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排序方式: 共有216条查询结果,搜索用时 15 毫秒
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Scott A. Beers Elizabeth A. Malloy Wei Wu Michael P. Wachter Uma Gunnia Druie Cavender Crafford Harris Janet Davis Ruth Brosius J.Lee Pellegrino-Gensey John Siekierka 《Bioorganic & medicinal chemistry》1997,5(12):2203-2211
A series of nitroarylhydroxymethylphosphonic acids was synthesized and evaluated as inhibitors of CD45. It was discovered that both the alpha hydroxy and nitro groups are essential for activity. Potency is enhanced by the addition of a large lipophilic group on the aryl ring adjacent to the phosphonic acid moiety. Kinetics studies have shown that these compounds are competitive inhibitors and thus bind at the active site of this enzyme 相似文献
63.
Huang S Cerny RE Qi Y Bhat D Aydt CM Hanson DD Malloy KP Ness LA 《Plant physiology》2003,131(3):1270-1282
Numerous plant hormones interact during plant growth and development. Elucidating the role of these various hormones on particular tissue types or developmental stages has been difficult with exogenous applications or constitutive expression studies. Therefore, we used tissue-specific promoters expressing CKX1 and gai, genes involved in oxidative cytokinin degradation and gibberellin (GA) signal transduction, respectively, to study the roles of cytokinin and GA in male organ development. Accumulation of CKX1 in reproductive tissues of transgenic maize (Zea mays) resulted in male-sterile plants. The male development of these plants was restored by applications of kinetin and thidiazuron. Similarly, expression of gai specifically in anthers and pollen of tobacco (Nicotiana tabacum) and Arabidopsis resulted in the abortion of these respective tissues. The gai-induced male-sterile phenotype exhibited by the transgenic plants was reversible by exogenous applications of kinetin. Our results provide molecular evidence of the involvement of cytokinin and GA in male development and support the hypothesis that the male development is controlled in concert by multiple hormones. These studies also suggest a potential method for generating maintainable male sterility in plants by using existing agrochemicals that would reduce the expense of seed production for existing hybrid crops and provide a method to produce hybrid varieties of traditionally non-hybrid crops. 相似文献
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Winter Patrick M.; Seshan Viswanathan; Makos Janice D.; Sherry A. Dean; Malloy Craig R.; Bansal Navin 《Journal of applied physiology》1998,85(5):1806-1812
A method ispresented to measure the absolute concentration of intracellularNa+([Na+]i)in vivo by using interleaved 23Na-and 31P-nuclear magnetic resonance(NMR) spectroscopy andTmDOTP5 as shift reagentand chemical marker of tissue extracellular space (ECS). The techniquewas used to determine[Na+]iand relative ECS in livers of control rats (21 ± 3 and0.11 ± 0.02 mM, respectively) and in rats exposed to carbontetrachloride (103 ± 29 and 0.23 ± 0.03 mM, respectively). TheNMR measurements were confirmed independently on excised tissue samplesby using atomic absorption spectroscopy. The results confirm thatTmDOTP5 can be used as acombined cation shift reagent and ECS marker, thereby allowingquantitation of[Na+]iin vivo by NMR. 相似文献
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Block of outward current in cardiac purkinje fibers by injection of quaternary ammonium ions 总被引:6,自引:5,他引:1 下载免费PDF全文
We have studied the effects of iontophoretic injection of the quaternary ammonium compounds tetraethylammonium (TEA) and tetrabutylammonium (TBA) in cardiac purkinje fibers. We find that TBA(+) is a more effective blocker than TEA(+), but injection of either compound reduces the time-dependent outward plateau currents, transient outward current (I(to)), and the delayed rectifier (I(x)). Our findings provide evidence that these outward cardiac currents are carried by channels that in some respects are pharmacologically similar to squid axon potassium channels. We demonstrate that this procedure is a new tool that can be useful in the analysis of membrane currents in the heart. 相似文献
69.
Eunsook S. Jin A. Dean Sherry Craig R. Malloy 《The Journal of biological chemistry》2015,290(51):30486-30497
Phosphoenolpyruvate (PEP) generated from pyruvate is required for de novo synthesis of glycerol and glycogen in skeletal muscle. One possible pathway involves synthesis of PEP from the citric acid cycle intermediates via PEP carboxykinase, whereas another could involve reversal of pyruvate kinase (PK). Earlier studies have reported that reverse flux through PK can contribute carbon precursors for glycogen synthesis in muscle, but the physiological importance of this pathway remains uncertain especially in the setting of high plasma glucose. In addition, although PEP is a common intermediate for both glyconeogenesis and glyceroneogenesis, the importance of reverse PK in de novo glycerol synthesis has not been examined. Here we studied the contribution of reverse PK to synthesis of glycogen and the glycerol moiety of acylglycerols in skeletal muscle of animals with high plasma glucose. Rats received a single intraperitoneal bolus of glucose, glycerol, and lactate under a fed or fasted state. Only one of the three substrates was 13C-labeled in each experiment. After 3 h of normal awake activity, the animals were sacrificed, and the contribution from each substrate to glycogen and the glycerol moiety of acylglycerols was evaluated. The fraction of 13C labeling in glycogen and the glycerol moiety exceeded the possible contribution from either plasma glucose or muscle oxaloacetate. The reverse PK served as a common route for both glyconeogenesis and glyceroneogenesis in the skeletal muscle of rats with high plasma glucose. The activity of pyruvate carboxylase was low in muscle, and no PEP carboxykinase activity was detected. 相似文献
70.
Swarbrick MM Waldenmaier B Pennacchio LA Lind DL Cavazos MM Geller F Merriman R Ustaszewska A Malloy M Scherag A Hsueh WC Rief W Mauvais-Jarvis F Pullinger CR Kane JP Dent R McPherson R Kwok PY Hinney A Hebebrand J Vaisse C 《PLoS biology》2005,3(9):e315
The demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention, and treatment of these conditions. Unequivocal proof of such an association, however, requires independent replication of initial positive findings. Recently, three (-243 A>G, +61450 C>A, and +83897 T>A) single nucleotide polymorphisms (SNPs) within glutamate decarboxylase 2 (GAD2) were found to be associated with class III obesity (body mass index > 40 kg/m2). The association was observed among 188 families (612 individuals) segregating the condition, and a case-control study of 575 cases and 646 lean controls. Functional data supporting a pathophysiological role for one of the SNPs (-243 A>G) were also presented. The gene GAD2 encodes the 65-kDa subunit of glutamic acid decarboxylase-GAD65. In the present study, we attempted to replicate this association in larger groups of individuals, and to extend the functional studies of the -243 A>G SNP. Among 2,359 individuals comprising 693 German nuclear families with severe, early-onset obesity, we found no evidence for a relationship between the three GAD2 SNPs and obesity, whether SNPs were studied individually or as haplotypes. In two independent case-control studies (a total of 680 class III obesity cases and 1,186 lean controls), there was no significant relationship between the -243 A>G SNP and obesity (OR = 0.99, 95% CI 0.83-1.18, p = 0.89) in the pooled sample. These negative findings were recapitulated in a meta-analysis, incorporating all published data for the association between the -243G allele and class III obesity, which yielded an OR of 1.11 (95% CI 0.90-1.36, p = 0.28) in a total sample of 1,252 class III obese cases and 1,800 lean controls. Moreover, analysis of common haplotypes encompassing the GAD2 locus revealed no association with severe obesity in families with the condition. We also obtained functional data for the -243 A>G SNP that does not support a pathophysiological role for this variant in obesity. Potential confounding variables in association studies involving common variants and complex diseases (low power to detect modest genetic effects, overinterpretation of marginal data, population stratification, and biological plausibility) are also discussed in the context of GAD2 and severe obesity. 相似文献