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排序方式: 共有350条查询结果,搜索用时 125 毫秒
11.
Marlys Hammond David G. Washburn Tram H. Hoang Sharada Manns James S. Frazee Hiroko Nakamura Jaclyn R. Patterson Walter Trizna Charlene Wu Leonard M. Azzarano Rakesh Nagilla Melanie Nord Rebecca Trejo Martha S. Head Baoguang Zhao Angela M. Smallwood Kendra Hightower Nicholas J. Laping Christine G. Schnackenberg Scott K. Thompson 《Bioorganic & medicinal chemistry letters》2009,19(15):4441-4445
The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. 相似文献
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Joseph E. Donnelly Jeffery J. Honas Bryan K. Smith Matthew S. Mayo Cheryl A. Gibson Debra K. Sullivan Jaehoon Lee Stephen D. Herrmann Kate Lambourne Rik A. Washburn 《Obesity (Silver Spring, Md.)》2013,21(3):E219-E228
Exercise is recommended by public health agencies for weight management; however, the role of exercise is generally considered secondary to energy restriction. Few studies exist that have verified completion of exercise, measured the energy expenditure of exercise, and prescribed exercise with equivalent energy expenditure across individuals and genders.
Objective:
The objective of this study was to evaluate aerobic exercise, without energy restriction, on weight loss in sedentary overweight and obese men and women.Design and Methods:
This investigation was a randomized, controlled, efficacy trial in 141 overweight and obese participants (body mass index, 31.0 ± 4.6 kg/m2; age 22.6 ± 3.9 years). Participants were randomized (2:2:1 ratio) to exercise at either 400 kcal/session or 600 kcal/session or to a nonexercise control. Exercise was supervised, 5 days/week, for 10 months. All participants were instructed to maintain usual ad libitum diets. Because of the efficacy design, completion of ≥90% of exercise sessions was an a priori definition of per protocol, and these participants were included in the analysis.Results:
Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9 kg (4.3%) and 5.2 ± 5.6 kg (5.7%), respectively, compared with weight gain for controls of 0.5 ± 3.5 kg (0.5%) (P < 0.05). Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant.Conclusions:
Supervised exercise, with equivalent energy expenditure, results in clinically significant weight loss with no significant difference between men and women. 相似文献14.
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Analysis of the microbial proteome 总被引:11,自引:0,他引:11
Proteomics has begun to provide insight into the biology of microorganisms. The combination of proteomics with genetics, molecular biology, protein biochemistry and biophysics is particularly powerful, resulting in novel methods to analyse complex protein mixtures. Emerging proteomic technologies promise to increase the throughput of protein identifications from complex mixtures and allow for the quantification of protein expression levels. 相似文献
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Joseph E. Donnelly Stephen D. Herrmann Kate Lambourne Amanda N. Szabo Jeffery J. Honas Richard A. Washburn 《PloS one》2014,9(1)
Background
The magnitude of the negative energy balance induced by exercise may be reduced due to compensatory increases in energy intake.Objective
To address the question: Does increased exercise or physical activity alter ad-libitum daily energy intake or macronutrient composition in healthy adults?Data Sources
PubMed and Embase were searched (January 1990–January 2013) for studies that presented data on energy and/or macronutrient intake by level of exercise, physical activity or change in response to exercise. Ninety-nine articles (103 studies) were included.Study Eligibility Criteria
Primary source articles published in English in peer-reviewed journals. Articles that presented data on energy and/or macronutrient intake by level of exercise or physical activity or changes in energy or macronutrient intake in response to acute exercise or exercise training in healthy (non-athlete) adults (mean age 18–64 years).Study Appraisal and Synthesis Methods
Articles were grouped by study design: cross-sectional, acute/short term, non-randomized, and randomized trials. Considerable heterogeneity existed within study groups for several important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and presented by study design.Results
No effect of physical activity, exercise or exercise training on energy intake was shown in 59% of cross-sectional studies (n = 17), 69% of acute (n = 40), 50% of short-term (n = 10), 92% of non-randomized (n = 12) and 75% of randomized trials (n = 24). Ninety-four percent of acute, 57% of short-term, 100% of non-randomized and 74% of randomized trials found no effect of exercise on macronutrient intake. Forty-six percent of cross-sectional trials found lower fat intake with increased physical activity.Limitations
The literature is limited by the lack of adequately powered trials of sufficient duration, which have prescribed and measured exercise energy expenditure, or employed adequate assessment methods for energy and macronutrient intake.Conclusions
We found no consistent evidence that increased physical activity or exercise effects energy or macronutrient intake. 相似文献19.
Kirk EP Washburn RA Bailey BW LeCheminant JD Donnelly JE 《Journal of strength and conditioning research / National Strength & Conditioning Association》2007,21(1):151-156
To determine the effects of a 6-month supervised low-volume resistance training (RT) program (1 set, 85-90%, one repetition maximum, 1RM, 3 d x wk(-1)) on muscular strength (1RM) and skeletal muscle mass (SMM) in previously sedentary, overweight men on an ad libitum diet. Nineteen men were randomly assigned to a control (CON, n = 8) or RT (n = 11) group. The exercise protocol consisted of 5 upper- and 4 lower-body exercises using weight machines. CON maintained their sedentary lifestyle. One RM for upper body (chest press [CP] + lat pull-down [LPD]) and lower body (leg press [LP]) and SMM were assessed at baseline, and at 3 and 6 months. Adherence was 96 +/- 2% with an average time to complete each exercise session of 15 +/- 2 minutes. Volume completed per exercise session significantly increased from baseline (2,812 +/- 670 kg) to 6 months (6,411 +/- 2,128 kg). There was a group by time interaction in 1RM for CP, LPD, and LP. Upper-body strength increased significantly (p < 0.001) (31.3 +/- 9.3%) from baseline to 3 months and from 3 to 6 months (17.9 +/- 8.7%). Lower-body strength also increased significantly from baseline to 3 months (17.8 +/- 16.6%) and from 3 to 6 months (32.0 +/- 33.7%). No changes in upper- or lower-body strength occurred in the CON group. There was no group by time interaction for SMM (CON, 34.5 +/- 2.9 kg vs. RT, 34.2 +/- 2.9 kg; p > 0.05) or for energy intake (p > 0.05). In conclusion, a single set resistance training program at 85% of 1RM, 3 d x wk(-1) resulted in continued increases in muscular strength and a very high adherence rate over a 6-month period in sedentary, overweight men independent of significant changes in SMM. This training protocol may increase adherence and produce long-term increases in muscular fitness as part of an adult fitness program. 相似文献
20.
Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence 总被引:2,自引:0,他引:2
Litovchick L Sadasivam S Florens L Zhu X Swanson SK Velmurugan S Chen R Washburn MP Liu XS DeCaprio JA 《Molecular cell》2007,26(4):539-551
The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence. 相似文献