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排序方式: 共有160条查询结果,搜索用时 93 毫秒
51.
Hansen KT Cronin JB Pickering SL Douglas L 《Journal of strength and conditioning research / National Strength & Conditioning Association》2011,25(9):2382-2391
The purpose of this study was to investigate the discriminative ability of rebound jump squat force-time and power-time measures in differentiating speed performance and competition level in elite and elite junior rugby union players. Forty professional rugby union players performed 3 rebound jump squats with an external load of 40 kg from which a number of force-time and power-time variables were acquired and analyzed. Additionally, players performed 3 sprints over 30 m with timing gates at 5, 10, and 30 m. Significant differences (p < 0.05) between the fastest 20 and slowest 20 athletes, and elite (n = 25) and elite junior (n = 15) players in speed and force-time and power-time variables were determined using independent sample t-tests. The fastest and slowest sprinters over 10 m differed in peak power (PP) expressed relative to body weight. Over 30 m, there were significant differences in peak velocity and relative PP and rate of power development. There was no significant difference in speed over any distance between elite and elite junior rugby union players; however, a number of force and power variables including peak force, PP, force at 100 milliseconds from minimum force, and force and impulse 200 milliseconds from minimum force were significantly (p < 0.05) different between playing levels. Although only power values expressed relative to body weight were able to differentiate speed performance, both absolute and relative force and power values differentiated playing levels in professional rugby union players. For speed development in rugby union players, training strategies should aim to optimize the athlete's power to weight ratio, and lower body resistance training should focus on movement velocity. For player development to transition elite junior players to elite status, adding lean mass is likely to be most beneficial. 相似文献
52.
Ethan Poteet Gourav Roy Choudhury Ali Winters Wenjun Li Myoung-Gwi Ryou Ran Liu Lin Tang Anuja Ghorpade Yi Wen Fang Yuan Stephen T. Keir Hai Yan Darell D. Bigner James W. Simpkins Shao-Hua Yang 《The Journal of biological chemistry》2013,288(13):9153-9164
Glioblastoma multiforme (GBM), like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg effect. Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consumption and reduction of lactate production in GBM cell lines. MB decreases GBM cell proliferation and halts the cell cycle in S phase. Through activation of AMP-activated protein kinase, MB inactivates downstream acetyl-CoA carboxylase and decreases cyclin expression. Structure-activity relationship analysis demonstrated that toluidine blue O, an MB derivative with similar bioenergetic actions, exerts similar action in GBM cell proliferation. In contrast, two other MB derivatives, 2-chlorophenothiazine and promethazine, exert no effect on cellular bioenergetics and do not inhibit GBM cell proliferation. MB inhibits cell proliferation in both temozolomide-sensitive and -insensitive GBM cell lines. In a human GBM xenograft model, a single daily dosage of MB does not activate AMP-activated protein kinase signaling, and no tumor regression was observed. In summary, the current study provides the first in vitro proof of concept that reversal of Warburg effect might be a novel therapy for GBM. 相似文献
53.
Sharmilee Gnanapavan Peggy Ho Wendy Heywood Sam Jackson Donna Grant Khadija Rantell Geoff Keir Kevin Mills Lawrence Steinman Gavin Giovannoni 《Journal of neurochemistry》2013,125(5):766-773
Multiple sclerosis (MS) is a CNS disorder characterized by demyelination and neurodegeneration. Although hallmarks of recovery (remyelination and repair) have been documented in early MS, the regenerative capacity of the adult CNS per se remains uncertain with the wide held belief that it is either limited or non‐existent. The neural cell adhesion molecule (NCAM) is a cell adhesion molecule that has been widely implicated in axonal outgrowth, guidance and fasciculation. Here, we used in vitro and in vivo of MS to investigate the role of NCAM in disease progression. We show that in health NCAM levels decrease over time, but this occurs acutely after demyelination and remains reduced in chronic disease. Our findings suggest that depletion of NCAM is one of the factors associated with or possibly responsible for disease progression in MS. 相似文献
54.
55.
Hulver Molly J. Trautman Julia P. Goodwin Amanda P. Roszczenko Sebastian K. Fogarty Keir H. Miller Heather B. 《Molecular biology reports》2020,47(3):1759-1772
Molecular Biology Reports - Human immunodeficiency virus type 1 (HIV-1) propagation requires many human cofactors. Multiple groups have demonstrated that Tat-specific factor 1 (Tat-SF1) is an HIV-1... 相似文献
56.
Hardin AH Sarkar SK Seol Y Liou GF Osheroff N Neuman KC 《Nucleic acids research》2011,39(13):5729-5743
Type IIA topoisomerases modify DNA topology by passing one segment of duplex DNA (transfer or T–segment) through a transient double-strand break in a second segment of DNA (gate or G–segment) in an ATP-dependent reaction. Type IIA topoisomerases decatenate, unknot and relax supercoiled DNA to levels below equilibrium, resulting in global topology simplification. The mechanism underlying this non-equilibrium topology simplification remains speculative. The bend angle model postulates that non-equilibrium topology simplification scales with the bend angle imposed on the G–segment DNA by the binding of a type IIA topoisomerase. To test this bend angle model, we used atomic force microscopy and single-molecule Förster resonance energy transfer to measure the extent of bending imposed on DNA by three type IIA topoisomerases that span the range of topology simplification activity. We found that Escherichia coli topoisomerase IV, yeast topoisomerase II and human topoisomerase IIα each bend DNA to a similar degree. These data suggest that DNA bending is not the sole determinant of non-equilibrium topology simplification. Rather, they suggest a fundamental and conserved role for DNA bending in the enzymatic cycle of type IIA topoisomerases. 相似文献
57.
Keir H. Fogarty Serkan Berk Iwen F. Grigsby Yan Chen Louis M. Mansky Joachim D. Mueller 《Journal of molecular biology》2014
The early events in the retrovirus assembly pathway, particularly the timing and nature of Gag translocation from the site of protein translation to the inner leaflet of the plasma membrane, are poorly understood. We have investigated the interrelationship between cytoplasmic Gag concentration and plasma membrane association using complementary live-cell biophysical fluorescence techniques in real time with both human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) Gag proteins. In particular, dual-color, z-scan fluorescence fluctuation spectroscopy in conjunction with total internal reflection fluorescence and conventional, epi-illumination imaging were utilized. Our results demonstrate that HTLV-1 Gag is capable of membrane targeting and particle assembly at low (i.e., nanomolar) cytoplasmic concentrations and that there is a critical threshold concentration (approaching micromolar) prior to the observation of HIV-1 Gag associated with the plasma membrane. These observations imply fundamental differences between HIV-1 and HTLV-1 Gag trafficking and membrane association. 相似文献
58.
59.
Bouthier de la Tour C Amrani L Cossard R Neuman KC Serre MC Duguet M 《The Journal of biological chemistry》2008,283(41):27395-27402
Reverse gyrase is a unique type IA topoisomerase that is able to introduce positive supercoils into DNA in an ATP-dependent process. ATP is bound to the helicase-like domain of the enzyme that contains most of the conserved motifs found in helicases of the SF1 and SF2 superfamilies. In this paper, we have investigated the role of the conserved helicase motifs I, II, V, VI, and Q by generating mutants of the Thermotoga maritima reverse gyrase. We show that mutations in motifs I, II, V, and VI completely eliminate the supercoiling activity of reverse gyrase and that a mutation in the Q motif significantly reduces this activity. Further analysis revealed that for most mutants, the DNA binding and cleavage properties are not significantly changed compared with the wild type enzyme, whereas their ATPase activity is impaired. These results clearly show that the helicase motifs are tightly involved in the coupling of ATP hydrolysis to the topoisomerase activity. The zinc finger motif located at the N-terminal end of reverse gyrases was also mutated. Our results indicate that this motif plays an important role in DNA binding. 相似文献
60.
Inhaled adenosine A(2A) receptor agonists for the treatment of chronic obstructive pulmonary disease
Mantell SJ Stephenson PT Monaghan SM Maw GN Trevethick MA Yeadon M Keir RF Walker DK Jones RM Selby MD Batchelor DV Rozze S Chavaroche H Hobson TJ Dodd PG Lemaitre A Wright KN Stuart EF 《Bioorganic & medicinal chemistry letters》2008,18(4):1284-1287
COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. A strategy of minimizing side-effect liability by maximizing systemic clearance was followed and pharmacological and pharmacokinetic SAR of a series of inhaled A(2A) agonists described. A sevenfold improvement in potency and 150-fold reduction in side-effect liability over the lead compound CGS-21680, were obtained. 相似文献