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Found 34832 matches. Displaying 41-50
Reich K
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Risankizumab compared with adalimumab in patients with

LANCET 2019 AUG 17; 394(10198):576-586
Background Psoriasis is an autoimmune disease that affects approximately
Raz A, Serrano A, Hernandez A, Euler CW, Fischetti VA
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Isolation of Phage Lysins That Effectively Kill Pseudomonas aeruginosa in Mouse Models of Lung and Skin Infection

Multidrug resistance (MDR) is rapidly increasing in prevalence among isolates of the opportunistic pathogen Pseudomonas aeruginosa, leaving few treatment options. Phage lysins are cell wall hydrolases that have a demonstrated therapeutic potential against Gram-positive pathogens; however, the outer membrane of Gram-negative bacteria prevents most lysins from reaching the peptidoglycan, making them less effective as therapeutics. Nevertheless, a few lysins from Gram-negative bacterial phage can penetrate the bacterial outer membrane with the aid of an amphipathic tail found in the molecule's termini. In this work, we took a phylogenetic approach to systematically identify those lysins from P. aeruginosa phage that would be most effective therapeutically. We isolated and performed preliminary characterization of 16 lysins and chose 2 lysins, PlyPa03 and PlyPa91, which exhibited >5-log killing activity against P. aeruginosa and other Gram-negative pathogens (particularly Klebsiella and Enterobacter). These lysins showed rapid killing kinetics and were active in the presence of high concentrations of salt and urea and under pH conditions ranging from 5.0 to 10.0. Activity was not inhibited in the presence of the pulmonary surfactant beractant (Survanta). While neither enzyme was active in 100% human serum, PlyPa91 retained activity in low serum concentrations. The lysins were effective in the treatment of a P. aeruginosa skin infection in a mouse model, and PlyPa91 protected mice in a lung infection model, making these lysins potential drug candidates for Gram-negative bacterial infections of the skin or respiratory mucosa.
Lu XD, Chu CSE, Fang T, Rayon-Estrada V, Fang F, Patke A, Qian Y, Clarke SH, Melnick AM, Zhang Y, Papavasiliou FN, Roeder RG
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MTA2/NuRD Regulates B Cell Development and Cooperates with OCA-B in Controlling the Pre-B to Immature B Cell Transition

CELL REPORTS 2019 JUL 9; 28(2):472-485.e5
The NuRD complex contains both chromatin remodeling and histone deacetylase activities. Mice lacking the MTA2 subunit of NuRD show developmental defects in pro-B, pre-B, immature B, and marginal zone B cells, and abnormal germinal center B cell differentiation during immune responses. Mta2 inactivation also causes a derepression of Igll1 and VpreB1 genes in pre-B cells. Furthermore, MTA2/NuRD interacts directly with AIOLOS/IKAROS and shows a striking overlap with AIOLOS/IKAROS target genes in human pre-B cells, suggesting a functional interdependence between MTA2/NuRD and AIOLOS. Mechanistically, MTA2 deficiency in mice leads to increased H3K27 acetylation at both Igll1 and VpreB1 promoters. Gene profiling analyses also identify distinct MTA2-dependent transcription programs in pro-B and pre-B cells. In addition, we find a strong synergy between MTA2 and OCA-B in repressing Igll1 and VpreB1 at the pre-B cell stage, and in regulating both the pre-B to immature B transition and splenic B cell development.
Chuang JS
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Homeorhesis and ecological succession quantified in synthetic microbial

The dynamics of ecological change following a major perturbation, known
Zhang MM, Liu N, Zhang YL, Rong BW, Wang XL, Xu CH, Xie YY, Shen SH, Zhu J, Nimer SD, Chen Z, Chen SJ, Roeder RG, Lan F, Wang L, Huang QH, Sun XJ
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Destabilization of AETFC through C/EBP alpha-mediated repression of LYL1 contributes to t(8;21) leukemic cell differentiation

LEUKEMIA 2019 JUL; 33(7):1822-1827
Lapointe T
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Effects of combined escitalopram and aripiprazole in rats: role of the

PSYCHOPHARMACOLOGY 2019 JUL; 236(7):2273-2281
RationalePre-clinical and clinical studies have suggested that the
Randesi M, Contoreggi NH, Zhou Y, Rubin BR, Bellamy JR, Yu FM, Gray JD, McEwen BS, Milner TA, Kreek MJ
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Sex Differences in Neuroplasticity- and Stress-Related Gene Expression and Protein Levels in the Rat Hippocampus Following Oxycodone Conditioned Place Preference

NEUROSCIENCE 2019 JUL 1; 410(?):274-292
Prescription opioid abuse is a serious public health issue. Recently, we showed that female and male Sprague-Dawley rats acquire conditioned place preference (CPP) to the mu opioid receptor agonist oxycodone. Anatomical analysis of the hippocampus from these rats unveiled sex differences in the opioid system in a way that would support excitation and opiate associative learning processes especially in females. In this study, we examined the expression and protein densities of opioid, plasticity, stress and related kinase and signaling molecules in the hippocampus of female and male rats following oxycodone CPP. Oxycodone CPP females have: a) increases in ARC (activity regulated cytoskeletal-associated protein)-immunoreactivity (ir) in CA3 pyramidal cells; b) decreases in Npy (neuropeptide Y) gene expression in the medial hippocampus but higher numbers of NPY-containing hilar interneurons compared to males; c) increases in Crhr2 (corticotropin releasing factor receptor 2) expression in CA2/3; d) increases in Akt1 (AKT serine/threonine kinase 1) expression in medial hippocampus; and e) decreases in phosphorylated MAPK (mitogen activated protein kinase)-ir in CA1 and dentate gyrus. Oxycodone CPP males have: a) increases in Bdnf (brain derived-neurotrophic factor) expression, which is known to be produced in granule cells, relative to females; b) elevated Mapk1 expression and pMAPK-ir in the dentate hilus which harbors newly generated granule cells; and c) increases in CRHR1-ir in CA3 pyramidal cell soma. These sex-specific changes in plasticity, stress and kinase markers in hippocampal circuitry parallel previously observed sex differences in the opioid system after oxycodone CPP. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
Xue BK, Sartori P, Leibler S
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Environment-to-phenotype mapping and adaptation strategies in varying environments

Biological organisms exhibit diverse strategies for adapting to varying environments. For example, a population of organisms may express the same phenotype in all environments ("unvarying strategy") or follow environmental cues and express alternative phenotypes to match the environment ("tracking strategy"), or diversify into coexisting phenotypes to cope with environmental uncertainty ("bet-hedging strategy"). We introduce a general framework for studying how organisms respond to environmental variations, which models an adaptation strategy by an abstract mapping from environmental cues to phenotypic traits. Depending on the accuracy of environmental cues and the strength of natural selection, we find different adaptation strategies represented by mappings that maximize the long-term growth rate of a population. The previously studied strategies emerge as special cases of our model: The tracking strategy is favorable when environmental cues are accurate, whereas when cues are noisy, organisms can either use an unvarying strategy or, remarkably, use the uninformative cue as a source of randomness to bet hedge. Our model of the environment-to-phenotype mapping is based on a network with hidden units; the performance of the strategies is shown to rely on having a high-dimensional internal representation, which can even be random.
Timberlake AT
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Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt,

Craniosynostosis (CS) is a frequent congenital anomaly featuring the
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Efficacy and cost-effectiveness of early antiretroviral therapy and

BMC INFECTIOUS DISEASES 2019 JUL 25; 19(?):? Article 663
BackgroundBiomedical interventions such as antiretroviral therapy (ART)