排序方式: 共有219条查询结果,搜索用时 343 毫秒
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Mazei-Robison MS Koo JW Friedman AK Lansink CS Robison AJ Vinish M Krishnan V Kim S Siuta MA Galli A Niswender KD Appasani R Horvath MC Neve RL Worley PF Snyder SH Hurd YL Cheer JF Han MH Russo SJ Nestler EJ 《Neuron》2011,72(6):977-990
While the abuse of opiate drugs continues to rise, the neuroadaptations that occur with long-term drug exposure remain poorly understood. We describe here a series of chronic morphine-induced adaptations in ventral tegmental area (VTA) dopamine neurons, which are mediated via downregulation of AKT-mTORC2 (mammalian target of rapamycin complex-2). Chronic opiates decrease the size of VTA dopamine neurons in rodents, an effect seen in humans as well, and concomitantly increase the excitability of the cells but decrease dopamine output to target regions. Chronic morphine decreases mTORC2 activity, and overexpression of Rictor,?a component of mTORC2, prevents morphine-induced changes in cell morphology and activity. Further, local knockout of Rictor in VTA decreases DA soma size and reduces rewarding responses to morphine, consistent with the hypothesis that these adaptations represent a mechanism of reward tolerance. Together, these findings demonstrate a novel role for AKT-mTORC2 signaling in mediating neuroadaptations to opiate drugs of abuse. 相似文献
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O'Leary B Fedosejevs ET Hill AT Bettridge J Park J Rao SK Leach CA Plaxton WC 《Journal of experimental botany》2011,62(15):5485-5495
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Jourden MJ Clarke CN Palmer AK Barth EJ Prada RC Hale RN Fraga D Snider MJ Edmiston PL 《Biochimica et biophysica acta》2007,1774(12):1519-1527
Eight variants of creatine kinase were created to switch the substrate specificity from creatine to glycocyamine using a rational design approach. Changes to creatine kinase involved altering several residues on the flexible loops that fold over the bound substrates including a chimeric replacement of the guanidino specificity loop from glycocyamine kinase into creatine kinase. A maximal 2,000-fold change in substrate specificity was obtained as measured by a ratio of enzymatic efficiency (k(cat)/K(M).K(d)) for creatine vs. glycocyamine. In all cases, a change in specificity was accompanied by a large drop in enzymatic efficiency. This data, combined with evidence from other studies, indicate that substrate specificity in the phosphagen kinase family is obtained by precise alignment of substrates in the active site to maximize k(cat)/K(M).K(d) as opposed to selective molecular recognition of one guanidino substrate over another. A model for the evolution of the dimeric forms of phosphagen kinases is proposed in which these enzymes radiated from a common ancestor that may have possessed a level of catalytic promiscuity. As mutational events occurred leading to greater degrees of substrate specificity, the dimeric phosphagen kinases became evolutionary separated such that the substrate specificity could not be interchanged by a small number of mutations. 相似文献
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Araújo Patrícia G. Nardelli Allyson E. Duran Reina Pereira Mariana S. Gelli Valéria C. Mandalka Andrea Eisner Peter Fujii Mutue T. Chow Fungyi 《Journal of applied phycology》2022,34(3):1677-1691
Journal of Applied Phycology - Antioxidant potential, carbohydrate content, ash, minerals, proteins, and amino acids of Kappaphycus alvarezii farmed along the São Paulo coast, Brazil, were... 相似文献
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Peña-Moreno Irina Charlot Castro Parente Denise da Silva Jackeline Maria Andrade Mendonça Allyson Rojas Lino Angel Valcarcel de Morais Junior Marcos Antonio de Barros Pita Will 《Journal of industrial microbiology & biotechnology》2019,46(2):209-220
Journal of Industrial Microbiology & Biotechnology - In the past few years, the yeast Dekkera bruxellensis has gained much of attention among the so-called non-conventional yeasts for its... 相似文献
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Terpenoid emissions from ponderosa pine (Pinus ponderosa subsp. scopulorum) were measured in Colorado, USA over two growing seasons to evaluate the role of incident light, needle temperature, and stomatal conductance in controlling emissions of 2-methyl-3-buten-2-ol (MBO) and several monoterpenes. MBO was the dominant daylight terpenoid emission, comprising on average 87 % of the total flux, and diurnal variations were largely determined by light and temperature. During daytime, oxygenated monoterpenes (especially linalool) comprised up to 75 % of the total monoterpenoid flux from needles. A significant fraction of monoterpenoid emissions was dependent on light and 13CO2 labeling studies confirmed de novo production. Thus, modeling of monoterpenoid emissions required a hybrid model in which a significant fraction of emissions was dependent on both light and temperature, while the remainder was dependent on temperature alone. Experiments in which stomata were forced to close using abscisic acid demonstrated that MBO and a large fraction of the monoterpene flux, presumably linalool, could be limited at the scale of seconds to minutes by stomatal conductance. Using a previously published model of terpenoid emissions, which explicitly accounts for the physico-chemical properties of emitted compounds, we were able to simulate these observed stomatal effects, whether induced experimentally or arising under naturally fluctuation conditions of temperature and light. This study shows unequivocally that, under naturally occurring field conditions, de novo light-dependent monoterpenes comprise a significant fraction of emissions in ponderosa pine. Differences between the monoterpene composition of ambient air and needle emissions imply a significant non-needle emission source enriched in Δ-3-carene. 相似文献
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Allyson L Byrd Joseph F Perez-Rogers Solaiappan Manimaran Eduardo Castro-Nallar Ian Toma Tim McCaffrey Marc Siegel Gary Benson Keith A Crandall William Evan Johnson 《BMC bioinformatics》2014,15(1)
Background
The use of sequencing technologies to investigate the microbiome of a sample can positively impact patient healthcare by providing therapeutic targets for personalized disease treatment. However, these samples contain genomic sequences from various sources that complicate the identification of pathogens.Results
Here we present Clinical PathoScope, a pipeline to rapidly and accurately remove host contamination, isolate microbial reads, and identify potential disease-causing pathogens. We have accomplished three essential tasks in the development of Clinical PathoScope. First, we developed an optimized framework for pathogen identification using a computational subtraction methodology in concordance with read trimming and ambiguous read reassignment. Second, we have demonstrated the ability of our approach to identify multiple pathogens in a single clinical sample, accurately identify pathogens at the subspecies level, and determine the nearest phylogenetic neighbor of novel or highly mutated pathogens using real clinical sequencing data. Finally, we have shown that Clinical PathoScope outperforms previously published pathogen identification methods with regard to computational speed, sensitivity, and specificity.Conclusions
Clinical PathoScope is the only pathogen identification method currently available that can identify multiple pathogens from mixed samples and distinguish between very closely related species and strains in samples with very few reads per pathogen. Furthermore, Clinical PathoScope does not rely on genome assembly and thus can more rapidly complete the analysis of a clinical sample when compared with current assembly-based methods. Clinical PathoScope is freely available at: http://sourceforge.net/projects/pathoscope/.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-262) contains supplementary material, which is available to authorized users. 相似文献70.