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Purification and cloning of amyloid precursor protein beta-secretase from human brain 总被引:40,自引:0,他引:40
Sinha S Anderson JP Barbour R Basi GS Caccavello R Davis D Doan M Dovey HF Frigon N Hong J Jacobson-Croak K Jewett N Keim P Knops J Lieberburg I Power M Tan H Tatsuno G Tung J Schenk D Seubert P Suomensaari SM Wang S Walker D Zhao J McConlogue L John V 《Nature》1999,402(6761):537-540
Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase. 相似文献
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Summary There is an active synthesis of DNA, RNA, protein, and carbohydrate in conidia incubated at 48°C. DNA increases more or less 3 times; while RNA, protein and carbohydrate are synthesized at a much faster rate. Conidia do not germinate at this temperature.Acknowledgments. Grateful thanks are due to Professor B. M. Johri for valuable suggestions. R. K. S. acknowledges with thanks a Senior Research Fellowship of the Council of Scientific and Industrial Research, New Delhi. 相似文献
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Sheela Banerjee S. L. Sahni D. P. Sinha 《Cellular and molecular life sciences : CMLS》1973,29(5):616-617
Zusammenfassung Begattete weiblicheCulex fatigans legen ihre Eier 72 h nach einem Blutmahl, wenn die Aktivität der medianen neurosekretorischen (MNSC) Zellen am höchsten ist. Die Corpora allata (CA) erreichen 24 h nach dieser Mahlzeit ihre höchste Aktivität und es wird daraus geschlossen, dass das Hormon der CA Eireifung und die Sekrete dér MNSC die Eiablage bewirken. 相似文献
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Chromatin-modifying enzymes as modulators of reprogramming 总被引:2,自引:0,他引:2
Onder TT Kara N Cherry A Sinha AU Zhu N Bernt KM Cahan P Marcarci BO Unternaehrer J Gupta PB Lander ES Armstrong SA Daley GQ 《Nature》2012,483(7391):598-602
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曼彻斯特大学是世界著名学府之一,其时装管理与营销专业也享有一定的盛名,通过对其<时装管理>课程的认识,从中可以了解到英国及发达国家的服装教育特色以及由此而产生的对我国服装高等教育的思考. 相似文献