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排序方式: 共有1228条查询结果,搜索用时 390 毫秒
971.
Christoph U. Correll Linmarie Sikich Gloria Reeves Jacqueline Johnson Courtney Keeton Marina Spanos Sandeep Kapoor Kristin Bussell Leslie Miller Tara Chandrasekhar Eva M. Sheridan Sara Pirmohamed Shauna P. Reinblatt Cheryl Alderman Abigail Scheer Irmgard Borner Terrence C. Bethea Sarah Edwards Robert M. Hamer Mark A. Riddle 《World psychiatry》2020,19(1):69-80
Antipsychotics are used for many psychiatric conditions in youth. Although developmentally inappropriate weight gain and metabolic abnormalities, which are risk factors for premature cardiovascular mortality, are especially frequent in youth, optimal strategies to reduce pediatric antipsychotic‐induced overweight/obesity are unclear. The Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) was a randomized, parallel group, 24‐week clinical trial which enrolled overweight/obese, psychiatrically stable youth, aged 8‐19 years, with a DSM‐IV diagnosis of severe mental illness (schizophrenia spectrum disorder, bipolar spectrum disorder or psychotic depression), at four US universities. All of them had developed substantial weight gain following treatment with a second‐generation antipsychotic. The centralized, computer‐based randomization system assigned participants to unmasked treatment groups: metformin (MET); antipsychotic switch (aripiprazole or, if already exposed to that drug, perphenazine or molindone; SWITCH); or continued baseline antipsychotic (CONTROL). All participants received healthy lifestyle education. The primary outcome was body mass index (BMI) z‐score change from baseline, analyzed using estimated least squares means. Altogether, 127 participants were randomized: 49 to MET, 31 to SWITCH, and 47 to CONTROL. BMI z‐score decreased significantly with MET (week 24: –0.09±0.03, p=0.002) and SWITCH (week 24: –0.11±0.04, p=0.003), while it increased non‐significantly with CONTROL (week 24: +0.04±0.03). On 3‐way comparison, BMI z‐score changes differed significantly (p=0.001). MET and SWITCH were each superior to CONTROL (p=0.002), with effect sizes of 0.68 and 0.81 respectively, while MET and SWITCH did not differ. More gastrointestinal problems occurred in MET than in SWITCH or CONTROL. The data safety monitoring board closed the perphenazine‐SWITCH arm because 35.2% of subjects discontinued treatment due to psychiatric worsening. These data suggest that pediatric antipsychotic‐related overweight/obesity can be reduced by adding metformin or switching to a lower risk antipsychotic. Healthy lifestyle education is not sufficient to prevent ongoing BMI z‐score increase. 相似文献
972.
Sandeep K. Agarwalla Priyanka Ruz Jyotirmayee Mohanty G. Sridhar V. Sudarsan 《Luminescence》2020,35(4):447-455
In this study, Bi3+ incorporation in NaYbF4:Er lattice and its influence on upconversion luminescence properties have been investigated in detail using techniques such as temperature‐dependent luminescence, Fourier transform infrared spectroscopy and X‐ray diffraction (XRD). The study was carried out to develop phosphors with improved upconversion luminescence. From photoluminescence and lifetime measurements it is inferred that luminescence intensity from NaYbF4:Er increases with Bi3+ addition. The sample containing 50 at.% Bi3+ ions exhibited optimum upconversion luminescence. Increased distance between Yb3+–Yb3+ and Er3+–Er3+ due to Bi3+ incorporation into the lattice and associated decrease in the extent of dipolar interaction/self‐quenching are responsible for increase in lifetime values and luminescence intensities from Er3+ ions. Incorporation of Bi3+ into NaYbF4:Er lattice reduced self‐quenching among Yb3+–Yb3+ions and this facilitated energy transfer from Yb3+ to Er3+. This situation also explains decrease in the extent of temperature‐assisted quenching of emission from thermally coupled 2H11/2 and 4S3/2 levels of Er3+. Based on Rietveld refinement of XRD patterns it was confirmed that a maximum of 10 at.% of Bi3+added was incorporated into the NaYbF4:Er lattice and the remaining complex co‐exists as a BiOF phase. These results are of significant interest in the area of development of phosphors based on Yb3+–Er3+ upconversion luminescence. 相似文献
973.
Ivelin S. Georgiev M. Gordon Joyce Yongping Yang Mallika Sastry Baoshan Zhang Ulrich Baxa Rita E. Chen Aliaksandr Druz Christopher R. Lees Sandeep Narpala Arne Sch?n Joseph Van Galen Gwo-Yu Chuang Jason Gorman Adam Harned Marie Pancera Guillaume B. E. Stewart-Jones Cheng Cheng Ernesto Freire Adrian B. McDermott John R. Mascola Peter D. Kwong 《Journal of virology》2015,89(10):5318-5329
974.
Ananya Kar Manpreet Kaur Tanushree Ghosh Md. Muntaz Khan Aparna Sharma Ritu Shekhar Akhil Varshney Sandeep Saxena 《Nucleic acids research》2015,43(10):4962-4974
The primary eukaryotic single-stranded DNA-binding protein, Replication protein A (RPA), binds to single-stranded DNA at the sites of DNA damage and recruits the apical checkpoint kinase, ATR via its partner protein, ATRIP. It has been demonstrated that absence of RPA incapacitates the ATR-mediated checkpoint response. We report that in the absence of RPA, human single-stranded DNA-binding protein 1 (hSSB1) and its partner protein INTS3 form sub-nuclear foci, associate with the ATR-ATRIP complex and recruit it to the sites of genomic stress. The ATRIP foci formed after RPA depletion are abrogated in the absence of INTS3, establishing that hSSB-INTS3 complex recruits the ATR-ATRIP checkpoint complex to the sites of genomic stress. Depletion of homologs hSSB1/2 and INTS3 in RPA-deficient cells attenuates Chk1 phosphorylation, indicating that the cells are debilitated in responding to stress. We have identified that TopBP1 and the Rad9-Rad1-Hus1 complex are essential for the alternate mode of ATR activation. In summation, we report that the single-stranded DNA-binding protein complex, hSSB1/2-INTS3 can recruit the checkpoint complex to initiate ATR signaling. 相似文献
975.
976.
Sathya Narayanan Nagarajan Sandeep Upadhyay Yogesh Chawla Shazia Khan Saba Naz Jayashree Subramanian Sheetal Gandotra Vinay Kumar Nandicoori 《The Journal of biological chemistry》2015,290(15):9626-9645
The essential mycobacterial protein kinases PknA and PknB play crucial roles in modulating cell shape and division. However, the precise in vivo functional aspects of PknA have not been investigated. This study aims to dissect the role of PknA in mediating cell survival in vitro as well as in vivo. We observed aberrant cell shape and severe growth defects when PknA was depleted. Using the mouse infection model, we observe that PknA is essential for survival of the pathogen in the host. Complementation studies affirm the importance of the kinase, juxtamembrane, and transmembrane domains of PknA. Surprisingly, the extracytoplasmic domain is dispensable for cell growth and survival in vitro. We find that phosphorylation of the activation loop at Thr172 of PknA is critical for bacterial growth. PknB has been previously suggested to be the receptor kinase, which activates multiple kinases, including PknA, by trans-phosphorylating their activation loop residues. Using phospho-specific PknA antibodies and conditional pknB mutant, we find that PknA autophosphorylates its activation loop independent of PknB. Fluorescently tagged PknA and PknB show distinctive distribution patterns within the cell, suggesting that although both kinases are known to modulate cell shape and division, their modes of action are likely to be different. This is supported by our findings that expression of kinase-dead PknA versus kinase-dead PknB in mycobacterial cells leads to different cellular phenotypes. Data indicate that although PknA and PknB are expressed as part of the same operon, they appear to be regulating cellular processes through divergent signaling pathways. 相似文献
977.
Poly(A) polymerases (PAPs) are found in most living organisms and have important roles in RNA function and metabolism. Here, we report the crystal structure of human PAPD1, a noncanonical PAP that can polyadenylate RNAs in the mitochondria (also known as mtPAP) and oligouridylate histone mRNAs (TUTase1). The overall structure of the palm and fingers domains is similar to that in the canonical PAPs. The active site is located at the interface between the two domains, with a large pocket that can accommodate the substrates. The structure reveals the presence of a previously unrecognized domain in the N-terminal region of PAPD1, with a backbone fold that is similar to that of RNP-type RNA binding domains. This domain (named the RL domain), together with a β-arm insertion in the palm domain, contributes to dimerization of PAPD1. Surprisingly, our mutagenesis and biochemical studies show that dimerization is required for the catalytic activity of PAPD1. 相似文献
978.
Bartocci E Singh R von Stein FB Amedome A Caceres AJ Castillo J Closser E Deards G Goltsev A Ines RS Isbilir C Marc JK Moore D Pardi D Sadhu S Sanchez S Sharma P Singh A Rogers J Wolinetz A Grosso-Applewhite T Zhao K Filipski AB Gilmour RF Grosu R Glimm J Smolka SA Cherry EM Clarke EM Griffeth N Fenton FH 《Advances in physiology education》2011,35(4):427-437
As part of a 3-wk intersession workshop funded by a National Science Foundation Expeditions in Computing award, 15 undergraduate students from the City University of New York(1) collaborated on a study aimed at characterizing the voltage dynamics and arrhythmogenic behavior of cardiac cells for a broad range of physiologically relevant conditions using an in silico model. The primary goal of the workshop was to cultivate student interest in computational modeling and analysis of complex systems by introducing them through lectures and laboratory activities to current research in cardiac modeling and by engaging them in a hands-on research experience. The success of the workshop lay in the exposure of the students to active researchers and experts in their fields, the use of hands-on activities to communicate important concepts, active engagement of the students in research, and explanations of the significance of results as the students generated them. The workshop content addressed how spiral waves of electrical activity are initiated in the heart and how different parameter values affect the dynamics of these reentrant waves. Spiral waves are clinically associated with tachycardia, when the waves remain stable, and with fibrillation, when the waves exhibit breakup. All in silico experiments were conducted by simulating a mathematical model of cardiac cells on graphics processing units instead of the standard central processing units of desktop computers. This approach decreased the run time for each simulation to almost real time, thereby allowing the students to quickly analyze and characterize the simulated arrhythmias. Results from these simulations, as well as some of the background and methodology taught during the workshop, is presented in this article along with the programming code and the explanations of simulation results in an effort to allow other teachers and students to perform their own demonstrations, simulations, and studies. 相似文献
979.
Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts
Agarwal SK Wu M Livingston CK Parks DH Mayes MD Arnett FC Tan FK 《Arthritis research & therapy》2011,13(1):R3
Introduction
Increased levels of genes in the type I interferon (IFN) pathway have been observed in patients with systemic sclerosis (SSc), or scleroderma. How type I IFN regulates the dermal fibroblast and its participation in the development of dermal fibrosis is not known. We hypothesized that one mechanism by which type I IFN may contribute to dermal fibrosis is through upregulation of specific Toll-like receptors (TLRs) on dermal fibroblasts. Therefore, we investigated the regulation of TLR expression on dermal fibroblasts by IFN. 相似文献980.
Given its complexity, high metabolic activity and excretory functions, the kidney is particularly susceptible to acute ischemic and toxin-mediated injury. Current therapies do not facilitate kidney regeneration, and there is an increasing interest in newer therapies that are based on cellular sources of kidney regeneration, such as stem cell therapy. Our understanding of cellular sources for kidney regeneration and stem cells present in the adult kidney has dramatically evolved over the recent years. Herein, we discuss the current understanding of kidney stem cells present in the adult mammalian kidney and their role in kidney regeneration. We have also summarized the best available evidence supporting the role of stem cells in kidney regeneration. 相似文献