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Shailesh Kumar Atma P. Dwivedi Vivek Kr. Kashyap A.K. Saxena A.K. Dwivedi Ranjana Srivastava Devi P. Sahu 《Bioorganic & medicinal chemistry letters》2013,23(8):2404-2407
Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 μg/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1× MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log10 reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition. 相似文献
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Kainate receptors (KARs) are a class of ionotropic glutamate receptors that are expressed throughout the central nervous system. The function and subcellular localization of KARs are tightly regulated by accessory proteins. We have previously identified the single-pass transmembrane proteins, Neto1 and Neto2, to be associated with native KARs. In the hippocampus, Neto1, but not Neto2, controls the abundance and modulates the kinetics of postsynaptic KARs. Here we evaluated whether Neto2 regulates synaptic KAR levels in the cerebellum where Neto1 expression is limited to the deep cerebellar nuclei. In the cerebellum, where Neto2 is present abundantly, we found a ∼40% decrease in GluK2-KARs at the postsynaptic density (PSD) of Neto2-null mice. No change, however, was observed in total level of GluK2-KARs, thereby suggesting a critical role of Neto2 on the synaptic localization of cerebellar KARs. The presence of a putative class II PDZ binding motif on Neto2 led us to also investigate whether it interacts with PDZ domain-containing proteins previously implicated in regulating synaptic abundance of KARs. We identified a PDZ-dependent interaction between Neto2 and the scaffolding protein GRIP. Furthermore, coexpression of Neto2 significantly increased the amount of GRIP associated with GluK2, suggesting that Neto2 may promote and/or stabilize GluK2:GRIP interactions. Our results demonstrate that Neto2, like Neto1, is an important auxiliary protein for modulating the synaptic levels of KARs. Moreover, we propose that the interactions of Neto1/2 with various scaffolding proteins is a critical mechanism by which KARs are stabilized at diverse synapses. 相似文献
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Audesh Bhat Anil Koul Ekta Rai Swarkar Sharma M. K. Dhar R. N. K. Bamezai 《Human genetics》2008,123(1):115
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Pawan K. Dhar 《Journal of biosciences》2007,32(1):1005-1008
Systems biology is an approach to explain the behaviour of a system in relation to its individual components. Synthetic biology uses key hierarchical and modular concepts of systems biology to engineer novel biological systems. In my opinion the next step in biology is to use molecule-to-phenotype data using these approaches and integrate them in the form a periodic table. A periodic table in biology would provide chassis to classify, systematize and compare diversity of component properties vis-a-vis system behaviour. Using periodic table it could be possible to compute higher-level interactions from component properties. This paper examines the concept of building a bio-periodic table using protein fold as the fundamental unit. 相似文献
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A K Srivastava C Pandey K P Dwivedi V K Singh 《Indian journal of biochemistry & biophysics》1989,26(3):199-200
QSAR studies have been performed on the homologues of 3-triazines, using molecular connectivity index and van der Waal volume as structural parameters. The regression analysis has shown good correlation between antitumour activity and the two structural parameters. 相似文献
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The effect of a morphactin -- CF1 -- (2-chloro-9-hydroxyfluorene-9-carbocylic acid-methyl ester) on the morphogenesis of shoot apical meristem was studied on L. usitatissimum L. at three levels of supply. CF1 at 10 and 100 parts/10(6) induced repeated gamophylly resembling a concentric cupulate structure. GA3 superimposed at two levels viz. 10 and 100 parts/10(6) did not reverse this effect. The effect of CF1 is dose-dependent and reversal to normal behaviour occurs when the effect of CF1 wears off. 相似文献
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While progesterone metabolites have long been known to be potent anesthetics in pharmacological doses, there is no available information as to their effects on behaviour at physiological levels. In this study, 5 alpha- and 5 beta-pregnanediones in silastic capsules were implanted in ovariectomized rats. Approximately 4 mg/kg/day was absorbed over a 24-day period. Rats receiving 5 beta-pregnanedione had decreased motor activity (58% control, P less than or equal to 0.001) while those receiving the 5 alpha-isomer had increased activity (143% control, P = 0.01). These studies suggest that these progesterone metabolites may be responsible for some behavioural changes. 相似文献
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