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81.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
82.
Péterfy M Ben-Zeev O Mao HZ Weissglas-Volkov D Aouizerat BE Pullinger CR Frost PH Kane JP Malloy MJ Reue K Pajukanta P Doolittle MH 《Nature genetics》2007,39(12):1483-1487
Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia. 相似文献
83.
1 Results This paper presents the development of platinum nanocomposites structures based on organically modified c.a.2 nm core platinum nanoparticles.The chemical modification of the 4-mercaptoaniline functionalized particles by various in coming molecules is evidenced and precisely quantified.The particles can be dissolved like molecules in various solvents depending on the features of the new crown and X-rays shows that the interparticle distance is affected by the crown modification.These platinum n... 相似文献
84.
Minagawa H Yoshida Y Kenmochi N Furuichi M Shimada J Kaneko H 《Cellular and molecular life sciences : CMLS》2007,64(1):77-81
Lactate oxidase is used in biosensors to measure the concentration of lactate in the blood and other body fluids. Increasing
the thermostability of lactate oxidase can significantly prolong the lifetime of these biosensors. We have previously obtained
a variant of lactate oxidase from Aerococcus viridans with two mutations (E160G/V198I) that is significantly more thermostable than the wild-type enzyme. Here we have attempted
to further improve the thermostability of E160G/V198I lactate oxidase using directed evolution. We made a mutant lactate oxidase
gene library by applying error-prone PCR and DNA shuffling, and screened for thermostable mutant lactate oxidase using a plate-based
assay. After three rounds of screening we obtained a thermostable mutant lactate oxidase, which has six mutations (E160G/V198I/G36S/T103S/A232S/F277Y).
The half-life of this lactate oxidase at 70 °C was about 2 times that of E160G/V198I and about 36 times that of the wild-type
enzyme. The amino acid mutation process suggests that the combined neutral mutations are important in protein evolution.
Received 15 September 2006; received after revision 21 October 2006; accepted 2 November 2006 相似文献
85.
Untangling the molecular nature of sperm-egg interactions is fundamental if we are to understand fertilization. These phenomena
have been studied for many years using biochemical approaches such as antibodies and ligands that interact with sperm or with
eggs and their vestments. However, when homologous genetic recombination techniques were applied, most of the phenotypic factors
of the gene-manipulated animals believed “essential” for fertilization were found to be dispensable. Of course, all biological
systems contain redundancies and compensatory mechanisms, but as a whole the old model of fertilization clearly requires significant
modification. In this review, we use the results of gene manipulation experiments in animals to propose the basis for a new
vision.
Received 26 January 2007; received after revision 7 March 2007; accepted 17 April 2007 相似文献
86.
Scherthan H 《Cellular and molecular life sciences : CMLS》2007,64(2):117-124
Telomeres are important segments of chromosomes that protect chromosome ends from nucleolytic degradation and fusion. At meiosis telomeres display an unprecedented behavior which involves their attachment and motility along the nuclear envelope. The movements become restricted to a limited nuclear sector during the so-called bouquet stage, which is widely conserved among species. Recent observations suggest that telomere clustering involves actin and/or microtubules, and is altered in the presence of impaired recombinogenic and chromosome related functions. This review aims to provide an overview of what is currently known about meiotic telomere attachment, dynamics and regulation in synaptic meiosis. 相似文献
87.
Kang J.Y. Xu F.C. 《中国科学基金(英文版)》2004,(2):57-58,64
1 Introduction
Nanoscale science and technology have attracted greatattention since the novel properties become dominant for well-known materials as their sizes reduced to some critical dimension. These properties frequently originate in lattice distortions, structure transformations etc[1]. The variations of size and structure ofnanocrystals lead to the change of their electronic structures. Very recently, nanoscale materials with different electronic structures were utilized in fabricating nanoscale junctions[2].
…… 相似文献
88.
煤矸石空心砖是一种新型环保墙体材料,符合国家及山西省出台的限制生产和使用实心黏土砖,鼓励发展新型建筑材料的政策。利用煤矸石制造的空心砖可以作为保温材料,既可节约建筑能耗,又可节约土地资源,减少环境污染。煤矸石空心砖同黏土实心砖相比,具有高强、轻质、隔音、隔热、保温、防震等优点,市场前景良好。 相似文献
89.
This paper assesses the information content of two survey indicators for consumption developments in the near future for eight European countries in the period 1985–1998. Empirical work on this topic typically focuses on consumer confidence, the perceptions of buyers of consumption goods. This paper examines whether perceptions of sellers of consumption goods, measured by retail trade surveys, may also improve short‐term monitoring of consumption. We find that both consumer confidence and retailer confidence embody valuable information, when analysed in isolation. For France, Italy and Spain we conclude that adding retail confidence does not improve the indicator model once consumer confidence has been included. For the UK the reverse case is obtained. For the remaining four countries we show that combining consumer sentiment and retail trade confidence into a composite indicator leads to optimal results. Our results suggest that incorporating information from retail trade surveys may offer significant benefits for the analysis of short‐term prospects of consumption. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
90.