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101.
Motor cortex output is capable of considerable reorganization, which involves modulation of excitability within the cortex. Does such reorganization also involve changes beyond the cortex, at the level of throughput from single motor cortex neurons to muscle activity? We examined such throughput during a paradigm that provided incentive for enhancing functional connectivity from motor cortex neurons to muscles. Short-latency throughput from a recorded neuron to muscle activity not present during some behavioral epochs often appeared during others. Such changes in throughput could not always be attributed to a higher neuron firing rate, to more ongoing muscle activity, or to neuronal synchronization, indicating that reorganization of motor cortex output may involve rapid changes in functional connectivity from single motor cortex neurons to alpha-motoneuron pools. 相似文献
102.
Wu CC Li TK Farh L Lin LY Lin TS Yu YJ Yen TJ Chiang CW Chan NL 《Science (New York, N.Y.)》2011,333(6041):459-462
Type II topoisomerases (TOP2s) resolve the topological problems of DNA by transiently cleaving both strands of a DNA duplex to form a cleavage complex through which another DNA segment can be transported. Several widely prescribed anticancer drugs increase the population of TOP2 cleavage complex, which leads to TOP2-mediated chromosome DNA breakage and death of cancer cells. We present the crystal structure of a large fragment of human TOP2β complexed to DNA and to the anticancer drug etoposide to reveal structural details of drug-induced stabilization of a cleavage complex. The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. The analysis of protein-drug interactions provides information applicable for developing an isoform-specific TOP2-targeting strategy. 相似文献
103.
104.
Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene 总被引:1,自引:0,他引:1
Elchebly M Payette P Michaliszyn E Cromlish W Collins S Loy AL Normandin D Cheng A Himms-Hagen J Chan CC Ramachandran C Gresser MJ Tremblay ML Kennedy BP 《Science (New York, N.Y.)》1999,283(5407):1544-1548
Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity. 相似文献
105.
Erythropoiesis in the rat: differential rates of DNA synthesis and cell proliferation 总被引:2,自引:0,他引:2
F C Monette J LoBue A S Gordon P Alexander P C Chan 《Science (New York, N.Y.)》1968,162(858):1132-1134
Direct in vivo estimates of DNA synthesis time in early and late erythroblasts were obtained by using the H(3)- and C(14)-thymidine double-la-beling technique. A double-emulsion autoradiographic procedure was used to resolve the two isotopes. Early erythroblasts were found to proliferate at a rate about five times that of late cells. This results primarily from a shorter mean DNA synthesis time in early cells (2.5 hours) than in late cells (6.5 hours). 相似文献
106.
Hypertensive action of 18-hydroxydeoxycorticosterone 总被引:2,自引:0,他引:2
J T Oliver M K Birmingham A Bartova M P Li T H Chan 《Science (New York, N.Y.)》1973,182(118):1249-1251
18-Hydroxydeoxycorticosterone is an adrenal steroid hormone causing salt and water retention and is secreted in greatly increased amounts in response to the pituitary hormone adrenocorticotropic hormone. Its production is abnormally high in some forms of hypertension in man and rat. Direct proof that 18-hydroxydeoxycorticosterone is capable of causing hypertension is present. Daily subcutaneous injections of 200 micrograms, a low physiological dose, significantly increase the blood pressure of unilaterally nephrectomized saline-treated rats after 2 weeks. This strengthens the hypothesis that 18-hydroxydeoxycorticosterone contributes to the etiology of hypertension, possibly by a mechanism involving stressinduced release of adrenocorticotropic hormone. 相似文献
107.
Russell CA Jones TC Barr IG Cox NJ Garten RJ Gregory V Gust ID Hampson AW Hay AJ Hurt AC de Jong JC Kelso A Klimov AI Kageyama T Komadina N Lapedes AS Lin YP Mosterin A Obuchi M Odagiri T Osterhaus AD Rimmelzwaan GF Shaw MW Skepner E Stohr K Tashiro M Fouchier RA Smith DJ 《Science (New York, N.Y.)》2008,320(5874):340-346
Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection. 相似文献
108.
Steed PM Tansey MG Zalevsky J Zhukovsky EA Desjarlais JR Szymkowski DE Abbott C Carmichael D Chan C Cherry L Cheung P Chirino AJ Chung HH Doberstein SK Eivazi A Filikov AV Gao SX Hubert RS Hwang M Hyun L Kashi S Kim A Kim E Kung J Martinez SP Muchhal US Nguyen DH O'Brien C O'Keefe D Singer K Vafa O Vielmetter J Yoder SC Dahiyat BI 《Science (New York, N.Y.)》2003,301(5641):1895-1898
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands. 相似文献
109.
Hasegawa K Martin F Huang G Tumas D Diehl L Chan AC 《Science (New York, N.Y.)》2004,303(5658):685-689
Protein tyrosine kinases and phosphatases cooperate to regulate normal immune cell function. We examined the role of PEST domain-enriched tyrosine phosphatase (PEP) in regulating T cell antigen-receptor function during thymocyte development and peripheral T cell differentiation. Although normal na?ve T cell functions were retained in pep-deficient mice, effector/memory T cells demonstrated enhanced activation of Lck. In turn, this resulted in increased expansion and function of the effector/memory T cell pool, which was also associated with spontaneous development of germinal centers and elevated serum antibody levels. These results revealed a central role for PEP in negatively regulating specific aspects of T cell development and function. 相似文献
110.
A persistent oxygen anomaly reveals the fate of spilled methane in the deep Gulf of Mexico 总被引:3,自引:0,他引:3
Kessler JD Valentine DL Redmond MC Du M Chan EW Mendes SD Quiroz EW Villanueva CJ Shusta SS Werra LM Yvon-Lewis SA Weber TC 《Science (New York, N.Y.)》2011,331(6015):312-315
Methane was the most abundant hydrocarbon released during the 2010 Deepwater Horizon oil spill in the Gulf of Mexico. Beyond relevancy to this anthropogenic event, this methane release simulates a rapid and relatively short-term natural release from hydrates into deep water. Based on methane and oxygen distributions measured at 207 stations throughout the affected region, we find that within ~120 days from the onset of release ~3.0 × 10(10) to 3.9 × 10(10) moles of oxygen were respired, primarily by methanotrophs, and left behind a residual microbial community containing methanotrophic bacteria. We suggest that a vigorous deepwater bacterial bloom respired nearly all the released methane within this time, and that by analogy, large-scale releases of methane from hydrate in the deep ocean are likely to be met by a similarly rapid methanotrophic response. 相似文献