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71.
Tandon VK Kumar M Awasthi AK Saxena HO Goswamy GK 《Bioorganic & medicinal chemistry letters》2004,14(12):3177-3180
The synthesis and pharmacological evaluation of substituted oximino-ethers 1 and 2 of naphth[1,2-b]- and naphth[2,1-b]-oxepin-5-ones (4 and 8) were carried out. The hypotensive activity of oximino-ethers 1 and 2 was evaluated on anaesthetized cats. The results indicated that 1c caused a fall of 80 mm/Hg for >100' at a dose of 5mg/kg iv in anaesthetized cats. 相似文献
72.
We have recently shown that IKK complex plays an important non-genomic role in platelet function, i.e., regulates SNARE machinery-dependent membrane fusion. In this connection, it is well known that MALT1, whose activity is modulated by proteasome, plays an important role in the regulation of IKK complex. Therefore, the present studies investigated the mechanism by which IKK signaling is regulated in the context of the platelet proteasome. It was found that platelets express a functional proteasome, and form CARMA/MALT1/Bcl10 (CBM) complex when activated. Using a pharmacological inhibitor, the proteasome was found to regulate platelet function (aggregation, integrin activation, secretion, phosphatidylserine exposure and changes in intracellular calcium). It was also found to regulate thrombogenesis and physiologic hemostasis. We also observed, upon platelet activation, that MALT1 is ubiquitinated, and this coincides with the activation of the IKK/NF-κB-signaling pathway. Finally, we observed that the proteasome inhibitor blocks CBM complex formation and the interaction of IKKγ and MALT1; abrogates SNARE formation, and the association of MALT1 with TAK1 and TAB2, which are upstream of the CBM complex. Thus, our data demonstrate that MALT1 ubiquitination is critical for the engagement of CBM and IKK complexes, thereby directing platelet signals to the NF-κB pathway. 相似文献
73.
Michael T. Bowen Shantala A. Hari Dass Jessica Booth Anastasia Suraev Ajai Vyas Iain S. McGregor 《Hormones and behavior》2014
An active coping style displayed under stress – which involves proactive investigatory responses toward environmental threats – has been associated with reduced vulnerability to psychiatric illness. However, the neurobiological determinants of coping styles are not well understood. When rats are exposed to a naturalistic stressor (cat fur) in a group, some individuals in the group show robust active investigation of the stimulus while others show a passive response involving retreat, immobility and close aggregation with conspecifics. Here we explored endocrine and epigenetic correlates of these contrasting coping styles. Male Wistar rats (n = 48) were exposed to cat fur in groups of 4 and the passive and active responders were identified and assessed for endocrine and epigenetic differences. Three days after the final cat fur exposure, active responders had substantially lower plasma levels of corticosterone and progesterone than passive responders. Plasma and testicular testosterone levels did not differ between active and passive responders. Active responders had markedly less methylation of the AVP CGCG promoter region located at base 4970 in the posterodorsal region of the medial amygdala but did not differ in the methylation status of the CCGG sequence located at base 2243. This is in agreement with prior research suggesting that AVP and progesterone act in opposition within the medial amygdala to modulate stress-related behaviors. The present study reports striking endocrine and epigenetic differences between active and passive responders, providing insight into potential systems involved in the manifestation of differing coping styles. 相似文献
74.
Garima Khandelwal Rebecca?A. Lee B. Jayaram David?L. Beveridge 《Biophysical journal》2014,106(11):2465-2473
We describe the development and testing of a simple statistical mechanics methodology for duplex DNA applicable to sequences of any composition and extensible to genomes. The microstates of a DNA sequence are modeled in terms of blocks of basepairs that are assumed to be fully closed (paired) or open. This approach generates an ensemble of bubblelike microstates that are used to calculate the corresponding partition function. The energies of the microstates are calculated as additive contributions from hydrogen bonding, basepair stacking, and solvation terms parameterized from a comprehensive series of molecular dynamics simulations including solvent and ions. Thermodynamic properties and nucleotide stability constants for DNA sequences follow directly from the partition function. The methodology was tested by comparing computed free energies per basepair with the experimental melting temperatures of 60 oligonucleotides, yielding a correlation coefficient of −0.96. The thermodynamic stability of genic/nongenic regions was tested in terms of nucleotide stability constants versus sequence for the Escherichia coli K-12 genome. It showed clear differentiation of the genes from promoters and captures genic regions with a sensitivity of 0.94. The statistical thermodynamic model presented here provides a seemingly new handle on the challenging problem of interpreting genomic sequences. 相似文献
75.
76.
Interactions of phage Mu enhancer and termini that specify the assembly of a topologically unique interwrapped transpososome 总被引:1,自引:0,他引:1
The higher-order DNA-protein complex that carries out the chemical steps of phage Mu transposition is organized by bridging interactions among three DNA sites, the left (L) and right (R) ends of Mu, and an enhancer element (E), mediated by the transposase protein MuA. A subset of the six subunits of MuA associated with their cognate sub-sites at L and R communicate with the enhancer to trigger the stepwise assembly of the functional transpososome. The DNA follows a well-defined path within the transpososome, trapping five supercoil nodes comprising two E-R crossings, one E-L crossing and two L-R crossings. The enhancer is a critical DNA element in specifying the unique interwrapped topology of the three-site LER synapse. In this study, we used multiple strategies to characterize Mu end-enhancer interactions to extend, modify and refine those inferred from earlier analyses. Directed placement of transposase subunits at their cognate sub-sites at L and R, analysis of the protein composition of transpososomes thus obtained, and their characterization using topological methods define the following interactions. R1-E interaction is essential to promote transpososome assembly, R3-E interaction contributes to the native topology of the transpososome, and L1-E and R2-E interactions are not required for assembly. The data on L2-E and L3-E interactions are not unequivocal. If they do occur, either one is sufficient to support the assembly process. Our results are consistent with two R-E and perhaps one L-E, being responsible for the three DNA crossings between the enhancer and the left and right ends of Mu. A 3D representation of the interwrapped complex (IW) obtained by modeling is consistent with these results. The model reveals straightforward geometric and topological relationships between the IW complex and a more relaxed enhancer-independent V-form of the transpososome assembled under altered reaction conditions. 相似文献
77.
Kaposi's sarcoma-associated herpesvirus induces sustained NF-kappaB activation during de novo infection of primary human dermal microvascular endothelial cells that is essential for viral gene expression 下载免费PDF全文
Sadagopan S Sharma-Walia N Veettil MV Raghu H Sivakumar R Bottero V Chandran B 《Journal of virology》2007,81(8):3949-3968
78.
Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides from dietary sources 总被引:1,自引:0,他引:1
Pectic polysaccharides from dietary sources such as Decalepis hamiltonii—swallow root (SRPP), Hemidesmus indicus (HPP), Nigella sativa—black cumin (BCPP), Andrographis serpyllifolia—(APP), Zingiber officinale—ginger (GRPP) and, citrus pectin (CPP) were examined for galectin inhibitory activity. Inhibition of (a) galectin-3 of MDA-MB-231
cells induced hemagglutination of red blood cells; (b) galectin-3 mediated interaction between normal/metastatic human buccal
cells (NBC)/(MBC) and; (c) invasion of MDA-MB-231 and MBC in the invasive chamber was assessed. Results indicated that SRPP
inhibited hemagglutination at Minimum Inhibitory Concentration (MIC) of 1.86 μg ml−1 equivalent of carbohydrate as apposed to those of BCPP (130 μg ml−1), APP (40 μg ml−1), HPP (40 μg ml−1) and CPP (25 μg ml−1). GRPP even at concentration >1–6 mg ml−1 did not inhibit agglutination. Also SRPP showed ∼15 and 2 fold potent anti hemagglutination activity relative to that of
galectin-3 specific sugars—galactose (MIC-27.1 μg ml−1) and lactose (MIC-4.16 μg ml−1) respectively. Further, SRPP at 10 μg ml−1 inhibited agglutination of NBC by galectin-3 of MDA-MB-231 cells. Modified swallow root pectic polysaccharide (MSRPP) of
50 kDa retained anti hemagglutination activity (MIC of 1.03 μg ml−1) and inhibited MDA-MB-231 and MBC invasion by 73 and 50% with an IC50 of 136 and 200 μg ml−1 respectively. Both SRPP and MSRPP induced apoptosis up to 80% at 100 μg ml−1 concentration by activating ∼2 and 8 folds of Caspase-3 activity. Sugar composition analysis and its correlation with the
galectin inhibitory property indicated that pectic polysaccharides with higher arabinose and galactose content—arabinogalactan
inhibited hemagglutination significantly. 相似文献
79.
Ahn YM Vogeti L Liu CJ Santhapuram HK White JM Vasandani V Mitscher LA Lushington GH Hanson PR Powell DR Himes RH Roby KF Ye Q Georg GI 《Bioorganic & medicinal chemistry》2007,15(2):702-713
The design and synthesis of a small library of 8-amidoflavone, 8-sulfonamidoflavone, 8-amido-7-hydroxyflavone, and heterocyclic analogues of flavopiridol is reported. The potential activity of these compounds as kinase inhibitors was evaluated by cytotoxicity studies in MCF-7 and ID-8 cancer cell lines and inhibition of CDK2-Cyclin A enzyme activity in vitro. The antiproliferative and CDK2-Cyclin A inhibitory activity of these analogues was significantly lower than the activity of flavopiridol. Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol. 相似文献
80.
A dipeptidyl peptidase (DPP) from goat brain has been purified. The purified enzyme showed a single band on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). It is a monomer with molecular weight of 69kDa with a pI of 4.5. The K(m) was estimated to be 39microM for Arg-Arg-4-methoxy-beta-naphthylamide (Arg-Arg-4mbetaNA). This enzyme is strongly inhibited by commonly used metallochelators and sulfhydryl reagents. Among various beta-naphthylamides examined, Arg-Arg-4mbetaNA was the most rapidly hydrolyzed substrate. Although, initially it was thought to be the DPP-III but on the basis of its molecular weight and inhibition studies, it was concluded that this enzyme is a functional homologue of DPP-III. 相似文献