9789": 0.12384103983640671, "9896": 0.5893046259880066, "10071": 0.23556606471538544, "10266": 0.7987030148506165, "10415": 1.0695481300354004, "10627": 0.10379679501056671, "10738": 0.02316705882549286, "10788": 0.27564704418182373, "10880": 0.6613984704017639, "10976": 0.2689530849456787, "11156": 0.38041436672210693, "11163": 0.3982778787612915, "11234": 0.8004589080810547, "11265": 0.7305257320404053, "11325": 0.45994341373443604, "11487": 0.5512100458145142, "11539": 0.0842406153678894, "11705": 0.05970508232712746, "11835": 0.5301685929298401, "11867": 0.9769153594970703, "12115": 0.5244048833847046, "12151": 0.22548456490039825, "12222": 0.4356052577495575, "12259": 0.5393219590187073, "12328": 0.8323994874954224, "12346": 0.1946154683828354, "12359": 0.4337083101272583, "12369": 0.3019835948944092, "12541": 0.6482070088386536, "12562": 0.40220460295677185, "12702": 0.7737906575202942, "12826": 0.026025565341114998, "12980": 0.25694093108177185, "12987": 0.956112265586853, "13231": 0.2763880789279938, "13458": 0.12642613053321838, "13462": 0.8509185314178467, "13599": 0.14686977863311768, "13625": 0.272677481174469, "13792": 0.5341835021972656, "13874": 0.0770333781838417, "13908": 0.7258110046386719, "14031": 0.9944084882736206, "14084": 0.08961215615272522, "14192": 0.3374483287334442, "14193": 0.036437395960092545, "14332": 0.6634125709533691, "14471": 0.255429208278656, "14573": 0.6989894509315491, "14639": 0.1913948506116867, "14828": 0.4831010699272156, "14847": 0.1889725625514984, "14988": 0.8152611255645752, "15176": 0.5751199722290039, "15698": 1.1230508089065552, "15756": 0.40481385588645935, "15774": 0.46670228242874146, "15821": 0.5074998140335083, "15955": 0.18573370575904846, "16012": 0.28963330388069153, "16129": 0.36358460783958435, "16285": 0.5612884759902954, "16387": 0.6538092494010925, "16405": 0.5174443125724792, "16478": 0.018384648486971855, "16578": 0.06246116757392883, "16790": 0.7987030148506165, "16924": 0.3656192123889923, "16952": 0.7537717819213867, "16965": 0.2447827309370041, "17132": 0.7809720039367676, "17181": 0.4974553883075714, "17250": 0.8748174905776978, "17367": 0.10291612148284912, "17879": 0.7951818704605103, "17881": 0.08244366943836212, "17908": 0.37907835841178894, "18089": 0.6400018334388733, "18439": 0.9021284580230713, "18749": 0.757441520690918, "18809": 1.001607894897461, "18886": 0.7067264318466187, "19251": 0.5729197263717651, "19293": 0.03266380727291107, "19330": 0.5990082025527954, "19345": 0.02792670577764511, "19541": 0.026976587250828743, "20011": 1.1381834745407104, "20062": 0.42926809191703796, "20253": 0.24401791393756866, "20576": 0.0606246218085289, "20582": 0.24018502235412598, "20611": 0.15860503911972046, "20806": 0.1710275560617447, "21017": 0.9470623731613159, "21032": 0.0606246218085289, "21252": 0.9363996982574463, "21453": 0.37102460861206055, "21575": 0.14518201351165771, "21903": 0.9613537192344666, "21919": 0.06886265426874161, "21935": 0.1212492436170578, "22196": 0.9531047344207764, "22287": 0.9922385215759277, "22330": 0.11430477350950241, "22618": 0.9455460906028748, "22694": 0.7610978484153748, "22963": 0.01934296265244484, "23130": 0.05786345899105072, "23189": 1.1018621921539307, "23700": 0.09317722171545029, "23924": 0.10291612148284912, "24051": 0.7755908370018005, "24558": 0.9386941194534302, "24587": 0.6744182109832764, "25202": 0.42735910415649414, "25778": 0.8057082891464233, "25952": 0.02792670577764511, "26266": 0.623910129070282, "26268": 0.053244512528181076, "26739": 0.38574060797691345, "26773": 0.5461324453353882, "27226": 0.20660123229026794, "27321": 1.031988263130188, "27532": 0.15777134895324707, "27811": 0.026976587250828743, "28156": 0.04674193635582924, "28406": 0.2105647772550583, "28625": 0.9256220459938049, "28788": 0.5301685929298401, "28848": 0.04860413447022438, "29076": 0.03925827145576477} | 13921526 | The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain. | An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. |
{"1011": 0.22079704701900482, "1021": 0.0058422754518687725, "1039": 1.0229004621505737, "1043": 0.9162907600402832, "1048": 0.021256839856505394, "2007": 0.013579257763922215, "2011": 0.32129061222076416, "2012": 0.6950984001159668, "2029": 0.35334911942481995, "2048": 0.06612417846918106, "2069": 0.8117979168891907, "2083": 0.04674193635582924, "2087": 0.28963330388069153, "2119": 0.36086538434028625, "2135": 0.4950772523880005, "2153": 0.05046287178993225, "2179": 0.058784693479537964, "2239": 0.5590575933456421, "2278": 0.6833335757255554, "2290": 0.9084475636482239, "2339": 0.15359249711036682, "2370": 0.018384648486971855, "2392": 1.162295937538147, "2475": 0.5104349255561829, "2512": 0.8264343738555908, "2515": 0.037378571927547455, "2550": 0.31560876965522766, "2581": 0.8813109993934631, "2644": 0.5767669677734375, "2683": 0.812664806842804, "2691": 0.4494072198867798, "2764": 0.12038381397724152, "2852": 0.29619070887565613, "2894": 0.007782140281051397, "2920": 0.040196798741817474, "2944": 0.20818853378295898, "2947": 0.12728634476661682, "2993": 0.6583697199821472, "3030": 0.18978065252304077, "3141": 0.026025565341114998, "3160": 0.5629584193229675, "3170": 0.38308101892471313, "3176": 0.12814582884311676, "3207": 0.7191727757453918, "3209": 0.4500300884246826, "3251": 0.151916041970253, "3265": 0.19782574474811554, "3298": 0.47584590315818787, "3303": 0.6492279767990112, "3351": 0.07793712615966797, "3366": 0.02792670577764511, "3378": 0.6228629946708679, "3426": 0.8323994874954224, "3445": 0.06612417846918106, "3458": 0.14095009863376617, "3466": 0.1710275560617447, "3603": 0.009718249551951885, "3625": 0.25088030099868774, "3638": 0.4734157919883728, "3654": 0.22782009840011597, "3668": 0.6369074583053589, "3670": 0.8065804839134216, "3755": 0.5080875158309937, "3896": 0.25995752215385437, "3917": 0.8366385698318481, "3936": 0.29400965571403503, "3965": 0.021256839856505394, "3980": 0.1358480453491211, "4013": 0.7210738658905029, "4048": 0.09317722171545029, "4138": 0.7182208299636841, "4140": 0.3923587501049042, "4141": 0.15275461971759796, "4167": 0.401551216840744, "4179": 0.7342816591262817, "4245": 0.04113444685935974, "4275": 0.2674594223499298, "4295": 0.4728073179721832, "4423": 1.1262223720550537, "4439": 0.11778303235769272, "4456": 0.09406650811433792, "4487": 0.4537591338157654, "4639": 0.4938860833644867, "4642": 0.010684899985790253, "4647": 0.09850110858678818, "4654": 0.04487626627087593, "4786": 0.3883931338787079, "4795": 0.3381449282169342, "4809": 0.39433568716049194, "4866": 0.24171993136405945, "4935": 0.7057625651359558, "4962": 0.8500841856002808, "5105": 0.08782484382390976, "5153": 0.004870930220931768, "5158": 0.05046287178993225, "5173": 0.040196798741817474, "5178": 0.7352184057235718, "5201": 0.23556606471538544, "5225": 0.2837681770324707, "5228": 0.3588210940361023, "5250": 0.8315495252609253, "5258": 0.02887592278420925, "5320": 0.8583967685699463, "5326": 0.17267228662967682, "5331": 0.13755162060260773, "5360": 0.0029254043474793434, "5387": 0.02887592278420925, "5403": 0.06977381557226181, "5421": 0.04207121208310127, "5449": 0.9710156321525574, "5533": 0.8298473954200745, "5537": 0.6624060273170471, "5567": 0.8492490649223328, "5603": 0.30989447236061096, "5620": 0.469759464263916, "5644": 0.2711893916130066, "5760": 0.8973627090454102, "5799": 0.10993985831737518, "5857": 0.013579257763922215, "5876": 0.040196798741817474, "6001": 0.31560876965522766, "6064": 0.5795059204101562, "6155": 0.2493593990802765, "6169": 0.13670019805431366, "6388": 0.04674193635582924, "6525": 0.9929623603820801, "6593": 0.036437395960092545, "6621": 0.18329764902591705, "6691": 0.1212492436170578, "6724": 0.1751343309879303, "6762": 0.14686977863311768, "6801": 0.004870930220931768, "6864": 0.8264343738555908, "6914": 0.7239188551902771, "6967": 0.0354953333735466, "7013": 0.5540198087692261, "7037": 0.9147270321846008, "7077": 0.4462870955467224, "7108": 0.1946154683828354, "7153": 0.854249119758606, "7337": 0.8212929964065552, "7366": 0.12038381397724152, "7403": 1.0458102226257324, "7458": 0.15359249711036682, "7461": 0.09584271162748337, "7487": 0.08154398202896118, "7645": 0.006812678650021553, "7657": 0.16524957120418549, "7818": 0.9123768210411072, "7870": 0.33115679025650024, "7883": 0.034552380442619324, "7888": 0.056018441915512085, "7900": 0.45623743534088135, "7949": 0.3339579105377197, "8020": 0.3353555500507355, "8040": 0.48670899868011475, "8050": 0.7491656541824341, "8171": 0.8340972661972046, "8335": 0.8083226680755615, "8385": 0.0029254043474793434, "8621": 0.4412745535373688, "8715": 0.1677299439907074, "8723": 0.09495500475168228, "8737": 0.5579402446746826, "8761": 0.1685553640127182, "8781": 0.29473719000816345, "8991": 0.272677481174469, "9002": 0.6634125709533691, "9007": 0.31560876965522766, "9048": 0.4980490207672119, "9099": 0.27044451236724854, "9113": 0.5557019114494324, "9165": 0.7683706283569336, "9186": 0.6139179468154907, "9252": 0.05046287178993225, "9297": 0.6348392367362976, "9377": 1.216973900794983, "9412": 0.2026219218969345, "9468": 0.018384648486971855, "9556": 0.5596157908439636, "9699": 0.4574742913246155, "9947": 0.41065993905067444, "9997": 0.0019512200960889459, "10071": 0.4673144817352295, "10091": 0.04674193635582924, "10381": 0.15023678541183472, "10383": 0.10291612148284912, "10507": 0.04767346754670143, "10572": 0.34508460760116577, "10595": 0.669430673122406, "10699": 0.4248080551624298, "10744": 0.06977381557226181, "10752": 0.03925827145576477, "10803": 0.029824240133166313, "10840": 0.13071982562541962, "10976": 0.822151780128479, "11265": 0.5584990978240967, "11369": 0.05786345899105072, "11393": 1.0641717910766602, "11423": 0.19862671196460724, "11457": 1.0116009712219238, "11528": 1.039613962173462, "11643": 0.18654440343379974, "11704": 1.160461664199829, "11717": 0.2105647772550583, "11721": 0.10993985831737518, "11792": 0.5347557663917542, "11850": 0.1358480453491211, "12098": 0.8764448165893555, "12130": 0.4145384132862091, "12167": 0.0752234235405922, "12184": 0.9363996982574463, "12328": 0.12642613053321838, "12349": 0.08603433519601822, "12590": 0.055094651877880096, "12650": 0.7239188551902771, "12732": 0.06246116757392883, "12735": 0.0038986403960734606, "12740": 0.0317181795835495, "12765": 0.6254787445068359, "12789": 0.0317181795835495, "12792": 0.3163207769393921, "12839": 0.12728634476661682, "12881": 0.2969166338443756, "12958": 0.011650617234408855, "12987": 1.222740888595581, "13091": 0.030771657824516296, "13096": 0.08871890604496002, "13103": 0.2493593990802765, "13330": 0.0770333781838417, "13458": 0.19381128251552582, "13467": 0.053244512528181076, "13512": 0.4145384132862091, "13871": 1.0966572761535645, "13922": 0.02887592278420925, "13938": 0.21687394380569458, "14193": 0.24018502235412598, "14447": 0.6286086440086365, "14471": 0.6128603219985962, "14480": 0.2516399025917053, "14494": 0.4831010699272156, "14613": 0.0770333781838417, "14800": 0.5220900774002075, "15115": 0.03360854089260101, "15192": 0.9936857223510742, "15316": 0.3241194784641266, "15412": 0.0038986403960734606, "15527": 0.42353010177612305, "15698": 0.014542185701429844, "15756": 0.22937409579753876, "15826": 0.1212492436170578, "16026": 0.11517547070980072, "16066": 0.6265231370925903, "16122": 0.2034190446138382, "16149": 0.5517725944519043, "16216": 0.10203468054533005, "16221": 0.7124901413917542, "16347": 1.3745063543319702, "16351": 0.21922965347766876, "16364": 0.09050461649894714, "16483": 0.24325250089168549, "16505": 0.4412745535373688, "16510": 1.018678069114685, "16529": 0.25694093108177185, "16567": 0.9776504039764404, "16571": 0.06429435312747955, "16605": 0.6563454270362854, "16706": 0.3656192123889923, "16754": 1.06349778175354, "16884": 0.42161011695861816, "16937": 0.15023678541183472, "17324": 0.01934296265244484, "17366": 0.08064348995685577, "17631": 0.4190443754196167, "17702": 0.09228714555501938, "17760": 0.29328158497810364, "17938": 0.6348392367362976, "17993": 1.2215901613235474, "18078": 0.11430477350950241, "18133": 0.06337817758321762, "18195": 1.360575795173645, "18259": 0.14264501631259918, "18433": 0.12986256182193756, "18700": 0.4450363218784332, "18981": 0.8492490649223328, "19137": 0.5882205963134766, "19335": 0.3163207769393921, "19345": 0.4909018874168396, "19421": 0.3005385100841522, "19429": 0.8748174905776978, "19470": 0.04860413447022438, "19539": 0.3423145115375519, "19601": 0.16690383851528168, "19653": 0.38041436672210693, "19696": 0.3824150264263153, "19739": 0.2763880789279938, "19841": 0.2478361576795578, "19872": 1.0305955410003662, "20117": 0.0354953333735466, "20303": 0.24859806895256042, "20310": 0.47584590315818787, "20316": 0.07612881064414978, "20420": 0.11343330889940262, "20467": 0.0842406153678894, "20567": 0.026976587250828743, "20569": 0.14686977863311768, "20850": 0.12814582884311676, "21017": 0.026976587250828743, "21057": 0.03925827145576477, "21081": 0.4500300884246826, "21230": 0.21687394380569458, "21255": 0.06703783571720123, "21262": 0.12556517124176025, "21314": 0.535327672958374, "21316": 0.3409265875816345, "21396": 0.18816383183002472, "21430": 0.10731173306703568, "21486": 0.06703783571720123, "21600": 0.19622190296649933, "21647": 0.17431432008743286, "21901": 0.8459017872810364, "21926": 0.007782140281051397, "22139": 0.4673144817352295, "22214": 0.0038986403960734606, "22423": 1.276475191116333, "22602": 0.4374985992908478, "22641": 0.6275664567947388, "22644": 0.0354953333735466, "22931": 0.0029254043474793434, "23033": 0.06246116757392883, "23130": 0.28670501708984375, "23296": 0.38174858689308167, "23318": 0.25845035910606384, "23427": 0.0770333781838417, "23563": 0.5438674688339233, "23606": 1.0464962720870972, "23683": 0.3170322775840759, "23737": 0.2184450328350067, "24054": 0.0038986403960734606, "24137": 0.040196798741817474, "24191": 0.5278670787811279, "24269": 0.8821197748184204, "24473": 0.1734936386346817, "24545": 0.4349733293056488, "24558": 0.23479416966438293, "24710": 0.1693800985813141, "24992": 0.1011524572968483, "25145": 0.06337817758321762, "25187": 0.08154398202896118, "25202": 0.1602703034877777, "25206": 0.18492233753204346, "25284": 0.680370569229126, "25338": 0.0038986403960734606, "25520": 0.09228714555501938, "25708": 0.4673144817352295, "25714": 0.8715548515319824, "25761": 0.15610189735889435, "25969": 0.1889725625514984, "26033": 0.07068414986133575, "26083": 0.9900637865066528, "26305": 0.018384648486971855, "26572": 0.7510106563568115, "26601": 0.11604541540145874, "26702": 0.500420093536377, "26835": 0.02887592278420925, "26986": 0.11951763927936554, "27723": 0.11691460013389587, "27989": 0.15023678541183472, "28046": 0.06520967930555344, "28102": 0.0029254043474793434, "28177": 0.37974658608436584, "28290": 0.1510767638683319, "28487": 0.02792670577764511, "28767": 1.3931070566177368, "28848": 0.5080875158309937, "29090": 0.8255793452262878, "29107": 0.31560876965522766, "29206": 0.1212492436170578, "29222": 0.08692999184131622, "29248": 0.18978065252304077, "29264": 0.20818853378295898, "29494": 0.09228714555501938, "29596": 0.22157983481884003} | 13921783 | An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. A fundamental question is whether toxicity is driven by the repeat RNA itself and/or by dipeptide repeat proteins generated by repeat-associated, non-ATG translation. To address this question, we developed in vitro and in vivo models to dissect repeat RNA and dipeptide repeat protein toxicity. Expression of pure repeats, but not stop codon–interrupted “RNA-only” repeats in Drosophila caused adult-onset neurodegeneration. Thus, expanded repeats promoted neurodegeneration through dipeptide repeat proteins. Expression of individual dipeptide repeat proteins with a non-GGGGCC RNA sequence revealed that both poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. These findings are consistent with a dual toxicity mechanism, whereby both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration. | C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins |
{"1011": 0.27712854743003845, "1016": 0.037378571927547455, "1018": 0.03925827145576477, "1042": 0.8057082891464233, "1043": 0.4196864068508148, "1050": 0.4938860833644867, "2003": 0.0797421783208847, "2005": 0.12642613053321838, "2011": 0.24859806895256042, "2012": 0.7086513638496399, "2015": 0.17922431230545044, "2026": 0.8583967685699463, "2029": 0.12470348179340363, "2075": 0.175953671336174, "2076": 0.1011524572968483, "2078": 0.5973974466323853, "2080": 0.05417001247406006, "2083": 0.036437395960092545, "2170": 0.29400965571403503, "2378": 0.5232481360435486, "2419": 0.11778303235769272, "2423": 0.021256839856505394, "2426": 0.23710809648036957, "2433": 0.8550800085067749, "2445": 0.0174254160374403, "2464": 0.176772341132164, "2475": 0.9123768210411072, "2487": 0.7647408246994019, "2490": 0.2478361576795578, "2512": 0.920189380645752, "2532": 0.05786345899105072, "2535": 0.48670899868011475, "2575": 0.06886265426874161, "2594": 0.3601844012737274, "2595": 0.6301699280738831, "2599": 0.055094651877880096, "2632": 1.013020396232605, "2656": 1.067535400390625, "2676": 0.3283478021621704, "2692": 0.036437395960092545, "2865": 0.9225212931632996, "2890": 0.2969166338443756, "2891": 0.6223390698432922, "2895": 0.6754127144813538, "2920": 0.1873544454574585, "2947": 0.034552380442619324, "3064": 0.007782140281051397, "3145": 0.4374985992908478, "3161": 0.28670501708984375, "3200": 0.0019512200960889459, "3248": 0.06977381557226181, "3283": 0.7210738658905029, "3378": 0.6502478122711182, "3433": 0.9248477816581726, "3436": 0.6327666640281677, "3445": 0.4512746334075928, "3447": 0.7276995778083801, "3450": 0.3191637098789215, "3466": 0.4337083101272583, "3491": 0.23787821829319, "3526": 0.4145384132862091, "3569": 0.2145126610994339, "3593": 0.7295845746994019, "3596": 0.16690383851528168, "3597": 0.7124901413917542, "3603": 0.05970508232712746, "3619": 0.0354953333735466, "3623": 0.5517725944519043, "3625": 0.045809537172317505, "3642": 0.011650617234408855, "3653": 0.36086538434028625, "3671": 0.5573811531066895, "3726": 0.3005385100841522, "3853": 0.012615402229130268, "3860": 0.2034190446138382, "3896": 0.3170322775840759, "3935": 1.3372600078582764, "3949": 0.3723714053630829, "4005": 0.026025565341114998, "4013": 0.7182208299636841, "4023": 0.6400018334388733, "4047": 0.42735910415649414, "4145": 0.3191637098789215, "4187": 0.6744182109832764, "4195": 0.10555581003427505, "4244": 0.27342069149017334, "4395": 0.31845372915267944, "4417": 0.1718502640724182, "4442": 0.6568518877029419, "4456": 0.016465263441205025, "4506": 0.5767669677734375, "4531": 0.0038986403960734606, "4539": 0.6872705817222595, "4588": 0.4400174915790558, "4621": 0.07884006202220917, "4649": 1.2404102087020874, "4668": 0.2223619967699051, "4747": 0.8281423449516296, "4758": 0.2089812457561493, "4820": 0.3077431619167328, "4852": 0.19220098853111267, "4895": 0.0354953333735466, "4921": 1.0375399589538574, "4962": 0.16690383851528168, "5022": 0.06429435312747955, "5072": 0.15693697333335876, "5082": 0.45251765847206116, "5083": 0.8633513450622559, "5144": 0.5517725944519043, "5250": 0.983511209487915, "5301": 0.34922540187835693, "5320": 0.0797421783208847, "5335": 0.4248080551624298, "5377": 0.4462870955467224, "5383": 0.037378571927547455, "5387": 0.6027565002441406, "5393": 0.15275461971759796, "5400": 0.06886265426874161, "5423": 0.10203468054533005, "5531": 0.011650617234408855, "5536": 1.117955207824707, "5576": 0.3070250153541565, "5648": 0.15442965924739838, "5719": 0.10026945173740387, "5769": 0.1401015669107437, "5813": 1.5127204656600952, "5838": 0.10291612148284912, "5850": 0.25694093108177185, "5876": 0.5162794589996338, "5886": 1.0207915306091309, "6024": 0.6123310327529907, "6072": 1.036847710609436, "6074": 0.21214580535888672, "6083": 0.10818854719400406, "6370": 0.0317181795835495, "6455": 0.9005423784255981, "6540": 0.3381449282169342, "6555": 0.09761575609445572, "6591": 0.11168810725212097, "6592": 0.2607102394104004, "6612": 0.7163142561912537, "6638": 0.34577593207359314, "6741": 0.8109301924705505, "6753": 0.08871890604496002, "6869": 0.42225050926208496, "6911": 0.7267557382583618, "7065": 0.08603433519601822, "7076": 0.012615402229130268, "7142": 0.28155985474586487, "7178": 0.24401791393756866, "7192": 0.05417001247406006, "7242": 0.7510106563568115, "7337": 0.3916989266872406, "7342": 0.40351006388664246, "7356": 0.0174254160374403, "7438": 0.18978065252304077, "7457": 0.4500300884246826, "7461": 0.10467668622732162, "7552": 0.11256109178066254, "7620": 0.7546905279159546, "7630": 0.8065804839134216, "7645": 0.040196798741817474, "7711": 0.09938567131757736, "7722": 0.09317722171545029, "7816": 0.4932899475097656, "7889": 0.7009293437004089, "8000": 0.8893690705299377, "8153": 0.09761575609445572, "8171": 0.9310253858566284, "8197": 0.12642613053321838, "8290": 0.0606246218085289, "8377": 0.5893046259880066, "8474": 0.06154331564903259, "8516": 0.669430673122406, "8521": 0.01934296265244484, "8524": 0.823009729385376, "8564": 0.7426811456680298, "8878": 0.5816917419433594, "8902": 1.1456648111343384, "8980": 0.083342544734478, "9007": 0.46486347913742065, "9014": 0.7038320899009705, "9078": 0.1693800985813141, "9211": 0.21922965347766876, "9229": 0.2018241584300995, "9312": 0.22937409579753876, "9314": 0.5827828645706177, "9350": 0.27712854743003845, "9353": 1.0312920808792114, "9376": 0.34300774335861206, "9412": 0.2561853528022766, "9416": 0.8517522215843201, "9462": 0.05417001247406006, "9474": 0.7144040465354919, "9556": 0.562402069568634, "9574": 0.0038986403960734606, "9597": 0.1685553640127182, "9821": 0.4400174915790558, "9849": 0.6634125709533691, "9885": 0.6960725784301758, "10258": 0.07159364968538284, "10266": 0.08603433519601822, "10288": 0.5909284353256226, "10395": 0.4093637466430664, "10509": 0.040196798741817474, "10548": 0.5244048833847046, "10572": 0.23864774405956268, "10595": 0.151916041970253, "10663": 0.9005423784255981, "10737": 0.029824240133166313, "10738": 0.33605360984802246, "10744": 0.07250232994556427, "10769": 0.8298473954200745, "10787": 0.7276995778083801, "10843": 0.03266380727291107, "10893": 0.04767346754670143, "10960": 0.5151132941246033, "11158": 0.3141832649707794, "11432": 0.48610860109329224, "11598": 0.034552380442619324, "11649": 0.8074519634246826, "11888": 1.0533316135406494, "11952": 1.202409029006958, "12044": 0.32199856638908386, "12222": 0.8212929964065552, "12328": 1.197703242301941, "12423": 0.19862671196460724, "12506": 0.28890204429626465, "12607": 0.29981520771980286, "12650": 0.2089812457561493, "12737": 0.6415454745292664, "12943": 0.2696990668773651, "13046": 0.43244171142578125, "13096": 1.1262223720550537, "13143": 0.06246116757392883, "13186": 0.13157635927200317, "13291": 0.4500300884246826, "13330": 0.1011524572968483, "13341": 0.4203280806541443, "13441": 0.10993985831737518, "13656": 0.022212404757738113, "13671": 0.10906458646059036, "13712": 0.28890204429626465, "13729": 0.11517547070980072, "13791": 0.5301685929298401, "13833": 0.890972912311554, "13922": 0.1930064558982849, "14074": 0.3810817003250122, "14120": 0.4879087805747986, "14126": 0.567397952079773, "14321": 0.9710156321525574, "14384": 0.2763880789279938, "14516": 0.11865071207284927, "14545": 0.010684899985790253, "14613": 0.40285754203796387, "14667": 0.30486753582954407, "14935": 0.3723714053630829, "14967": 0.7380234599113464, "14971": 0.0174254160374403, "15006": 0.015504186972975731, "15059": 0.18654440343379974, "15176": 0.2561853528022766, "15241": 0.8109301924705505, "15669": 0.08603433519601822, "16081": 0.7047978043556213, "16116": 0.22937409579753876, "16185": 0.37304413318634033, "16285": 0.18573370575904846, "16330": 0.3388410806655884, "16341": 0.8957691192626953, "16412": 0.10026945173740387, "16749": 0.0009760859538801014, "16922": 0.04767346754670143, "16993": 0.259204238653183, "17079": 0.28963330388069153, "17086": 0.43434104323387146, "17119": 0.0842406153678894, "17261": 0.5404602885246277, "17350": 1.1205062866210938, "17379": 0.6358738541603088, "17441": 0.27934664487838745, "17703": 0.5393219590187073, "17827": 1.6008070707321167, "17913": 0.38574060797691345, "18098": 0.9635916948318481, "18227": 0.2317005842924118, "18349": 1.1786550283432007, "18419": 0.4709797203540802, "18714": 0.37371641397476196, "18715": 0.02412080205976963, "18853": 1.039613962173462, "18906": 0.06795065850019455, "18954": 0.33605360984802246, "18985": 0.3374483287334442, "19037": 0.07793712615966797, "19129": 0.6624060273170471, "19301": 0.8973627090454102, "19362": 0.567951500415802, "19454": 0.13670019805431366, "19577": 0.2531573474407196, "19601": 0.4512746334075928, "19653": 0.2659635543823242, "19737": 0.18654440343379974, "19872": 1.1051015853881836, "20017": 0.0606246218085289, "20187": 1.1406835317611694, "20544": 0.6410312056541443, "20679": 1.0841858386993408, "20752": 0.22626367211341858, "20806": 0.006812678650021553, "20868": 0.0317181795835495, "20872": 0.08513788133859634, "20900": 0.1485546976327896, "20974": 1.0464962720870972, "20992": 0.13071982562541962, "21150": 0.17020416259765625, "21262": 0.5139457583427429, "21449": 0.29619070887565613, "21471": 0.17020416259765625, "21486": 0.09672962874174118, "21497": 0.3297532796859741, "21575": 0.26296505331993103, "21618": 0.20739519596099854, "21647": 0.016465263441205025, "21709": 0.996573805809021, "21716": 0.013579257763922215, "21733": 1.0546929836273193, "21901": 0.07612881064414978, "21903": 0.2478361576795578, "22260": 0.1401015669107437, "22415": 0.14939609169960022, "22520": 1.2737466096878052, "22543": 0.22392450273036957, "22597": 0.06246116757392883, "22901": 0.38574060797691345, "22931": 0.010684899985790253, "22943": 0.2160874605178833, "23041": 0.006812678650021553, "23060": 0.7845434546470642, "23150": 1.0841858386993408, "23216": 0.053244512528181076, "23586": 0.0842406153678894, "23750": 0.09672962874174118, "23833": 0.7692760229110718, "23900": 0.02792670577764511, "23943": 0.10026945173740387, "23971": 0.1332872211933136, "24054": 0.38041436672210693, "24171": 0.10291612148284912, "24269": 0.2531573474407196, "24501": 0.3963087201118469, "24840": 0.11081436276435852, "25015": 0.15777134895324707, "25117": 1.2549926042556763, "25281": 0.00875066313892603, "25293": 0.1011524572968483, "25456": 0.1905880719423294, "25510": 0.7038320899009705, "26261": 0.13071982562541962, "26402": 0.3588210940361023, "26435": 0.3554046154022217, "26633": 0.05970508232712746, "26651": 0.24401791393756866, "26773": 0.41065993905067444, "26785": 0.9515975713729858, "26942": 0.7352184057235718, "27108": 0.9769153594970703, "27115": 0.14179791510105133, "27144": 0.07250232994556427, "27641": 0.06337817758321762, "27651": 0.07341018319129944, "27673": 0.4158279001712799, "27697": 0.7898768186569214, "27790": 1.0546929836273193, "27833": 0.07793712615966797, "27854": 0.2247048318386078, "27937": 1.094698429107666, "28024": 0.520350456237793, "28156": 0.2837681770324707, "28487": 0.9987343549728394, "28674": 0.11865071207284927, "28715": 0.6533012986183167, "28829": 0.7454653382301331, "28915": 0.05046287178993225, "28927": 0.3423145115375519, "28965": 0.056018441915512085, "28991": 0.6624060273170471, "29166": 1.2065086364746094, "29304": 0.7987030148506165} | 13923069 | Chronic, nonresolving inflammation is a critical factor in the clinical progression of advanced atherosclerotic lesions. In the normal inflammatory response, resolution is mediated by several agonists, among which is the glucocorticoid-regulated protein called annexin A1. The proresolving actions of annexin A1, which are mediated through its receptor N-formyl peptide receptor 2 (FPR2/ALX), can be mimicked by an amino-terminal peptide encompassing amino acids 2–26 (Ac2-26). Collagen IV (Col IV)–targeted nanoparticles (NPs) containing Ac2-26 were evaluated for their therapeutic effect on chronic, advanced atherosclerosis in fat-fed Ldlr−/− mice. When administered to mice with preexisting lesions, Col IV–Ac2-26 NPs were targeted to lesions and led to a marked improvement in key advanced plaque properties, including an increase in the protective collagen layer overlying lesions (which was associated with a decrease in lesional collagenase activity), suppression of oxidative stress, and a decrease in plaque necrosis. In mice lacking FPR2/ALX in myeloid cells, these improvements were not seen. Thus, administration of a resolution-mediating peptide in a targeted NP activates its receptor on myeloid cells to stabilize advanced atherosclerotic lesions. These findings support the concept that defective inflammation resolution plays a role in advanced atherosclerosis, and suggest a new form of therapy. | Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice |
{"1009": 0.32270604372024536, "1011": 0.3127557039260864, "1016": 0.574020504951477, "1017": 0.41840189695358276, "1040": 0.06886265426874161, "1045": 0.013579257763922215, "1056": 0.8004589080810547, "2004": 0.0842406153678894, "2006": 0.11951763927936554, "2007": 0.175953671336174, "2011": 0.24171993136405945, "2013": 0.23324857652187347, "2029": 0.2822965085506439, "2035": 0.39762192964553833, "2048": 0.3656192123889923, "2063": 0.3012613356113434, "2093": 0.11430477350950241, "2094": 0.6223390698432922, "2104": 0.2881702482700348, "2129": 0.04860413447022438, "2182": 0.16359257698059082, "2188": 0.7086513638496399, "2245": 0.3141832649707794, "2265": 0.18573370575904846, "2339": 0.3683255612850189, "2349": 0.03831886500120163, "2475": 0.7445381283760071, "2509": 0.8893690705299377, "2522": 0.36426326632499695, "2537": 0.4487839937210083, "2549": 0.7295845746994019, "2550": 0.1970241367816925, "2571": 0.18248429894447327, "2659": 0.045809537172317505, "2696": 0.17840765416622162, "2765": 0.6980181336402893, "2890": 0.2447827309370041, "2896": 0.11430477350950241, "2920": 0.05417001247406006, "3065": 0.10026945173740387, "3084": 0.0019512200960889459, "3145": 0.6522845029830933, "3155": 0.3019835948944092, "3231": 0.6970458030700684, "3276": 0.08244366943836212, "3279": 0.00875066313892603, "3303": 0.11951763927936554, "3330": 0.4450363218784332, "3373": 0.04394211992621422, "3378": 0.1930064558982849, "3426": 0.3012613356113434, "3433": 0.05970508232712746, "3463": 0.40546512603759766, "3466": 0.2689530849456787, "3491": 0.2954642176628113, "3495": 0.41065993905067444, "3497": 0.020300358533859253, "3526": 0.5324648022651672, "3603": 0.012615402229130268, "3625": 0.01934296265244484, "3662": 0.007782140281051397, "3670": 0.9005423784255981, "3671": 0.4330752193927765, "3729": 0.7969439625740051, "3853": 0.3916989266872406, "3896": 0.1734936386346817, "3989": 0.2969166338443756, "4078": 0.6476961374282837, "4187": 0.43623676896095276, "4295": 0.9710156321525574, "4307": 0.2145126610994339, "4359": 0.6999598741531372, "4442": 0.680370569229126, "4504": 0.30486753582954407, "4525": 0.27786844968795776, "4671": 0.01934296265244484, "4719": 0.32764431834220886, "4758": 0.08064348995685577, "4760": 0.06520967930555344, "4957": 0.26146242022514343, "4962": 0.9363996982574463, "4972": 0.007782140281051397, "5012": 1.0409941673278809, "5014": 0.1510767638683319, "5158": 0.05694137513637543, "5224": 0.35677260160446167, "5228": 0.472198486328125, "5250": 0.22157983481884003, "5258": 0.1332872211933136, "5292": 0.4950772523880005, "5320": 0.5278670787811279, "5387": 0.3601844012737274, "5441": 0.5551415085792542, "5547": 0.5215105414390564, "5604": 0.5197699069976807, "5646": 0.05417001247406006, "5665": 0.14433705806732178, "5686": 0.5718178153038025, "5703": 0.4788752794265747, "5714": 0.9005423784255981, "5799": 0.5540198087692261, "5852": 0.4709797203540802, "5876": 0.14179791510105133, "6022": 0.18329764902591705, "6032": 0.25239890813827515, "6064": 0.5069117546081543, "6099": 0.022212404757738113, "6162": 0.1358480453491211, "6190": 0.35745587944984436, "6309": 0.28670501708984375, "6335": 1.3207136392593384, "6845": 0.0019512200960889459, "6882": 0.24401791393756866, "6970": 0.812664806842804, "7028": 0.11168810725212097, "7274": 0.7408206462860107, "7312": 0.6624060273170471, "7337": 0.6892333030700684, "7355": 0.23402166366577148, "7366": 0.043007105588912964, "7403": 1.0519683361053467, "7461": 0.21135559678077698, "7645": 0.31845372915267944, "7711": 0.20102575421333313, "7718": 0.3526630103588104, "7816": 0.7314660549163818, "7870": 0.8195732831954956, "7872": 0.15275461971759796, "7900": 0.3683255612850189, "8000": 1.2387138605117798, "8091": 0.5941681861877441, "8100": 0.27044451236724854, "8161": 0.2539152204990387, "8171": 0.11951763927936554, "8285": 1.2840756177902222, "8360": 0.07250232994556427, "8469": 0.0019512200960889459, "8498": 0.6118015646934509, "8761": 0.3353555500507355, "8803": 0.04767346754670143, "8873": 0.04953393340110779, "8909": 1.1935672760009766, "8991": 0.2652147710323334, "9007": 0.4500300884246826, "9096": 0.07431721687316895, "9165": 0.848413348197937, "9319": 0.5662899017333984, "9350": 0.29981520771980286, "9507": 0.28963330388069153, "9509": 0.05970508232712746, "9617": 0.025073638185858727, "9820": 0.03925827145576477, "9885": 0.3339579105377197, "9932": 0.07431721687316895, "10047": 0.791648268699646, "10066": 0.306306391954422, "10210": 0.058784693479537964, "10244": 0.5607312321662903, "10371": 0.7182208299636841, "10514": 0.7333439588546753, "10548": 0.49864232540130615, "10580": 0.03831886500120163, "10595": 0.4938860833644867, "10738": 0.777387797832489, "10744": 0.17922431230545044, "10840": 0.436867892742157, "11020": 0.440646231174469, "11211": 0.1401015669107437, "11311": 1.2985725402832031, "11423": 0.4132472574710846, "11432": 0.04113444685935974, "11658": 1.0553730726242065, "11892": 0.16607704758644104, "11983": 0.19622190296649933, "12042": 0.25088030099868774, "12115": 0.2247048318386078, "12207": 0.25239890813827515, "12222": 0.5778634548187256, "12248": 0.0752234235405922, "12260": 0.9287132620811462, "12328": 1.1350497007369995, "12402": 0.0770333781838417, "12732": 0.04394211992621422, "12839": 0.04674193635582924, "12997": 0.022212404757738113, "13070": 0.8195732831954956, "13143": 0.030771657824516296, "13368": 0.1229778528213501, "13416": 0.3656192123889923, "13458": 0.06612417846918106, "13464": 0.7528522610664368, "13490": 0.0174254160374403, "13531": 0.0019512200960889459, "13685": 1.0655186176300049, "13776": 0.175953671336174, "13791": 0.14433705806732178, "13806": 0.7863243818283081, "13833": 0.1064341589808464, "13922": 0.05970508232712746, "14049": 0.6139179468154907, "14193": 0.1808556467294693, "14228": 1.1947507858276367, "14343": 0.7701805830001831, "14442": 0.07884006202220917, "14454": 0.7408206462860107, "14471": 0.6522845029830933, "14494": 0.46670228242874146, "14639": 0.14686977863311768, "14800": 0.4537591338157654, "15059": 0.12814582884311676, "15074": 0.10731173306703568, "15176": 0.47827014327049255, "15403": 0.7969439625740051, "15527": 0.3963087201118469, "15581": 0.020300358533859253, "15909": 0.0019512200960889459, "15911": 0.04394211992621422, "16026": 0.14602625370025635, "16096": 0.058784693479537964, "16127": 0.6265231370925903, "16221": 0.5990082025527954, "16387": 0.14349138736724854, "16463": 0.1994270235300064, "16514": 0.04674193635582924, "16515": 0.319873183965683, "16530": 0.2711893916130066, "16610": 0.07068414986133575, "16706": 1.2181298732757568, "16902": 0.5590575933456421, "16910": 0.018384648486971855, "17254": 0.022212404757738113, "17404": 0.12470348179340363, "17788": 0.820433497428894, "17913": 0.1913948506116867, "18002": 0.3374483287334442, "18275": 0.09495500475168228, "18714": 0.21135559678077698, "18715": 1.167778730392456, "18847": 0.04487626627087593, "18888": 0.5762182474136353, "19037": 0.0317181795835495, "19293": 0.28597161173820496, "19345": 0.5472630262374878, "19389": 0.4950772523880005, "19470": 0.08692999184131622, "19500": 0.304147332906723, "19539": 0.3560888469219208, "19653": 0.11951763927936554, "19847": 0.29109421372413635, "19872": 0.1401015669107437, "20017": 0.07884006202220917, "20120": 0.1693800985813141, "20132": 0.2719337046146393, "20187": 0.20739519596099854, "20598": 0.013579257763922215, "20752": 0.12814582884311676, "20806": 0.036437395960092545, "21508": 0.10906458646059036, "21575": 0.4041621685028076, "21618": 0.306306391954422, "21647": 0.021256839856505394, "21778": 0.1602703034877777, "21903": 0.4349733293056488, "21926": 0.0058422754518687725, "22022": 0.12470348179340363, "22248": 0.1619328260421753, "22330": 0.6415454745292664, "22834": 0.11604541540145874, "22907": 0.012615402229130268, "22930": 0.1718502640724182, "22931": 0.6674286723136902, "23041": 1.262204885482788, "23150": 1.0748957395553589, "23606": 0.9194108247756958, "23777": 0.09761575609445572, "23833": 0.15023678541183472, "23892": 0.1602703034877777, "23900": 0.7737906575202942, "24395": 0.4093637466430664, "24473": 0.034552380442619324, "24582": 0.151916041970253, "24759": 0.41065993905067444, "24848": 0.9591107368469238, "25006": 0.38308101892471313, "25206": 0.48430517315864563, "25219": 0.07341018319129944, "25426": 0.18492233753204346, "25605": 0.25239890813827515, "25644": 0.18248429894447327, "26305": 0.6244332790374756, "26534": 0.10291612148284912, "26601": 0.022212404757738113, "26633": 0.053244512528181076, "26657": 1.036847710609436, "26741": 1.202995777130127, "26773": 0.5540198087692261, "26786": 0.9123768210411072, "26835": 0.07884006202220917, "26874": 1.005902886390686, "27641": 0.17267228662967682, "27642": 0.4067663550376892, "27781": 0.39433568716049194, "27915": 0.8475768566131592, "27929": 0.026976587250828743, "27989": 0.06977381557226181, "28024": 0.4126010537147522, "28156": 0.45623743534088135, "28227": 0.4728073179721832, "28290": 0.3318578004837036, "28309": 0.025073638185858727, "28466": 0.05046287178993225, "28696": 1.2140778303146362, "28828": 0.16524957120418549, "28829": 0.12642613053321838, "28873": 0.38308101892471313, "28896": 0.0019512200960889459, "29125": 0.7728893756866455, "29206": 0.09317722171545029, "29490": 0.05694137513637543} | 13923140 | Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2). In order to test directly that an approximately twofold reduction in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory effects of the naturally occurring susceptibility alleles of Il2. Reduced IL-2 production achieved by either genetic mechanism correlates with reduced function of CD4+ CD25+ regulatory T cells, which are critical for maintaining immune homeostasis. | Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity |
{"1011": 0.3177432417869568, "1015": 0.5855054259300232, "1042": 0.6734226942062378, "1043": 0.7565253376960754, "1052": 0.7163142561912537, "1996": 0.09317722171545029, "1999": 0.22157983481884003, "2003": 0.2478361576795578, "2007": 0.1332872211933136, "2008": 0.24325250089168549, "2028": 0.3005385100841522, "2029": 0.2637155055999756, "2072": 0.2830325961112976, "2073": 0.1889725625514984, "2179": 0.46608972549438477, "2239": 0.3615458607673645, "2284": 0.025073638185858727, "2306": 0.23247487843036652, "2312": 0.40089741349220276, "2334": 0.7239188551902771, "2487": 1.0158531665802002, "2532": 0.3897167444229126, "2546": 0.2105647772550583, "2550": 0.0752234235405922, "2556": 0.09672962874174118, "2571": 0.5244048833847046, "2609": 0.40220460295677185, "2649": 0.4041621685028076, "2832": 0.011650617234408855, "2920": 0.04487626627087593, "2922": 0.3903779089450836, "2988": 0.26446542143821716, "3078": 0.5209306478500366, "3130": 0.4537591338157654, "3252": 0.4764525294303894, "3366": 1.0001721382141113, "3397": 0.38308101892471313, "3406": 0.052318159490823746, "3464": 0.04113444685935974, "3526": 0.29255300760269165, "3550": 0.11865071207284927, "3563": 0.013579257763922215, "3603": 0.175953671336174, "3605": 0.6096806526184082, "3670": 0.5833279490470886, "3736": 0.16690383851528168, "3853": 0.00875066313892603, "3989": 0.23710809648036957, "4095": 0.043007105588912964, "4138": 1.1714173555374146, "4517": 0.4311734735965729, "4573": 0.6301699280738831, "4697": 0.10906458646059036, "4747": 0.31489628553390503, "4820": 0.6857960224151611, "4838": 0.2689530849456787, "4962": 0.5307431221008301, "5041": 0.16524957120418549, "5090": 0.3870677351951599, "5158": 0.02316705882549286, "5228": 0.18329764902591705, "5250": 1.024303913116455, "5258": 0.08154398202896118, "5383": 0.5021947622299194, "5387": 1.1236859560012817, "5391": 0.176772341132164, "5422": 0.0009760859538801014, "5449": 0.40481385588645935, "5512": 0.23247487843036652, "5537": 0.9500881433486938, "5589": 0.06977381557226181, "5769": 0.10467668622732162, "5812": 0.2317005842924118, "5876": 0.7276995778083801, "5884": 0.6793810129165649, "6064": 0.32270604372024536, "6083": 0.0019512200960889459, "6364": 0.3622259199619293, "6438": 0.2089812457561493, "6592": 0.17020416259765625, "6648": 0.0009760859538801014, "6774": 0.05970508232712746, "7011": 0.4337083101272583, "7092": 0.020300358533859253, "7246": 0.5662899017333984, "7275": 0.05694137513637543, "7356": 0.04674193635582924, "7361": 0.45994341373443604, "7366": 0.24325250089168549, "7772": 0.6548244953155518, "7959": 0.3824150264263153, "8018": 0.083342544734478, "8031": 1.061472773551941, "8171": 0.8957691192626953, "8185": 1.0403043031692505, "8290": 0.2954642176628113, "8332": 0.07159364968538284, "8524": 0.2317005842924118, "8583": 0.10379679501056671, "8676": 0.010684899985790253, "9007": 1.001607894897461, "9031": 0.006812678650021553, "9096": 0.20818853378295898, "9165": 0.08154398202896118, "9233": 0.176772341132164, "9276": 0.7047978043556213, "9307": 0.5651806592941284, "9556": 0.06154331564903259, "9572": 0.2918238639831543, "10057": 0.22782009840011597, "10071": 0.5045560002326965, "10085": 0.9225212931632996, "10210": 1.27701997756958, "10266": 0.38574060797691345, "10343": 0.3325583338737488, "10354": 0.27044451236724854, "10371": 0.19541899859905243, "10548": 0.083342544734478, "10636": 0.15275461971759796, "10737": 0.00875066313892603, "11022": 0.7342816591262817, "11163": 0.762009859085083, "11253": 0.19381128251552582, "11475": 0.5272908806800842, "11539": 0.0174254160374403, "11663": 0.37640097737312317, "11721": 0.03360854089260101, "11835": 0.5968599319458008, "12061": 0.025073638185858727, "12359": 0.47463157773017883, "12377": 0.6332852244377136, "12562": 0.2689530849456787, "12604": 0.8764448165893555, "12789": 0.3464667797088623, "12987": 1.4678382873535156, "12990": 0.13670019805431366, "13013": 0.9232974052429199, "13091": 0.11168810725212097, "13100": 0.8796916007995605, "13122": 0.7201237678527832, "13149": 0.22626367211341858, "13502": 0.8264343738555908, "13922": 0.27044451236724854, "13938": 0.07431721687316895, "13995": 0.6317287683486938, "14187": 0.5057345628738403, "14192": 0.6862877607345581, "14193": 0.4337083101272583, "14194": 0.9131608605384827, "14774": 0.2852376699447632, "14788": 0.09406650811433792, "14830": 0.43434104323387146, "14988": 0.7951818704605103, "15094": 0.10731173306703568, "15115": 0.13925230503082275, "15273": 1.1205062866210938, "15422": 0.5506471395492554, "15543": 0.1685553640127182, "16216": 0.48068851232528687, "16246": 0.8893690705299377, "16285": 0.8315495252609253, "16305": 0.0317181795835495, "16308": 0.7528522610664368, "16420": 0.2830325961112976, "17009": 0.23479416966438293, "17202": 0.02792670577764511, "17235": 0.890972912311554, "17254": 0.06429435312747955, "17257": 0.25694093108177185, "17427": 0.18573370575904846, "18260": 0.21135559678077698, "18429": 0.052318159490823746, "19022": 0.2852376699447632, "19137": 0.026976587250828743, "19143": 0.14686977863311768, "19395": 0.6358738541603088, "19470": 0.2493593990802765, "19817": 0.18816383183002472, "20299": 0.6664261221885681, "20817": 0.6054253578186035, "20939": 0.3656192123889923, "21338": 0.11430477350950241, "21520": 0.4437839686870575, "21709": 0.9139442443847656, "21903": 0.1930064558982849, "22330": 0.678390383720398, "22574": 0.4926934838294983, "22694": 0.6970458030700684, "22731": 0.2539152204990387, "22747": 1.7153451442718506, "22869": 0.23092569410800934, "23079": 1.5084083080291748, "23722": 0.21372433006763458, "23767": 0.2674594223499298, "23797": 0.03266380727291107, "24051": 0.7182208299636841, "24345": 0.0029254043474793434, "24558": 0.4203280806541443, "24665": 1.3060075044631958, "25100": 0.0354953333735466, "25117": 0.12038381397724152, "25354": 0.129004567861557, "26534": 0.15693697333335876, "26652": 0.18167030811309814, "27152": 0.07431721687316895, "27598": 0.8748174905776978, "27998": 0.7969439625740051, "28031": 0.2223619967699051, "28177": 0.32199856638908386, "28314": 0.4824984669685364, "28466": 0.5186077356338501, "28691": 1.018678069114685, "28835": 0.025073638185858727, "28848": 0.5855054259300232, "29021": 0.05786345899105072} | 13931771 | Various specialized domains have been described in the cytosol and the nucleus; however, little is known about compartmentalization within the mitochondrial matrix. GRSF1 (G-rich sequence factor 1) is an RNA binding protein that was previously reported to localize in the cytosol. We found that an isoform of GRSF1 accumulates in discrete foci in the mitochondrial matrix. These foci are composed of nascent mitochondrial RNA and also contain RNase P, an enzyme that participates in mitochondrial RNA processing. GRSF1 was found to interact with RNase P and to be required for processing of both classical and tRNA-less RNA precursors. In its absence, cleavage of primary RNA transcripts is abnormal, leading to decreased expression of mitochondrially encoded proteins and mitochondrial dysfunction. Our findings suggest that the foci containing GRSF1 and RNase P correspond to sites where primary RNA transcripts converge to be processed. We have termed these large ribonucleoprotein structures "mitochondrial RNA granules. " | GRSF1 Regulates RNA Processing in Mitochondrial RNA Granules |
{"1014": 0.22392450273036957, "1038": 0.23787821829319, "1047": 0.05139094591140747, "1609": 0.2394166737794876, "2001": 0.10026945173740387, "2004": 0.2561853528022766, "2020": 0.045809537172317505, "2043": 0.16276304423809052, "2076": 0.11604541540145874, "2077": 0.1384023278951645, "2086": 0.3084607720375061, "2094": 0.5421652793884277, "2095": 0.1064341589808464, "2130": 0.20102575421333313, "2152": 0.4938860833644867, "2158": 0.013579257763922215, "2166": 0.7124901413917542, "2167": 0.5151132941246033, "2172": 0.32058215141296387, "2177": 0.5640701055526733, "2193": 0.0770333781838417, "2214": 0.10467668622732162, "2220": 0.27712854743003845, "2273": 0.49686139822006226, "2287": 0.7951818704605103, "2289": 0.42225050926208496, "2308": 0.6118015646934509, "2313": 0.23015019297599792, "2397": 0.5313173532485962, "2444": 0.1808556467294693, "2450": 0.36967599391937256, "2470": 0.32058215141296387, "2501": 0.056018441915512085, "2504": 0.6400018334388733, "2511": 0.0174254160374403, "2523": 0.1358480453491211, "2542": 0.07250232994556427, "2561": 0.47036975622177124, "2636": 0.2674594223499298, "2641": 0.1510767638683319, "2642": 0.8877626657485962, "2662": 0.9635916948318481, "2668": 0.11256109178066254, "2690": 0.6348392367362976, "2692": 0.09850110858678818, "2727": 0.16276304423809052, "2729": 0.2576959431171417, "2740": 0.41195443272590637, "2753": 0.14095009863376617, "2765": 0.14264501631259918, "2779": 0.07341018319129944, "2786": 0.06612417846918106, "2807": 0.5116065740585327, "2817": 0.6583697199821472, "2846": 0.5816917419433594, "2861": 0.06612417846918106, "2871": 0.34370049834251404, "2902": 0.2607102394104004, "2913": 0.5307431221008301, "2931": 0.21135559678077698, "2933": 0.32270604372024536, "2944": 0.36290550231933594, "2951": 0.41001203656196594, "2959": 0.18329764902591705, "2966": 0.38441169261932373, "2967": 0.27564704418182373, "3026": 0.22392450273036957, "3029": 0.7182208299636841, "3041": 0.045809537172317505, "3054": 1.1641268730163574, "3080": 0.0019512200960889459, "3141": 0.16690383851528168, "3156": 0.5629584193229675, "3231": 0.0038986403960734606, "3263": 0.6512666940689087, "3273": 0.3464667797088623, "3276": 0.07068414986133575, "3278": 0.5930894017219543, "3284": 0.08782484382390976, "3285": 0.0606246218085289, "3287": 0.15023678541183472, "3289": 0.0770333781838417, "3319": 0.14095009863376617, "3348": 0.22079704701900482, "3378": 0.5220900774002075, "3381": 0.6980181336402893, "3429": 0.5057345628738403, "3445": 0.5415972471237183, "3448": 0.020300358533859253, "3452": 0.18411032855510712, "3463": 0.40220460295677185, "3517": 0.0317181795835495, "3546": 0.7537717819213867, "3551": 0.12728634476661682, "3556": 0.06154331564903259, "3623": 0.3019835948944092, "3624": 0.07250232994556427, "3638": 0.5729197263717651, "3643": 0.22859740257263184, "3671": 0.37035053968429565, "3675": 0.7987030148506165, "3767": 0.12384103983640671, "3778": 0.012615402229130268, "3798": 0.6848117709159851, "3801": 0.2247048318386078, "3867": 0.14602625370025635, "3891": 0.7647408246994019, "3979": 0.09938567131757736, "4094": 0.13071982562541962, "4106": 0.5751199722290039, "4118": 0.2918238639831543, "4146": 0.46853771805763245, "4167": 0.3297532796859741, "4179": 0.5584990978240967, "4244": 0.5607312321662903, "4275": 0.22392450273036957, "4278": 0.026976587250828743, "4295": 0.678885817527771, "4328": 0.6563454270362854, "4343": 0.25995752215385437, "4411": 0.28082266449928284, "4431": 0.5410289764404297, "4568": 0.7276995778083801, "4583": 0.3170322775840759, "4725": 0.4487839937210083, "4748": 1.0030416250228882, "4769": 0.14433705806732178, "4793": 0.1734936386346817, "4795": 0.14433705806732178, "4800": 0.2954642176628113, "4805": 0.07250232994556427, "4812": 0.31560876965522766, "5002": 0.00875066313892603, "5022": 0.1401015669107437, "5174": 0.02792670577764511, "5285": 0.011650617234408855, "5300": 0.06886265426874161, "5333": 0.007782140281051397, "5345": 0.6872705817222595, "5359": 0.35745587944984436, "5387": 0.5290185213088989, "5388": 0.09317722171545029, "5393": 0.5092619061470032, "5396": 0.175953671336174, "5401": 0.09584271162748337, "5423": 0.7482418417930603, "5531": 0.2954642176628113, "5636": 0.21765978634357452, "5739": 0.21372433006763458, "5758": 0.11430477350950241, "5769": 0.06246116757392883, "5776": 0.08244366943836212, "5790": 0.037378571927547455, "5876": 0.6522845029830933, "5907": 0.06429435312747955, "5986": 0.27934664487838745, "5989": 0.27342069149017334, "5997": 0.1229778528213501, "6001": 0.02887592278420925, "6022": 0.21687394380569458, "6187": 0.7009293437004089, "6391": 0.06612417846918106, "6421": 0.11865071207284927, "6444": 0.129004567861557, "6463": 0.46055975556373596, "6480": 0.52266925573349, "6612": 0.14264501631259918, "6614": 0.3923587501049042, "6678": 0.18492233753204346, "6758": 0.058784693479537964, "6818": 0.7105726003646851, "6851": 0.4818955361843109, "6909": 0.7907629609107971, "6959": 0.940220832824707, "6987": 0.04674193635582924, "7012": 0.2470736801624298, "7017": 0.3034266233444214, "7091": 0.417115718126297, "7189": 0.3318578004837036, "7197": 0.03266380727291107, "7457": 0.15023678541183472, "7551": 0.08513788133859634, "7594": 0.055094651877880096, "7604": 0.13243216276168823, "7667": 0.0913962796330452, "7784": 0.23787821829319, "7809": 0.8109301924705505, "7812": 0.07612881064414978, "7863": 0.32341301441192627, "7870": 0.49864232540130615, "7965": 0.09672962874174118, "8030": 0.13157635927200317, "8182": 0.011650617234408855, "8244": 0.347847044467926, "8280": 0.5186077356338501, "8319": 0.5450005531311035, "8422": 0.06520967930555344, "8445": 0.762009859085083, "8556": 0.4349733293056488, "8704": 0.42096930742263794, "8713": 0.23787821829319, "8777": 0.5528968572616577, "9312": 0.7239188551902771, "9349": 0.04767346754670143, "9367": 0.10291612148284912, "9463": 0.8161250352859497, "9556": 0.1930064558982849, "9574": 0.9248477816581726, "9580": 0.2409527748823166, "9601": 0.03266380727291107, "9629": 0.04953393340110779, "9750": 0.34577593207359314, "9871": 0.4450363218784332, "9905": 0.10731173306703568, "9998": 0.09228714555501938, "10174": 0.0029254043474793434, "10250": 0.4974553883075714, "10318": 0.6613984704017639, "10426": 0.3325583338737488, "10545": 0.8666408061981201, "10699": 0.4500300884246826, "10751": 0.19622190296649933, "10817": 0.2493593990802765, "10831": 0.36358460783958435, "10847": 0.5506471395492554, "10857": 0.17431432008743286, "11031": 0.678390383720398, "11100": 0.30558720231056213, "11207": 0.12642613053321838, "11460": 0.5244048833847046, "11538": 0.2026219218969345, "11709": 0.19862671196460724, "11816": 0.1808556467294693, "11952": 0.3381449282169342, "12044": 0.13670019805431366, "12377": 0.025073638185858727, "12389": 0.083342544734478, "12407": 0.10291612148284912, "12411": 0.28082266449928284, "12436": 0.9425065517425537, "12520": 0.27786844968795776, "12930": 0.05786345899105072, "13004": 0.11604541540145874, "13029": 0.48068851232528687, "13105": 0.025073638185858727, "13153": 0.5209306478500366, "13180": 0.4556184411048889, "13331": 0.11865071207284927, "13356": 0.021256839856505394, "13371": 0.08154398202896118, "13692": 0.5324648022651672, "14155": 0.32199856638908386, "14267": 0.8109301924705505, "14358": 0.05970508232712746, "14671": 0.9108069539070129, "15262": 0.10291612148284912, "15306": 0.4158279001712799, "15354": 0.029824240133166313, "15418": 0.05139094591140747, "15502": 0.029824240133166313, "15509": 0.9084475636482239, "15559": 0.6699305176734924, "15676": 1.4678382873535156, "15995": 0.23324857652187347, "16029": 0.026025565341114998, "16042": 0.02792670577764511, "16134": 0.4709797203540802, "16157": 0.13499516248703003, "16166": 0.5010119676589966, "16330": 0.47463157773017883, "16364": 0.21530038118362427, "16478": 0.3325583338737488, "16480": 1.0312920808792114, "16519": 0.0019512200960889459, "16571": 0.052318159490823746, "16578": 0.1358480453491211, "17119": 0.2800849378108978, "17620": 0.083342544734478, "17760": 0.23402166366577148, "17844": 0.5238267183303833, "17850": 0.66441810131073, "17881": 0.02792670577764511, "17908": 0.3027053773403168, "18120": 0.1946154683828354, "18249": 0.2674594223499298, "18423": 0.016465263441205025, "18827": 0.3519764244556427, "18949": 0.04113444685935974, "19037": 0.10555581003427505, "19064": 0.1358480453491211, "19188": 0.04767346754670143, "20162": 0.07159364968538284, "20194": 0.7047978043556213, "20310": 0.4337083101272583, "20576": 0.16690383851528168, "20591": 0.23633737862110138, "20915": 0.6729245185852051, "21449": 0.841701865196228, "21469": 0.7057625651359558, "21879": 0.5534584522247314, "21901": 1.4505887031555176, "22010": 0.5284429788589478, "22238": 0.05970508232712746, "23489": 0.04207121208310127, "23628": 0.3883931338787079, "23683": 0.13157635927200317, "23688": 0.6664261221885681, "23760": 0.46055975556373596, "23900": 0.09050461649894714, "24110": 0.015504186972975731, "24209": 0.5528968572616577, "24992": 0.11081436276435852, "25022": 0.46363574266433716, "25510": 0.5080875158309937, "25808": 0.08692999184131622, "26163": 0.1358480453491211, "26462": 0.6471850275993347, "26497": 0.12728634476661682, "26906": 0.15359249711036682, "27615": 0.15442965924739838, "27794": 0.8340972661972046, "27833": 1.5187265872955322, "28055": 0.436867892742157, "28093": 0.3910386264324188, "28487": 0.09228714555501938, "28767": 1.452418565750122, "28977": 0.2652147710323334, "29048": 0.5404602885246277} | 13933299 | Aims: To investigate midlife cholesterol in relation to Alzheimer’s disease (AD) and vascular dementia (VaD) in a large multiethnic cohort of women and men. Methods: The Kaiser Permanente Northern California Medical Group (healthcare delivery organization) formed the database for this study. The 9,844 participants underwent detailed health evaluations during 1964–1973 at ages 40–45 years; they were still members of the health plan in 1994. AD and VaD were ascertained by medical records between 1 January 1994 and 1 June 2007. Cox proportional hazards models – adjusted for age, education, race/ethnic group, sex, midlife diabetes, hypertension, BMI and late-life stroke – were conducted. Results: In total, 469 participants had AD and 127 had VaD. With desirable cholesterol levels (<200 mg/dl) as a reference, hazard ratios (HR) and 95% CI for AD were 1.23 (0.97–1.55) and 1.57 (1.23–2.01) for borderline (200–239 mg/dl) and high cholesterol (≥240 mg/dl), respectively. HR and 95% CI for VaD were 1.50 (1.01–2.23) for borderline and 1.26 (0.82–1.96) for high cholesterol. Further analyses for AD (cholesterol quartiles, 1st quartile reference) indicated that cholesterol levels >220 mg/dl were a significant risk factor: HR were 1.31 (1.01–1.71; 3rd quartile, 221–248 mg/dl) and 1.58 (1.22–2.06; 4th quartile, 249–500 mg/dl). Conclusion: Midlife serum total cholesterol was associated with an increased risk of AD and VaD. Even moderately elevated cholesterol increased dementia risk. Dementia risk factors need to be addressed as early as midlife, before underlying disease(s) or symptoms appear. | Midlife Serum Cholesterol and Increased Risk of Alzheimer’s and Vascular Dementia Three Decades Later |
{"1003": 0.23247487843036652, "1022": 0.06337817758321762, "1052": 0.1384023278951645, "1997": 0.23864774405956268, "2004": 0.22704219818115234, "2007": 0.052318159490823746, "2012": 0.16110190749168396, "2013": 0.176772341132164, "2020": 0.00875066313892603, "2035": 0.3750596046447754, "2058": 0.07612881064414978, "2060": 0.16276304423809052, "2073": 0.15777134895324707, "2084": 0.06154331564903259, "2086": 0.42990362644195557, "2088": 0.5116065740585327, "2097": 0.036437395960092545, "2106": 0.11343330889940262, "2111": 0.7370892763137817, "2116": 0.3560888469219208, "2142": 0.19381128251552582, "2146": 0.03925827145576477, "2149": 0.20818853378295898, "2158": 0.0842406153678894, "2163": 0.08064348995685577, "2166": 0.16607704758644104, "2169": 0.2184450328350067, "2174": 0.025073638185858727, "2177": 0.2478361576795578, "2179": 0.025073638185858727, "2184": 0.10203468054533005, "2193": 0.6502478122711182, "2203": 0.1212492436170578, "2214": 0.5209306478500366, "2216": 0.08064348995685577, "2241": 0.2969166338443756, "2248": 0.18654440343379974, "2273": 0.5021947622299194, "2275": 0.15023678541183472, "2287": 1.04512357711792, "2308": 0.4938860833644867, "2312": 0.27786844968795776, "2313": 0.952351450920105, "2321": 0.08961215615272522, "2323": 0.1477125883102417, "2330": 0.10467668622732162, "2336": 0.0913962796330452, "2339": 0.3318578004837036, "2406": 0.6754127144813538, "2408": 0.1485546976327896, "2426": 0.7028654217720032, "2444": 0.2822965085506439, "2450": 0.2674594223499298, "2458": 0.29036402702331543, "2470": 0.5963221788406372, "2491": 0.5925496220588684, "2515": 0.0752234235405922, "2522": 0.23402166366577148, "2529": 0.10291612148284912, "2542": 0.23710809648036957, "2554": 0.04674193635582924, "2591": 0.010684899985790253, "2599": 0.2881702482700348, "2609": 0.5450005531311035, "2625": 0.3339579105377197, "2634": 0.7163142561912537, "2637": 0.1332872211933136, "2660": 0.10203468054533005, "2676": 0.32199856638908386, "2689": 0.36358460783958435, "2690": 1.1018621921539307, "2691": 0.1602703034877777, "2711": 0.3134697377681732, "2729": 0.5816917419433594, "2740": 0.7201237678527832, "2744": 0.35950297117233276, "2752": 0.13925230503082275, "2765": 0.4734157919883728, "2779": 0.1384023278951645, "2796": 0.3297532796859741, "2802": 0.013579257763922215, "2817": 0.4318077862262726, "2822": 0.7482418417930603, "2827": 0.04487626627087593, "2846": 0.6197150945663452, "2859": 1.0123108625411987, "2866": 0.1734936386346817, "2892": 0.4462870955467224, "2896": 0.15860503911972046, "2904": 0.18248429894447327, "2913": 0.2741633653640747, "2922": 0.3956514894962311, "2925": 0.3883931338787079, "2931": 0.07068414986133575, "2951": 0.23324857652187347, "2966": 0.052318159490823746, "2967": 0.02316705882549286, "2969": 0.46853771805763245, "2973": 0.4654768109321594, "2981": 0.8500841856002808, "2988": 0.32764431834220886, "3026": 0.7124901413917542, "3032": 0.9363996982574463, "3054": 0.43244171142578125, "3072": 0.48068851232528687, "3080": 1.0116009712219238, "3088": 0.15860503911972046, "3092": 0.1718502640724182, "3115": 0.47827014327049255, "3141": 0.5156965255737305, "3145": 0.07431721687316895, "3160": 0.5290185213088989, "3189": 0.09495500475168228, "3209": 0.1384023278951645, "3268": 0.04113444685935974, "3273": 0.5925496220588684, "3278": 0.15860503911972046, "3283": 0.08603433519601822, "3287": 0.02887592278420925, "3290": 0.6989894509315491, "3318": 0.5410289764404297, "3343": 0.38174858689308167, "3344": 0.32553088665008545, "3350": 0.013579257763922215, "3378": 0.21687394380569458, "3391": 0.3423145115375519, "3431": 0.5618454217910767, "3433": 0.4574742913246155, "3445": 0.7105726003646851, "3446": 0.3416208028793335, "3451": 0.1619328260421753, "3452": 0.12728634476661682, "3463": 0.49030399322509766, "3466": 0.2026219218969345, "3471": 0.007782140281051397, "3488": 0.00875066313892603, "3497": 0.7009293437004089, "3515": 0.40351006388664246, "3517": 0.10731173306703568, "3541": 0.8383291959762573, "3550": 0.036437395960092545, "3558": 0.5952457785606384, "3563": 0.40806588530540466, "3577": 0.14433705806732178, "3616": 0.5936289429664612, "3618": 0.0038986403960734606, "3623": 0.7182208299636841, "3633": 0.11168810725212097, "3652": 0.39762192964553833, "3672": 0.22079704701900482, "3686": 0.08513788133859634, "3741": 0.35813871026039124, "3747": 0.05417001247406006, "3767": 0.07612881064414978, "3785": 0.43623676896095276, "3791": 0.1619328260421753, "3795": 0.5707147121429443, "3801": 0.12038381397724152, "3842": 0.09938567131757736, "3867": 0.6400018334388733, "3896": 0.20739519596099854, "3915": 0.5069117546081543, "3920": 0.0029254043474793434, "3923": 0.567951500415802, "3930": 0.15359249711036682, "3973": 0.06886265426874161, "3980": 0.4158279001712799, "3991": 0.6317287683486938, "4090": 0.49864232540130615, "4094": 0.09228714555501938, "4106": 0.19220098853111267, "4118": 0.3423145115375519, "4125": 0.6674286723136902, "4146": 0.03831886500120163, "4162": 0.28670501708984375, "4167": 0.08603433519601822, "4254": 0.08064348995685577, "4281": 0.8004589080810547, "4286": 0.10291612148284912, "4295": 0.7629209756851196, "4321": 0.21293537318706512, "4336": 0.06429435312747955, "4353": 0.0009760859538801014, "4357": 0.5133614540100098, "4358": 0.6704301834106445, "4380": 0.0770333781838417, "4403": 0.3588210940361023, "4504": 0.2837681770324707, "4531": 0.12470348179340363, "4573": 0.812664806842804, "4583": 0.010684899985790253, "4587": 0.32129061222076416, "4639": 0.05786345899105072, "4650": 0.3381449282169342, "4652": 0.36358460783958435, "4725": 0.5186077356338501, "4758": 0.4067663550376892, "4793": 0.7163142561912537, "4803": 0.33605360984802246, "4805": 0.19622190296649933, "4812": 0.14264501631259918, "4841": 0.05046287178993225, "4852": 0.7124901413917542, "4903": 0.03925827145576477, "4916": 0.5898461937904358, "4957": 0.25995752215385437, "4969": 0.9037119746208191, "5002": 0.7863243818283081, "5079": 0.010684899985790253, "5084": 0.6270449161529541, "5137": 0.0606246218085289, "5198": 0.06795065850019455, "5201": 0.23324857652187347, "5221": 0.11604541540145874, "5278": 0.08603433519601822, "5333": 0.11604541540145874, "5360": 0.3683255612850189, "5377": 0.045809537172317505, "5381": 0.16690383851528168, "5468": 0.037378571927547455, "5531": 0.25467249751091003, "5535": 0.18004031479358673, "5619": 0.129004567861557, "5635": 0.17922431230545044, "5636": 0.052318159490823746, "5714": 0.020300358533859253, "5761": 0.006812678650021553, "5764": 0.26446542143821716, "5776": 0.021256839856505394, "5790": 0.12470348179340363, "5799": 0.7827593088150024, "5857": 0.5364705324172974, "5876": 0.08871890604496002, "5901": 0.28743788599967957, "5907": 0.04767346754670143, "5915": 0.49626702070236206, "5921": 0.3191637098789215, "5984": 0.007782140281051397, "6001": 0.31489628553390503, "6022": 0.6502478122711182, "6043": 0.42799583077430725, "6075": 0.23247487843036652, "6165": 0.11778303235769272, "6217": 0.0009760859538801014, "6245": 0.8315495252609253, "6422": 0.5139457583427429, "6459": 0.025073638185858727, "6463": 0.49864232540130615, "6505": 0.25467249751091003, "6551": 0.4267219603061676, "6577": 0.013579257763922215, "6643": 0.9100211262702942, "6648": 0.4734157919883728, "6653": 0.49030399322509766, "6689": 0.1332872211933136, "6691": 0.7960633039474487, "6698": 0.13071982562541962, "6747": 0.4770587682723999, "6758": 0.4002431631088257, "6768": 0.10993985831737518, "6818": 0.57457035779953, "6869": 0.13499516248703003, "6905": 0.04767346754670143, "6909": 0.684319257736206, "6918": 0.2607102394104004, "6923": 0.06520967930555344, "6936": 0.07068414986133575, "6937": 0.7047978043556213, "6950": 0.0606246218085289, "7017": 0.6892333030700684, "7080": 0.5021947622299194, "7091": 0.5139457583427429, "7108": 0.09317722171545029, "7304": 0.8633513450622559, "7320": 0.3005385100841522, "7355": 0.1930064558982849, "7379": 0.10731173306703568, "7394": 0.956112265586853, "7403": 0.31132611632347107, "7457": 0.6338034868240356, "7461": 0.2247048318386078, "7587": 0.03266380727291107, "7636": 0.5455666780471802, "7711": 0.40351006388664246, "7778": 0.016465263441205025, "7790": 1.2878543138504028, "7870": 0.7258110046386719, "7965": 0.10906458646059036, "8020": 0.3750596046447754, "8029": 0.06429435312747955, "8186": 0.06886265426874161, "8317": 0.15359249711036682, "8326": 0.8550800085067749, "8344": 0.1221139207482338, "8353": 0.17267228662967682, "8377": 0.0029254043474793434, "8381": 0.0606246218085289, "8483": 0.13925230503082275, "8554": 0.26146242022514343, "8556": 0.2696990668773651, "8569": 0.5472630262374878, "8583": 0.09495500475168228, "8715": 0.06612417846918106, "8729": 0.2741633653640747, "8761": 0.10026945173740387, "8778": 0.6950984001159668, "8781": 0.21372433006763458, "8817": 0.06612417846918106, "8991": 0.06886265426874161, "9002": 0.7067264318466187, "9041": 0.10906458646059036, "9048": 0.1229778528213501, "9113": 0.13755162060260773, "9156": 0.23092569410800934, "9174": 0.27044451236724854, "9183": 0.14433705806732178, "9186": 0.05786345899105072, "9355": 0.08871890604496002, "9470": 0.20501139760017395, "9556": 0.4158279001712799, "9560": 0.12642613053321838, "9642": 0.7314660549163818, "9723": 0.11430477350950241, "9739": 0.12642613053321838, "9740": 0.6950984001159668, "9750": 1.0312920808792114, "9756": 0.3519764244556427, "9776": 0.6931471824645996, "9835": 0.055094651877880096, "9839": 0.31489628553390503, "9871": 0.31560876965522766, "9874": 0.2447827309370041, "9895": 0.0009760859538801014, "10035": 0.4879087805747986, "10104": 0.8813109993934631, "10111": 0.004870930220931768, "10173": 0.22704219818115234, "10174": 0.5528968572616577, "10189": 0.06429435312747955, "10197": 0.43875885009765625, "10300": 0.0019512200960889459, "10318": 0.8238670229911804, "10641": 0.04394211992621422, "10699": 0.1229778528213501, "10723": 0.05970508232712746, "10726": 0.39433568716049194, "10744": 0.23710809648036957, "10753": 0.025073638185858727, "10833": 0.083342544734478, "10840": 0.129004567861557, "10847": 0.5618454217910767, "10859": 0.1401015669107437, "10880": 0.57457035779953, "10960": 0.34370049834251404, "10976": 0.574020504951477, "11036": 0.13925230503082275, "11121": 0.056018441915512085, "11160": 0.469759464263916, "11265": 0.29400965571403503, "11282": 0.29619070887565613, "11310": 0.14939609169960022, "11383": 0.02887592278420925, "11436": 0.06886265426874161, "11441": 0.3381449282169342, "11509": 0.026025565341114998, "11538": 0.0038986403960734606, "11616": 0.28082266449928284, "11656": 0.1873544454574585, "11724": 0.015504186972975731, "11765": 0.7482418417930603, "11779": 0.08603433519601822, "11837": 0.4002431631088257, "11856": 0.1930064558982849, "11888": 1.0264055728912354, "11922": 0.1011524572968483, "11980": 0.8699195384979248, "12099": 0.8187123537063599, "12102": 0.052318159490823746, "12130": 0.4950772523880005, "12265": 0.6155022978782654, "12335": 0.17431432008743286, "12353": 0.0029254043474793434, "12381": 0.25845035910606384, "12412": 0.3005385100841522, "12473": 0.00875066313892603, "12520": 0.7601850032806396, "12530": 0.9333322048187256, "12654": 0.09317722171545029, "12867": 0.2089812457561493, "12876": 0.28155985474586487, "12878": 0.1946154683828354, "12884": 0.6654226183891296, "13105": 0.11517547070980072, "13180": 0.5438674688339233, "13204": 0.12814582884311676, "13331": 0.07250232994556427, "13356": 0.1619328260421753, "13376": 0.5914691090583801, "13449": 0.5139457583427429, "13491": 0.030771657824516296, "13538": 0.42096930742263794, "13544": 0.07068414986133575, "13597": 0.5010119676589966, "13661": 0.8340972661972046, "13692": 0.49030399322509766, "13806": 0.34508460760116577, "13884": 0.13670019805431366, "13908": 0.0752234235405922, "14120": 0.2470736801624298, "14155": 0.05046287178993225, "14267": 0.0019512200960889459, "14343": 0.6882523894309998, "14373": 0.03831886500120163, "14376": 1.2688164710998535, "14388": 0.06795065850019455, "14613": 0.08871890604496002, "14773": 0.17431432008743286, "14777": 0.20977331697940826, "15074": 0.0770333781838417, "15157": 0.7305257320404053, "15258": 0.03925827145576477, "15266": 0.23864774405956268, "15278": 0.28082266449928284, "15291": 0.8925741910934448, "15306": 0.4709797203540802, "15332": 0.6415454745292664, "15432": 0.5844172835350037, "15445": 0.0029254043474793434, "15448": 0.19381128251552582, "15451": 0.08064348995685577, "15509": 0.00875066313892603, "15545": 0.19381128251552582, "15578": 0.020300358533859253, "15596": 0.3269403576850891, "15822": 0.4400174915790558, "15982": 1.1929750442504883, "15995": 0.6853039860725403, "16014": 0.2501201331615448, "16112": 0.06246116757392883, "16134": 0.46117570996284485, "16211": 0.11168810725212097, "16227": 0.0038986403960734606, "16263": 0.0038986403960734606, "16281": 0.052318159490823746, "16302": 0.16690383851528168, "16311": 0.24325250089168549, "16340": 0.4487839937210083, "16367": 0.1994270235300064, "16452": 0.6853039860725403, "16454": 0.09317722171545029, "16515": 0.3027053773403168, "16519": 0.012615402229130268, "16530": 0.1677299439907074, "16605": 0.4041621685028076, "16744": 0.3241194784641266, "16754": 0.2145126610994339, "16778": 0.040196798741817474, "16803": 0.2026219218969345, "16860": 0.14686977863311768, "16884": 0.5773153901100159, "16893": 0.2830325961112976, "16902": 0.29109421372413635, "17119": 0.5701626539230347, "17208": 0.46117570996284485, "17237": 0.026976587250828743, "17245": 0.1384023278951645, "17289": 0.012615402229130268, "17459": 0.3622259199619293, "17503": 0.007782140281051397, "17975": 0.5640701055526733, "18075": 0.7665573358535767, "18234": 0.47827014327049255, "18240": 0.06977381557226181, "18249": 0.77198725938797, "18345": 0.2145126610994339, "18349": 0.015504186972975731, "18402": 0.6502478122711182, "18422": 0.29473719000816345, "18609": 0.11691460013389587, "18642": 1.27701997756958, "18786": 0.040196798741817474, "18804": 0.5483922958374023, "18886": 0.6149744987487793, "18949": 0.4400174915790558, "18976": 0.055094651877880096, "19064": 0.23015019297599792, "19353": 0.49982786178588867, "19389": 0.23247487843036652, "19654": 0.056018441915512085, "19879": 0.11430477350950241, "19939": 0.0797421783208847, "20074": 0.034552380442619324, "20110": 0.08064348995685577, "20155": 0.05139094591140747, "20177": 0.2447827309370041, "20272": 1.278652548789978, "20302": 0.469759464263916, "20310": 0.26296505331993103, "20390": 0.09406650811433792, "20576": 0.03925827145576477, "20592": 0.13925230503082275, "20806": 0.08064348995685577, "20881": 0.791648268699646, "20969": 0.11778303235769272, "21040": 0.4487839937210083, "21150": 0.018384648486971855, "21675": 0.3464667797088623, "21718": 0.2160874605178833, "21758": 0.12642613053321838, "21879": 0.5232481360435486, "21901": 0.6950984001159668, "22035": 0.006812678650021553, "22166": 0.42608439922332764, "22248": 0.07612881064414978, "22835": 0.3519764244556427, "22865": 0.7229714393615723, "22939": 0.10818854719400406, "23025": 1.1406835317611694, "23042": 0.2852376699447632, "23130": 0.7276995778083801, "23274": 0.6476961374282837, "23389": 0.004870930220931768, "23683": 0.04953393340110779, "23807": 0.9576126337051392, "23900": 0.5186077356338501, "24155": 0.28963330388069153, "24394": 1.1555536985397339, "24528": 0.15777134895324707, "24552": 0.2105647772550583, "24658": 0.15359249711036682, "24757": 0.14686977863311768, "24821": 0.10291612148284912, "24846": 0.022212404757738113, "25172": 0.8707374930381775, "25284": 0.058784693479537964, "25519": 0.13243216276168823, "25647": 0.013579257763922215, "25737": 0.18654440343379974, "25750": 0.2089812457561493, "26118": 0.0029254043474793434, "26163": 0.12814582884311676, "26319": 0.06703783571720123, "26462": 0.2918238639831543, "26629": 0.007782140281051397, "26745": 0.6563454270362854, "26786": 0.7314660549163818, "26855": 0.4855078160762787, "26906": 0.0038986403960734606, "27197": 0.7610978484153748, "27484": 0.01934296265244484, "27564": 0.2674594223499298, "27794": 0.48670899868011475, "27805": 0.24171993136405945, "28055": 0.30558720231056213, "28093": 0.022212404757738113, "28139": 0.04394211992621422, "28297": 0.12470348179340363, "28321": 0.8989537954330444, "28466": 0.10291612148284912, "28498": 0.18654440343379974, "28648": 0.12814582884311676, "28694": 0.8039615154266357, "28767": 1.3238370418548584, "28986": 0.07159364968538284, "29295": 0.37035053968429565, "29392": 0.07793712615966797, "29458": 0.05970508232712746, "29516": 0.034552380442619324} | 13934676 | BACKGROUND The number of older people is set to increase dramatically worldwide. Demographic changes are likely to result in the rise of age-related chronic diseases which largely contribute to years lived with a disability and future dependence. However dependence is much less studied although intrinsically linked to disability. We investigated the prevalence and correlates of dependence among older people from middle income countries. METHODS A one-phase cross-sectional survey was carried out at 11 sites in seven countries (urban sites in Cuba, Venezuela, and Dominican Republic, urban and rural sites in Peru, Mexico, China and India). All those aged 65 years and over living in geographically defined catchment areas were eligible. In all, 15,022 interviews were completed with an informant interview for each participant. The full 10/66 Dementia Research Group survey protocol was applied, including ascertainment of depression, dementia, physical impairments and self-reported diagnoses. Dependence was interviewer-rated based on a key informant's responses to a set of open-ended questions on the participant's needs for care. We estimated the prevalence of dependence and the independent contribution of underlying health conditions. Site-specific prevalence ratios were meta-analysed, and population attributable prevalence fractions (PAPF) calculated. RESULTS The prevalence of dependence increased with age at all sites, with a tendency for the prevalence to be lower in men than in women. Age-standardised prevalence was lower in all sites than in the USA. Other than in rural China, dementia made the largest independent contribution to dependence, with a median PAPF of 34% (range 23%-59%). Other substantial contributors were limb impairment (9%, 1%-46%), stroke (8%, 2%-17%), and depression (8%, 1%-27%). CONCLUSION The demographic and health transitions will lead to large and rapid increases in the numbers of dependent older people particularly in middle income countries (MIC). The prevention and control of chronic neurological and neuropsychiatric diseases and the development of long-term care policies and plans should be urgent priorities. | "The contribution of chronic diseases to the prevalence of dependence among older people in Latin America, China and India: a 10/66 Dementia Research Group population-based survey" |
{"1996": 0.02316705882549286, "2003": 0.0058422754518687725, "2005": 0.011650617234408855, "2011": 0.319873183965683, "2012": 0.5506471395492554, "2025": 0.3381449282169342, "2026": 0.8989537954330444, "2033": 0.012615402229130268, "2046": 0.34023189544677734, "2064": 0.22001366317272186, "2066": 0.026976587250828743, "2067": 0.6654226183891296, "2072": 0.6218147873878479, "2073": 0.07341018319129944, "2075": 0.306306391954422, "2078": 0.48068851232528687, "2079": 0.34715715050697327, "2090": 0.00875066313892603, "2098": 0.306306391954422, "2129": 0.083342544734478, "2220": 0.49923527240753174, "2241": 0.5197699069976807, "2282": 0.03266380727291107, "2334": 0.8600510358810425, "2339": 0.36426326632499695, "2344": 0.03831886500120163, "2362": 0.08603433519601822, "2389": 0.5174443125724792, "2407": 0.6054253578186035, "2444": 0.29109421372413635, "2462": 0.3127557039260864, "2465": 0.11604541540145874, "2483": 0.1873544454574585, "2491": 0.07250232994556427, "2512": 0.1619328260421753, "2515": 0.3106105625629425, "2535": 0.13243216276168823, "2552": 0.9485763907432556, "2562": 0.4891071021556854, "2590": 0.06337817758321762, "2595": 0.3662964701652527, "2599": 0.02792670577764511, "2644": 0.6734226942062378, "2649": 0.0038986403960734606, "2719": 0.004870930220931768, "2738": 0.24325250089168549, "2771": 0.10026945173740387, "2825": 0.0058422754518687725, "2852": 0.5174443125724792, "2877": 0.21214580535888672, "2921": 0.27342069149017334, "2936": 0.23787821829319, "3030": 0.19622190296649933, "3041": 0.20818853378295898, "3078": 0.7592713832855225, "3085": 0.1485546976327896, "3161": 0.5629584193229675, "3206": 0.7755908370018005, "3252": 0.3864043951034546, "3334": 0.48430517315864563, "3399": 0.19862671196460724, "3466": 0.07250232994556427, "3491": 0.1734936386346817, "3526": 0.9531047344207764, "3584": 0.5805994272232056, "3619": 0.006812678650021553, "3675": 0.24401791393756866, "3685": 0.06246116757392883, "3701": 0.2576959431171417, "3724": 0.8748174905776978, "3796": 0.3757305145263672, "3800": 0.1946154683828354, "3816": 0.4494072198867798, "3818": 0.5903874635696411, "3853": 0.6813592314720154, "3952": 0.0797421783208847, "3973": 0.30989447236061096, "3975": 0.03831886500120163, "4012": 0.25239890813827515, "4047": 0.22157983481884003, "4055": 0.6704301834106445, "4066": 0.9379299283027649, "4072": 0.42990362644195557, "4081": 0.1332872211933136, "4106": 0.06703783571720123, "4111": 0.5871354341506958, "4114": 0.2026219218969345, "4176": 0.6080870032310486, "4195": 0.19381128251552582, "4237": 0.8212929964065552, "4328": 0.8187123537063599, "4363": 0.3262358605861664, "4442": 1.0001721382141113, "4490": 0.41195443272590637, "4541": 0.2105647772550583, "4652": 0.4196864068508148, "4666": 0.5506471395492554, "4748": 0.7683706283569336, "4758": 0.37102460861206055, "4761": 0.6070231795310974, "4863": 0.5472630262374878, "4935": 0.1229778528213501, "4942": 0.12986256182193756, "4958": 0.6181373596191406, "4962": 0.036437395960092545, "4972": 0.48430517315864563, "5072": 0.14686977863311768, "5090": 0.4437839686870575, "5158": 0.018384648486971855, "5245": 0.6960725784301758, "5274": 0.5957841277122498, "5320": 0.1710275560617447, "5441": 0.25088030099868774, "5459": 0.42926809191703796, "5516": 0.27712854743003845, "5579": 0.016465263441205025, "5700": 0.24859806895256042, "5716": 0.255429208278656, "5741": 0.1401015669107437, "5812": 0.33605360984802246, "5819": 0.18329764902591705, "5830": 1.0601204633712769, "5860": 0.26820653676986694, "5963": 0.347847044467926, "5991": 0.4412745535373688, "6083": 0.11951763927936554, "6137": 0.1808556467294693, "6149": 0.29400965571403503, "6177": 0.17020416259765625, "6183": 0.38174858689308167, "6192": 1.004473328590393, "6228": 0.04860413447022438, "6296": 0.0842406153678894, "6364": 0.1064341589808464, "6375": 0.11865071207284927, "6378": 0.04767346754670143, "6459": 0.052318159490823746, "6509": 0.14939609169960022, "6537": 0.27786844968795776, "6573": 0.1751343309879303, "6592": 0.06520967930555344, "6593": 0.29109421372413635, "6600": 0.05139094591140747, "6622": 0.13414156436920166, "6645": 0.30558720231056213, "6650": 0.3656192123889923, "6740": 0.5707147121429443, "6761": 0.7881022095680237, "6762": 0.5800528526306152, "6809": 0.9515975713729858, "6827": 0.4132472574710846, "6897": 0.04767346754670143, "6914": 0.07884006202220917, "6958": 0.1510767638683319, "6970": 0.846739649772644, "7028": 0.5816917419433594, "7197": 1.013020396232605, "7246": 0.8608771562576294, "7321": 0.08513788133859634, "7337": 0.960606575012207, "7361": 0.3683255612850189, "7362": 0.04674193635582924, "7366": 0.4349733293056488, "7372": 1.0881409645080566, "7458": 0.19541899859905243, "7461": 0.06154331564903259, "7468": 0.1734936386346817, "7526": 0.22001366317272186, "7578": 0.08154398202896118, "7607": 0.35403475165367126, "7645": 0.49030399322509766, "7711": 0.3339579105377197, "7747": 0.0317181795835495, "7816": 0.8004589080810547, "7906": 0.5936289429664612, "7926": 0.10379679501056671, "7940": 0.11691460013389587, "8000": 0.06612417846918106, "8010": 0.16524957120418549, "8029": 0.34370049834251404, "8058": 0.17922431230545044, "8106": 0.06612417846918106, "8153": 0.8780695199966431, "8156": 0.07431721687316895, "8184": 0.010684899985790253, "8278": 0.055094651877880096, "8288": 0.010684899985790253, "8311": 0.3519764244556427, "8332": 0.1477125883102417, "8360": 0.20421554148197174, "8382": 0.5963221788406372, "8458": 0.2561853528022766, "8462": 0.07612881064414978, "8524": 0.10026945173740387, "8553": 0.1808556467294693, "8581": 0.25239890813827515, "8729": 0.11168810725212097, "8745": 0.4537591338157654, "8758": 0.04113444685935974, "8803": 0.9798521995544434, "8848": 0.18411032855510712, "8878": 0.23479416966438293, "8902": 0.24401791393756866, "9007": 0.04113444685935974, "9014": 0.14095009863376617, "9138": 1.02149498462677, "9233": 0.05970508232712746, "9319": 0.1994270235300064, "9591": 0.015504186972975731, "9632": 0.6624060273170471, "9662": 0.11865071207284927, "9728": 0.26820653676986694, "9756": 0.2493593990802765, "9777": 0.06977381557226181, "9990": 0.083342544734478, "10210": 0.8074519634246826, "10250": 0.7683706283569336, "10277": 0.0797421783208847, "10329": 0.02412080205976963, "10351": 0.42225050926208496, "10381": 0.371698260307312, "10448": 1.1431772708892822, "10467": 0.06246116757392883, "10580": 0.41001203656196594, "10595": 0.8633513450622559, "10599": 0.5092619061470032, "10671": 0.18329764902591705, "10698": 0.045809537172317505, "10723": 0.014542185701429844, "10737": 0.07250232994556427, "10738": 0.31560876965522766, "10744": 0.77198725938797, "10804": 0.1384023278951645, "10836": 0.5696102976799011, "10939": 0.4437839686870575, "11016": 0.09050461649894714, "11043": 0.09584271162748337, "11095": 0.010684899985790253, "11140": 0.21922965347766876, "11234": 0.1734936386346817, "11307": 0.4412745535373688, "11443": 0.678390383720398, "11463": 0.6446255445480347, "11553": 0.3923587501049042, "11595": 0.3464667797088623, "11658": 1.1846466064453125, "11705": 0.7881022095680237, "11767": 0.1808556467294693, "11841": 0.026976587250828743, "11901": 0.40546512603759766, "11919": 0.40481385588645935, "12222": 0.6410312056541443, "12328": 0.1808556467294693, "12477": 0.1384023278951645, "12562": 0.5313173532485962, "12604": 0.0038986403960734606, "12617": 0.7537717819213867, "12650": 0.2470736801624298, "12702": 0.0842406153678894, "12745": 0.18248429894447327, "12928": 0.6902132034301758, "13070": 0.33953672647476196, "13122": 0.5404602885246277, "13153": 0.14939609169960022, "13164": 0.09850110858678818, "13228": 0.175953671336174, "13464": 0.9455460906028748, "13500": 1.0172666311264038, "13562": 0.09850110858678818, "13571": 1.1941591501235962, "13590": 0.06703783571720123, "13734": 0.07159364968538284, "13759": 0.058784693479537964, "13791": 0.4196864068508148, "13833": 0.14602625370025635, "13956": 0.4286321699619293, "13995": 0.040196798741817474, "14095": 0.7854343056678772, "14151": 0.010684899985790253, "14313": 0.11691460013389587, "14443": 0.4914994537830353, "14449": 0.1510767638683319, "14573": 0.45623743534088135, "14613": 0.009718249551951885, "14738": 0.04860413447022438, "14754": 0.5272908806800842, "14769": 0.15943801403045654, "14774": 0.37707099318504333, "14828": 0.13071982562541962, "15023": 0.05694137513637543, "15053": 0.2918238639831543, "15176": 0.6038249135017395, "15196": 0.7220231294631958, "15273": 1.483910083770752, "15314": 0.1930064558982849, "15369": 0.28963330388069153, "15630": 0.5410289764404297, "15663": 0.4855078160762787, "15923": 0.15023678541183472, "16007": 0.022212404757738113, "16023": 0.9139442443847656, "16146": 0.020300358533859253, "16263": 0.4926934838294983, "16341": 0.07341018319129944, "16389": 0.09850110858678818, "16505": 0.16442140936851501, "16599": 0.6476961374282837, "16691": 0.2659635543823242, "16762": 0.09406650811433792, "16790": 0.007782140281051397, "16882": 0.10818854719400406, "16892": 1.0409941673278809, "16940": 0.8829278349876404, "17034": 0.09761575609445572, "17146": 0.3134697377681732, "17296": 0.4374985992908478, "17347": 0.4500300884246826, "17379": 0.055094651877880096, "17439": 0.37907835841178894, "17503": 0.10555581003427505, "17657": 0.7389566898345947, "17666": 0.1905880719423294, "17736": 0.13157635927200317, "17790": 0.03925827145576477, "17874": 0.08961215615272522, "17959": 0.2470736801624298, "18274": 0.016465263441205025, "18330": 0.0038986403960734606, "18414": 0.03266380727291107, "18445": 0.75193190574646, "18600": 0.472198486328125, "18622": 0.0770333781838417, "18688": 0.8748174905776978, "18757": 0.020300358533859253, "18771": 0.7144040465354919, "18903": 0.8306987881660461, "18938": 0.10731173306703568, "18969": 0.04487626627087593, "19009": 0.5174443125724792, "19136": 0.030771657824516296, "19137": 0.6588751673698425, "19146": 0.2089812457561493, "19202": 0.18411032855510712, "19241": 0.15275461971759796, "19601": 0.11951763927936554, "19612": 0.04953393340110779, "19616": 0.9310253858566284, "19723": 0.23710809648036957, "19765": 0.08244366943836212, "19802": 0.05694137513637543, "19872": 0.2145126610994339, "20049": 1.0695481300354004, "20065": 0.4349733293056488, "20214": 0.6813592314720154, "20250": 0.9084475636482239, "20307": 0.07068414986133575, "20363": 0.319873183965683, "20389": 0.27564704418182373, "20464": 0.014542185701429844, "20487": 0.6096806526184082, "20567": 0.11865071207284927, "20582": 0.18573370575904846, "20679": 0.015504186972975731, "20936": 0.2852376699447632, "21012": 0.23402166366577148, "21032": 0.23324857652187347, "21083": 0.05139094591140747, "21109": 0.21687394380569458, "21466": 0.4177590310573578, "21471": 1.3175804615020752, "21575": 0.4531385898590088, "21579": 0.7978238463401794, "21618": 0.42990362644195557, "21628": 0.19381128251552582, "21716": 0.8264343738555908, "21754": 0.3374483287334442, "21963": 0.16110190749168396, "21967": 0.5278670787811279, "21991": 0.14602625370025635, "22139": 0.007782140281051397, "22210": 1.2894693613052368, "22248": 0.22157983481884003, "22277": 0.0058422754518687725, "22330": 0.7500885725021362, "22422": 0.083342544734478, "22571": 0.6186635494232178, "22574": 0.11081436276435852, "22658": 0.1970241367816925, "22822": 0.7144040465354919, "22863": 0.13925230503082275, "22869": 0.39893341064453125, "22910": 0.07793712615966797, "22933": 0.25694093108177185, "23046": 0.12814582884311676, "23072": 0.8633513450622559, "23079": 0.2089812457561493, "23148": 0.02316705882549286, "23228": 0.17840765416622162, "23267": 0.1011524572968483, "23536": 0.22548456490039825, "23586": 0.7067264318466187, "23737": 0.417115718126297, "23924": 0.8022117614746094, "23965": 0.7969439625740051, "24054": 0.6389714479446411, "24278": 0.22859740257263184, "24314": 0.3141832649707794, "24374": 0.006812678650021553, "24382": 0.7276995778083801, "24554": 0.0009760859538801014, "24587": 0.15610189735889435, "24854": 0.0019512200960889459, "24879": 0.1332872211933136, "24939": 0.16359257698059082, "25202": 0.4914994537830353, "25238": 0.32905077934265137, "25276": 0.15943801403045654, "25293": 0.02792670577764511, "25324": 0.11168810725212097, "25354": 0.8813109993934631, "25456": 0.4794800877571106, "25644": 0.12642613053321838, "25700": 0.13157635927200317, "25709": 0.02316705882549286, "25761": 1.0695481300354004, "25778": 0.022212404757738113, "25780": 0.022212404757738113, "26083": 1.0992631912231445, "26268": 0.16110190749168396, "26402": 1.0264055728912354, "26520": 0.006812678650021553, "26524": 0.0174254160374403, "26721": 0.1619328260421753, "26773": 0.5685047507286072, "26872": 0.129004567861557, "27118": 0.7845434546470642, "27226": 0.38374659419059753, "27846": 0.07612881064414978, "27998": 1.2964379787445068, "28041": 0.06520967930555344, "28086": 1.3750003576278687, "28283": 0.09495500475168228, "28409": 0.006812678650021553, "28424": 0.40481385588645935, "28577": 0.04953393340110779, "28644": 0.1889725625514984, "28696": 0.16690383851528168} | 13936152 | Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries. | An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos |
{"1011": 0.0174254160374403, "1019": 0.32341301441192627, "1020": 0.23402166366577148, "1037": 0.11517547070980072, "1048": 0.10026945173740387, "1997": 0.05694137513637543, "2000": 0.020300358533859253, "2005": 0.08513788133859634, "2022": 0.1477125883102417, "2035": 0.17840765416622162, "2043": 0.11081436276435852, "2051": 0.09584271162748337, "2052": 0.3949938118457794, "2064": 0.18816383183002472, "2065": 0.020300358533859253, "2071": 0.3949938118457794, "2073": 0.20739519596099854, "2086": 0.49626702070236206, "2095": 0.07068414986133575, "2109": 0.5444341897964478, "2111": 0.5729197263717651, "2116": 0.35403475165367126, "2129": 0.1602703034877777, "2140": 0.6317287683486938, "2146": 0.4926934838294983, "2166": 0.11081436276435852, "2177": 0.35745587944984436, "2181": 0.29255300760269165, "2188": 0.6011518239974976, "2193": 0.012615402229130268, "2210": 0.20501139760017395, "2212": 0.669430673122406, "2214": 0.6400018334388733, "2216": 0.09406650811433792, "2220": 0.0038986403960734606, "2224": 0.5069117546081543, "2241": 0.14686977863311768, "2265": 0.0019512200960889459, "2274": 0.17431432008743286, "2275": 0.3662964701652527, "2278": 0.018384648486971855, "2287": 1.158010721206665, "2302": 0.6270449161529541, "2313": 0.823009729385376, "2321": 0.5069117546081543, "2323": 0.151916041970253, "2336": 0.7352184057235718, "2339": 0.18167030811309814, "2342": 0.09938567131757736, "2381": 0.6054253578186035, "2385": 0.7898768186569214, "2403": 0.6512666940689087, "2411": 0.1212492436170578, "2416": 0.05694137513637543, "2426": 0.7018978595733643, "2428": 0.07612881064414978, "2470": 0.42735910415649414, "2478": 0.4374985992908478, "2501": 0.436867892742157, "2529": 0.020300358533859253, "2546": 0.20022670924663544, "2553": 1.06619131565094, "2556": 0.10993985831737518, "2560": 0.026976587250828743, "2583": 0.20022670924663544, "2592": 0.10906458646059036, "2636": 0.1485546976327896, "2641": 0.02316705882549286, "2668": 0.7755908370018005, "2680": 0.4855078160762787, "2711": 0.5033760666847229, "2729": 0.0354953333735466, "2734": 0.08064348995685577, "2741": 0.7863243818283081, "2752": 0.3127557039260864, "2775": 0.66441810131073, "2787": 0.10026945173740387, "2800": 0.6064908504486084, "2817": 0.7201237678527832, "2825": 0.2674594223499298, "2864": 0.3554046154022217, "2902": 0.17759032547473907, "2913": 0.5033760666847229, "2951": 0.29036402702331543, "2966": 0.39367714524269104, "2967": 0.3995884954929352, "2988": 0.043007105588912964, "2989": 0.02887592278420925, "3012": 0.3877306580543518, "3026": 0.29255300760269165, "3032": 0.0606246218085289, "3041": 0.05694137513637543, "3080": 0.6654226183891296, "3088": 0.3519764244556427, "3231": 0.34715715050697327, "3247": 0.7201237678527832, "3251": 0.2954642176628113, "3273": 0.2667117714881897, "3274": 0.00875066313892603, "3284": 0.3757305145263672, "3344": 0.013579257763922215, "3405": 0.37035053968429565, "3424": 0.9621002674102783, "3439": 0.34023189544677734, "3479": 0.15359249711036682, "3540": 0.16524957120418549, "3556": 0.07612881064414978, "3563": 0.4794800877571106, "3572": 0.841701865196228, "3591": 0.5069117546081543, "3594": 0.1011524572968483, "3633": 0.04487626627087593, "3659": 0.14518201351165771, "3669": 0.7067264318466187, "3698": 0.12556517124176025, "3711": 0.17020416259765625, "3734": 0.07068414986133575, "3867": 0.33325836062431335, "3891": 0.07068414986133575, "3898": 0.18654440343379974, "3949": 0.5483922958374023, "3978": 0.46486347913742065, "3979": 0.3283478021621704, "4008": 0.5968599319458008, "4072": 0.5528968572616577, "4094": 0.0029254043474793434, "4118": 0.1677299439907074, "4146": 0.36426326632499695, "4194": 0.1913948506116867, "4217": 0.10993985831737518, "4225": 0.2561853528022766, "4268": 0.21922965347766876, "4286": 0.09850110858678818, "4292": 0.23324857652187347, "4295": 0.43623676896095276, "4319": 0.3027053773403168, "4340": 0.1477125883102417, "4453": 0.28082266449928284, "4454": 0.18978065252304077, "4468": 0.6527929902076721, "4484": 0.11951763927936554, "4488": 0.3034266233444214, "4520": 0.05139094591140747, "4555": 0.3519764244556427, "4567": 0.14433705806732178, "4587": 0.05786345899105072, "4604": 0.4093637466430664, "4608": 0.022212404757738113, "4621": 0.07612881064414978, "4632": 0.46853771805763245, "4639": 0.4794800877571106, "4652": 0.02316705882549286, "4685": 0.2659635543823242, "4725": 0.026025565341114998, "4730": 0.2954642176628113, "4733": 0.3027053773403168, "4758": 0.0770333781838417, "4760": 0.029824240133166313, "4788": 0.2516399025917053, "4793": 0.18167030811309814, "4848": 0.11168810725212097, "4877": 0.6338034868240356, "5022": 0.20739519596099854, "5070": 0.036437395960092545, "5173": 0.52266925573349, "5198": 0.07884006202220917, "5381": 0.1332872211933136, "5396": 0.17267228662967682, "5417": 0.17267228662967682, "5535": 0.4944818615913391, "5537": 0.4286321699619293, "5589": 0.175953671336174, "5593": 0.38041436672210693, "5604": 0.30917787551879883, "5630": 0.08603433519601822, "5646": 0.33115679025650024, "5751": 0.4580921530723572, "5764": 0.7827593088150024, "5776": 0.35745587944984436, "5845": 0.4624064862728119, "5850": 0.43623676896095276, "5852": 0.083342544734478, "5921": 0.09584271162748337, "5950": 0.2741633653640747, "6001": 0.6754127144813538, "6016": 0.14349138736724854, "6179": 0.820433497428894, "6210": 0.21372433006763458, "6273": 0.014542185701429844, "6364": 0.38374659419059753, "6388": 0.1994270235300064, "6422": 0.06886265426874161, "6567": 0.436867892742157, "6577": 0.12986256182193756, "6587": 0.07341018319129944, "6612": 1.286776065826416, "6679": 1.0285027027130127, "6709": 0.27934664487838745, "6721": 0.16359257698059082, "6726": 0.7809720039367676, "6742": 0.34300774335861206, "6747": 0.23556606471538544, "6779": 0.27342069149017334, "6818": 0.24171993136405945, "6878": 0.09406650811433792, "7012": 0.3353555500507355, "7017": 0.4849066734313965, "7032": 0.39433568716049194, "7080": 0.49923527240753174, "7099": 0.14264501631259918, "7143": 0.0913962796330452, "7218": 0.12384103983640671, "7242": 0.0797421783208847, "7275": 0.021256839856505394, "7314": 0.009718249551951885, "7316": 0.06795065850019455, "7320": 0.4437839686870575, "7387": 0.037378571927547455, "7426": 0.0606246218085289, "7438": 0.46055975556373596, "7453": 0.07341018319129944, "7551": 0.20501139760017395, "7591": 0.8264343738555908, "7691": 0.25088030099868774, "7709": 0.2105647772550583, "7712": 0.0038986403960734606, "7718": 0.05694137513637543, "7741": 0.18816383183002472, "7784": 0.06795065850019455, "7801": 0.1221139207482338, "7870": 0.2674594223499298, "7885": 0.0913962796330452, "7938": 1.1864371299743652, "8010": 0.012615402229130268, "8030": 0.5984715819358826, "8082": 0.006812678650021553, "8089": 0.09584271162748337, "8148": 0.46363574266433716, "8168": 0.0752234235405922, "8189": 0.17759032547473907, "8192": 0.03266380727291107, "8312": 0.4248080551624298, "8321": 0.14686977863311768, "8487": 0.08064348995685577, "8553": 0.15526613593101501, "8777": 0.960606575012207, "8822": 0.03925827145576477, "8832": 0.2034190446138382, "8833": 0.13157635927200317, "8873": 0.9240728616714478, "8985": 0.15860503911972046, "9016": 0.9878844022750854, "9032": 0.1332872211933136, "9128": 0.02887592278420925, "9181": 0.02887592278420925, "9283": 0.09317722171545029, "9349": 0.9287132620811462, "9367": 0.0913962796330452, "9398": 0.11168810725212097, "9458": 0.2145126610994339, "9469": 0.8004589080810547, "9511": 0.3949938118457794, "9526": 0.05046287178993225, "9665": 0.11604541540145874, "9701": 0.1946154683828354, "9710": 0.8682814836502075, "9750": 0.5156965255737305, "9798": 0.36290550231933594, "9867": 0.055094651877880096, "9896": 1.2980393171310425, "9932": 0.29981520771980286, "9992": 0.7818660736083984, "10031": 0.25088030099868774, "10071": 0.24248650670051575, "10092": 0.9754437208175659, "10210": 0.09672962874174118, "10255": 0.04860413447022438, "10411": 0.1693800985813141, "10521": 0.007782140281051397, "10539": 0.018384648486971855, "10561": 0.18816383183002472, "10640": 0.27712854743003845, "10788": 0.3963087201118469, "10886": 0.7791815400123596, "10928": 0.07793712615966797, "10980": 0.13071982562541962, "11129": 0.016465263441205025, "11156": 0.33325836062431335, "11253": 0.02412080205976963, "11311": 0.004870930220931768, "11326": 0.5438674688339233, "11343": 0.3723714053630829, "11346": 0.23787821829319, "11375": 0.15023678541183472, "11382": 0.8534175157546997, "11441": 0.7987030148506165, "11487": 0.35334911942481995, "11498": 0.9591107368469238, "11616": 0.9915141463279724, "11619": 0.11865071207284927, "11656": 0.16524957120418549, "11718": 0.03266380727291107, "11860": 0.5364705324172974, "12132": 0.1011524572968483, "12238": 0.2830325961112976, "12318": 0.24554696679115295, "12353": 0.14518201351165771, "12411": 0.083342544734478, "12477": 0.3388410806655884, "12515": 0.052318159490823746, "12519": 0.19381128251552582, "12520": 0.1677299439907074, "12546": 0.021256839856505394, "12702": 0.9531047344207764, "12808": 0.016465263441205025, "12811": 0.24401791393756866, "12858": 0.14179791510105133, "12898": 0.20580662786960602, "13070": 0.31204116344451904, "13105": 0.007782140281051397, "13180": 0.15526613593101501, "13185": 0.18816383183002472, "13356": 0.18411032855510712, "13369": 0.0752234235405922, "13376": 0.17020416259765625, "13441": 0.2561853528022766, "13462": 0.4145384132862091, "13509": 0.2763880789279938, "13642": 0.022212404757738113, "13792": 1.3321186304092407, "14031": 0.052318159490823746, "14044": 0.12986256182193756, "14203": 0.8941729068756104, "14211": 0.11604541540145874, "14244": 0.2749055027961731, "14545": 0.0038986403960734606, "14631": 0.053244512528181076, "14639": 0.9783848524093628, "14644": 0.5751199722290039, "14667": 0.4248080551624298, "15078": 0.07793712615966797, "15189": 0.18492233753204346, "15215": 0.3910386264324188, "15396": 0.1718502640724182, "15442": 0.14433705806732178, "15485": 0.04207121208310127, "15488": 0.6054253578186035, "15502": 0.10379679501056671, "15643": 0.05786345899105072, "15728": 0.19381128251552582, "15870": 0.3248254358768463, "15982": 0.025073638185858727, "15995": 0.0913962796330452, "16014": 0.31132611632347107, "16048": 0.2223619967699051, "16227": 0.034552380442619324, "16253": 0.18816383183002472, "16474": 0.7380234599113464, "16483": 0.9455460906028748, "16548": 0.14095009863376617, "16670": 0.36290550231933594, "16725": 0.058784693479537964, "16774": 0.16607704758644104, "16861": 0.3676496744155884, "16898": 0.15860503911972046, "16907": 0.0058422754518687725, "16932": 0.1332872211933136, "17044": 0.20501139760017395, "17181": 0.1332872211933136, "17261": 0.06886265426874161, "17404": 0.43623676896095276, "17591": 0.25088030099868774, "17630": 0.9680526852607727, "17785": 0.04767346754670143, "17830": 0.04487626627087593, "17844": 0.3519764244556427, "17865": 0.5127768516540527, "18002": 0.06795065850019455, "18075": 0.3070250153541565, "18133": 0.13670019805431366, "18137": 0.06703783571720123, "18382": 0.2749055027961731, "18384": 0.04860413447022438, "18452": 0.04487626627087593, "18547": 0.20022670924663544, "18641": 0.07431721687316895, "18780": 0.4891071021556854, "18949": 0.12642613053321838, "19132": 1.5776891708374023, "19475": 0.03925827145576477, "19723": 0.07431721687316895, "19761": 0.2447827309370041, "19818": 0.129004567861557, "19888": 0.3956514894962311, "19940": 0.029824240133166313, "19960": 0.10379679501056671, "20165": 0.22157983481884003, "20272": 0.29400965571403503, "20302": 0.14095009863376617, "20428": 0.8212929964065552, "20502": 0.05139094591140747, "20589": 0.15693697333335876, "20600": 0.21687394380569458, "20992": 0.10203468054533005, "21124": 0.5816917419433594, "21150": 0.3615458607673645, "21198": 0.9217445850372314, "21391": 0.15526613593101501, "21670": 0.09938567131757736, "21748": 0.00875066313892603, "21996": 0.3027053773403168, "22210": 0.1718502640724182, "22254": 0.05970508232712746, "22334": 0.1946154683828354, "22529": 0.28743788599967957, "22537": 0.25995752215385437, "22564": 0.009718249551951885, "22769": 0.0913962796330452, "22939": 0.3134697377681732, "22945": 0.1510767638683319, "22987": 0.06520967930555344, "23032": 0.09406650811433792, "23041": 0.3325583338737488, "23138": 0.10731173306703568, "23238": 0.1212492436170578, "23329": 0.04394211992621422, "23559": 0.12814582884311676, "23569": 0.6970458030700684, "23614": 0.22859740257263184, "23927": 0.7210738658905029, "23996": 0.9363996982574463, "24010": 0.11430477350950241, "24013": 0.025073638185858727, "24096": 0.35334911942481995, "24290": 0.21530038118362427, "24479": 0.15860503911972046, "24558": 0.18816383183002472, "24685": 0.5936289429664612, "24755": 0.1229778528213501, "24971": 0.09495500475168228, "25027": 0.18167030811309814, "25219": 0.06246116757392883, "25353": 0.20977331697940826, "25437": 0.15359249711036682, "25481": 0.05786345899105072, "25732": 0.5387523174285889, "25947": 0.00875066313892603, "26045": 0.5930894017219543, "26305": 0.10731173306703568, "26396": 0.12556517124176025, "26462": 0.29036402702331543, "26492": 0.6144463419914246, "26651": 0.0058422754518687725, "26728": 0.07250232994556427, "26745": 0.9394577741622925, "26775": 0.2652147710323334, "26777": 0.2719337046146393, "26941": 0.3622259199619293, "26957": 0.3601844012737274, "26994": 0.034552380442619324, "27144": 0.036437395960092545, "27152": 0.0770333781838417, "27354": 0.010684899985790253, "27491": 0.6181373596191406, "27605": 0.5640701055526733, "27718": 0.06337817758321762, "27891": 0.06977381557226181, "28032": 0.8764448165893555, "28093": 0.2317005842924118, "28639": 0.319873183965683, "28935": 0.36290550231933594, "29165": 0.06977381557226181, "29234": 0.02412080205976963, "29361": 0.007782140281051397, "29458": 0.175953671336174} | 13938878 | We conducted a study to determine whether clinical algorithms would be useful in malaria diagnosis among people living in an area of moderate malaria transmission within Kilifi District in Kenya. A total of 1602 people of all age groups participated. We took smears and recorded clinical signs and symptoms (prompted or spontaneous) of all those presenting to the study clinic with a history of fever. A malaria case was defined as a person presenting to the clinic with a history of fever and concurrent parasitaemia. A set of clinical signs and symptoms (algorithms) with the highest sensitivity and specificity for diagnosing a malaria case was selected for the age groups </=5 years, 6-14 years and >/=15 years. These age-optimized derived algorithms were able to identify about 66% of the cases among those <15 years of age but only 23% of cases among adults. Were these algorithms to be used as a basis for a decision on treatment among those presenting to the clinic, 16% of children </=5 years, 44% of those 6-14 years of age and 66% of the adults who had a history of fever and parasitaemia >/=5000 parasites/microl of blood would be sent home without treatment. Clinical algorithms therefore appear to have little utility in malaria diagnosis, performing even worse in the older age groups, where avoiding unnecessary use of anti-malarials would make more drugs available to the really needy population of children under 5 years of age. | Clinical algorithms for malaria diagnosis lack utility among people of different age groups. |
{"1015": 0.791648268699646, "1016": 0.47827014327049255, "1045": 0.18167030811309814, "1052": 0.2231435477733612, "1055": 0.6522845029830933, "1056": 0.8074519634246826, "2007": 0.0029254043474793434, "2015": 0.0174254160374403, "2028": 0.38574060797691345, "2029": 0.20660123229026794, "2048": 0.14349138736724854, "2050": 0.06977381557226181, "2075": 0.056018441915512085, "2085": 0.12642613053321838, "2094": 0.6139179468154907, "2155": 0.05970508232712746, "2177": 0.37371641397476196, "2179": 0.16442140936851501, "2182": 0.23633737862110138, "2184": 0.07793712615966797, "2193": 0.16442140936851501, "2247": 0.04113444685935974, "2312": 0.15610189735889435, "2334": 0.755608320236206, "2403": 0.06246116757392883, "2408": 0.2089812457561493, "2470": 0.45870962738990784, "2475": 0.8682814836502075, "2487": 0.9005423784255981, "2491": 0.34715715050697327, "2504": 0.27342069149017334, "2511": 0.09672962874174118, "2523": 1.001607894897461, "2527": 1.1586239337921143, "2555": 0.9987343549728394, "2571": 0.32905077934265137, "2659": 0.058784693479537964, "2752": 0.20022670924663544, "2777": 0.16524957120418549, "2791": 0.4624064862728119, "2817": 0.6280876994132996, "2828": 0.4709797203540802, "2846": 0.18654440343379974, "2871": 0.014542185701429844, "2896": 0.6553317308425903, "2898": 0.9500881433486938, "2913": 0.77198725938797, "2920": 0.1913948506116867, "2944": 0.0317181795835495, "2951": 0.0606246218085289, "2967": 0.43244171142578125, "2981": 0.8433839678764343, "3141": 0.18004031479358673, "3164": 0.38441169261932373, "3231": 0.2561853528022766, "3273": 0.28082266449928284, "3283": 0.083342544734478, "3295": 0.03360854089260101, "3356": 0.029824240133166313, "3378": 0.9333322048187256, "3393": 0.04674193635582924, "3426": 0.2763880789279938, "3429": 0.03925827145576477, "3433": 0.4196864068508148, "3446": 0.10026945173740387, "3449": 0.05786345899105072, "3491": 0.06154331564903259, "3550": 0.32270604372024536, "3556": 0.018384648486971855, "3563": 0.20818853378295898, "3603": 0.08064348995685577, "3643": 0.12038381397724152, "3653": 0.46853771805763245, "3734": 0.1510767638683319, "3798": 0.3870677351951599, "3818": 0.009718249551951885, "3853": 0.20421554148197174, "3963": 0.1358480453491211, "3979": 0.16276304423809052, "3989": 0.77198725938797, "4081": 0.32270604372024536, "4106": 0.5290185213088989, "4127": 0.09672962874174118, "4140": 0.4926934838294983, "4226": 0.8004589080810547, "4235": 0.35403475165367126, "4295": 0.8074519634246826, "4307": 0.33325836062431335, "4328": 0.07068414986133575, "4340": 0.2026219218969345, "4453": 0.6476961374282837, "4456": 0.15442965924739838, "4520": 0.10993985831737518, "4531": 0.1808556467294693, "4539": 0.6608943343162537, "4649": 0.029824240133166313, "4655": 1.0423725843429565, "4697": 0.12814582884311676, "4758": 0.1332872211933136, "4812": 0.010684899985790253, "4866": 0.43875885009765625, "4962": 1.1038070917129517, "5012": 0.19782574474811554, "5084": 0.12814582884311676, "5250": 0.15860503911972046, "5320": 0.09228714555501938, "5345": 0.5668440461158752, "5360": 0.15610189735889435, "5387": 0.07431721687316895, "5393": 0.15023678541183472, "5482": 0.026976587250828743, "5537": 0.15023678541183472, "5604": 0.34300774335861206, "5638": 0.052318159490823746, "5646": 0.10731173306703568, "5665": 0.3409265875816345, "5699": 0.2830325961112976, "5769": 0.2018241584300995, "5799": 0.24325250089168549, "5852": 0.24018502235412598, "5997": 0.004870930220931768, "6026": 0.37304413318634033, "6064": 0.684319257736206, "6075": 0.8500841856002808, "6083": 0.49626702070236206, "6191": 0.37304413318634033, "6227": 0.11517547070980072, "6335": 1.222740888595581, "6388": 0.25995752215385437, "6463": 0.6202403903007507, "6541": 0.9732321500778198, "6592": 0.5398913025856018, "6648": 0.5080875158309937, "6709": 0.48008447885513306, "6721": 0.045809537172317505, "6747": 0.38041436672210693, "6839": 0.037378571927547455, "6845": 0.016465263441205025, "6869": 0.28597161173820496, "6873": 0.015504186972975731, "6897": 0.0842406153678894, "6903": 0.06246116757392883, "6970": 0.8074519634246826, "7012": 0.22937409579753876, "7017": 0.26446542143821716, "7023": 1.0207915306091309, "7028": 0.09406650811433792, "7099": 0.4067663550376892, "7127": 0.018384648486971855, "7246": 0.43875885009765625, "7275": 0.16690383851528168, "7290": 0.07159364968538284, "7356": 0.022212404757738113, "7366": 0.09761575609445572, "7403": 0.9302552938461304, "7551": 0.0029254043474793434, "7591": 0.25088030099868774, "7645": 0.20421554148197174, "7711": 0.33675122261047363, "7718": 0.07884006202220917, "7721": 0.7854343056678772, "7778": 0.823009729385376, "7870": 0.5707147121429443, "7885": 0.2969166338443756, "7889": 0.6181373596191406, "7900": 0.9440274834632874, "8168": 0.35334911942481995, "8180": 0.18654440343379974, "8211": 0.018384648486971855, "8290": 0.1710275560617447, "8314": 0.1677299439907074, "8343": 0.05139094591140747, "8349": 0.6430866718292236, "8360": 0.9037119746208191, "8386": 0.0913962796330452, "8715": 0.11256109178066254, "8720": 0.0842406153678894, "8761": 0.11951763927936554, "8924": 0.8583967685699463, "8991": 0.8315495252609253, "9007": 0.11691460013389587, "9032": 0.012615402229130268, "9104": 0.5186077356338501, "9165": 0.9470623731613159, "9174": 0.31204116344451904, "9276": 0.06429435312747955, "9416": 0.8837352395057678, "9556": 0.043007105588912964, "9657": 0.058784693479537964, "9723": 0.01934296265244484, "9896": 0.034552380442619324, "9932": 0.0029254043474793434, "10047": 0.08064348995685577, "10071": 0.020300358533859253, "10176": 0.4437839686870575, "10238": 0.9857001900672913, "10266": 0.04113444685935974, "10318": 0.016465263441205025, "10381": 0.1930064558982849, "10383": 0.05139094591140747, "10395": 0.03831886500120163, "10514": 0.47463157773017883, "10521": 0.7701805830001831, "10548": 0.06977381557226181, "10640": 0.176772341132164, "10665": 0.7510106563568115, "10744": 0.3464667797088623, "10769": 0.8813109993934631, "10788": 0.06246116757392883, "10928": 0.010684899985790253, "10960": 0.15275461971759796, "11020": 0.2689530849456787, "11156": 0.38905516266822815, "11311": 0.960606575012207, "11363": 0.12986256182193756, "11441": 0.013579257763922215, "11487": 0.1913948506116867, "11616": 0.1064341589808464, "12115": 0.2852376699447632, "12151": 0.45870962738990784, "12248": 0.19381128251552582, "12260": 0.19782574474811554, "12273": 0.347847044467926, "12322": 0.0019512200960889459, "12430": 0.0019512200960889459, "12503": 0.13157635927200317, "12515": 0.0913962796330452, "12717": 0.11778303235769272, "12839": 0.6674286723136902, "13070": 0.46302130818367004, "13100": 0.06337817758321762, "13139": 0.4654768109321594, "13359": 0.4500300884246826, "13458": 1.0382318496704102, "13464": 0.6613984704017639, "13483": 0.981317400932312, "13656": 0.0770333781838417, "13791": 0.01934296265244484, "13833": 0.8057082891464233, "13845": 0.2184450328350067, "13874": 0.21293537318706512, "13912": 0.7482418417930603, "13938": 0.11778303235769272, "13974": 0.10291612148284912, "14025": 0.669430673122406, "14031": 0.07159364968538284, "14120": 0.2983669638633728, "14126": 0.5261374711990356, "14142": 0.07884006202220917, "14163": 0.012615402229130268, "14193": 0.1064341589808464, "14228": 1.2889312505722046, "14471": 0.5562619566917419, "14494": 0.4450363218784332, "14622": 0.0752234235405922, "14639": 0.13925230503082275, "14671": 1.293763518333435, "14798": 0.16110190749168396, "14800": 0.6773988008499146, "14847": 0.33115679025650024, "15059": 0.053244512528181076, "15113": 0.052318159490823746, "15258": 0.045809537172317505, "15361": 0.0770333781838417, "15403": 0.5313173532485962, "15527": 0.25845035910606384, "15543": 0.2034190446138382, "15581": 0.2470736801624298, "15851": 0.06520967930555344, "15909": 0.20580662786960602, "16012": 0.6410312056541443, "16014": 0.3170322775840759, "16221": 0.6301699280738831, "16227": 0.05786345899105072, "16275": 0.9394577741622925, "16281": 0.0842406153678894, "16387": 0.0317181795835495, "16478": 0.2659635543823242, "16505": 0.06795065850019455, "16515": 0.401551216840744, "16530": 0.0606246218085289, "16576": 0.21135559678077698, "16578": 0.05417001247406006, "16706": 1.2012346982955933, "16902": 0.21687394380569458, "17174": 0.9531047344207764, "17350": 0.0019512200960889459, "17547": 0.018384648486971855, "17592": 0.03360854089260101, "17702": 0.6461620330810547, "17715": 0.15442965924739838, "17908": 0.25088030099868774, "18002": 0.13755162060260773, "18212": 0.15275461971759796, "18423": 0.5162794589996338, "18678": 0.10026945173740387, "18715": 0.34577593207359314, "18960": 0.2247048318386078, "19064": 0.09317722171545029, "19129": 0.6160298585891724, "19155": 0.574020504951477, "19293": 0.18573370575904846, "19345": 0.2976420819759369, "19500": 0.14602625370025635, "19539": 0.1384023278951645, "20155": 0.2689530849456787, "20272": 0.13499516248703003, "20353": 0.0797421783208847, "20467": 0.176772341132164, "20567": 0.8383291959762573, "20569": 0.12384103983640671, "20576": 0.15777134895324707, "20647": 0.0019512200960889459, "20688": 0.8989537954330444, "20828": 0.013579257763922215, "20915": 1.2012346982955933, "21144": 0.18329764902591705, "21647": 0.8534175157546997, "21677": 0.42353010177612305, "21879": 0.4831010699272156, "21903": 0.22782009840011597, "22026": 0.18167030811309814, "22107": 0.17840765416622162, "22318": 0.3903779089450836, "22407": 0.8550800085067749, "22458": 0.48610860109329224, "22490": 0.3084607720375061, "22517": 0.37707099318504333, "22543": 0.14518201351165771, "22571": 0.6533012986183167, "22574": 0.9915141463279724, "22597": 0.5979346632957458, "22643": 0.05139094591140747, "22834": 0.045809537172317505, "22931": 0.45994341373443604, "22939": 0.22079704701900482, "22989": 0.10291612148284912, "23041": 0.5762182474136353, "23079": 0.026976587250828743, "23150": 0.08692999184131622, "23606": 0.8400169610977173, "23691": 0.1718502640724182, "23746": 0.1358480453491211, "23758": 0.16690383851528168, "23784": 0.0038986403960734606, "23900": 0.1734936386346817, "24345": 0.9060825705528259, "24395": 0.0058422754518687725, "24501": 0.6744182109832764, "24529": 0.24171993136405945, "24558": 0.34370049834251404, "24582": 0.010684899985790253, "24590": 0.1212492436170578, "24594": 0.011650617234408855, "24759": 0.045809537172317505, "24879": 0.007782140281051397, "24950": 0.12728634476661682, "25206": 0.4580921530723572, "25281": 0.1510767638683319, "25426": 0.22782009840011597, "25524": 0.2852376699447632, "25643": 0.08064348995685577, "25665": 0.08154398202896118, "26237": 0.07159364968538284, "26305": 0.9650808572769165, "26319": 0.21530038118362427, "26419": 0.20977331697940826, "26601": 0.27786844968795776, "26651": 1.0992631912231445, "26721": 0.09495500475168228, "26741": 0.5092619061470032, "26835": 0.2607102394104004, "26874": 1.0144377946853638, "26986": 0.05786345899105072, "26994": 0.5696102976799011, "27373": 0.4356052577495575, "27480": 0.08154398202896118, "27642": 0.6573580503463745, "27781": 0.3547199070453644, "28024": 0.3622259199619293, "28093": 0.16359257698059082, "28102": 0.817850649356842, "28225": 0.13157635927200317, "28290": 0.045809537172317505, "28436": 0.10467668622732162, "28518": 0.09761575609445572, "28873": 0.35813871026039124, "29206": 0.11778303235769272, "29458": 0.2719337046146393, "29490": 0.09584271162748337} | 13940200 | Genome-wide association studies are now identifying disease-associated chromosome regions. However, even after convincing replication, the localization of the causal variant(s) requires comprehensive resequencing, extensive genotyping and statistical analyses in large sample sets leading to targeted functional studies. Here, we have localized the type 1 diabetes (T1D) association in the interleukin 2 receptor alpha (IL2RA) gene region to two independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5′ regions of IL2RA and RBM17 (odds ratio = 2.04, 95% confidence interval = 1.70–2.45; P = 1.92 × 10−28; control frequency = 0.635). Furthermore, we have associated IL2RA T1D susceptibility genotypes with lower circulating levels of the biomarker, soluble IL-2RA (P = 6.28 × 10−28), suggesting that an inherited lower immune responsiveness predisposes to T1D. | Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes |
{"1015": 0.20022670924663544, "1020": 0.10818854719400406, "1039": 0.44566190242767334, "1062": 0.32058215141296387, "1081": 0.5762182474136353, "2011": 0.04953393340110779, "2020": 0.14179791510105133, "2043": 0.004870930220931768, "2049": 0.13157635927200317, "2057": 0.6202403903007507, "2058": 0.13157635927200317, "2076": 0.03831886500120163, "2077": 0.175953671336174, "2079": 0.037378571927547455, "2104": 0.1718502640724182, "2106": 0.2447827309370041, "2129": 0.04487626627087593, "2146": 0.15359249711036682, "2152": 0.5272908806800842, "2184": 0.25467249751091003, "2193": 0.38308101892471313, "2287": 0.5364705324172974, "2308": 0.3547199070453644, "2339": 0.255429208278656, "2382": 0.2516399025917053, "2388": 0.8298473954200745, "2391": 0.33675122261047363, "2401": 0.40806588530540466, "2450": 0.04207121208310127, "2458": 0.28963330388069153, "2475": 0.01934296265244484, "2487": 0.20421554148197174, "2491": 0.5995445251464844, "2509": 0.6624060273170471, "2515": 0.30989447236061096, "2535": 0.11865071207284927, "2556": 0.4412745535373688, "2583": 0.259204238653183, "2599": 0.029824240133166313, "2618": 0.17922431230545044, "2659": 0.007782140281051397, "2685": 0.1734936386346817, "2706": 0.1401015669107437, "2744": 0.4568560719490051, "2765": 0.1710275560617447, "2817": 0.2034190446138382, "2879": 0.0797421783208847, "2896": 0.5197699069976807, "2913": 0.10203468054533005, "2931": 0.5968599319458008, "2943": 0.7333439588546753, "2944": 0.2018241584300995, "3008": 0.2822965085506439, "3012": 0.25694093108177185, "3020": 0.056018441915512085, "3031": 0.0019512200960889459, "3070": 0.0752234235405922, "3093": 0.7038320899009705, "3120": 0.016465263441205025, "3132": 0.7239188551902771, "3134": 0.07159364968538284, "3145": 0.6471850275993347, "3180": 0.15610189735889435, "3231": 0.2184450328350067, "3273": 0.1905880719423294, "3276": 0.07068414986133575, "3283": 0.20501139760017395, "3287": 0.5957841277122498, "3336": 0.1677299439907074, "3351": 0.5495203733444214, "3366": 0.49626702070236206, "3370": 0.3910386264324188, "3378": 0.757441520690918, "3426": 0.10818854719400406, "3429": 0.6212902665138245, "3445": 0.17020416259765625, "3463": 0.08064348995685577, "3466": 0.6160298585891724, "3491": 0.21687394380569458, "3508": 0.4909018874168396, "3525": 0.1510767638683319, "3526": 0.4909018874168396, "3566": 0.5893046259880066, "3616": 0.14518201351165771, "3618": 0.23247487843036652, "3623": 0.08064348995685577, "3635": 0.43875885009765625, "3653": 0.3012613356113434, "3668": 0.13243216276168823, "3670": 0.7182208299636841, "3754": 0.6043586730957031, "3767": 0.40806588530540466, "3798": 0.10203468054533005, "3801": 0.5336109399795532, "3811": 0.0038986403960734606, "3853": 0.014542185701429844, "3867": 0.175953671336174, "3893": 0.6223390698432922, "3896": 0.6619023680686951, "3930": 0.055094651877880096, "3977": 0.861702561378479, "4013": 0.8550800085067749, "4102": 0.3269403576850891, "4119": 0.4568560719490051, "4167": 0.058784693479537964, "4176": 0.1602703034877777, "4182": 0.0770333781838417, "4245": 0.026025565341114998, "4254": 0.10467668622732162, "4292": 0.24325250089168549, "4304": 0.9147270321846008, "4328": 0.19220098853111267, "4344": 0.9225212931632996, "4359": 0.31560876965522766, "4413": 0.9186317324638367, "4423": 0.3526630103588104, "4442": 0.8065804839134216, "4489": 0.1930064558982849, "4541": 0.14518201351165771, "4724": 0.06795065850019455, "4730": 0.6054253578186035, "4745": 0.2741633653640747, "4758": 0.49030399322509766, "4863": 0.2674594223499298, "4935": 1.0101795196533203, "4945": 0.49626702070236206, "4958": 0.7583568692207336, "4962": 0.6704301834106445, "5149": 0.77198725938797, "5201": 0.0770333781838417, "5228": 0.3019835948944092, "5250": 0.6461620330810547, "5320": 0.05694137513637543, "5360": 0.255429208278656, "5387": 0.6254787445068359, "5401": 0.04674193635582924, "5438": 0.12814582884311676, "5477": 0.4891071021556854, "5547": 0.46055975556373596, "5642": 0.4158279001712799, "5666": 0.6522845029830933, "5703": 0.4938860833644867, "5787": 0.4349733293056488, "5799": 0.2659635543823242, "5876": 0.4531385898590088, "5907": 0.0009760859538801014, "5966": 0.11081436276435852, "5983": 0.11081436276435852, "6022": 0.08154398202896118, "6064": 1.0478670597076416, "6081": 0.839173436164856, "6309": 0.09050461649894714, "6459": 0.2954642176628113, "6499": 0.7009293437004089, "6537": 0.6405166387557983, "6638": 1.0881409645080566, "6687": 0.347847044467926, "6691": 0.14686977863311768, "6698": 0.0913962796330452, "6775": 0.30558720231056213, "6873": 0.9348671436309814, "6875": 0.43812891840934753, "6897": 0.05139094591140747, "6914": 0.7528522610664368, "7017": 0.40220460295677185, "7088": 0.45870962738990784, "7108": 0.02887592278420925, "7231": 0.8004589080810547, "7337": 0.5607312321662903, "7349": 0.09050461649894714, "7356": 0.10818854719400406, "7366": 0.11865071207284927, "7388": 0.09050461649894714, "7403": 0.6207655072212219, "7461": 0.4437839686870575, "7526": 0.4909018874168396, "7551": 0.06429435312747955, "7590": 0.10026945173740387, "7607": 0.05694137513637543, "7645": 0.4944818615913391, "7711": 0.4818955361843109, "7818": 0.7047978043556213, "7831": 0.2160874605178833, "7860": 0.4568560719490051, "7872": 0.1718502640724182, "7885": 0.020300358533859253, "7900": 0.30917787551879883, "7949": 0.10026945173740387, "8000": 0.950843095779419, "8020": 0.4531385898590088, "8119": 0.680370569229126, "8153": 0.8829278349876404, "8171": 0.4158279001712799, "8213": 0.18654440343379974, "8215": 0.10555581003427505, "8315": 0.8813109993934631, "8449": 0.3464667797088623, "8469": 0.1930064558982849, "8481": 0.4794800877571106, "8521": 0.3269403576850891, "8738": 0.7220231294631958, "8761": 0.06977381557226181, "8843": 0.0009760859538801014, "8991": 0.056018441915512085, "9002": 0.371698260307312, "9007": 0.0354953333735466, "9031": 0.010684899985790253, "9067": 0.4286321699619293, "9165": 0.5450005531311035, "9186": 0.4400174915790558, "9350": 0.5186077356338501, "9353": 0.08064348995685577, "9412": 0.7182208299636841, "9530": 0.7028654217720032, "9585": 0.026025565341114998, "9587": 0.4624064862728119, "9588": 0.07431721687316895, "9742": 0.40089741349220276, "9756": 0.21687394380569458, "9885": 0.10818854719400406, "10032": 0.6312094330787659, "10061": 0.09228714555501938, "10318": 0.49626702070236206, "10368": 0.23556606471538544, "10442": 0.022212404757738113, "10521": 0.6301699280738831, "10527": 0.20660123229026794, "10548": 0.04860413447022438, "10572": 0.6038249135017395, "10580": 0.3127557039260864, "10595": 0.5573811531066895, "10624": 0.04674193635582924, "10673": 0.13670019805431366, "10744": 0.20580662786960602, "10756": 0.5278670787811279, "10814": 0.9732321500778198, "10840": 0.16524957120418549, "11031": 0.846739649772644, "11062": 1.3960126638412476, "11179": 0.9170717000961304, "11423": 0.15777134895324707, "11432": 0.6778947114944458, "11598": 0.40285754203796387, "11636": 0.5662899017333984, "11896": 0.02412080205976963, "12042": 0.175953671336174, "12130": 0.32129061222076416, "12260": 0.0354953333735466, "12285": 0.020300358533859253, "12328": 1.2318994998931885, "12380": 0.2741633653640747, "12412": 0.14433705806732178, "12435": 0.020300358533859253, "12516": 0.10906458646059036, "12546": 0.32553088665008545, "12608": 0.10467668622732162, "12654": 0.2969166338443756, "12839": 0.1401015669107437, "12928": 0.2026219218969345, "12955": 0.09050461649894714, "13195": 1.179255723953247, "13210": 0.06612417846918106, "13416": 0.34370049834251404, "13433": 0.13670019805431366, "13458": 0.1718502640724182, "13531": 0.23787821829319, "13599": 0.058784693479537964, "13791": 0.05786345899105072, "13845": 0.034552380442619324, "13908": 0.630689799785614, "13944": 0.0058422754518687725, "14095": 0.6043586730957031, "14193": 0.9131608605384827, "14313": 0.2659635543823242, "14353": 0.09938567131757736, "14471": 0.11778303235769272, "14627": 0.1693800985813141, "14760": 0.29255300760269165, "14800": 0.3923587501049042, "14828": 0.02316705882549286, "14879": 0.11951763927936554, "15070": 0.0797421783208847, "15100": 0.981317400932312, "15112": 0.5127768516540527, "15527": 0.17020416259765625, "15543": 0.9900637865066528, "15578": 1.1994705200195312, "15660": 0.7969439625740051, "15671": 0.04674193635582924, "15758": 0.304147332906723, "15813": 0.9037119746208191, "15946": 0.04674193635582924, "16012": 0.1685553640127182, "16221": 0.17840765416622162, "16231": 0.1358480453491211, "16505": 1.1462857723236084, "16515": 0.401551216840744, "16530": 0.6553317308425903, "16558": 0.3443928062915802, "16605": 0.4177590310573578, "16691": 0.4067663550376892, "16706": 0.15693697333335876, "16884": 0.2576959431171417, "16902": 0.6522845029830933, "16984": 0.38574060797691345, "17042": 0.0038986403960734606, "17183": 0.9470623731613159, "17188": 0.07068414986133575, "17278": 0.8022117614746094, "17442": 0.12470348179340363, "17487": 0.3949938118457794, "17552": 0.17759032547473907, "17819": 0.29328158497810364, "17913": 0.06154331564903259, "17926": 0.0174254160374403, "17959": 0.3241194784641266, "18047": 0.04953393340110779, "18089": 0.6989894509315491, "18114": 0.06337817758321762, "18178": 0.7491656541824341, "18275": 0.052318159490823746, "18419": 0.0019512200960889459, "18643": 0.5010119676589966, "18647": 0.029824240133166313, "18714": 0.1221139207482338, "18938": 0.7592713832855225, "19009": 0.04394211992621422, "19101": 0.49982786178588867, "19345": 0.2539152204990387, "19539": 0.083342544734478, "19653": 0.8366385698318481, "19723": 0.8550800085067749, "19825": 0.06886265426874161, "20120": 0.2223619967699051, "20250": 0.19541899859905243, "20403": 0.03360854089260101, "20582": 1.105748176574707, "20662": 0.07250232994556427, "20688": 0.8861536383628845, "20752": 0.04674193635582924, "20958": 0.839173436164856, "20961": 0.03360854089260101, "21032": 0.306306391954422, "21081": 0.11778303235769272, "21104": 0.8264343738555908, "21112": 0.3622259199619293, "21157": 0.33605360984802246, "21230": 0.04207121208310127, "21262": 0.05046287178993225, "21281": 0.05417001247406006, "21376": 0.2478361576795578, "21453": 0.8869584798812866, "21472": 0.1751343309879303, "21486": 0.08961215615272522, "21700": 0.18978065252304077, "21799": 0.05417001247406006, "21890": 0.688742995262146, "22407": 0.0009760859538801014, "22415": 0.25995752215385437, "22466": 0.07341018319129944, "22540": 0.8247235417366028, "22571": 0.6764062643051147, "22595": 0.07793712615966797, "22718": 0.40089741349220276, "22963": 0.02792670577764511, "23079": 0.3897167444229126, "23676": 0.47827014327049255, "23737": 1.1121915578842163, "23777": 0.129004567861557, "23900": 0.9553611874580383, "23924": 0.46363574266433716, "23943": 0.7220231294631958, "24226": 0.1913948506116867, "24269": 0.29473719000816345, "24278": 0.5495203733444214, "24279": 0.1751343309879303, "24374": 0.37974658608436584, "24545": 0.0913962796330452, "24552": 1.5005991458892822, "25003": 0.9900637865066528, "25300": 0.11778303235769272, "25565": 0.1064341589808464, "25714": 0.151916041970253, "25937": 0.11168810725212097, "25950": 0.06612417846918106, "25972": 0.5557019114494324, "26010": 0.1064341589808464, "26083": 0.39893341064453125, "26166": 0.3084607720375061, "26305": 0.1889725625514984, "26512": 0.7863243818283081, "26534": 0.0770333781838417, "26632": 0.8306987881660461, "26657": 0.037378571927547455, "26741": 0.04394211992621422, "26775": 0.04394211992621422, "26786": 0.19381128251552582, "26976": 0.14349138736724854, "27133": 1.264413595199585, "27287": 0.7537717819213867, "27321": 0.7067264318466187, "27427": 0.18654440343379974, "27480": 0.026025565341114998, "27556": 0.03831886500120163, "27753": 0.42990362644195557, "27814": 0.15526613593101501, "27815": 0.1011524572968483, "27885": 0.6649205088615417, "27989": 0.06429435312747955, "28086": 0.4920966327190399, "28156": 0.5244048833847046, "28173": 0.8264343738555908, "28290": 0.14433705806732178, "28311": 0.9317949414253235, "28466": 0.7683706283569336, "28517": 0.04487626627087593, "28573": 0.23324857652187347, "28637": 0.07793712615966797, "28691": 0.0029254043474793434, "28788": 0.026025565341114998, "28795": 0.1693800985813141, "28804": 0.8583967685699463, "29172": 0.0009760859538801014, "29206": 0.9240728616714478, "29290": 0.3134697377681732, "29516": 0.08961215615272522} | 13944805 | KEY POINTS Maternal obesity reduces adipogenic progenitor density in offspring adipose tissue. The ability of adipose tissue expansion in the offspring of obese mothers is limited and is associated with metabolic dysfunction of adipose tissue when challenged with a high-fat diet. Maternal obesity induces DNA demethylation in the promoter of zinc finger protein 423, which renders progenitor cells with a high adipogenic capacity. Maternal obesity demonstrates long-term effects on the adipogenic capacity of progenitor cells in offspring adipose tissue, demonstrating a developmental programming effect. ABSTRACT Maternal obesity (MO) programs offspring obesity and metabolic disorders, although the underlying mechanisms remain poorly defined. Progenitor cells are the source of new adipocytes. The present study aimed to test whether MO epigenetically predisposes adipocyte progenitors in the fat of offspring to adipogenic differentiation and subsequent depletion, which leads to a failure of adipose tissue plasticity under positive energy balance, contributing to adipose tissue metabolic dysfunction. C57BL/6 female mice were fed either a control diet (10% energy from fat) or a high-fat diet (45% energy from fat) for 8 weeks before mating. Male offspring of control (Con) and obese (OB) dams were weaned onto a regular (Reg) or obesogenic (Obe) diet until 3 months of age. At weaning, male OB offspring had a higher expression of Zinc finger protein 423 (zfp423), a key transcription factor in adipogenesis, as well as lower DNA methylation of its promoter in progenitors of epididymal fat compared to Con offspring, which was correlated with enhanced adipogenic differentiation. At 3 months of age, progenitor density was 30.9 ± 9.7% lower in OB/Obe compared to Con/Obe mice, accompanied by a limited expansion of the adipocyte number when challenged with a high-energy diet. This difference was associated with lower DNA methylation in the zfp423 promoter in the epididymal fat of OB/Obe offspring, which was correlated with greater macrophage chemotactic protein-1 and hypoxia-inducible factor 1α expression. In summary, MO epigenetically limits the expansion capacity of offspring adipose tissue, providing an explanation for the adipose metabolic dysfunction of male offspring in the setting of MO. | Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice. |
{"1011": 0.03925827145576477, "1999": 0.11604541540145874, "2003": 0.22626367211341858, "2004": 0.0797421783208847, "2005": 0.42353010177612305, "2011": 0.06886265426874161, "2013": 0.16110190749168396, "2020": 0.13925230503082275, "2024": 0.2105647772550583, "2053": 0.04860413447022438, "2073": 0.22157983481884003, "2076": 0.23556606471538544, "2078": 0.66441810131073, "2079": 0.043007105588912964, "2109": 0.37707099318504333, "2140": 0.2822965085506439, "2179": 0.39893341064453125, "2241": 1.0312920808792114, "2362": 0.14939609169960022, "2378": 0.3485364317893982, "2391": 0.39433568716049194, "2392": 0.7898768186569214, "2396": 0.08961215615272522, "2478": 0.03925827145576477, "2506": 0.04487626627087593, "2515": 0.10291612148284912, "2527": 0.38308101892471313, "2618": 0.10291612148284912, "2677": 0.3283478021621704, "2797": 0.1913948506116867, "2836": 0.5162794589996338, "2915": 0.24018502235412598, "2918": 0.47584590315818787, "2979": 0.3269403576850891, "3022": 0.5662899017333984, "3032": 0.1710275560617447, "3049": 0.4248080551624298, "3088": 0.09761575609445572, "3111": 0.23479416966438293, "3161": 0.777387797832489, "3170": 0.4311734735965729, "3231": 0.6254787445068359, "3397": 0.4067663550376892, "3424": 0.9100211262702942, "3430": 0.05417001247406006, "3490": 0.3019835948944092, "3563": 0.33953672647476196, "3573": 0.11604541540145874, "3603": 0.13157635927200317, "3619": 0.09406650811433792, "3686": 0.8731874823570251, "3737": 0.7951818704605103, "3816": 0.1602703034877777, "3830": 0.05417001247406006, "3861": 0.23015019297599792, "3941": 0.23710809648036957, "3949": 0.7370892763137817, "3979": 0.176772341132164, "3981": 0.14602625370025635, "4004": 0.7258110046386719, "4005": 0.040196798741817474, "4021": 0.9857001900672913, "4106": 0.5421652793884277, "4117": 0.5110208988189697, "4149": 0.04953393340110779, "4156": 0.0038986403960734606, "4179": 0.6022219061851501, "4180": 0.7258110046386719, "4200": 0.3464667797088623, "4232": 0.6980181336402893, "4319": 0.7951818704605103, "4403": 0.39893341064453125, "4417": 0.08782484382390976, "4453": 0.30558720231056213, "4620": 0.1229778528213501, "4632": 0.7239188551902771, "4643": 1.0735615491867065, "4655": 0.1011524572968483, "4710": 0.8161250352859497, "4745": 0.19541899859905243, "4820": 0.9240728616714478, "4838": 0.5990082025527954, "4877": 0.5080875158309937, "4942": 0.5063233375549316, "5002": 0.5330380201339722, "5067": 0.1477125883102417, "5080": 0.6471850275993347, "5173": 0.08154398202896118, "5257": 1.1192315816879272, "5302": 0.15526613593101501, "5324": 0.2830325961112976, "5383": 0.7872136831283569, "5393": 0.16524957120418549, "5498": 1.036847710609436, "5576": 0.13670019805431366, "5604": 0.5427330136299133, "5693": 0.07068414986133575, "5733": 0.524982750415802, "5740": 0.4349733293056488, "5769": 0.10026945173740387, "5845": 0.46608972549438477, "5850": 0.8893690705299377, "5852": 0.42608439922332764, "5886": 0.8813109993934631, "5892": 0.5092619061470032, "6074": 0.32341301441192627, "6137": 0.07159364968538284, "6293": 0.8332487344741821, "6310": 0.036437395960092545, "6381": 0.3963087201118469, "6412": 0.3177432417869568, "6504": 0.48430517315864563, "6522": 1.2307592630386353, "6643": 0.03266380727291107, "6687": 0.7934166193008423, "6845": 0.07250232994556427, "6904": 0.7665573358535767, "6939": 0.052318159490823746, "7011": 0.09495500475168228, "7040": 0.05046287178993225, "7076": 0.04113444685935974, "7099": 0.6353566646575928, "7146": 0.2881702482700348, "7172": 0.06977381557226181, "7242": 0.6950984001159668, "7438": 0.6862877607345581, "7594": 0.010684899985790253, "7629": 0.02412080205976963, "7685": 0.036437395960092545, "7718": 0.7210738658905029, "7810": 0.9798521995544434, "7816": 0.14264501631259918, "7888": 0.09317722171545029, "7889": 0.011650617234408855, "7895": 0.1011524572968483, "8008": 0.22937409579753876, "8127": 0.0038986403960734606, "8168": 0.6857960224151611, "8252": 0.5127768516540527, "8387": 0.08782484382390976, "8417": 0.6212902665138245, "8520": 0.29328158497810364, "8524": 0.1384023278951645, "8564": 0.18167030811309814, "8675": 0.1011524572968483, "8700": 0.9463045597076416, "8757": 0.07250232994556427, "8878": 0.04487626627087593, "8893": 0.3318578004837036, "8977": 0.012615402229130268, "9031": 0.75193190574646, "9067": 0.9769153594970703, "9141": 1.068206787109375, "9207": 0.026976587250828743, "9331": 0.791648268699646, "9526": 0.24325250089168549, "9614": 0.9379299283027649, "9861": 0.14349138736724854, "9983": 0.05970508232712746, "10077": 0.19622190296649933, "10210": 0.1685553640127182, "10586": 0.27044451236724854, "10610": 0.5871354341506958, "10631": 0.06429435312747955, "10651": 0.2741633653640747, "10698": 0.3163207769393921, "10738": 0.5767669677734375, "10788": 0.5410289764404297, "10980": 0.9783848524093628, "11024": 0.18573370575904846, "11027": 0.19862671196460724, "11050": 1.0668635368347168, "11156": 0.7934166193008423, "11166": 0.02887592278420925, "11211": 0.1693800985813141, "11368": 0.8366385698318481, "11375": 0.31132611632347107, "11487": 0.7124901413917542, "11493": 0.10906458646059036, "11506": 0.18248429894447327, "11514": 0.6461620330810547, "11566": 0.4624064862728119, "11787": 0.26146242022514343, "12016": 0.12728634476661682, "12086": 0.19220098853111267, "12222": 0.3784096837043762, "12265": 0.32341301441192627, "12318": 0.37035053968429565, "12335": 0.18248429894447327, "12399": 0.9440274834632874, "12407": 0.04674193635582924, "12565": 0.12814582884311676, "12599": 0.6128603219985962, "12620": 1.4283655881881714, "12668": 0.574020504951477, "12717": 0.07068414986133575, "12760": 0.5186077356338501, "12811": 1.1300151348114014, "13046": 0.8091925978660583, "13070": 0.1946154683828354, "13341": 0.9363996982574463, "13423": 0.31489628553390503, "13441": 0.5139457583427429, "13463": 0.07793712615966797, "13537": 0.11168810725212097, "13585": 0.23633737862110138, "13819": 1.0179725885391235, "13859": 0.1332872211933136, "14045": 0.736154317855835, "14057": 0.11778303235769272, "14277": 0.07431721687316895, "14409": 0.0058422754518687725, "14413": 0.1401015669107437, "14455": 0.05417001247406006, "14468": 0.7342816591262817, "14667": 0.6086184978485107, "14709": 0.11778303235769272, "14736": 0.058784693479537964, "14808": 0.40546512603759766, "14887": 0.04394211992621422, "14930": 0.8400169610977173, "15017": 0.20501139760017395, "15026": 0.07431721687316895, "15106": 1.1337933540344238, "15227": 0.2800849378108978, "15289": 0.1384023278951645, "15345": 0.004870930220931768, "15349": 0.14686977863311768, "15356": 0.05046287178993225, "15396": 0.0038986403960734606, "15459": 0.052318159490823746, "15472": 1.20884370803833, "15709": 0.42608439922332764, "15728": 0.8796916007995605, "15877": 0.0770333781838417, "16185": 1.0788878202438354, "16227": 0.05786345899105072, "16330": 0.013579257763922215, "16414": 0.2105647772550583, "16510": 0.969535231590271, "16578": 0.07884006202220917, "16666": 0.029824240133166313, "16670": 0.38174858689308167, "16710": 0.5855054259300232, "16745": 0.7389566898345947, "16942": 0.8534175157546997, "17261": 0.29400965571403503, "17404": 0.2561853528022766, "17473": 0.2478361576795578, "17640": 0.1221139207482338, "17696": 0.1477125883102417, "17826": 0.016465263441205025, "17908": 0.3963087201118469, "18095": 0.14179791510105133, "18117": 0.07341018319129944, "18178": 0.022212404757738113, "18231": 0.4500300884246826, "18251": 0.1718502640724182, "18433": 0.16442140936851501, "18452": 0.23324857652187347, "18595": 0.2881702482700348, "18622": 0.16690383851528168, "18701": 0.06246116757392883, "18747": 0.6338034868240356, "18752": 0.8400169610977173, "18847": 0.9005423784255981, "18891": 0.056018441915512085, "18900": 0.04767346754670143, "18901": 0.012615402229130268, "18925": 0.055094651877880096, "19063": 1.5398868322372437, "19105": 0.10906458646059036, "19132": 1.5109978914260864, "19496": 0.08244366943836212, "19729": 1.1128336191177368, "19737": 0.5517725944519043, "19872": 0.009718249551951885, "19960": 0.2247048318386078, "20228": 0.7258110046386719, "20233": 0.2786078155040741, "20377": 0.08513788133859634, "20576": 0.007782140281051397, "20614": 0.4067663550376892, "20900": 0.2637155055999756, "20992": 0.5045560002326965, "21150": 0.10467668622732162, "21198": 0.31560876965522766, "21354": 1.1274882555007935, "21391": 0.21687394380569458, "21515": 1.2070930004119873, "21673": 0.6980181336402893, "21716": 0.6482070088386536, "21774": 0.6684301495552063, "21778": 0.1212492436170578, "22458": 0.46363574266433716, "22529": 0.09850110858678818, "22618": 0.016465263441205025, "22870": 0.030771657824516296, "22916": 0.7881022095680237, "22931": 0.05694137513637543, "23041": 0.2711893916130066, "23309": 0.037378571927547455, "23427": 0.43875885009765625, "23631": 0.2881702482700348, "23983": 0.21922965347766876, "23996": 0.176772341132164, "24004": 0.0038986403960734606, "24054": 0.13071982562541962, "24185": 0.43875885009765625, "24198": 0.036437395960092545, "24479": 0.3870677351951599, "24996": 0.469759464263916, "25025": 0.77198725938797, "25027": 0.27934664487838745, "25090": 0.06886265426874161, "25952": 0.11430477350950241, "26348": 0.603290855884552, "26661": 0.08513788133859634, "26773": 0.12384103983640671, "26794": 0.021256839856505394, "26957": 0.034552380442619324, "27144": 0.24018502235412598, "27292": 0.03925827145576477, "27781": 0.0354953333735466, "27974": 0.18411032855510712, "28173": 0.13755162060260773, "28475": 0.021256839856505394, "28775": 0.18248429894447327, "28847": 0.28963330388069153, "28935": 0.1011524572968483, "29154": 0.11256109178066254, "29167": 0.04953393340110779, "29490": 0.45994341373443604, "29596": 0.30989447236061096} | 13948920 | Artemisinin-based combination therapies are the frontline treatment of Plasmodium falciparum malaria. The circulation of falsified and substandard artemisinin-based antimalarials in Southeast Asia has been a major predicament for the malaria elimination campaign. To provide an update of this situation, we purchased 153 artemisinin-containing antimalarials, as convenience samples, in private drug stores from different regions of Myanmar. The quality of these drugs in terms of their artemisinin derivative content was tested using specific dipsticks for these artemisinin derivatives, as point-of-care devices. A subset of these samples was further tested by high-performance liquid chromatography (HPLC). This survey identified that > 35% of the collected drugs were oral artesunate and artemether monotherapies. When tested with the dipsticks, all but one sample passed the assays, indicating that the detected artemisinin derivative content corresponded approximately to the labeled contents. However, one artesunate injection sample was found to contain no active ingredient at all by the dipstick assay and subsequent HPLC analysis. The continued circulation of oral monotherapies and the description, for the first time, of falsified parenteral artesunate provides a worrisome picture of the antimalarial drug quality in Myanmar during the malaria elimination phase, a situation that deserves more oversight from regulatory authorities. | Quality Testing of Artemisinin-Based Antimalarial Drugs in Myanmar. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.