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排序方式: 共有2919条查询结果,搜索用时 15 毫秒
121.
Marissa J. Schafer Daniel L. Mazula Ashley K. Brown Thomas A. White Elizabeth Atkinson Vesselina M. Pearsall Zaira Aversa Grace C. Verzosa Leslie A. Smith Aleksey Matveyenko Jordan D. Miller Nathan K. LeBrasseur 《Aging cell》2019,18(4)
Aging and obesity increase multimorbidity and disability risk, and determining interventions for reversing healthspan decline is a critical public health priority. Exercise and time‐restricted feeding (TRF) benefit multiple health parameters when initiated in early life, but their efficacy and safety when initiated at older ages are uncertain. Here, we tested the effects of exercise versus TRF in diet‐induced obese, aged mice from 20 to 24 months of age. We characterized healthspan across key domains: body composition, physical, metabolic, and cardiovascular function, activity of daily living (ADL) behavior, and pathology. We demonstrate that both exercise and TRF improved aspects of body composition. Exercise uniquely benefited physical function, and TRF uniquely benefited metabolism, ADL behavior, and circulating indicators of liver pathology. No adverse outcomes were observed in exercised mice, but in contrast, lean mass and cardiovascular maladaptations were observed following TRF. Through a composite index of benefits and risks, we conclude the net healthspan benefits afforded by exercise are more favorable than those of TRF. Extrapolating to obese older adults, exercise is a safe and effective option for healthspan improvement, but additional comprehensive studies are warranted before recommending TRF. 相似文献
122.
Vicuna Requesens Deborah Gonzalez Romero Maria Elena Devaiah Shivakumar P. Chang Yeun-Kyung Flory Ashley Streatfield Stephen Ring Rebecca Phillips Cassie Hood Nathan C. Marbaniang Cyrus Dean Howard John A. Hood Elizabeth E. 《Transgenic research》2019,28(5-6):537-547
Transgenic Research - Expression of recombinant proteins in plants is a technology for producing vaccines, pharmaceuticals and industrial enzymes. For the past several years, we have produced... 相似文献
123.
Yumin Dai Ashley N. Peralta Jessica E. Wynn Chringma Sherpa Hao Li Astha Verma Stuart F.J. Le Grice Webster L. Santos 《Bioorganic & medicinal chemistry》2019,27(8):1759-1765
Interaction of HIV-1 rev response element (RRE) RNA with its cognate protein, Rev, is critical for HIV-1 replication. Understanding the mode of interaction between RRE RNA and ligands at the binding site can facilitate RNA molecular recognition as well as provide a strategy for developing anti-HIV therapeutics. Our approach utilizes branched peptides as a scaffold for multivalent binding to RRE IIB (high affinity rev binding site) with incorporation of unnatural amino acids to increase affinity via non-canonical interactions with the RNA. Previous high throughput screening of a 46,656-member library revealed several hits that bound RRE IIB RNA in the sub-micromolar range. In particular, the lead compound, 4B3, displayed a Kd value of 410?nM and demonstrated selectivity towards RRE. A ribonuclease protection assay revealed that 4B3 binds to the stem-loop structure of RRE IIB RNA, which was confirmed by SHAPE analysis with 234 nt long NL4-3 RRE RNA. Our studies further indicated interaction of 4B3 with both primary and secondary Rev binding sites. 相似文献
124.
Susan K. Boehlein Peng Liu Ashley Webster Camila Ribeiro Masaharu Suzuki Shan Wu Jiahn‐Chou Guan Jon D. Stewart William F. Tracy A. Mark Settles Donald R. McCarty Karen E. Koch Larkin C. Hannah Tracie A. Hennen‐Bierwagen Alan M. Myers 《The Plant journal : for cell and molecular biology》2019,99(1):23-40
125.
Qingping Xu Matthew Biancalana Joanna C. Grant Hsiu‐Ju Chiu Lukasz Jaroszewski Mark W. Knuth Scott A. Lesley Adam Godzik Marc‐Andr Elsliger Ashley M. Deacon Ian A. Wilson 《Protein science : a publication of the Protein Society》2019,28(9):1676-1689
Free‐standing single‐layer β‐sheets are extremely rare in naturally occurring proteins, even though β‐sheet motifs are ubiquitous. Here we report the crystal structures of three homologous, single‐layer, anti‐parallel β‐sheet proteins, comprised of three or four twisted β‐hairpin repeats. The structures reveal that, in addition to the hydrogen bond network characteristic of β‐sheets, additional hydrophobic interactions mediated by small clusters of residues adjacent to the turns likely play a significant role in the structural stability and compensate for the lack of a compact hydrophobic core. These structures enabled identification of a family of secreted proteins that are broadly distributed in bacteria from the human gut microbiome and are putatively involved in the metabolism of complex carbohydrates. A conserved surface patch, rich in solvent‐exposed tyrosine residues, was identified on the concave surface of the β‐sheet. These new modular single‐layer β‐sheet proteins may serve as a new model system for studying folding and design of β‐rich proteins. 相似文献
126.
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128.
Ayşegül Özen Kristina Prachanronarong Ashley N. Matthew Djade I. Soumana 《Critical reviews in biochemistry and molecular biology》2019,54(1):11-26
Direct acting antivirals have dramatically increased the efficacy and tolerability of hepatitis C treatment, but drug resistance has emerged with some of these inhibitors, including nonstructural protein 3/4?A protease inhibitors (PIs). Although many co-crystal structures of PIs with the NS3/4A protease have been reported, a systematic review of these crystal structures in the context of the rapidly emerging drug resistance especially for early PIs has not been performed. To provide a framework for designing better inhibitors with higher barriers to resistance, we performed a quantitative structural analysis using co-crystal structures and models of HCV NS3/4A protease in complex with natural substrates and inhibitors. By comparing substrate structural motifs and active site interactions with inhibitor recognition, we observed that the selection of drug resistance mutations correlates with how inhibitors deviate from viral substrates in molecular recognition. Based on this observation, we conclude that guiding the design process with native substrate recognition features is likely to lead to more robust small molecule inhibitors with decreased susceptibility to resistance. 相似文献
129.
Angela M. Mech Kathryn A. Thomas Travis D. Marsico Daniel A. Herms Craig R. Allen Matthew P. Ayres Kamal J. K. Gandhi Jessica Gurevitch Nathan P. Havill Ruth A. Hufbauer Andrew M. Liebhold Kenneth F. Raffa Ashley N. Schulz Daniel R. Uden Patrick C. Tobin 《Ecology and evolution》2019,9(21):12216-12230
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130.
Ashley M. Jensen Nicholas P. O'Neil Andrew N. Iwaniuk Theresa M. Burg 《Ecology and evolution》2019,9(10):5572-5592
The amount of dispersal that occurs among populations can be limited by landscape heterogeneity, which is often due to both natural processes and anthropogenic activity leading to habitat loss or fragmentation. Understanding how populations are structured and mapping existing dispersal corridors among populations is imperative to both determining contemporary forces mediating population connectivity, and informing proper management of species with fragmented populations. Furthermore, the contemporary processes mediating gene flow across heterogeneous landscapes on a large scale are understudied, particularly with respect to widespread species. This study focuses on a widespread game bird, the Ruffed Grouse (Bonasa umbellus), for which we analyzed samples from the western extent of the range. Using three types of genetic markers, we uncovered multiple factors acting in concert that are responsible for mediating contemporary population connectivity in this species. Multiple genetically distinct groups were detected; microsatellite markers revealed six groups, and a mitochondrial marker revealed four. Many populations of Ruffed Grouse are genetically isolated, likely by macrogeographic barriers. Furthermore, the addition of landscape genetic methods not only corroborated genetic structure results, but also uncovered compelling evidence that dispersal resistance created by areas of unsuitable habitat is the most important factor mediating population connectivity among the sampled populations. This research has important implications for both our study species and other inhabitants of the early successional forest habitat preferred by Ruffed Grouse. Moreover, it adds to a growing body of evidence that isolation by resistance is more prevalent in shaping population structure of widespread species than previously thought. 相似文献