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281.
Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter 总被引:2,自引:0,他引:2
Baughman JM Perocchi F Girgis HS Plovanich M Belcher-Timme CA Sancak Y Bao XR Strittmatter L Goldberger O Bogorad RL Koteliansky V Mootha VK 《Nature》2011,476(7360):341-345
Mitochondria from diverse organisms are capable of transporting large amounts of Ca(2+) via a ruthenium-red-sensitive, membrane-potential-dependent mechanism called the uniporter. Although the uniporter's biophysical properties have been studied extensively, its molecular composition remains elusive. We recently used comparative proteomics to identify MICU1 (also known as CBARA1), an EF-hand-containing protein that serves as a putative regulator of the uniporter. Here, we use whole-genome phylogenetic profiling, genome-wide RNA co-expression analysis and organelle-wide protein coexpression analysis to predict proteins functionally related to MICU1. All three methods converge on a novel predicted transmembrane protein, CCDC109A, that we now call 'mitochondrial calcium uniporter' (MCU). MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU in cultured cells or in vivo in mouse liver severely abrogates mitochondrial Ca(2+) uptake, whereas mitochondrial respiration and membrane potential remain fully intact. MCU has two predicted transmembrane helices, which are separated by a highly conserved linker facing the intermembrane space. Acidic residues in this linker are required for its full activity. However, an S259A point mutation retains function but confers resistance to Ru360, the most potent inhibitor of the uniporter. Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca(2+) uniporter. 相似文献
282.
侯学凌 《科技情报开发与经济》2004,14(6):308-310
针对某一高层建筑地下室渗漏现象,采用高分子树脂高压注浆治理方案处理.堵漏效果良好,对各类工程的渗漏具有推广应用价值。详细论述了高分子CROUTING树脂高压注浆堵漏的施工工艺,以及该树脂的特性及技术指标和应用范围等。 相似文献
283.
Atomic structure and chemistry of human serum albumin. 总被引:74,自引:0,他引:74
The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin. 相似文献
284.
A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands 总被引:10,自引:0,他引:10
X Estivill M Farrall P J Scambler G M Bell K M Hawley N J Lench G P Bates H C Kruyer P A Frederick P Stanier 《Nature》1987,326(6116):840-845
A genomic sequence close to the cystic fibrosis locus with the characteristics of an HTF island has been selectively cloned and characterized. Two markers flanking this sequence, which is conserved throughout mammalian evolution, show a very much greater disequilibrium than that found with any existing marker. A single mutational event accounts for most cases of cystic fibrosis. The sequence is expressed, and is a candidate for the cystic fibrosis gene. 相似文献
285.
Long-term potentiation of chemical synapses is closely related to memory and learning. Studies of this process have concentrated on chemically mediated excitatory synapses. By contrast, activity-dependent modification of gap junctions, which also widely exist in higher structures such as hippocampus and neocortex, has not been described. Here we report that at mixed synapses between sensory afferents and an identified reticulospinal neuron, the electrotonic coupling potential can be potentiated, as well as the chemically mediated excitatory postsynaptic potential, for a prolonged time period using a stimulation paradigm like that which produces long-term potentiation in hippocampus. The effect on coupling is due to an increase in gap-junctional conductance. Our data indicate that the potentiation of both synaptic components requires an increase in intracellular calcium, involves activation of NMDA (N-methyl-D-aspartate) receptors, and is specific to the tetanized pathway. 相似文献
286.
国有企业委托—代理问题探析 总被引:2,自引:0,他引:2
闫向连 《科技情报开发与经济》2004,14(6):251-252
从《制度经济学》中有关企业的委托—代理问题出发,阐述了我国国企目前的状况,通过分析其原因,提出了解决国有企业委托—代理问题的思路。 相似文献
287.
Yang L.X. 《中国科学基金(英文版)》2004,(2):20-23
Introduction
The focus of research on Agricultural Economics and Management (AEM) has been switching from developed countries to developing countries. In important international journals on AEM such as “American Journal of Agricultural Economics“ and “Agricultural Economics“, the research objectives mainly focus on AEM problems in developing countries, e.g. the effects of globalization and liberalization on agricultural production in developing countries, and problems in agricultural resources and environmental protections in developing countries.
…… 相似文献
288.
简述了我国科研院所改制的概况,对改制后科技企业内部控制现状进行了分析,并针对存在的问题提出了完善内部控制环境、加强会计控制、加强内部审计控制、建立良好的信息沟通系统等相应对策。 相似文献
289.
290.
分流模型PID与鲁棒补偿的复合控制策略 总被引:1,自引:0,他引:1
提出了一种基于分流模型PID与鲁棒补偿的复合控制策略,这种控制器具有非线性滤波、增益自调整、鲁棒性好等优良特性。由于分流模型的输出是稳定、光滑且有界,可以构造一类具有输出光滑、有界并且增益自调整的PID控制器,其可设计一类安全控制系统.将分流模型PID与鲁棒补偿控制相结合,有效地解决了参数不确定情况下的一类非线性系统的鲁棒控制问题。通过倒立摆控制系统的仿真研究,验证了控制策略的有效性。 相似文献