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51.
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
52.
衰荡腔光谱技术检测混合气体中甲醛含量 总被引:2,自引:0,他引:2
利用光参量振荡技术产生2.2~3.97μm的宽调谐窄线宽中红外相干辐射.采用该中红外光源和衰荡腔光谱技术建立了一痕量气体成分光谱检测系统,并使用该系统对混合气体中的甲醛成分进行了测量,得到了72×10-9的检测灵敏度.整个光谱检测系统具有很好的光谱分辨率、选择性以及测量灵敏度,适用于大气中多种污染或温室效应气体成分的检测. 相似文献
53.
Endangered species and the law. 总被引:10,自引:0,他引:10
Taxonomy does not deserve its reputation as an arcane science. As the following examples from ungulate taxonomy show, classification has important implications for conservation legislation. 相似文献
54.
高压静电场对水稻干湿种子生物学效应的影响 总被引:3,自引:0,他引:3
用高压静电场分别处理干的水稻种子和30℃预浸种吸水24h的水稻种子,计算种子的活力指数、发芽指数、幼苗干重,研究电场处理对2种水稻种子活力的影响是否有差异.结果表明:水稻种子吸水24h后,种子吸胀结束,开始进入萌发阶段,经电场处理后种子的发芽指数、幼苗干重和活力指数显著高于对照.而经电场处理的水稻干种子活力与对照相比无显著差异.种子的吸水程度显著影响高压静电场对水稻种子的生物学效应. 相似文献
55.
Genome sequencing in microfabricated high-density picolitre reactors 总被引:21,自引:0,他引:21
Margulies M Egholm M Altman WE Attiya S Bader JS Bemben LA Berka J Braverman MS Chen YJ Chen Z Dewell SB Du L Fierro JM Gomes XV Godwin BC He W Helgesen S Ho CH Ho CH Irzyk GP Jando SC Alenquer ML Jarvie TP Jirage KB Kim JB Knight JR Lanza JR Leamon JH Lefkowitz SM Lei M Li J Lohman KL Lu H Makhijani VB McDade KE McKenna MP Myers EW Nickerson E Nobile JR Plant R Puc BP Ronan MT Roth GT Sarkis GJ Simons JF Simpson JW Srinivasan M Tartaro KR Tomasz A Vogt KA Volkmer GA Wang SH Wang Y Weiner MP 《Nature》2005,437(7057):376-380
The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine. 相似文献
56.
研究了光束钎焊获得的对接和搭接钎焊接头的力学性能及其在拉伸载荷作用下的变形行为。光束钎焊对接接头的断裂强度σb、相对延伸率δ、断面收缩率ψ均低于被钎焊母材。同质接头的弹性极限σ0.01、屈服极限σ0.2与母材相当,而异质接头的σ0.01、σ0.2值仅取决于低屈服极限的母材,与高屈服极限的母材无关。对接接头在拉伸载荷作用下的变形是非均匀的,同质接头中的钎缝和近缝区的塑性变形量最小,而异质接头中屈服极限较高的母材一侧几乎无塑性变形。搭接接头在拉伸载荷作用下下会产生“折弯效应”,折弯程度随被钎焊母材屈服极限的增加而减小。对接接头的断裂是由纯拉应力导致的,而搭接接头的断裂是剪应力和拉应力综合作用的结果。 相似文献
57.
RNAi-mediated gene silencing in non-human primates 总被引:2,自引:0,他引:2
Zimmermann TS Lee AC Akinc A Bramlage B Bumcrot D Fedoruk MN Harborth J Heyes JA Jeffs LB John M Judge AD Lam K McClintock K Nechev LV Palmer LR Racie T Röhl I Seiffert S Shanmugam S Sood V Soutschek J Toudjarska I Wheat AJ Yaworski E Zedalis W Koteliansky V Manoharan M Vornlocher HP MacLachlan I 《Nature》2006,441(7089):111-114
The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs. 相似文献
58.
Hereditary spherocytosis (HS) is a common, clinically heterogeneous haemolytic anaemia in which the primary erythrocyte defect is believed to be some abnormality in the spectrin-actin membrane skeleton, leading to loss of surface membrane. Recessively inherited spectrin deficiency with extreme erythrocyte fragility and spherocytosis has been identified in certain mutant mice and two severely anaemic humans. Although suspected, deficiency of spectrin has not been demonstrated in less severe forms of human HS. We not report the quantitation of erythrocytes spectrin by radioimmunoassay. We found that normal erythrocytes contained 240,000 copies of spectrin heterodimer, whereas erythrocytes from 14 patients with a variety of types of HS were all partially deficient in spectrin (range 74,000-200,000 copies), the magnitude of the deficiency correlating with the severity of the disease. Spectrin deficiency of varying degrees is common in HS and probably represents the principal structural defect leading to loss of surface membrane. 相似文献
59.
1 Results The enantioselective addition of allylic organometallic reagents to aldehydes is a fundamental tool in organic synthesis.The high degree of both diastereo-and enantioselectivity gives the possibility to obtain a wide series of homoallylic alcohols,versatile intermediates in a great number of synthesis[1]. One of the most successful approaches is related to the discovery that organocatalytic activation of the nucleophilic allyltrichlorosilanes by means of neutral Lewis bases,such as formamides,... 相似文献
60.