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71.
Cashman JR MacDonald M Ghirmai S Okolotowicz KJ Sergienko E Brown B Garcia X Zhai D Dahl R Reed JC 《Bioorganic & medicinal chemistry letters》2010,20(22):6560-6564
High-throughput screening of 66,000 compounds using competitive binding of peptides comprising the BH3 domain to anti-apoptotic Bfl-1 led to the identification of 14 validated 'hits' as inhibitors of Bfl-1. N-Aryl maleimide 1 was among the validated 'hits'. A chemical library encompassing over 280 analogs of 1 was prepared following a two-step synthesis. Structure-activity studies for inhibition of Bfl-1 by analogs of N-aryl maleimide 1 revealed a preference for electron-withdrawing substituents in the N-aryl ring and hydrophilic amines appended to the maleimide core. Inhibitors of Bfl-1 are potential development candidates for anti-cancer therapeutics. 相似文献
72.
Abundance of Fabaceae declines in representation through post-fire-succession in fynbos vegetation of the Cape Floristic Region (CFR). This reduction in legume occurrence coincides with a known decline in post-fire soil P availability. It was hypothesized that the disappearance of legume species during post-fire succession is due to an inability to acquire P effectively from sparingly soluble sources. P-acquisition strategies and response to P supply were compared between legume (Aspalathus, Cyclopia, Indigofera, Podalyria) and non-legume (Elegia, Leucadendron, Protea) genera when supplied with 1 or 10 mg P kg?1 dry sand. Each genus consisted of a seeder (non-persistent) and resprouter (persistent) species. Non-legumes showed a greater investment in below-ground biomass, more root clusters, with higher concentrations of carboxylates exuded by cluster roots and carboxylates that were better suited to the mobilization of sparingly soluble P compared to legumes. The growth response to increased P supply was 53% higher in legumes than in non-legumes. The lack of a growth response to an elevated P supply in the non-legumes was attributed to N-limitation. Legume resprouters had a higher investment in cluster-root biomass and a lower capacity to down-regulate P-uptake than the seeders. Therefore the inability to acquire sufficient P from low concentration and sparingly soluble soil P-sources may contribute to the lack of indigenous legume persistence in fynbos vegetation of the CFR. 相似文献
73.
74.
Badosa E Ferre R Planas M Feliu L Besalú E Cabrefiga J Bardají E Montesinos E 《Peptides》2007,28(12):2276-2285
A 125-member library of synthetic linear undecapeptides was prepared based on a previously described peptide H-K1KLFKKILKF10L-NH2 (BP76) that inhibited in vitro growth of the plant pathogenic bacteria Erwinia amylovora, Xanthomonas axonopodis pv. vesicatoria, and Pseudomonas syringae pv. syringae at low micromolar concentrations. Peptides were designed using a combinatorial chemistry approach by incorporating amino acids possessing various degrees of hydrophobicity and hydrophilicity at positions 1 and 10 and by varying the N-terminus. Library screening for in vitro growth inhibition identified 27, 40 and 113 sequences with MIC values below 7.5 μM against E. amylovora, P. syringae and X. axonopodis, respectively. Cytotoxicity, bactericidal activity and stability towards protease degradation of the most active peptides were also determined. Seven peptides with a good balance between antibacterial and hemolytic activities were identified. Several analogues displayed a bactericidal effect and low susceptibility to protease degradation. The most promising peptides were tested in vivo by evaluating their preventive effect of inhibition of E. amylovora infection in detached apple and pear flowers. The peptide H-KKLFKKILKYL-NH2 (BP100) showed efficacies in flowers of 63–76% at 100 μM, being more potent than BP76 and only less effective than streptomycin, currently used for fire blight control. 相似文献
75.
We investigate an artificial neural network model with a modified Hebb rule. It is an auto-associative neural network similar to the Hopfield model and to the Willshaw model. It has properties of both of these models. Another property is that the patterns are sparsely coded and are stored in cycles of synchronous neural activities. The cycles of activity for some ranges of parameter increase the capacity of the model. We discuss basic properties of the model and some of the implementation issues, namely optimizing of the algorithms. We describe the modification of the Hebb learning rule, the learning algorithm, the generation of patterns, decomposition of patterns into cycles and pattern recall. 相似文献
76.
Systemic inflammatory markers in patients with aortic sclerosis 总被引:1,自引:0,他引:1
Rugina M Caras I Jurcut R Jurcut C Serbanescu F Salageanu A Apetrei E 《Roumanian archives of microbiology and immunology》2007,66(1-2):10-16
The aim of the study was to evaluate several mediators of inflammation in patients with aortic sclerosis in relation to severity of cardiovascular disease. Serum level of cytokines, soluble intracellular adhesion molecule 1, matrix metalloproteinase (MMP) 2 and 9 and their tissue inhibitor TIMP-1, were measured by ELISA and MMPs activity by zymography in 51 aortic sclerosis patients. The increase in MMPs expression positively correlated with their gelatinase activity; also there was a positive correlation between MMP-9 and TIMP-1 serum levels. Moreover, IL-6 concentration positively correlated with both serum level and activity of MMP-9. The level of IL-6 and IL-1Ra were higher in patients with a great burden of atherosclerosis. Noteworthy, statistically significant higher levels of IL-6 were noticed for patients with coronary artery disease. There was a significant increase in IL-6 serum level as well as a significant decrease in IL-1Ra for patients with a history of myocardial infarction. A trend toward higher concentration of inflammatory mediators was noticed in relation to the increase in severity of the aortic valve disease. Our results support the hypothesis of an "inflammatory pattern" associated with AS pathology and suggest the persistence of a chronic inflammation in patients who experienced acute coronary events. 相似文献
77.
Association of the FADS2 gene with omega-6 and omega-3 PUFA Concentration in the egg yolk of Japanese quail 总被引:1,自引:0,他引:1
Khang NT Jennen DG Tholen E Tesfaye D Mennicken L Hoelker M Schellander K Ponsuksili S Murani E Wimmers K 《Animal biotechnology》2007,18(3):189-201
This study focused on the association of polymorphisms of the FADS2 gene with fatty acid profiles in egg yolk of eight Japanese quail lines selected for high and low omega-6:omega-3 PUFA ratio (h2 = 0.36-0.38). For the identification of polymorphisms within the FADS2 gene 1350 bp of cDNA sequence were obtained encoding 404 amino acids. Five synonymous SNPs were found by comparative sequencing of animals of the high and low lines. These SNPs were genotyped by single base extension on 160 Japanese quail. The association analysis, comprising analysis of variance and family based association test (FBAT), revealed significant effects of SNP3 and SNP4 genotypes on the egg yolk fatty acid profiles, especially the omega-6 and omega-3 PUFAs (P < 0.05). No effects of the other SNPs were found - indicating that these are not in linkage disequilibrium with the causal polymorphism. The results of this study promote FADS2 as a functional candidate gene for traits related to omega-6 and omega-3 PUFA concentration in the egg yolk. 相似文献
78.
Vinokur V Leibowitz G Grinberg L Eliashar R Berenshtein E Chevion M 《Redox report : communications in free radical research》2007,12(6):246-256
Both type 1 and type 2 diabetes (insulin-dependent and non-insulin dependent diabetes, respectively) are associated with increased risk for microvascular and macrovascular complications including retinopathy, neuropathy, nephropathy and atherosclerosis. Type 2 diabetes markedly increases the risk for cardiovascular morbidity and mortality, which has major public health implications. In this review, molecular mechanisms pertaining to diabetes-induced heart pathology are addressed. 相似文献
79.
The use of peptides as in vivo and in vitro ligand binding agents is hampered by the high flexibility, low stability and lack of intrinsic detection signal of peptide aptamers. Recent attempts to overcome these limitations included the integration of the binding peptide into a stable protein scaffold. In this paper, we present the optimization and testing of a circularly permuted variant of the green fluorescent protein (GFP). We examined the ability of the optimized scaffold to accept peptide insertions at three different regions. The three regions chosen are localized in close spatial proximity to each other and support different conformations of the inserted peptides. In all the three regions peptides with a biased, but still comprehensive, amino acid repertoire could be presented without disturbing the function of the optimized GFP-scaffold. 相似文献
80.