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191.
Ali MA Ismail R Choon TS Pandian S Hassan Ansari MZ 《Journal of enzyme inhibition and medicinal chemistry》2011,26(4):598-602
In this study, a series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized and evaluated for antimycobacterial activity against Mycobacterium tuberculosis (MTB) H(37)Rv and isoniazid resistant M. tuberculosis (INHR-MTB). All the newly synthesized compounds were showing moderate to high inhibitory activities. The compound 6,7-dimethoxy-3-(4-chloro phenyl)-4H-indeno[1,2-c]isoxazole (4b) was found to be the most promising compound, active against MTB H(37)Rv and INHR-MTB with minimum inhibitory concentrations of 0.22 and 0.34 μM. 相似文献
192.
Wild Silkmoth cocoons are difficult or impossible to reel under conditions that work well for cocoons of the Mulberry silkmoth, Bombyx mori . Here we report evidence that this is caused by mineral reinforcement of Wild Silkmoth cocoons and that washing these minerals out allows for the reeling of commercial lengths of good quality fibers with implications for the development of the "Wild Silk" industry. We show that in the Lasiocampid silkmoth Gonometa postica , the mineral is whewellite (calcium oxalate monohydrate). Evidence is presented that its selective removal by ethylenediaminetetraacetic acid (EDTA) leaves the gum substantially intact, preventing collapse and entanglement of the network of fibroin brins, enabling wet reeling. Therefore, this method clearly differs from the standard "degumming" and should be referred to as "demineralizing". Mechanical testing shows that such preparation results in reeled silks with markedly improved breaking load and extension to break by avoiding the damage produced by the rather harsh degumming, carding, or dry reeling methods currently in use, what may be important for the development of the silk industries not only in Asia but also in Africa and South America. 相似文献
193.
The SIBLING (small integrin-binding ligand N-linked glycoproteins) family is the major group of noncollagenous proteins in bone and dentin. These extremely acidic and highly phosphorylated extracellular proteins play critical roles in the formation of collagenous mineralized tissues. Whereas the lack of individual SIBLINGs causes significant mineralization defects in vivo, none of them led to a complete cessation of mineralization suggesting that these proteins have overlapping functions. To assess whether different SIBLINGs regulate biomineralization in a similar manner and how phosphorylation impacts their activity, we studied the effects of two SIBLINGs, dentin matrix protein 1 (DMP1) and dentin phosphophoryn (DPP), on mineral morphology and organization in vitro. Our results demonstrate distinct differences in the effects of these proteins on mineralization. We show that phosphorylation has a profound effect on the regulation of mineralization by both proteins. Specifically, both phosphorylated proteins facilitated organized mineralization of collagen fibrils and phosphorylated DMP1-induced formation of organized mineral bundles in the absence of collagen. In summary, these results indicate that the primary structure and phosphorylation uniquely determine functions of individual SIBLINGs in regulation of mineral morphology and organization. 相似文献
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Takahashi S Toyoda A Sekiyama Y Takagi H Nogawa T Uramoto M Suzuki R Koshino H Kumano T Panthee S Dairi T Ishikawa J Ikeda H Sakaki Y Osada H 《Nature chemical biology》2011,7(7):461-468
Spiroacetal compounds are ubiquitous in nature, and their stereospecific structures are responsible for diverse pharmaceutical activities. Elucidation of the biosynthetic mechanisms that are involved in spiroacetal formation will open the door to efficient generation of stereospecific structures that are otherwise hard to synthesize chemically. However, the biosynthesis of these compounds is poorly understood, owing to difficulties in identifying the responsible enzymes and analyzing unstable intermediates. Here we comprehensively describe the spiroacetal formation involved in the biosynthesis of reveromycin A, which inhibits bone resorption and bone metastases of tumor cells by inducing apoptosis in osteoclasts. We performed gene disruption, systematic metabolite analysis, feeding of labeled precursors and conversion studies with recombinant enzymes. We identified two key enzymes, dihydroxy ketone synthase and spiroacetal synthase, and showed in vitro reconstruction of the stereospecific spiroacetal structure from a stable acyclic precursor. Our findings provide insights into the creation of a variety of biologically active spiroacetal compounds for drug leads. 相似文献
196.
Eddins MJ Marblestone JG Suresh Kumar KG Leach CA Sterner DE Mattern MR Nicholson B 《Cell biochemistry and biophysics》2011,60(1-2):113-118
Progressive muscle wasting, also known as myopathy or muscle atrophy is a debilitating and life-threatening disorder. Myopathy is a pathological condition of many diseases including cancer, diabetes, COPD, and AIDS and is a natural consequence of inactivity and aging (sarcopenia). Muscle atrophy occurs when there is a net loss of muscle mass resulting in a change in the balance between protein synthesis and protein degradation. The ubiquitin pathway and specific ubiquitin pathway enzymes have been directly implicated in the progression of atrophy. The ubiquitin E3 ligase Muscle-specific RING Finger E3 ligase (MuRF1) is upregulated and increases protein degradation and muscle wasting in numerous muscle atrophy models. The inhibition of MuRF1 could be a novel mechanism to prevent or reverse muscle wasting associated with various pathologies. We screened a small molecule library for inhibitors to MuRF1 activity and identified P013222, an inhibitor of MuRF1 autoubiquitylation. Further, P013222 was shown to inhibit MuRF1-dependent substrate ubiquitylation, and was active in inhibiting MuRF1 in a cellular atrophy model. Thus MuRF1 can be targeted in a specific manner and produce positive results in cellular atrophy models. 相似文献
197.
Terrill Philip I. Suresh Sadasivam Wilson Stephen J. Cooper David M. 《Sleep and biological rhythms》2011,9(2):112-116
Sleep and Biological Rhythms - The ALICE5 software package provides a commercially available automated sleep staging system designed for infants. This study aims to evaluate the accuracy of this... 相似文献
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199.
Mapping of the secretome of primary isolates of mammalian cells, stem cells and derived cell lines 总被引:1,自引:0,他引:1
Within a mammalian organism, the interaction among cells both at short and long distances is mediated by soluble factors released by cells into the extracellular environment. The secreted proteins may involve extracellular matrix proteins, proteinases, growth factors, protein hormones, immunoregulatory cytokines, chemokines or other bioactive molecules that have a direct impact on target cell phenotype. Stem cells of mesenchymal, adipose, neural and embryonic origin, fibroblast feeder cells as well as primary isolates of astrocytes, endothelial and muscle cells have recently become targets of intensive secretome profiling with the search for proteins regulating cell survival, proliferation, differentiation or inflammatory response. Recent advances and challenges of the stem cell and primary cell secretome analysis together with the most relevant results are discussed in this review. 相似文献
200.