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BACKGROUND AND AIMS: Extensive clonal (vegetative) reproduction in lianas is a common and important life history strategy for regeneration and colonization success. However, few studies have evaluated the contribution of clonal reproduction to stand-level distribution of lianas in their natural habitat using genetic tools. The objectives of the present study were to investigate (1) the contribution of clonal reproduction to the distribution of Wisteria floribunda, (2) the size of clonal patches and (3) how the distribution patterns of W. floribunda clones are affected by micro-topography. METHODS: The contribution of clonal reproduction to the distribution of the deciduous liana species W. floribunda was evaluated using genetic analysis across a 6-ha plot of an old-growth temperate forest in Japan and preference in landform between clonal ramets and non-clonal ramets was assessed. KEY RESULTS: Of the 391 ramets sampled, clonal reproduction contributed to 71 and 62 % of the total abundance and basal area, respectively, or 57 and 31 % when the largest ramet within a genet was excluded. The large contribution of clonal reproduction to the density and basal area of W. floribunda was consistent with previous observational studies. The largest genet included a patch size of 0.47 ha and ranged over 180 m. Preferred landforms of clonal and non-clonal ramets were significantly different when evaluated by both abundance and basal area. Non-clonal ramets distributed more on lower part of the slope than other landforms in comparison with clonal ramets and trees, possibly reflecting the limitation of clonal growth by stolons. CONCLUSIONS: Using genetic analysis, the present study found evidence of a large contribution of clonal reproduction on the distribution of W. floribunda in its natural habitat. The results indicate that clonal reproduction plays an important role not only in the formation of populations but also in determining the distribution patterns of liana species. | Wisteria |
BACKGROUND: Nurse researchers are constantly seeking novel methods of maintaining philosophical congruence while advancing their knowledge of the human condition using paradigmatically diverse means. AIM: To provide an overview of the research philosophies underpinning the mixed methods grounded theory (MM-GT) methodology, illustrate its optimal use and introduce a quality-appraisal tool being developed with reference to extant literature. DISCUSSION: The utility of MM-GT has been effectively demonstrated in the nursing and health literature. Yet, there are examples of how it has been under-used and sub-optimally applied. This article includes a two-phase MM-GT study protocol guided by a pragmatic research philosophy and best practice recommendations that aims to explain neonatal nurses' professional quality of life. CONCLUSION: Optimal use of MM-GT's five essential components - purposive sampling, constant comparative methods with iterative coding and analysis, theoretical saturation, memoing and theory development - combine to produce high-quality, defensible research outputs and new nursing theory. IMPLICATIONS FOR PRACTICE: Research outputs, such as publication and presentation, expounding the multifactorial influences affecting neonatal nurses' professional quality of life will not only benefit the neonatal nursing community but also contribute to the corpus of nursing and midwifery research and enhance the health, well-being and retention of nurses and midwives more broadly. | Grounded Theory |
OBJECTIVE: To determine the impact of owning a hearing dog on self-reported hearing handicap, quality of life (QoL), and social functioning. DESIGN: Group comparison study design, utilising five surveys (General Information Survey, Hearing Information Survey, Hearing Handicap Inventory for the Elderly/Adults, Medical Outcomes Survey, and Social Functioning Questionnaire). STUDY SAMPLE: 23 respondents from the 2019 Australian Lions Hearing Dog waitlist (controls) and 58 respondents from all clients who had received a hearing dog through the Australian Lions Hearing Dog service (cases). RESULTS: No significant difference was found in Hearing Handicap Inventory or Social Functioning Questionnaire scores between the groups, although there was a tendency for improvement with dog ownership. The owner group scored significantly lower than the waitlist group on three Medical Outcomes Survey sub-items (general health, physical functioning, and role limitations due to physical health), along with total health-related QoL. These results contrasted with the broad emotional and psychosocial benefits identified through thematic analysis of responses. CONCLUSIONS: It is feasible, yet not certain, that owning a hearing dog may bring a reduction in hearing handicap, as well as emotional and social benefits to the QoL of individuals, but it also appears to be associated with poorer perception of health. | Service Animals |
Mitochondrial transcription factor A is a key regulator involved in mitochondrial DNA transcription and replication. In a poorly differentiated rat hepatoma, Morris hepatoma 3924A, the mRNA and protein levels of this factor were elevated about 10- and 11-fold, respectively, relative to the host liver. The mRNA levels for the hepatoma cytochrome c oxidase I, II, and NADH dehydrogenase 5, 6, the downstream targets of Tfam, were augmented 10-, 8-, 5-, and 3-fold, respectively. Interestingly, Tfam was also found in the hepatoma nucleus. The mRNA levels for nuclear respiratory factor 1 and 2 (NRF-1 and -2), the proteins that are known to interact with specific regulatory elements on human TFAM promoter, were 5- and 3-fold higher, respectively, in the hepatoma relative to the host liver. Unlike the human promoter, the rat Tfam promoter did not form a specific complex with the NRF-1 in the liver or hepatoma nuclear extracts, which is consistent with the absence of an NRF-1 consensus sequence in the proximal rat promoter. A single specific complex formed between the rat promoter and the NRF-2 protein was comparable in the two extracts. The DNA binding activity of Sp1 in the hepatoma nuclear extract was 4-fold greater than that in the liver extract. In vivo genomic footprinting showed occupancy of NRF-2 and Sp1 consensus sites on the promoter of rat Tfam gene. Tfam was also up-regulated in other hepatoma cells. Together, these results show up-regulation of Tfam in some tumors, particularly the liver tumors. Further, the relatively high level of Sp1 binding to the promoter in the hepatoma could play a major role in the up-regulation of Tfam in these tumor cells. | NF-E2-Related Factor 1 |
We investigated the effects of acute i.p. injections of the Ca(2+)-dependent K(+) channel blocker, apamin, on water maze spatial navigation and radial arm maze performance in mice with partial hippocampal-lesions. In the radial arm maze, apamin 0.06 and 0.2 mg/kg dose-dependently reversed the lesion-induced defect. In the water maze, apamin 0.2 mg/kg alleviated the defect, but a lower dose 0.06 mg/kg was ineffective. At a higher dose, 0.4 mg/kg, apamin impaired the water maze performance. These results suggest that Ca(2+)-dependent K(+) channel blockers can alleviate the spatial reference memory and working memory impairment induced by partial hippocampal lesions. | Apamin |
This community-based research applied environmental dispossession as a theoretical framework for understanding Anishinabe youth perceptions about health, social relationships and contemporary Anishinabe way of life in Northern Ontario, Canada. Qualitative interviews with 19 youth reveal considerable worry about their community's health. Youth perceive changes in the Anishinabe way of life, including decreased access to their traditional lands, to be central to poor health at the community level. Youth emphasized the importance of social relationships for fostering healthy behaviours and developing community wide initiatives that will provide opportunities for reconnecting to land, and for learning and practicing Indigenous Knowledge. This study builds on the growing body of decolonizing research with Indigenous communities, and it concludes by offering the concept of environmental repossession as a way forward for studies on the Indigenous environment-health interface." | Health Knowledge, Attitudes, Practice |
Two cases of facial lymphangitis have been described, and the pathophysiology of erysipelas has been discussed. Now rarely observed by hospital residents, this potentially serious infection can create considerable diagnostic confusion in medical as well as dental services. Rapid response of erysipelas to penicillin therapy is the modern expectation. | Erysipelas |
Arabinose is considered as an ideal feedstock for the microbial production of value-added chemicals due to its abundance in hemicellulosic wastes. In this study, the araBAD operon from Escherichia coli was introduced into succinate-producing Corynebacterium glutamicum, which enabled aerobic production of succinate using arabinose as sole carbon source. The engineered strain ZX1 (pXaraBAD, pEacsAgltA) produced 74.4 mM succinate with a yield of 0.58 mol (mol arabinose)(-1), which represented 69.9% of the theoretically maximal yield. Moreover, this strain produced 110.2 mM succinate using combined substrates of glucose and arabinose. To date, this is the highest succinate production under aerobic conditions in minimal medium. | Isopropyl Thiogalactoside |
BACKGROUND: Porcine Teschovirus (PTV), also named Teschovirus A, is prevalent in pig populations, mainly causing neurological symptoms, diarrhea, pneumonia, and reproductive failure, however the morbidity and mortality are usually low in pig farms. CASE PRESENTATION: In this study, we reported a PTV outbreak investigation in one large-scale pig farm in China with severe symptoms including diarrhea, lethargy, locomotor ataxia, nystagmus, paralysis of the hind limbs, and coma in piglets. More importantly, the mortality reached 38% in suckling pigs, which is remarkably high in PTV history. A novel PTV strain, named HeNZ1, was isolated from cerebral samples of one suckling pig and the genome sequence was obtained by NGS sequencing. Phylogenetic and evolutionary divergence analyses revealed that HeNZ1 belongs to PTV genotype 2. Surprisingly, the VP1 coding region of HeNZ1 shares the highest sequence similarity with European PTV-2 strains, instead of China domestic PTV-2 strains, implying it may not derive from China local PTV-2 strains. Multiple sequence alignment and B cell epitope prediction of PTV VP1 and VP2 protein revealed 10 B cell epitopes, 5 mutant clusters and 36 unique mutation sites, of which 19 unique mutation sites are located in B cell epitopes and exposed on the surface of VP1 or VP2, implying significant antigenic drift potential of HeNZ1. CONCLUSION: These results indicate that HeNZ1 is a highly virulent PTV-2 strain, which capable of causing severe neurological symptoms and high mortality in piglets. Bioinformatic analysis suggest that HeNZ1 is genetically and antigenically different from other Chinese PTV-2 strains. Overall, current case expanded our understanding of PTV-2 clinical spectrum and revealed the emergence of a highly virulent PTV-2 strain with substantial genetic diversity and antigenic drift potential in VP1 and VP2. | Teschovirus |
BACKGROUND: Ocular dominance has been studied for many years, and there have been many attempts to correlate eye dominance with athletic performance. Although many reports have failed to show a correlation, some reports have shown a relationship between sports performance and eye dominance. METHODS: This report reviews some of those studies and the tests of eye dominance used in the reports. Additionally, we review the physical basis of eye dominance and the role of the binocular visual system in its determination. Lastly, a review of common facts and fallacies relating to ocular dominance is provided. RESULTS/CONCLUSION: It is suggested that the visual system is designed as a binocular system, and only tests that allow for maintenance of binocular vision during the determination of ocular preference should be used if an accurate evaluation is to be made. | Vision, Binocular |
OBJECTIVE: To investigate the effects of tibolone and its main metabolites on breast homeostasis. DESIGN: In vitro studies in primary cultures of normal breast cells and in breast cancer cell lines. SETTING: Hospital-based academic research center. PATIENT(S): Human breast cells were obtained from women undergoing surgery for hypermastia. Breast cancer cell lines (MCF-7, T47-D, and ZR75-1) were routinely obtained from subcultures. INTERVENTION(S): Cells were incubated with tibolone, its various metabolites, the pure pregnane Org 2058, and the androgen dihydrotestosterone. MAIN OUTCOME MEASURE(S): Proliferation was determined by using a morphometric growth index, apoptosis by using morphologic analysis and flow cytometry, and antiapoptotic proteins bcl-2 and bclx(L) by using Western blot assay. Activity of 17beta-hydroxysteroid dehydrogenase was measured as an epithelial differentiation marker. RESULT(S): Tibolone and its delta(4) isomer were antiproliferative in normal breast cells. Tibolone and its delta(4) isomer increased apoptosis in breast cells. These proapoptotic effects were at least partially mediated through decreased expression of the antiapoptotic proteins bcl-2 and bclx(L). An increase in HSD activity was observed after tibolone administration. CONCLUSION(S): Tibolone is antiproliferative and proapoptotic and induces differentiation in normal breast cells. It is also proapoptotic in breast cancer cell lines. | Norpregnenes |
Bacteroides fragilis (B. fragilis) is a commensal Gram-negative obligate anaerobe that resides in the mammalian lower gut and can profoundly affect the susceptibility of the host to inflammatory diseases. Previous studies have identified B. fragilis as a common opportunistic pathogen in clinical infections and suggested that it may be responsible for a range of diseases involving a permeable intestinal barrier. However, recent studies of the relationship between nontoxigenic B. fragilis and the immune system have indicated that several B. fragilis strains may be potential probiotic. In the present review, we summarize the factors influencing the intestinal abundance of B. fragilis and discuss the biological interactions between this microbe and the host. Immune system development, age, individual dietary habits, physical condition, drug intake and personal lifestyle habits can all affect the abundance of B. fragilis in the human intestine. Polysaccharide A or outer membrane vesicles from nontoxigenic B. fragilis may mediate beneficial interactions with the host, whereas enterotoxigenic B. fragilis toxin or lipopolysaccharide may stimulate colitis or even systemic inflammation. Generally, this review summarizes the biological characteristics of B. fragilis and describes future application of probiotics. | Bacteroides fragilis |
The propensity of patients with carcinoma in situ (CIS) of the bladder to progress to invasive and metastatic disease is clearly established. Today, the standard therapy in treating patients with CIS of the bladder is intravesical bacillus Calmette-Guerin (BCG). Nevertheless, patients who fail intravesical BCG have few viable options except to undergo a radical cystectomy. Valrubicin (N-trifluoroacetyladriamycin-14-valerate) is a new semisynthetic derivative of the anthracycline antibiotic doxorubicin that has been shown to benefit patients with BCG-refractory CIS of the bladder. Intravesical instillation of valrubicin is well-tolerated, safe and can be durable. Early non-randomised studies show promise and the current utilisation of this drug is limited to patients with BCG-refractory CIS of the bladder who are not good surgical candidates. Randomised studies of intravesical valrubicin for the treatment of superficial bladder cancer are ongoing. | Doxorubicin |
Monitoring of peritoneovenous Le Veen shunt by duplex ultrasonography was first performed in 1993 in 10 patients. The duplex signal was picked up selectively in the venous tube and the peak velocity was measured at forced inspiration. Thirty-two examinations were performed. Of these, 13 had follow-up examinations by other modalities (radionuclide imaging, shuntography, or surgical exploration), all of which confirmed the findings of duplex ultrasonography. Shuntography was avoided in all instances with a patent shunt. Duplex ultrasonography allows noninvasive assessment of Le Veen shunt patency and appears reliable for determining the need for invasive diagnostic modalities or surgical shunt correction." | Ultrasonography, Doppler, Duplex |
The effects of perphenazine, cocaine, diethylpropion and d-amphetamine on responding maintained by both food delivery and electric shock avoidance were determined using a multiple schedule of reinforcement in rhesus monkeys. This schedule had three components, each separated by a timeout: a fixed-ratio schedule of food delivery, a schedule of spaced responding (differential reinforcement of low rates) maintained by food delivery and a fixed-ratio schedule of shock avoidance. Control rates of responding on both ratio schedules were similar and were high relative to the low rates generated by the schedule of spaced responding. Perphenazine decreased rates on all three schedules in a dose-dependent fashion. All three psychomotor stimulants decreased food-maintained ratio responding at doses which had little effect on or increased rates of shock avoidance. Except for diethylpropion and d-amphetamine in one animal in which rates were increased, low rates of spaced responding were also decreased. | Diethylpropion |
Excitatory amino acid transporters (EAATs) remove glutamate from the synaptic cleft. In the retina, EAAT1 and EAAT2 are considered the major glutamate transporters. However, it has not yet been possible to determine how EAAT5 shapes the retinal light responses because of the lack of a selective EAAT5 blocker or EAAT5 knock-out (KO) animal model. In this study, EAAT5 was found to be expressed in a punctate manner close to release sites of glutamatergic synapses in the mouse retina. Light responses from retinae of wild-type (WT) and of a newly generated model with a targeted deletion of EAAT5 (EAAT5(-/-)) were recorded in vitro using multielectrode arrays (MEAs). Flicker resolution was considerably lower in EAAT5(-/-) retinae than in WT retinae. The close proximity to the glutamate release site makes EAAT5 an ideal tool to improve temporal information processing in the retina by controlling information transfer at glutamatergic synapses." | Excitatory Amino Acid Transporter 5 |
We show that arrays of nanopit structures etched in a nanoslit can control the positioning and conformation of single DNA molecules in nanofluidic devices. By adjusting the spacing, organization and placement of the nanopits it is possible to immobilize DNA at predetermined regions of a device without additional chemical modification and achieve a high degree of control over local DNA conformation. DNA can be extended between two nanopits and in closely spaced arrays will self-assemble into connect-the-dots" conformations consisting of locally pinned segments joined by fluctuating linkers. These results have broad implications for nanotechnology fields that require methods for the nanoscale positioning and manipulation of DNA." | Nanotechnology |
Antitrust litigation involving hospitals is common. This paper describes recent developments and underlying issues in antitrust law with respect to hospital-hospital relations, hospital-physician relations, and hospital-payer relations. A key unanswered question in each of these areas is how government regulation and public purchasing affect competitive markets for hospital services. | Legislation, Hospital |
Rats were trained to discriminate injections of either 5-OMe DMT (1.5 mg/kg) or LSD (0.096 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performances were attained (greater than 85%) in each group, dose-response generalizations between the two groups of animals were examined. The results revealed that the 5-OMe DMT-stimulus response generalized to LSD and that the LSD-stimulus response generalized to 5-OMe DMT. Furthermore, both the 5-OMe DMT-stimulus and the LSD-stimulus could be significantly attenuated by the serotonin antagonist BC-105. However, the pattern of the dose-related antagonism by BC-105 was different between the drug stimuli. It was concluded that while the discriminative stimulus effects of 5-OMe DMT and LSD may be mediated via a common serotonergic system, the receptor interaction of these agents within that pharmacological system may be somewhat different. | Methoxydimethyltryptamines |
Flecainide is an important addition to the therapeutic armamentarium because it is a potent agent for the treatment of paroxysmal supraventricular tachycardia in patients without structural heart disease. Flecainide also may be useful in patients with debilitating nonsustained ventricular arrhythmias in the absence of structural heart disease. It is rarely useful in the management of life-threatening sustained ventricular arrhythmias. | Flecainide |
The first neonicotinoid insecticide, imidacloprid, was launched in 1991. Today this class of insecticides comprises at least seven major compounds with a market share of more than 25% of total global insecticide sales. Neonicotinoid insecticides are highly selective agonists of insect nicotinic acetylcholine receptors and provide farmers with invaluable, highly effective tools against some of the world's most destructive crop pests. These include sucking pests such as aphids, whiteflies, and planthoppers, and also some coleopteran, dipteran and lepidopteran species. Although many insect species are still successfully controlled by neonicotinoids, their popularity has imposed a mounting selection pressure for resistance, and in several species resistance has now reached levels that compromise the efficacy of these insecticides. Research to understand the molecular basis of neonicotinoid resistance has revealed both target-site and metabolic mechanisms conferring resistance. For target-site resistance, field-evolved mutations have only been characterized in two aphid species. Metabolic resistance appears much more common, with the enhanced expression of one or more cytochrome P450s frequently reported in resistant strains. Despite the current scale of resistance, neonicotinoids remain a major component of many pest control programmes, and resistance management strategies, based on mode of action rotation, are of crucial importance in preventing resistance becoming more widespread. In this review we summarize the current status of neonicotinoid resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management. | Nicotinic Agonists |
This experiment investigated the underlying mechanism of ultrasonic-assisted stewing to enhance the aroma intensity of chicken broth by measuring fat content, oil droplet sizes, zeta potential, viscosity, surface protein loading, lipid oxidation, and aroma compound concentrations. As the thermo-ultrasound time increased, the fat content increased from 0.3 % to 1.2 %, resulting in a milky white appearance. After 1 h of thermo-ultrasound, the broth had the smallest particle size and the highest surface protein load, viscosity, and emulsion stability, as well as the highest total amount of aroma-active compounds of 314.70 ng/mg. With the further extension of thermo-ultrasound time, lipid oxidation increased, but the stability of chicken broth decreased, lowering the content of aroma-active compounds. These outcomes suggested that thermo-ultrasound could enhance the aroma intensity of chicken broth by increasing the fat content and the emulsion stability of the broth. | Odorants |
BACKGROUND: There have been reports investigating the use of olfactory training in olfactory dysfunction after COVID-19. OBJECTIVE: We evaluated the effect of olfactory training on the olfactory dysfunction of patients infected with COVID-19. METHODS: We searched PubMed, EMBASE, the Web of Science, the Cochrane database, SCOPUS, and Google Scholar up to May 2022. We retrieved studies that compared the extents of olfactory dysfunction before and after olfactory training. We performed a subgroup analysis by the duration of olfactory dysfunction. RESULTS: The olfactory score after olfactory training (standard mean difference [SMD] = 1.0830, 95% confidence interval [CI] [0.6416; 1.5245], P < .0001, I(2) = 90.4%) was higher than that before training. The olfactory dysfunction rate differed significantly (OR = 0.0232, 95% CI [0.0052; 0.1044], P < .0001, I(2) = 63.1%) before and after olfactory training. On subgroup analysis, although patients with both acute (onset < 30 days prior) and chronic (onset > 30 days prior) olfactory dysfunction evidenced clinically significant improvements, training during acute dysfunction (compared to acute dysfunction) increased the olfactory score to a greater extent (SMD = 1.7779, 95% CI [1.0077; 2.5481] vs 0.6928 [0.2143; 1.1712], P = 0.0190). Moreover, as a result of subgroup analysis by dividing the included studies into2 using 2-month training period as standard, there was no statistically significant difference in the effect of the training period in the included study. CONCLUSION: Olfactory training improved olfactory disorders caused by COVID-19. Such training was effective in both the acute and chronic phases. | Olfactory Training |
The spinocerebellar ataxias (SCAs) form an ever-growing group of neurodegenerative disorders causing dysfunction of the cerebellum and loss of motor control in patients. Currently, 41 different genetic causes have been identified, with each mutation affecting a different gene. Interestingly, these diverse genetic causes all disrupt cerebellar function and produce similar symptoms in patients. In order to understand the disease better, and define possible therapeutic targets for multiple SCAs, the field has been searching for common ground among the SCAs. In this review, we discuss the physiology of climbing fibers and the possibility that climbing fiber dysfunction is a point of convergence for at least a subset of SCAs. | Spinocerebellar Ataxias |
A recent report that microinjection of the SH3 domain of PLC-gamma1 could induce DNA synthesis raised the functional importance of the SH3 domain of PLC-gamma1 in mitogenic signaling. In this report, we provide evidence that SOS1, a p21Ras-specific guanine nucleotide exchange factor, directly binds to the SH3 domain of PLC-gamma1, and that the SH3 domain of PLC-gamma1 is involved in SOS1-mediated p21Ras activation. SOS1 was coprecipitated with the GST-fused SH3 domain of PLC-gamma1 in vitro. The interaction between SOS1 and the PLC-gamma1 SH3 domain is mediated by direct physical interaction. The carboxyl-terminal proline-rich domain of SOS1 is involved in the interaction with the PLC-gamma1 SH3 domain. Moreover, PLC-gamma1 could be co-immunoprecipitated with SOS1 antibody in cell lysates. From transient expression studies, we could demonstrate that the SH3 domain of PLC-gamma1 is necessary for the association with SOS1 in vivo. Intriguingly, overexpression of the SH3 domain of PLC-gamma1, lipase-inactive PLC-gamma1, or wild-type PLC-gamma1 elevated p21Ras activity and ERK activity when compared with vector transfected cells. The PLC-gamma1 mutant lacking the SH3 domain could not activate p21Ras. p21Ras activities in cell lines overexpressing either PLC-gamma1 or the SH2-SH2-SH3 domain of PLC-gamma1 were elevated about 2-fold compared to vector transfected cells. This study is the first to demonstrate that the PLC-gamma1 SH3 domain enhances p21Ras activity, and that the SH3 domain of PLC-gamma1 may be involved in the SOS1-mediated signaling pathway. | SOS1 Protein |
Addition of LDA to a mixture of trimethylborate and dibromomethane in THF at a temperature of -78 degrees C leads to the formation of dibromomethyllithium and its capture by borate ester. ClB(OMe)(2) converts the resulting borate salt to dimethoxy(dibromomethyl)borane 2. N,N-Dimethylamino(methoxy)(dibromomethyl)borane 3 and N,N-bis(dimethylamino)(dibromomethyl)borane 4 were prepared by an amination reaction between N,N-dimethylaminotrimethylsilane and dimethoxy(dibromomethyl)borane 2. To obtain dichlorotrimethylsilylmethylborane 7 not containing the alpha-halomethyl group, N,N-bis(dimethylamino)(trimethylsilylmethyl)borane 5 was first obtained from the reaction of ClB(NMe(2))(2) with an organolithium reagent. Dimethoxy(trimethylsilylmethyl)borane 6 was then prepared by methoxylation of compound 5. Finally, compound 7 was prepared by chlorination of 6 using BCl(3). The chemical structures of these compounds were determined using (13)C, (1)H, (11)B NMR and GC/MS/MS techniques. | Boranes |
Malva parviflora is used as food in the gastronomy of some regions of Mexico and, also, in Mexican traditional medicine for inflammation-related conditions like rheumatoid arthritis. The objective of this work was to evaluate its antiarthritic activity in a mice model. In ICR, female mice were tested the dichloromethane extract (MpD) and fractions MpF4 (extracted with a dichoromethane:methanol system) and MpFphy (a precipitate by acetone:methanol) by using the mono-arthritis with kaolin/carrageenan model. During the treatment, joint inflammation was measured daily, and hyperalgesia was measured using the hot plate test. The treatments diminished both joint inflammation and pain. At the end of the evaluation, the left joint and spleen were extracted for determination of pro- and anti-inflammatory cytokines. The results showed that the MpD, MpF4, and MpFphy treatments modulated the concentration of these proteins. Specifically, MpFphy at 1.0 mg/kg increased IL-4 and IL-10 and decreased IL-17, IL-1beta, and TNF-alpha. GC-MS analysis showed that MpF4 contained a mixture of a total of nine compounds, three of them newly reported for the species. The studies confirmed the presence of five sterols in the MpFphy fraction, including stigmasterol and beta-sitosterol. These results confirm the anti-rheumatoid and anti-inflammatory activities of a fraction rich in sterols from Malva parviflora. Graphical abstract. | Malva |
Detailed investigations on the physicochemical and structural characterization of chlorophyll loaded microcapsules and their storage stability have not previously been conducted. Therefore, our objective was to encapsulate unstable chlorophylls using different blends of gum Arabic (GA) and maltodextrin (MD) (GA-MD ratios of 5:5, 3:7, and 0:10) by spray-drying to improve storage stability of chlorophylls. An increase in concentration of MD in wall materials was associated with lower moisture content (0.56%), higher encapsulation efficiency (77.19%), chlorophyll content (46.78â¯microg/g dry powder), degree of crystallinity, and thermal stability of microcapsules. Furthermore, FTIR, XRD, and DSC analyses confirmed inclusion of chlorophylls within microcapsules. The entrapment of chlorophylls within microcapsules enhanced their storage stability at all temperatures (4, 20, and 40⯠degrees C) for ten days; notably, microcapsules coated with MD alone showed the highest storage stability (94.7-97.5%). In conclusion, microencapsulation of chlorophylls using MD alone was optimal for enhancing chlorophylls' storage stability. | Drug Storage |
Effects of ligand binding on protein dynamics are studied via molecular dynamics (MD) simulations on two different enzymes, dihydrofolate reductase (DHFR) and triosephosphate isomerase (TIM), in their unliganded (free) and liganded states. Domain motions in MD trajectories are analyzed by collectivities and rotation angles along the principal components (PCs). DHFR in the free state has well-defined domain rotations, whereas rotations are slightly damped in the binary complex with nicotinamide adenine dinucleotide phosphate (NADPH), and remarkably distorted in the presence of NADP(+) , showing that NADP(+) is solely responsible for the loss of correlation of the domains in DHFR. Although mean square fluctuations of MD simulations in the same PC subspaces are similar for different ligation states, linear stochastic time series models show that backbone flexibility along the first five PCs is decreased upon NADPH and NADP(+) binding in subpicosecond scale. This shows that mobility of the protein along the PCs is closely related with intraminimum dynamics, and alterations in ligation states may change the intraminimum dynamics significantly. Low vibrational frequencies of the alpha-carbon atoms of DHFR are determined from the time series models of a larger number of low indexed PCs, and it is found that number of modes in the lowest frequencies is reduced upon ligand binding. A similar result is obtained for TIM in the unliganded and dihydroxyacetone phosphate bound states. We suggest that stochastic time series modeling is a promising method to be used in determining subtle perturbations in protein dynamics." | Tetrahydrofolate Dehydrogenase |
OBJECTIVE: In this paper, Dr. Joan Stevenson's work on assessment of the effects of lifting, supporting and transporting loads is reviewed. A defining attribute of this work is the use of objective, biomechanical measures as the basis from which a fuller understanding of all factors affecting worker performance can be obtained, and how such performance should be measured and evaluated. METHODS: The central objectives and conclusions of Dr. Stevenson's research programs spanning the years from 1985 through 2012 are summarized and discussed in terms of an overall research trajectory. CONCLUSIONS: The guiding principle of Dr. Stevenson's work is to reduce the potential harm to which workers are exposed through the development of bona fide occupational standards, a better understanding of risk factors leading to low back pain, and the establishment of an enhanced objective design process for functional load-bearing clothing and equipment. | Lifting |
BACKGROUND: In past reports, researchers have seldom attached importance to achievements in transforming digital anatomy to radiological diagnosis. However, investigators have been able to illustrate communication relationships in the retroperitoneal space by drawing potential routes in computerized tomography (CT) images or a virtual anatomical atlas. We established a new imaging anatomy research method for comparisons of the communication relationships of the retroperitoneal space in combination with the Visible Human Project and CT images. Specifically, the anatomic pathways of peripancreatic fluid extension to the mediastinum that may potentially transform into fistulas were studied. METHODS: We explored potential pathways to the mediastinum based on American and Chinese Visible Human Project datasets. These drainage pathways to the mediastinum were confirmed or corrected in CT images of 51 patients with recurrent acute pancreatitis in 2011. We also investigated whether additional routes to the mediastinum were displayed in CT images that were not in Visible Human Project images. PRINCIPAL FINDINGS: All hypothesized routes to the mediastinum displayed in Visible Human Project images, except for routes from the retromesenteric plane to the bilateral retrorenal plane across the bilateral fascial trifurcation and further to the retrocrural space via the aortic hiatus, were confirmed in CT images. In addition, route 13 via the narrow space between the left costal and crural diaphragm into the retrocrural space was demonstrated for the first time in CT images. CONCLUSION: This type of exploration model related to imaging anatomy may be used to support research on the communication relationships of abdominal spaces, mediastinal spaces, cervical fascial spaces and other areas of the body. | Visible Human Projects |
When attending veterinarians are not provided adequate job security by research in-stitutions, there is no guarantee that they are reliable allies of nonhuman animals and implement the provisions set forth in the federal animal welfare regulations. | Contract Services |
The family Matonaviridae comprises enveloped viruses with positive-sense RNA genomes of 9.6-10 kb. The genus Rubivirus includes rubella virus (species Rubivirus rubellae) infecting humans, ruhugu virus (species Rubivirus ruteetense) infecting bats and rustrela virus (species Rubivirus strelense) infecting rodents and zoo animals. Rubella virus is spread via droplets. Postnatal infection leads to benign disease with rash and fever. Infection of seronegative women with rubella virus during the first trimester of pregnancy will often result in severe foetal malformations, known as congenital rubella syndrome. Vaccines are globally available. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Matonaviridae, which is available at ictv.global/report/matonaviridae. | Rubivirus |
BACKGROUND: Cough-suppressant therapy, previously termed nonspecific antitussive therapy, incorporates the use of pharmacologic agents with mucolytic effects and/or inhibitory effects on the cough reflex itself. The intent of this type of therapy is to reduce the frequency and/or intensity of coughing on a short-term basis. METHODS: Data for this review were obtained from several National Library of Medicine (PubMed) searches (from 1960 to 2004), which were performed between May and September 2004, of the literature published in the English language, limited to human studies, using combinations of the search terms cough," "double-blind placebo-controlled," "antitussive," "mucolytic," "cough clearance," "common cold," "protussive," "guaifenesin," "glycerol," and "zinc." RESULTS: Mucolytic agents are not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Peripheral and central antitussive agents can be useful in patients with chronic bronchitis, but can have little efficacy in patients with cough due to upper respiratory infection. Some protussive agents are effective in increasing cough clearance, but their long-term effectiveness has not been established. DNase is not effective as a protussive agent in patients with cystic fibrosis. Inhaled mannitol is acutely effective in this patient population, but its therapeutic potential must be investigated further. CONCLUSIONS: These findings suggest that suppressant therapy is most effective when used for the short-term reduction of coughing. Relatively few drugs are effective as cough suppressants." | Antitussive Agents |
There are limited methods available to study skeletal stem, progenitor, and progeny cell activity in normal and diseased contexts. Most protocols for skeletal stem cell isolation are based on the extent to which cells adhere to plastic or whether they express a limited repertoire of surface markers. Here, we describe a flow cytometry-based approach that does not require in vitro selection and that uses eight surface markers to distinguish and isolate mouse skeletal stem cells (mSSCs); bone, cartilage, and stromal progenitors (mBCSPs); and five downstream differentiated subtypes, including chondroprogenitors, two types of osteoprogenitors, and two types of hematopoiesis-supportive stroma. We provide instructions for the optimal mechanical and chemical digestion of bone and bone marrow, as well as the subsequent flow-cytometry-activated cell sorting (FACS) gating schemes required to maximally yield viable skeletal-lineage cells. We also describe a methodology for renal subcapsular transplantation and in vitro colony-formation assays on the isolated mSSCs. The isolation of mSSCs can be completed in 9 h, with at least 1 h more required for transplantation. Experience with flow cytometry and mouse surgical procedures is recommended before attempting the protocol. Our system has wide applications and has already been used to study skeletal response to fracture, diabetes, and osteoarthritis, as well as hematopoietic stem cell-niche interactions in the bone marrow. | Colony-Forming Units Assay |
The partitioning of 10% (w/w) lactic acid in ethylene oxide propylene oxide (EOPO) random copolymers and dextran T500 aqueous two-phase systems was studied. An analysis of variance design was applied to investigate the effect of pH, polymer concentration, and addition of polyethyleneimine to the aqueous two-phase systems. The lowest lactate partition coefficient of 0.09 was obtained at pH 6 in the systems containing 7.2% (w/w) polyethyleneimine. The use of polyethyleneimine as titrating base during the fermentative production of lactic acid was evaluated in batch fermentations with 100 g/l glucose. Yield and productivity of polyethyleneimine titrated fermentations compared with those obtained in fermentations titrated with NaOH and KOH. | Polyenes |
The role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-alpha), interferon beta (IFN-beta), interferon gamma (IFN-gamma), interferon lambda (IFN-lambda), pro-interleukin(IL)-1beta (pro-IL-1beta), and IL-18 was determined on admission, between 5-9 days, and between 10-15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4. | Toll-Like Receptor 3 |
Chlorobutanol (CB) is a pharmaceutical preservative and the active ingredient in certain sedatives and anesthetics and produces adverse effects in adult tissues and mouse embryos in vitro. Chlorobutanol is slowly eliminated in humans, but little is known about its serum levels in other species or placental transfer in any species. Pregnant mice gavaged with 80 mg CB/kg on gestational day (gd) 9.5 provided serum at 10 min to 36 h post-dosing for a time course study. Additional mice gavaged with 0, 8, 40 or 80 mg CB/kg on gd 9.5 provided maternal serum and embryos 2 h post-dosing for a placental transfer study, and CB levels were measured using capillary gas chromatography with electron capture detection. Dosing with 80 mg CB/kg produced maternal serum levels between 30.8 micrograms/mL (10 min) and < 1 microgram/mL (36 h), with a half-life of 7.45 h. Embryonic CB levels increased with maternal dose and were correlated with maternal serum levels. Serum levels of CB in the mouse appeared to follow a time course similar to humans, with rapid absorption and slow elimination. Placental transfer, as demonstrated here in the mouse, may allow embryonic accumulation of CB to potentially toxic levels. | Chlorobutanol |
The costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with FcgammaR interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8(N/C)EGa1, consisting of three anti-4-1BB single-chain variable fragments and three anti-EGFR single-domain antibodies positioned in an extended hexagonal conformation around the collagen XVIII homotrimerization domain. The1D8(N/C)EGa1 trimerbody demonstrated high-avidity binding to 4-1BB and EGFR and a potent in vitro costimulatory capacity in the presence of EGFR. The trimerbody rapidly accumulates in EGFR-positive tumors and exhibits anti-tumor activity similar to IgG-based 4-1BB-agonistic mAbs. Importantly, treatment with 1D8(N/C)EGa1 does not induce systemic inflammatory cytokine production or hepatotoxicity associated with IgG-based 4-1BB agonists. These results implicate FcgammaR interactions in the 4-1BB-agonist-associated immune abnormalities, and promote the use of the non-canonical antibody presented in this work for safe and effective costimulatory strategies in cancer immunotherapy." | Tumor Necrosis Factor Receptor Superfamily, Member 9 |
Granulomatous disease may be due to multiple etiologies, including infections, inflammation, and foreign substances. A granuloma results from the accumulation of immune cells around this agent that the body recognizes as unnatural. While often nonspecific, unique clues may be ascertained with appropriate history and correlation across modalities that allow for a specific diagnosis without the need for an unnecessary biopsy. | Granuloma, Foreign-Body |
BACKGROUND: Obesity in Canada is a growing concern, but little is known about the available services for managing obesity in adults. Our objectives were to (a) survey and describe programs dedicated to weight management and (b) evaluate program adherence to established recommendations for care. METHODS: We conducted an online environmental scan in 2011 to identify adult weight management services throughout Canada. We examined the degree to which programs adhered to the 2006 Canadian Clinical Practice Guidelines on the Management and Prevention of Obesity in Adults and Children (CCPGO) and the analysis criteria developed by the Association pour la Sante Publique du Quebec (ASPQ). RESULTS: A total of 83 non-surgical (34 community-based, 42 primary care-based, 7 hospital-based) and 33 surgical programs were identified. All programs encouraged patient self-management. However, few non-surgical programs adhered to the CCPGO recommendations for assessment and intervention, and there was a general lack of screening for eating disorders, depression and other psychiatric diseases across all programs. Concordance with the ASPQ criteria was best among primary care-based programs, but less common in other settings with deficits most frequently revealed in multidisciplinary health assessment/management and physical activity counselling. CONCLUSIONS: With more than 60% of Canadians overweight or obese, our findings highlight that availability of weight management services is far outstripped by need. Our observation that evidence-based recommendations are applied inconsistently across the country validates the need for knowledge translation of effective health services for managing obesity in adults. | Weight Reduction Programs |
Few who were actively engaged in malaria vaccine research 20 years ago (including myself) would have imagined that, in 2005, there would still be a prediction of a 10-20-year horizon before vaccines become part of malaria-control strategies. Why is it still proving so challenging to produce effective vaccines? | Malaria Vaccines |
An ellagitannin with a 2,4-acyl group, named macabarterin (1), and a new ellagic acid glycoside, 3-O-methylellagic acid 4-O-beta-d-xylopyranoside (2), were isolated from the stem bark extract of Macaranga barteri along with five known phenolic compounds, ellagic acid (3), 3-O-methylellagic acid (4), gallic acid (5), methyl gallate (6), and scopoletin (7). The structures of 1 and 2, as well as those of the known compounds, were elucidated on the basis of spectroscopic data and by comparison with reported data. Compounds 1-5 and 7 were tested for their anti-inflammatory potential in a cell-based respiratory burst assay, compound 1 being found an inhibitor of the superoxides produced in the cellular system. | Ellagic Acid |
Piper betle (PB) is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs) was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%), presenescent (127.3%), and senescent (157.3%) HDFs. Increased expressions of PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions of SOD1 increased, whereas GPX1, PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways. | Piper betle |
INTRODUCTION: A prospective payment system per DRG is announced in Belgium. Is this kind of financing system adequate for oncology? Objectives of this study are: to analyze medical and economical characteristics of oncological inpatients and evaluate the homogeneity of costs and length of stay per DRG. METHODS: The study was realized in 14 Belgian hospitals, with 2010 data. Inpatients with primary diagnosis of neoplasms were selected in medical and administrative databases. Characteristics of patients as well as length of stay and cost (hospital perspective) were analyzed. The homogeneity of costs and length of stay is measured by calculating the coefficient of variation (standard deviation divided by the mean). RESULTS: The length of stay (standard deviation) is 9.72 days (12.64). The variation is high per DRG. The average cost (standard deviation) is 7689.28euro (10,418) and is also variable from one DRG to another one. There are 5% of high-length of stay outliers and 0.2% of low-length of stay outliers. There are 4.7% of high-cost outliers and 0.2% of low-cost outliers. The withdrawal of outliers improves the homogeneity of cost and length of stay per APR-DRG. DISCUSSION AND CONCLUSION: There is a homogeneity of costs and length of stay per DRG and per severity of illness. A prospective payment system per DRG would probably be applicable for these patients. It is however necessary to plan an appropriate and additional financing of all elements susceptible to stimulate innovation in the management of oncology and to stimulate the quality of care by adding financial stimulants. | Outliers, DRG |
Circular RNAs (circRNAs) are highly expressed in the brain and their expression increases during neuronal differentiation. The factors regulating circRNAs in the developing mouse brain are unknown. NOVA1 and NOVA2 are neural-enriched RNA-binding proteins with well-characterized roles in alternative splicing. Profiling of circRNAs from RNA-seq data revealed that global circRNA levels were reduced in embryonic cortex of Nova2 but not Nova1 knockout mice. Analysis of isolated inhibitory and excitatory cortical neurons lacking NOVA2 revealed an even more dramatic reduction of circRNAs and establishes a widespread role for NOVA2 in enhancing circRNA biogenesis. To investigate the cis-elements controlling NOVA2-regulation of circRNA biogenesis, we generated a backsplicing reporter based on the Efnb2 gene. We found that NOVA2-mediated backsplicing of circEfnb2 was impaired when YCAY clusters located in flanking introns were mutagenized. CLIP (cross-linking and immunoprecipitation) and additional reporter analyses demonstrated the importance of NOVA2 binding sites located in both flanking introns of circRNA loci. NOVA2 is the first RNA-binding protein identified to globally promote circRNA biogenesis in the developing brain." | Neuro-Oncological Ventral Antigen |
Cyanobacteria are prokaryotic photosynthetic microorganisms that pose a serious threat to aquatic environments because they are able to form blooms under eutrophic conditions and produce toxins. Cylindrospermopsis raciborskii is a planktonic heterocystous filamentous cyanobacterium initially assigned to the tropics but currently being found in more temperate regions such as Portugal, the southernmost record for this species in Europe. Cylindrospermopsin originally isolated from C. raciborskii is a cytotoxic alkaloid that affects the liver, kidney, and other organs. It has a great environmental impact associated with cattle mortality and human morbidity. Aiming in monitoring this cyanobacterium and its related toxin, a shallow pond located in the littoral center of Portugal, Vela Lake, used for agriculture and recreational purposes was monitored for a 2-year period. To accomplish this, we used the real-time PCR methodology in field samples to quantify the variation of specific genetic markers with primers previously described characterizing total cyanobacteria (16S rRNA), C. raciborskii (rpoC1), and cylindrospermopsin synthetase gene (pks). The results report the high abundance of both cyanobacteria and C. raciborskii in Vela Lake, with C. raciborskii representing 0.4% to 58% of the total cyanobacteria population. Cylindrospermopsin synthetase gene was detected in one of the samples. We believe that with the approach developed in this study, it will be possible to monitor C. raciborskii population dynamics and seasonal variation, as well as the potential toxin production in other aquatic environments. | Cylindrospermopsis |
Actin is composed of two well-separated globular domains which are further subdivided into two subdomains [Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., & Holmes, K. C. (1990) Nature 347, 37-44]. Subdomains 1 and 2 constitute the small domain, and subdomains 3 and 4 comprise the large domain. In order to test a hinge bending domain motion in actin such as observed in many kinases, fluorescence resonance energy transfer between two probes attached to each of the two domains was measured by steady-state and time-resolved fluorometers. The adenine base is bound in a hydrophobic pocket between subdomains 3 and 4, and Tyr-69 is located at subdomain 2. In the present study, the adenine moiety was labeled with a fluorescence donor, epsilon ATP, and tyrosine-69 was labeled with the energy acceptor, dansyl chloride. Assuming the random orientation factor k2 = 2/3, the distance between epsilon-adenine moiety and dansyl chloride attached to Tyr-69 in G-actin was determined to be 2.46 nm from steady-state fluorescence measurements. The addition of DNase I did not appreciably change the distance (less than 0.1 nm). The distance decreased to 2.27 nm during polymerization by the addition of phalloidin under physiological salt conditions. On the other hand, time-resolved fluorescence energy transfer measurements have been used to investigate a distribution of distances for a donor-acceptor pair. In G-actin, the mean distance between probes was 2.79 nm with a full width at half-maximum of 3.91 nm, indicating a large number of conformational substates in solution.(ABSTRACT TRUNCATED AT 250 WORDS) | Ethenoadenosine Triphosphate |
In this essay I explore the risks of activism I witnessed in two protesters' accounts of participating in collective protest. Listening to their stories led me to reflect on matters of well-being, embodiment and vulnerability, vicarious trauma, and the prospect of physical and emotional burnout. Protesters often put themselves in harm's way to fight for a greater good. I contend that participating in peaceful protest serves personal well-being while also contributing to broader societal senses of what constitutes a well-lived life. For better and worse, every instance etches itself on vulnerable flesh, blood, and being-in-the-world. | Personal Satisfaction |
The IGFBPs are a family of homologous proteins that have co-evolved with the IGFs and that confer upon the IGF regulatory system both functional and tissue specificity. IGFBPs are not merely carrier proteins for IGFs, but hold a central position in IGF ligand-receptor interactions through influences on both the bioavailability and distribution of IGFs in the extracellular environment. In addition, IGFBPs appear to have intrinsic biological activity independent of IGFs. The current status of research on IGFBPs is reviewed herein. Following a brief introduction to the entire IGF/IGFBP system, separate sections for each of the six cloned mammalian IGFBPs, the most extensive for IGFBP3, cover selected topics that emphasize the dynamics of IGFBPs--that is, their regulation in cells, their functionally important post-translational modifications, and their interactions in the cellular microenvironment--and how these dynamics influence physiological function." | Insulin-Like Growth Factor Binding Proteins |
Nursing care for a patient with AIP can be challenging. AIP is a complex disease with various signs and symptoms and is often misdiagnosed. Recognition of the signs and symptoms of AIP could be life-saving. Ways to avoid exacerbations, as well as counseling regarding possible genetic transmission, are important aspects of the nursing care of individuals with AIP. | Porphyrias, Hepatic |
Endothelial microparticles (EMP) released from activated or apoptotic endothelial cells (EC) are emerging as useful markers for detection of EC dysfunction. Our recent observation that EMP carry von Willebrand factor (vWf) led us to investigate their interaction with platelets. EMP were incubated with normal washed platelets in the presence or absence of ristocetin, then platelet aggregates were measured by flow cytometry. In the absence of ristocetin, negligible EMP conjugated with platelets (< 5%) but in the presence of ristocetin (1 mg mL(-1)), EMP induced up to 95% of platelets to aggregate. EMP-platelet interaction was 80% blocked by anti-CD42b, or by 0.1 microm filtration to remove EMP. Platelet aggregates induced by normal plasma or high molecular weight vWf (Humate-P) dissociated 50% within 15-25 min following 1:20 dilution. In contrast, aggregates formed with EMP persisted two- to threefold longer with the same treatment, indicating greater stability. A similar degree of prolongation of dissociation was observed using plasma from thrombotic thrombocytopenic purpura (TTP) patients compared with normal plasma. Addition of EMP to plasma from severe von Willebrand disease restored his ristocetin-induced platelet aggregation. Multimer analysis of vWf on EMP showed unusually large vWf (ULvWf). In summary, EMP carries ULvWf multimers, promote platelet aggregates, and increase the stability of the aggregates thus formed. | Ristocetin |
Cyclic diadenosine monophosphate (c-di-AMP) is a bacterial cyclic dinucleotide (CDN) comprising two adenosine monophosphates covalently linked by two 3',5'-phosphodiester bonds. c-di-AMP works as a second messenger, regulating many biological processes in bacteria such as cell wall homeostasis, DNA integrity, and sporulation via specific protein and/or RNA receptors. Moreover, c-di-AMP can function as an immunomodulatory agent in eukaryote cells via the stimulator of interferon genes (STING) signaling pathway. This protocol describes the chemical synthesis of two c-di-AMP analogs with a sulfur atom at the 4'-position of the furanose ring instead of an oxygen atom: c-di-4'-thioAMP (1) and cAMP-4'-thioAMP (2). Analogs 1 and 2 have resistance to phosphodiesterase-mediated degradation and are therefore useful for understanding the diverse biological phenomena regulated by c-di-AMP. In this protocol, two 4'-thioadenosine monomers are initially prepared via a Pummerer-like reaction assisted by hypervalent iodine. The CDN skeleton is then constructed through two key reactions based on phosphoramidite chemistry: dimerization of two appropriately protected nucleoside monomers to produce a linear dinucleotide, followed by macrocyclization of the resulting linear dinucleotide to form the CDN skeleton. (c) 2023 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 4'-thioadenosine monomers 13 and 14 Basic Protocol 2: Preparation of c-di-4'-thioAMP (1) and cAMP-4'-thioAMP (2). | Thionucleosides |
BACKGROUND: Adalimumab dose escalation is often recommended for inflammatory bowel disease patients in cases of loss of response. The usual adalimumab intensification regimen was 40 mg every week. Recently the pharmaceutical companies commercialized the 80mg injection pen. In the biosimilars era, this pen was sold at the same price as the 40mg pen. Due to this and for patient comfort, we proposed that our stable intensified adalimumab patients on a 40mg every-week regimen, change to a dose of 80mg every-other-week. AIM AND METHODS: an observational study was performed to monitor outcome through this posologic change. Clinical, analytic parameters and adalimumab trough levels were prospectively obtained at baseline, 4 and 12 months after posologic change. The evolution of this cohort and calculates savings were described. RESULTS: 13 patients were included in the study and the median time of adalimumab intensification prior to posologic change to 80mg eow was 32 months (IQR 29-63). At 4 months, all patients maintained adalimumab 80mg every-other-week. After month 4, two patients returned to the previous regimen after mild worsening, without significant changes in CRP, calprotectin or adalimumab-trough-levels. At 1 year, adalimumab was stopped in one patient in remission with undetectable levels and positive adalimumab-antibodies. No significant differences in adalimumab-trough-levels were noted before and after the posologic change. Costs fell from 16276 euro/patient/year of treatment to 8812.15 euro/patient/year of treatment. CONCLUSION: In IBD patients with stable response to adalimumab intensification regimen of 40 mg every-week, changing to 80mg every-other-week seems to maintain response and similar adalimumab-trough-levels. Furthermore, it is cost-saving, although some patients may perceive mild symptoms. | Adalimumab |
Preoperative weight loss before a bariatric surgery reduces long-term complications, but there is no solid evidence for short-term or perioperative complications. This review highlights recent evidence on dietary protocols and the possible correlation between weight loss and surgical complications. Updated evidence was searched in PubMedDirect with the terms preoperative very low-calorie diet or very-low-calorie ketogenic diet or low-fat diet or intermittent fasting or Mediterranean diet and bariatric surgery or bariatric surgery complications." The main characteristics of each diet, achievements related to weight loss, liver reduction, peri and postoperative outcomes, surgical complications, tolerance, and adherence to the diet are presented from the selected studies. There are few reports about the Mediterranean diet as a strategy to reach these goals. The VLCKD has been associated with better body weight reduction and lesser postoperative complications risk. However, the results in animal models are still controversial. When comparing VLCD with an LCD, there is no apparent superiority between one against the other one. However, LCD has shown better tolerance and adherence than VLCD. There is still a need for more controlled studies to define the best preoperative dietary treatment for weight loss before bariatric surgery since there are controversial positions regarding this issue." | Caloric Restriction |
Nodular mucinosis of the breast is an extraordinarily rare lesion that occurs in patients who do not have Carney syndrome. Typically, the affected patients are young women with no medical history and a nodule under 1 nipple. Histopathologic examination has, until now, shown a multinodular myxoid lesion containing scattered capillaries and histiocytes but void of epithelial components. We present the case of a 72-year-old woman with a history of mucinous carcinoma of the breast who now presents with a painful subareolar nodule of the same breast. Biopsy and histological examination confirmed nodular mucinosis of the breast. | Mucinoses |
The majority of colorectal cancers harbor loss-of-function mutations in APC, a negative regulator of canonical Wnt signaling, leading to intestinal polyps that are predisposed to malignant progression. Comparable murine APC alleles also evoke intestinal polyps, which are typically confined to the small intestine and proximal colon, but do not progress to carcinoma in the absence of additional mutations. The Cdx transcription factors Cdx1 and Cdx2 are essential for homeostasis of the intestinal epithelium, and loss of Cdx2 has been associated with more aggressive subtypes of colorectal cancer in the human population. Consistent with this, concomitant loss of Cdx1 and Cdx2 in a murine APC mutant background leads to an increase in polyps throughout the intestinal tract. These polyps also exhibit a villous phenotype associated with the loss of EphrinB1. However, the basis for these outcomes is poorly understood. To further explore this, we modeled Cdx2 loss in SW480 colorectal cancer cells. We found that Cdx2 impacted Notch signaling in SW480 cells, and that EphrinB1 is a Notch target gene. As EphrinB1 loss also leads to a villus tumor phenotype, these findings evoke a mechanism by which Cdx2 impacts colorectal cancer via Notch-dependent EphrinB1 signaling. | CDX2 Transcription Factor |
The modulation of apoptosis has emerged as an important weapon in the pathogenic arsenal of multiple intracellular protozoan parasites. Cryptosporidium parvum, Leishmania spp., Trypanosoma cruzi, Theileria spp., Toxoplasma gondii and Plasmodium spp. have all been shown to inhibit the apoptotic response of their host cell. While the pathogen mediators responsible for this modulation are unknown, the parasites are interacting with multiple apoptotic regulatory systems to render their host cell refractory to apoptosis during critical phases of intracellular infection, including parasite invasion, establishment and replication. Additionally, emerging evidence suggests that the parasite life cycle stage impacts the modulation of apoptosis and possibly parasite differentiation. Dissection of the host-pathogen interactions involved in modulating apoptosis reveals a dynamic and complex interaction that recent studies are beginning to unravel. | Eukaryota |
The stability of N-formimidoylthienamycin in aqueous solution at 25 and 40 degrees was determined. In pH 5-8 nonnucleophilic inert buffers, pseudo-first-order ring opening was observed with dilute solutions (1 or 2 mg/ml initially). At higher initial concentrations, a second-order reaction also was evident. The rate data were compared with literature data for various cephalosporins and penicillins. | Lactams |
Herein we report the conversion of aldehyde-containing potassium and tetrabutylammonium organotrifluoroborates to the corresponding amines through reductive amination protocols. Potassium formate facilitated by catalytic palladium acetate, sodium triacetoxyborohydride, and pyridine borane have all served as effective hydride donors, reducing the initially formed imines or iminium ions to provide the corresponding amines. | Borates |
Skeletal muscle cells are noteworthy for their syncytial nature, with each myofiber accumulating hundreds or thousands of nuclei derived from resident muscle stem cells (MuSCs). These nuclei are accrued through cell fusion, which is controlled by the two essential fusogens Myomaker and Myomerger that are transiently expressed within the myogenic lineage. While the absolute requirement of fusion for muscle development has been known for decades, the underlying need for the magnitude of multinucleation in muscle remains mysterious. Possible advantages of multinucleation include the potential it affords for transcriptional diversity within these massive cells, and as a means of increasing DNA content to support optimal cell size and function. In this article, we review recent advances that elucidate the relationship between myonuclear numbers and establishment of myofiber size, and discuss how this new information refines our understanding of the concept of myonuclear domains (MND), the cytoplasmic volumes that each resident myonucleus can support. Finally, we explore the potential consequences and costs of multinucleation and its impacts on myonuclear transcriptional reserve capacity, growth potential, myofiber size regulation, and muscle adaptability. We anticipate this report will not only serve to highlight the latest advances in the basic biology of syncytial muscle cells but also provide information to help design the next generation of therapeutic strategies to maintain muscle mass and function. | Muscle Development |
An extract of leaves and stems of Peperomia villipetiola has been found to contain myristicin (3-methoxy-4,5-methylenedioxy-allylbenzene) and seven chromenes, whose structures are methyl 5-hydroxy-7-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (1), methyl 5-methoxy-7-methyl-2,2-dimethyl-2H-1-chromene-8-carboxylate (2), methyl 7-hydroxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (3), methyl 7-methoxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (4), 5-methanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (5), 5-methanol-7-methoxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (6), and methyl 5-acetoxymethanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate (7). A biosynthetic rationale for 1-7 suggests that orsellinic acid may be a common intermediate. The anti-fungal activities of the chromenes were measured bioautographically against Cladosporium cladosporioides and Cladosporium sphaerospermum: compounds 6 and 7 were found to be the most active. | Peperomia |
Nitric oxide is generated under normal and pathophysiological conditions by three distinct isoforms of nitric oxide synthase (NOS). A small-molecule inhibitor of NOS (3-Br-7-nitroindazole, 7-NIBr) is profoundly neuroprotective in mouse models of stroke and Parkinson's disease. We report the crystal structure of the catalytic heme domain of endothelial NOS complexed with 7-NIBr at 1.65 A resolution. Critical to the binding of 7-NIBr at the substrate site is the adoption by eNOS of an altered conformation, in which a key glutamate residue swings out toward one of the heme propionate groups. Perturbation of the heme propionate ensues and eliminates the cofactor tetrahydrobiopterin-heme interaction. We also present three crystal structures that reveal how alterations at the substrate site facilitate 7-NIBr and structurally dissimilar ligands to occupy the cofactor site. | Nitroarginine |
There is considerable evidence that chronic moderate-to-high alcohol consumption increases blood pressure. The mechanisms by which this occurs are not clear. Alcohol consumption can induce oxidative stress and cytochrome P450 (CYP450) isoforms that are associated with oxidative stress and may influence vascular tone. To study the role of such mechanisms we examined whether reducing alcohol intake in moderate-to-heavy drinkers (40-110 g/day) resulted in changes in urinary excretion of 20-HETE, a CYP450 metabolite of arachidonic acid, and plasma and urinary F(2)-isoprostanes as markers of lipid peroxidation. After a 4-week run-in period during which healthy men maintained their usual drinking pattern they were randomized to a two-way crossover intervention study. In each of the 4-week treatment periods subjects either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake. Plasma and urinary F(2)-isoprostanes and urinary 20-HETE were measured by gas chromatography mass spectrometry, and serum gamma-glutamyl transpeptidase (gamma-GT) was measured as a biomarker of alcohol consumption, at the end of each study period. Sixteen healthy men age 51.0+/-2.7 years and with a BMI of 26.4+/-0.61 kg/m(2) completed the study. The reductions in alcohol intake (72.4+/-5.0 vs 7.9+/-1.6 g/day, p<0.001) and serum gamma-GT (geometric mean 24.4 U/L (95% CI 19.7, 30.2) vs 18.6 U/L (95% CI 15.5, 22.2, p<0.01) were accompanied by a significant fall in blood pressure as well as urinary 20-HETE excretion (158+/-23 vs 109+/-19 pmol/mmol creatinine, p<0.001) and plasma F(2)-isoprostanes (3438+/-158 vs 2929+/-145 pmol/L, p=0.01). A substantial reduction in alcohol consumption in healthy men lowered plasma F(2)-isoprostanes and urinary 20-HETE. Increased oxidative stress and 20-HETE production may be linked, at least in part, to the pathogenesis of alcohol-related hypertension. | F2-Isoprostanes |
INTRODUCTION: This review summarizes the research conducted on botulinum toxin (BoTx) from 1943 to 1956 by a small group of Camp Detrick investigators and their staff. A systematic, cross-disciplinary approach was used to develop effective vaccines against this biological warfare threat agent. In response to the potential need for medical countermeasures against BoTx during World War II, the refinement of isolation and purification techniques for BoTx successfully led to the large-scale production of botulinum toxoid vaccines. In addition, the work at Camp Detrick provided the foundation for the subsequent use of BoTx as a tool for studying the trophic regulation of skeletal muscle within motor neuron terminals and, more recently, for elucidation of the intricate details of neurotransmitter release at the molecular level. Indirectly, Camp Detrick investigators also played a significant role in studies that culminated in the use of BoTx as a pharmaceutical product that has been approved by the U.S. Food and Drug Administration for treating movement disorders, autonomic dysfunctions, and other conditions. METHODS: Online literature searches were performed with Google, Google Scholar, PubMed, the bibliography from the Camp Detrick technical library, and at the Defense Technical Information Center. Reference lists in some of the primary research publications and reviews also provided source material. Search terms included botulinum, botulinus, and Camp Detrick. References related to the subsequent impacts of the Camp Detrick results were selected and cited from reviews and primary references in the more recent literature. Notes on toxin nomenclature and potential sources of error in this study are presented. RESULTS: The literature searches returned 27 citations of Camp Detrick authors, 24 of which were articles in peer-reviewed journals. The publications by these investigators included several disciplines such as biochemistry, immunology, pharmacology, physiology, and toxicology. A fundamental finding was the identification of critical nutritional components for improved growth of Clostridium botulinum and the increased production of BoTx serotype A. The purification processes that were developed at Camp Detrick allowed for the production of crystalline material to be scaled up for the manufacture of toxoid vaccine. Based on the research by Camp Detrick scientists, a toxoid supply of over 1 million units was available to vaccinate ~300,000 troops before the large-scale operations of D-Day. CONCLUSIONS: BoTx research during the period 1943 to 1956 resulted in refinements in the techniques for isolating and purifying the crystalline BoTx type A. These results led to the development and manufacture of a toxoid vaccine that was available in a sufficient quantity to protect ~300,000 warfighters in a large-scale military operation. One of the most important long-term consequences derived from the knowledge gained by the efforts at Camp Detrick was the development in the 1980s of safe and effective therapeutic uses for BoTx type A, the most lethal biological substance known. | Biological Warfare Agents |
Recently, we demonstrated a biphasic induction of the epithelial broad-spectrum matrix metalloproteinase (MMP) stromelysin-2 during cutaneous wound healing. Now we have generated a murine wound cDNA libary and have used it to isolate the putative cDNA of this murine matrix metalloproteinase. The predicted sequence of the protein shows 76 and 89% identity with its human and rat analogues, respectively. Stromelysin-2 and stromelysin-1 transcripts were both detected at very low levels in the lung and the heart of adult Balb/c mice, whereas stromelysin-2 mRNA expression alone was found at comparatively high levels in the small intestine, a tissue characterized by continuous epithelial renewal. Recombinant forms of murine stromelysin-1 and -2 produced in transfected COS cells were secreted and could be induced to undergo autocatalytic processing by addition of the organomercurial salt 4-aminophenylmercuric acetate (APMA). | Phenylmercuric Acetate |
The lung is a common site of metastatic involvement and 5-year survival rates after complete surgical resection of lung metastases vary between 16 and 42%. As isolated limb or liver perfusion, isolated lung perfusion offers a new therapeutic option to deliver high-dose chemotherapy with minimal systemic side-effects (chapter 1). In our laboratory isolated lung perfusion was studied in a model of pulmonary metastatic adenocarcinoma in the rat and compared with intravenous chemotherapy. To improve results, techniques for intubation and anesthesia were modified and a new approach of catheterization of the pulmonary artery was developed (chapter 2). In a first series of experiments isolated lung perfusion was studied in a model of bilateral pulmonary metastases. Left isolated lung perfusion with melphalan and tumor necrosis factor was evaluated with the contralateral side serving as control (chapter 3). Toxicity, pharmacokinetic and toxicity studies were performed. Left lung melphalan levels were significantly higher after isolated lung perfusion compared to intravenous injection and significantly fewer left lung nodules were found. Tumor necrosis factor didn't show any significant effect in our model. In a second series of experiments long-term survival was evaluated after isolated lung perfusion with melphalan in a model of unilateral pulmonary metastases (chapter 4). All animals treated with melphalan intravenously died of massive tumor replacement of the left lung with a median survival time of 38 days. Rats undergoing isolated lung perfusion with melphalan had a significantly longer median survival time of 84 days (p < 0.0004). The left lung of three of the rats perfused with melphalan was even tumor-free at 3 months. In conclusion, isolated lung perfusion is effective in a rat model of pulmonary metastatic adenocarcinoma. Clinical studies are necessary to determine its effect on pulmonary metastases in man, especially in case of unresectable disease or possibly as adjuvant therapy after surgical resection." | Chemotherapy, Cancer, Regional Perfusion |
The C-terminal cytoplasmic tail of polycystin-2 (PC2/TRPP2), a Ca(2+)-permeable channel, is frequently mutated or truncated in autosomal dominant polycystic kidney disease. We have previously shown that this tail consists of three functional regions: an EF-hand domain (PC2-EF, 720-797), a flexible linker (798-827), and an oligomeric coiled coil domain (828-895). We found that PC2-EF binds Ca(2+) at a single site and undergoes Ca(2+)-dependent conformational changes, suggesting it is an essential element of Ca(2+)-sensitive regulation of PC2 activity. Here we describe the NMR structure and dynamics of Ca(2+)-bound PC2-EF. Human PC2-EF contains a divergent non-Ca(2+)-binding helix-loop-helix (HLH) motif packed against a canonical Ca(2+)-binding EF-hand motif. This HLH motif may have evolved from a canonical EF-hand found in invertebrate PC2 homologs. Temperature-dependent steady-state NOE experiments and NMR R(1) and R(2) relaxation rates correlate with increased molecular motion in the EF-hand, possibly due to exchange between apo and Ca(2+)-bound states, consistent with a role for PC2-EF as a Ca(2+)-sensitive regulator. Structure-based sequence conservation analysis reveals a conserved hydrophobic surface in the same region, which may mediate Ca(2+)-dependent protein interactions. We propose that Ca(2+)-sensing by PC2-EF is responsible for the cooperative nature of PC2 channel activation and inhibition. Based on our results, we present a mechanism of regulation of the Ca(2+) dependence of PC2 channel activity by PC2-EF. | EF Hand Motifs |
BACKGROUND: Critical pathways for the management of patients with severe traumatic brain injury (STBI) may contribute to reducing the incidence of hospital complications, length of hospitalization stay, and cost of care. Such pathways have previously been developed for departments with significant resource availability. In Mexico, STBI is the most important cause of complications and length of stay in neurotrauma services at public hospitals. Although current treatment is designed basically in accordance with the Brain Trauma Foundation guidelines, shortfalls in the availability of local resources make it difficult to comply with these standards, and no critical pathway is available that accords with the resources of public hospitals. The purpose of the present study was to design and to validate a critical pathway for managing STBI patients that would be suitable for implementation in neurotrauma departments of middle-income level countries. METHODS: The study comprised two phases: design (through literature review and design plan) and validation (content, construct, and appearance) of the critical pathway. RESULTS: The validated critical pathway for managing STBI patients entails four sequential subprocesses summarizing the hospital's care procedures, and includes three components: (1) nodes and criteria (in some cases, indicators are also included); (2) health team members in charge of the patient; (3) maximum estimated time for compliance with recommendations. CONCLUSIONS: This validated critical pathway is based on the current scientific evidence and accords with the availability of resources of middle-income countries. | Critical Pathways |
Evidence shows that oral glycerol supplementation during the early stages of rat liver cancer reduces the growth of preneoplastic lesions. Besides, human hepatocellular carcinoma (HCC) cells display decreased expression of glycerol channel aquaporin 9 (AQP9) and also diminished glycerol-3-phosphate (G3P) content. According to this, we analyzed glycerol metabolism during the initial stages of rat liver carcinogenesis. Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group) or left untreated (control, C group). Different features of glycerol metabolism were compared between both groups. IP animals showed increased plasma free glycerol levels and liver AQP9 protein expression. Also, IP rats showed increased glycerol kinase (GK) and glycerol-3-phosphate dehydrogenase (GPDH) hepatic activities. Gluconeogenesis from glycerol both in vivo and in isolated perfused liver was higher in rats having liver preneoplasia. Nevertheless, preneoplastic foci notably reduced AQP9 and GK protein expressions, displaying a reduced ability to import glycerol and to convert it into G3P, as a way to preserve preneoplastic hepatocytes from the deleterious effect of G3P. In conclusion, the metabolic shift that takes place in the initial stages of liver cancer development comprises an increased hepatic utilization of glycerol for gluconeogenesis. Enhanced glucose production from glycerol is mostly carried out by the surrounding non-preneoplastic tissue and can be used as an energy source for the early transformed liver cells. | Glycerol Kinase |
OBJECTIVES: The efficacy of microwave ablation (MWA) for hepatocellular carcinoma (HCC) as bridge therapy has been gradually confirmed. We aimed to compare the recurrence beyond the Milan criteria (RBM) rates in potentially transplantable patients with HCC receiving MWA or radiofrequency ablation (RFA) as bridge therapy. METHODS: In total, 307 potentially transplantable patients with single HCC </= 3 cm who initially received MWA (n = 82) or RFA (n = 225) were included. RBM, recurrence-free survival (RFS), and overall survival (OS) were compared between MWA and RFA groups by using propensity score matching (PSM). Competing risks Cox regression was used to identify predictors of RBM. RESULTS: After PSM, the 1-, 3-, and 5-year cumulative RBM rates were 6.8%, 18.3%, and 39.3% in the MWA group (n = 75), and 7.4%,18.5%, and 27.7% in the RFA group (n = 137), respectively, with no significant difference (p = 0.386). MWA and RFA were not the independent risk factors of RBM, and patients with higher alpha-fetoprotein, non-antiviral treatment, and higher MELD score were at greater risk of RBM. Neither corresponding RFS rates (66.7%, 39.2% and 21.4% vs. 70.8%, 47% and 34.7%, p = 0.310) nor OS rates (97.3%, 88.0%, and 75.4% vs. 97.8%, 85.1%, and 70.7%, p = 0.384) for 1-, 3- and 5-years were significantly different between the MWA and RFA groups. The MWA group showed more frequent major complications (21.4% vs. 7.1%, p = 0.004) and longer hospital stays (4 days vs. 2 days, p < 0.001) compared with the RFA group. CONCLUSION: MWA showed comparable RBM, RFS, and OS rates to RFA in potentially transplantable patients with single HCC </= 3 cm. Compared to RFA, MWA might provide the same effect as bridge therapy. | Bridge Therapy |
BACKGROUND: Torque teno virus (TTV) is a widespread anellovirus that establishes persistent infections in humans and represents the most abundant component of the human virome. TTV encodes microRNAs (miRNA) which are found both in viremic and not viremic subjects being potentially ideal tools for the virus to evade the immune system response and to maintain chronic infection in the host. OBJECTIVE: To investigate TTV-DNA loads and TTV-miRNAs expression in cerebrospinal fluids (CSF) from subjects under analysis for the assessment of neurological diseases. STUDY DESIGN: Detection of TTV-DNA and TTV-miRNAs (e. g. miRNA t1a, t3b, and tth8) were carried out from CSF samples of 93 subjects with neurological diseases by using universal real-time PCR, real-time RT-PCR, and next-generation sequencing (NGS) analyses. RESULTS: TTV-DNA was detected in 11 of 93 (12 %) CSFs with a mean TTV load of 155 copies/mL. Conversely, 29 CSF samples (31 %) were positive for at least one TTV-miRNA, while 15 (16 %) CSFs contained all the TTV-miRNAs examined. Overall, TTV-miRNA tth8 was detected in 62 % of samples, followed by TTV miRNA t3b (56 %), and t1a (29 %). Interestingly, TTV-miRNAs were found in CSF samples that were negative for the presence of TTV-DNA. Next-generation sequencing analysis carried out from 4 TTV-DNA negative CSF samples detected reads mapped in TTV-miRNA sequences region. CONCLUSIONS: These results shed novel light on the relationship between TTV and the central nervous system and make compelling furthered studies for investigating the potential role of TTV-miRNAs in neurological disorders. | Anelloviridae |
The often studied stretch reflex is fundamental to the involuntary control of posture and movement. Nevertheless, there remains controversy regarding its functional role. Many studies have demonstrated that stretch reflexes can be modulated in a task appropriate manner. This review focuses on modulation of the long-latency stretch reflex, thought to be mediated, at least in part, by supraspinal pathways. For example, this component of the stretch reflex increases in magnitude during interactions with compliant environments, relative to its sensitivity during interactions with rigid environments. This suggests that reflex sensitivity increases to augment limb stability when that stability is not provided by the environment. However, not all results support the stabilizing role of stretch reflexes. Some studies have demonstrated that involuntary responses within the time period corresponding to the long-latency reflex can destabilize limb posture. We propose that this debate stems from the fact that multiple perturbation-sensitive pathways can contribute to the long-latency stretch reflex and that these pathways have separate functional roles. The presented studies suggest that neural activity occurring within the period normally ascribed to the long-latency stretch reflex is highly adaptable to current task demands and possibly should be considered more intelligent than reflexive"." | Reflex, Stretch |
BACKGROUND: Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non-erosive reflux disease (NERD) patients. METHODS: In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability. KEY RESULTS: Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar. CONCLUSIONS & INFERENCES: Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception. | Heartburn |
Macroalgae, in particular red and green species, are gaining interest as protein-rich foods for human consumption and sources of proteinaceous biofunctional peptide ingredients. During protein extraction the starting raw material, the cell disruption method utilized and the reagents employed have a major effect on the yield of protein recovered. A method is described herein for extraction and semi-purification of food-grade aqueous and alkaline soluble proteins from red and green macroalgae. Dried milled macroalgae are disrupted by osmotic shock with subsequent removal of aqueous soluble proteins by centrifugation. Alkaline soluble proteins are removed following consecutive treatment of the resultant pellet with an alkaline solution. Aqueous and alkaline soluble proteins are then enriched from the crude extracts by isoelectric precipitation. | Rhodophyta |
Obstetric ultrasound has become well integrated into management of pregnancy, labor, and delivery. An increasing number of nurse-midwives have expanded their roles to include the use of this technology. This article reviews the basic principles of ultrasound physics, the content of ultrasound examinations, and the performance of basic scans. The uses of limited scans for third-trimester antepartum assessment and intrapartum management are reviewed. Issues surrounding the use of obstetric ultrasound, including limited scans, routine ultrasound screening, and necessary education, are discussed. Information on incorporating the use of ultrasound procedures into nurse-midwifery practice is included. | Ultrasonography, Prenatal |
This paper examines the biology, morphology, and pathogenicity for mice of an amoeboflagellate isolated from human nasal mucosa. The biological and morphological relationships of this isolate with the amoebae (Lobosea) and the true slime molds (Eumycetoza) are discussed though the taxonomic affinities of the organism have not been determined. | Tubulina |
Mutations in the gene encoding Lamin B receptor (LBR), a nuclear-membrane protein with sterol reductase activity, have been linked to rare human disorders. Phenotypes range from a benign blood disorder, such as Pelger-Huet anomaly (PHA), affecting the morphology and chromatin organization of white blood cells, to embryonic lethality as for Greenberg dysplasia (GRBGD). Existing PHA mouse models do not fully recapitulate the human phenotypes, hindering efforts to understand the molecular etiology of this disorder. Here we show, using CRISPR/Cas-9 gene editing technology, that a 236bp N-terminal deletion in the mouse Lbr gene, generating a protein missing the N-terminal domains of LBR, presents a superior model of human PHA. Further, we address recent reports of a link between Lbr and defects in X chromosome inactivation (XCI) and show that our mouse mutant displays minor X chromosome inactivation defects that do not lead to any overt phenotypes in vivo. We suggest that our N-terminal deletion model provides a valuable pre-clinical tool to the research community and will aid in further understanding the etiology of PHA and the diverse functions of LBR. | Pelger-Huet Anomaly |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel type b coronavirus responsible for the COVID-19 pandemic. With over 224 million confirmed infections with this virus and more than 4.6 million people dead because of it, it is critically important to define the immunological processes occurring in the human response to this virus and pathogenetic mechanisms of its deadly manifestation. This perspective focuses on the contribution of the recently discovered interaction of SARS-CoV-2 Spike protein with neuropilin 1 (NRP1) receptor, NRP1 as a virus entry receptor for SARS-CoV-2, its role in different physiologic and pathologic conditions, and the potential to target the Spike-NRP1 interaction to combat virus infectivity and severe disease manifestations. | Neuropilin-1 |
Cholesterol and apolipoprotein D (apo D) concentrations were measured in cyst fluids and sera from 66 women with gross cystic disease of the breast. Intracystic cholesterol concentrations are about twofold greater than those found in serum, whereas apo D, the major cyst fluid protein, is present in concentrations as much as 1000-fold greater than found in serum. We classified the cyst fluids into two groups by K+/Na+ ratio and albumin concentration and measured intracystic cholesterol and apo D concentrations in each group. Type I cysts had an average content of cholesterol (12.7 mmol/L) moderately lower than that in Type II cysts (17.6 mmol/L). By contrast, the average concentration of apo D in Type I cyst fluids (15.1 g/L) was slightly higher than that in Type II cysts (13.7 g/L). The absence of a correlation between cholesterol concentration and apo D concentration and the results from previous binding analysis suggest that this protein is not involved in the accumulation of cholesterol in breast-cyst fluid. | Apolipoproteins D |
Modern subunit vaccines have many benefits compared to live vaccines such as convenient and competitive large scale production, better reproducibility and safety. However, the poor immunogenicity of subunit vaccines usually requires the addition of potent adjuvants or drug delivery vehicles. Accordingly, researchers are investigating different adjuvants and particulate vaccine delivery vehicles to boost the immunogenicity of subunit vaccines. Despite the rapidly growing knowledge in this field, a comparison of different adjuvants is sparsely found. Until today, little is known about efficient combinations of the different adjuvants and particulate vaccine delivery vehicles. In this study we compared three adjuvants with respect to their immune stimulatory potential and combined them with different particulate vaccine delivery vehicles. For this reason, we investigated two types of polyI:C and a CL264 base analogue and combined these adjuvants with differently sized and shaped particulate vaccine delivery vehicles. A high molecular weight polyI:C combined with a spherical nano-sized particulate vaccine delivery vehicle promoted the strongest dendritic cells activation. | Vaccines, Subunit |
The dura mater performs a major functional role in the stability and mechanical response of the spinal cord complex. Computational techniques investigating the etiology of spinal cord injury require an accurate mechanical description of the dura mater. Previous studies investigating the mechanical response of the dura mater have reported conflicting results regarding the anisotropic stiffness of the dura in the longitudinal and circumferential direction. The aim of this study was to investigate the biaxial response of the dura mater in order to establish the tissue level mechanical behavior under physiological loading scenarios. To this end, square sections of the dura were tested in a custom biaxial setup under a comprehensive uniaxial and biaxial loading protocol. The resultant data were fit via a transversely isotropic continuum model and an anisotropic continuum constitutive model. The transversely isotropic formulation failed to accurately predict the dura materós uniaxial behavior. The anisotropic formulation accurately predicted the uniaxial response in both longitudinal and circumferential directions. Significantly higher stiffness (p<0.0001) was observed in the circumferential direction as compared to the longitudinal direction. Further, the longitudinal direction displayed a significantly lower degree of nonlinearity (p<0.045) and significantly higher degree of collagen fiber dispersion (p<0.032) as compared to the circumferential direction. Results indicate that the dura mater has differential mechanical response in the longitudinal and circumferential directions and future studies should utilize an anisotropic two fiber family continuum model to accurately describe dura mater mechanics. | Dura Mater |
Neovascular AMD (nAMD) leads to vision loss and is a leading cause of visual impairment in the industrialised world. Current treatments that target blood vessel growth have not been able to treat subretinal fibrosis and nAMD patients continue to lose vision. The molecular mechanisms involved in the development of fibrotic lesions in nAMD are not well understood. The aim of this study was to further understand subretinal fibrosis in the laser photocoagulation model of choroidal neovascularization (CNV) by studying the whole transcriptome of the RPE/choroid following CNV and the application of an anti-fibrotic following CNV. Seven days after laser induced CNV, RPE and choroid tissue was separated and underwent RNAseq. Differential expression analysis and pathway analysis revealed an over representation of immune signalling and fibrotic associated pathways in CNV compared to control RPE/choroid tissue. Comparisons between the mouse CNV model to human CNV revealed an overlap in upregulated expression for immune genes (Ccl2, Ccl8 and Cxcl9) and extracellular matrix remodeling genes (Comp, Lrcc15, Fndc1 and Thbs2). Comparisons between the CNV model and other fibrosis models showed an overlap of over 60% of genes upregulated in either lung or kidney mouse models of fibrosis. Treatment of CNV using a novel cinnamoyl anthranilate anti-fibrotic (OCX063) in the laser induced CNV model was selected as this class of drugs have previously been shown to target fibrosis. CNV lesion leakage and fibrosis was found to be reduced using OCX063 and gene expression of genes within the TGF-beta signalling pathway. Our findings show the presence of fibrosis gene expression pathways present in the laser induced CNV mouse model and that anti-fibrotic treatments offer the potential to reduce subretinal fibrosis in AMD. | Chemokine CCL8 |
The human natural killer-1 (HNK-1) epitope is a unique sulfated trisaccharide sequence presented on O- and N-glycans of various glycoproteins and on glycolipids. It is overexpressed in the nervous system and plays crucial roles in nerve regeneration, synaptic plasticity, and neuronal diseases. However, the investigation of functional roles of HNK-1 in a more complex glycan context at the molecular level remains a big challenge due to lack of access to related structurally well-defined complex glycans. Herein, we describe a highly efficient chemoenzymatic approach for the first collective synthesis of HNK-1-bearing O-mannose glycans with different branching patterns, and for their nonsulfated counterparts. The successful strategy relies on both chemical glycosylation of a trisaccharide lactone donor for the introduction of sulfated HNK-1 branch and substrate promiscuities of bacterial glycosyltransferases that can tolerate sulfated substrates for enzymatic diversification. Glycan microarray analysis with the resulting complex synthetic glycans demonstrated their recognition by two HNK-1-specific antibodies including anti-HNK-1/N-CAM (CD57) and Cat-315, which provided further evidence for the recognition epitopes of these antibodies and the essential roles of the sulfate group for HNK-1 glycan-antibody recognition. | Mannose |
The use of simple spreadsheets is described to create simulations of complex pharmacokinetic phenomena. The basics of spreadsheets are first described and are developed to demonstrate classical pharmacokinetics without the use of differential or integral calculus. Using standard spreadsheet commands, the technique is shown to be applicable to the full range of advanced pharmacokinetic simulations. Demonstrations of the effect of a variety of physiological eventualities are included to show the versatility of the technique. The technique is very simple to use and is always in the complete control of the modeller. | Drug Administration Schedule |
Vpr, an accessory protein of HIV, is known to affect viral replication as well as cell growth, differentiation, and apoptosis in vitro. To investigate its pathogenicity in vivo, we have produced mice transgenic for the HIV-1 vpr gene with the CD4 enhancer/promoter. Interestingly, apoptotic death of T lymphocytes was enhanced in those mice, causing marked reduction of T cells in lymphatic organs and peripheral blood. Involvement of Bcl-x, Bax, and Caspase-1, but not of the Fas-Fas ligand system, was suggested in the apoptotic processes. These observations suggest that Vpr is involved in the pathogenesis of T cell depletion in HIV-infected people. | Gene Products, vpr |
Behavioural therapy and anticholinergics are the mainstays in the treatment of symptoms of overactive bladder in patients with idiopathic and neurogenic detrusor overactivity; they are the first-line treatment. Oxybutynin, propiverine, tolterodine and trospium chloride as well as the newcomers" solifenacin and darifenacin are comparable in regards to their efficacy. However, based on different pharmacokinetics and pharmacodynamics with different resorption velocity, different metabolisation and different CNS penetration, the profile of adverse events is different, qualitatively and quantitatively. Substances that are resorbed slowly or available as slow-release formulations are tolerated better. Lipophilic anticholinergics which pass the blood-brain barrier may compromise cognitive functions, especially in geriatric patients, who are already on cholinesterase inhibitors due to memory disorders. The following article gives an overview of the anticholinergics currently prescribed in patients with symptoms of overactive bladder with special attention to the influence of pharmacokinetics/pharmacodynamics on the adverse events profile including possible CNS side effects." | Cholinergic Antagonists |
The influence of aniline and hydrazine derivatives on the reversible oxygenation of cobaltous complexes of etioporphyrin I and alpha,beta,gamma,delta-tetraphenylporphin has been studied by means of ESR and electronic spectra. The formation of stable six-coordinated complexes with the said reagents prevents the oxygenation. The excess of hydrazines cause the destruction of porphyrin nucleus. The formation of intermediate dihydroporphyrins (chlorins) has been noticed. | Etioporphyrins |
HLA-A, B, C typing was performed on 37 unrelated healthy blood donors with selective deficiency (less than 0.05 g/l) or total lack (less than 0.00002 g/l) of serum IgA. A significant increase in HLA-B8 and A1 antigen frequency was found in the 15 individuals with lack of serum IgA. This was not observed among those 22, who had only deficiency of serum IgA (0.00002-0.05 g/l). The HLA antigen frequencies were compared to those of 900 randomly selected healthy blood donors. Increased frequency of HLA-A1 and B8 in association with total lack of serum IgA, but not with deficiency has not been demonstrated before. On the basis of this result it seems conceivable that lack of serum IgA may be caused by a different, perhaps genetically determined, mechanism than IgA deficiency. | HLA-B8 Antigen |
The COVID-19 pandemic has led to the suspension, termination or alteration of thousands of clinical trials as the health emergency escalated globally. Whilst the rapid suspension of certain clinical trials was necessary to ensure the safety of high-risk or vulnerable trial participants as well as healthcare workers, the long-term ramifications that this delay will have on the field of urologic oncology is unknown. The COVID-19 pandemic has highlighted the need to plan for and implement new strategies to advance our understanding of unmet areas of need in urologic oncology. The COVID-19 pandemic has led to the suspension, termination or alteration of thousands of clinical trials as the health emergency escalated globally. Whilst the rapid suspension of certain clinical trials was necessary to ensure the safety of high-risk or vulnerable trial participants as well as healthcare workers, the long-term ramifications that this delay will have on the field of urologic oncology is unknown. The COVID-19 pandemic has highlighted the need to plan for and implement new strategies to advance our understanding of unmet areas of need in urologic oncology. | Change Management |
The remodelling of flagella into attachment structures is a common and important event in the trypanosomatid life cycle. Lotmaria passim and Crithidia mellificae can parasitize Apis mellifera, and as a result they might have a significant impact on honeybee health. However, there are details of their life cycle and the mechanisms underlying their pathogenicity in this host that remain unclear. Here we show that both L. passim promastigotes and C. mellificae choanomastigotes differentiate into haptomonad stages covering the ileum and rectum of honeybees. These haptomonad cells remain attached to the host surface via zonular hemidesmosome-like structures, as revealed by transmission electron microscopy. This work describes for the first known time the haptomonad morphotype of these species and their hemidesmosome-like attachments in A. mellifera, a key trait used by other trypanosomatid species to proliferate in the insect host hindgut. | Kinetoplastida |
The secretion and synthesis of renin were studied in mice by measuring aortic, right and left renal vein renin, renal renin, and mRNA for renin. The role of the macula densa was evaluated in a kidney made hydronephrotic by tying the ureter 6 weeks earlier. There was no net secretion of renin from the left hydronephrotic kidney even when the mice were placed in a high secretory state by sodium restriction or enalapril. Sodium restriction and enalapril increased renin content to a similar extent in the normal and hydronephrotic kidney. High sodium intake decreased renin content in the normal and hydronephrotic kidney and also decreased the enalapril-stimulated renin content. Changes in mRNA in the same direction to renal renin implied that this was due to increased synthesis. Thus secretion and synthesis of renin can be disassociated. The macula densa is important for renin secretion but not for the stimulation of synthesis. | Renin |
Home care professionals are responsible for keeping abreast of the latest therapies used to treat specific disease entities to provide comprehensive and quality care. This article gives an overview of bone marrow transplantation, a complex treatment used for malignant and nonmalignant diseases. The transplant process, complications, and the role of home care for this population are discussed. | Bone Marrow Transplantation |
Hyperkalemia is a potentially fatal condition and is defined by a serum potassium level (K+) of greater than 5.5 mmol/L. The associated prevalence of cardiac arrhythmia increases directly with the degree of hyperkalemia. The danger in the majority of hyperkalemia cases is cardiac dysrhythmia, and often ventricular fibrillation or asystole is the terminating event. Although there are many previous reports addressing this threatening problem and associated therapeutic maneuvers, there have not been many previous reports citing the fatal concentration of hyperkalemia irrespective of the causes. However, it is uniformly accepted that a K+ concentration greater than 10.0 mmol/L is fatal unless urgent treatment is instituted. This report describes a case of nonfatal hyperkalemia of 14 mmol/L with intact survival and complete recovery. Potassium homeostasis is revisited, and some explanations are proffered regarding the protective mechanism against hyperkalemia, including transcellular flux, renal tubular function, and endocrine responses. | Hyperkalemia |
This work investigates, for the first time, the occurrence of 10 drugs of abuse, six metabolites, and three benzodiazepines in surface waters from the Jarama and Manzanares Rivers in the Madrid Region, the most densely populated area in Spain and one of the most densely populated in Europe. The results of this study have shown the presence of 14 out of the 19 compounds analyzed at concentrations ranging from 1.45 to 1020 ng L(-1). The most ubiquitous compounds, found in 100% of the samples, were the cocaine metabolite benzoylecgonine (BE), the amphetamine-like compound ephedrine (EPH), the opioids morphine (MOR), methadone (METH), and the METH metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and the three investigated benzodiazepines alprazolam (ALP), diazepam (DIA) and lorazepam (LOR). Meanwhile, the largest concentrations observed corresponded to EPH (up to 1020 ng L(-1)), BE (823 ng L(-1)), EDDP (151 ng L(-1)), and LOR (167 ng L(-1)). The only not detected compounds were heroin (HER) and its metabolite 6-acetylmorphine (6ACM), lysergic acid diethylamide (LSD) and its metabolite 2-oxo-3-hydroxy-LSD (OH-LSD), and Delta(9)-tetrahydrocannabinol (THC). Overall, the levels measured are comparatively higher than those previously reported in Europe. Comparison of the results obtained for samples collected on different days (Thursday and Sunday) did not show meaningful differences between weekdays and weekends. The lack of (eco)toxicological data does not permit to predict or disregard potential adverse effects on wildlife. Risk assessment in humans would require further knowledge, not currently available, on exposure to these compounds through other routes like drinking water and/or food. | Lysergic Acid Diethylamide |
In Sonic hedgehog (SHH) signaling, GLI family zinc finger (GLI)-mediated diverse gene transcription outcomes are strictly regulated and are important for SHH function in both development and disease. However, how the GLI factors differentially regulate transcription in response to variable SHH activities is incompletely understood. Here, using a newly generated, tagged Gli3 knock-in mouse (Gli3(TAP) ), we performed proteomic analyses and identified the chromatin-associated SAFB-like transcription modulator (SLTM) as a GLI-interacting protein that context-dependently regulates GLI activities. Using immunoprecipitation and immunoblotting, RT-quantitative PCR, and ChIP assays, we show that SLTM interacts with all three GLI proteins and that its cellular levels are regulated by SHH. We also found that SLTM enhances GLI3 binding to chromatin and increases GLI3 repressor (GLI3R) form protein levels. In a GLI3-dependent manner, SLTM promoted the formation of a repressive chromatin environment and functioned as a GLI3 co-repressor. In the absence of GLI3 or in the presence of low GLI3 levels, SLTM co-activated GLI activator (GLIA)-mediated target gene activation and cell differentiation. Moreover, in vivo Sltm deletion generated through CRISPR/Cas9-mediated gene editing caused perinatal lethality and SHH-related abnormal ventral neural tube phenotypes. We conclude that SLTM regulates GLI factor binding to chromatin and contributes to the transcriptional outcomes of SHH signaling via a novel molecular mechanism. | Zinc Finger Protein Gli3 |
Third generation Hepatitis C virus (HCV) NS3/4A protease inhibitors (PIs), glecaprevir and voxilaprevir, are highly effective across genotypes and against many resistant variants. Unlike earlier PIs, these compounds have fluorine substitutions on the P2-P4 macrocycle and P1 moieties. Fluorination has long been used in medicinal chemistry as a strategy to improve physicochemical properties and potency. However, the molecular basis by which fluorination improves potency and resistance profile of HCV NS3/4A PIs is not well understood. To systematically analyze the contribution of fluorine substitutions to inhibitor potency and resistance profile, we used a multi-disciplinary approach involving inhibitor design and synthesis, enzyme inhibition assays, co-crystallography, and structural analysis. A panel of inhibitors in matched pairs were designed with and without P4 cap fluorination, tested against WT protease and the D168A resistant variant, and a total of 22 high-resolution co-crystal structures were determined. While fluorination did not significantly improve potency against the WT protease, PIs with fluorinated P4 caps retained much better potency against the D168A protease variant. Detailed analysis of the co-crystal structures revealed that PIs with fluorinated P4 caps can sample alternate binding conformations that enable adapting to structural changes induced by the D168A substitution. Our results elucidate molecular mechanisms of fluorine-specific inhibitor interactions that can be leveraged in avoiding drug resistance." | HCV NS3-4A Protease Inhibitors |
Arginase is one of the key enzymes responsible for maintaining the essential levels of nitrogen among plants, but biochemical and functional characterization of arginase among plants is limited. While screening for stable plant arginase, we found cilantro possessing an abundant and stable arginase. We purified arginase to apparent homogeneity (3300-fold purification) with a specific activity of 81,728â¯nmoles of urea formed/mg of protein/min and its eight-tryptic fragments had amino acid sequences identical to Arabidopsis thaliana arginase. Cilantro arginase exhibited absolute requirement for Mn(2+) (0.5â¯mM-1â¯mM). Unlike other known plant arginases, cilantro arginase did not hydrolyse d-arginine and other arginine analogues. While for sulfhydryl reagents the enzyme was sensitive, l-NOHA, an arginase inhibitor showed only moderate inhibition - a property distinct from tomato arginase. We also found arginine derived amino acids and polyamines can regulate cilantro arginase in vitro. In addition, we also noticed an increase in cilantro arginase activity to both biotic and abiotic stress. We conclude that, cilantro may be used as a model plant to study plant arginases and to delineate arginase role, beyond its classical role in nitrogen recycling and polyamine biosynthesis. | Ureohydrolases |
OBJECTIVES: Physicians in training may be particularly vulnerable to the negative effects of discrimination and inappropriate behaviors by patients. We sought to determine the frequency of inappropriate behaviors by patients toward Internal Medicine (IM) residents, residents' confidence to manage the behaviors, and differences among demographic characteristics, including race, sex, and level of clinical experience. METHODS: We developed a curricular session to equip IM residents and faculty to respond to discrimination or inappropriate behaviors by patients. Before the session, we surveyed residents about their experiences with macroaggressions, microaggressions, and other inappropriate behaviors using a 16-question survey instrument. We used descriptive statistics to summarize the participants' characteristics and the chi(2) or Fisher exact test for comparison between groups. RESULTS: Eighty-two percent (27 of 33) of residents who attended the workshop completed the survey. We found that the majority of residents experienced patient macro- and microaggressions. More than 50% had a personal experience or witnessed experience with a macroaggression related to race (56%) or gender (59%). Seventy percent of residents personally experienced a microaggression by a patient. Women and residents of color are more likely to experience these types of encounters, which become more common in residents with higher postgraduate year level. Confidence in how to appropriately respond to such encounters is low. CONCLUSIONS: Our study highlights that macro- and microaggressions by patients toward IM residents are common. Curricula are needed to equip trainees with tools to appropriately respond during such encounters. | Medical Staff, Hospital |
The physico-chemical properties of lipid components isolated from zoospores of the aquatic phycomycete, Blastocladiella emersonii, were investigated with electron spin resonance (ESR) spectroscopy using the spin label, 5-nitroxystearate. Lipid dispersions were made from zoospore phospholipids and glycolipids, both singly and in combination with each other and with isolated neutral lipid components. Plots of the hyperfine splitting parameter (2T parallel) vs. temperature indicate that it is the zoospore glycolipids rather than the phospholipids which are responsible for the phase transformations previously observed in aqueous dispersions of the total lipids extracted from zoospores and in zoospores in vivo. The discontinuities observed in the glycolipid dispersions seem to represent the onset and completion of a gel-to-liquid-crystalline phase transition. Over the temperature range tested, Ca2+ increased the rigidity of the glycolipid dispersions, the major component of which is probably a diglucosyldiglyceride, but had no effect on the phospholipid dispersions. The increase in 2T parallel was not affected by inclusion of neutral lipids into the glycolipid dispersion but was eliminated at high (5 : 1, w/w) phospholipid-to-glycolipid ratios. The Ca2+ effect was relatively independent of both the absolute rigidity of the dispersion and its phase (gel or liquid-crystalline), suggesting an interaction with the glycolipid head group rather than the hydrocarbon core. The Ca2+-induced increase in 2T was neither prevented nor reversed by the presence of K+. The presence of two spin label populations co-existing in a dynamic equilibrium was found in glycolipid/neutral lipid dispersions. Plots of the percentage ([HA/(HA + HB)] X 100 of the spin label population, as measured by the peak height of the low-field peaks, corresponding to the more immobilized component (HA) vs. temperature indicated two break points. The temperatures at which these break points occurred are similar to those obtained for the glycolipid dispersions, and match the break points (TL and TH) found in ESR experiments using zoospores in vivo. The importance of the glycolipids in the development of this organism is discussed. | Blastocladiomycota |
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