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Marks B  Stowell MH  Vallis Y  Mills IG  Gibson A  Hopkins CR  McMahon HT 《Nature》2001,410(6825):231-235
Dynamin is a large GTPase with a relative molecular mass of 96,000 (Mr 96K) that is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Although its function is apparently essential for scission of newly formed vesicles from the plasma membrane, the nature of dynamin's role in the scission process is still unclear. It has been proposed that dynamin is a regulator (similar to classical G proteins) of downstream effectors. Here we report the analysis of several point mutants of dynamin's GTPase effector (GED) and GTPase domains. We show that oligomerization and GTP binding alone, by dynamin, are not sufficient for endocytosis in vivo. Rather, efficient GTP hydrolysis and an associated conformational change are also required. These data argue that dynamin has a mechanochemical function in vesicle scission.  相似文献   

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Timoshenko薄壁梁双向弯曲与扭转耦合的振动方程及求解   总被引:1,自引:0,他引:1  
基于薄壁杆件理论,研究了Timoshenko薄壁梁双向弯曲与扭转耦合的振动问题。根据Timoshenko梁的受力特性,考虑了剪切效应影响,给出了薄壁梁质点的位移系数和空间位移场。根据能量泛函变分原理导出了Timoshenko薄壁梁的振动微分方程。运用降阶法和频率扫描法求得微分方程的解析解。算例计算表明,此解析解与有限元法的结果吻合较好。  相似文献   

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Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. Although these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as a candidate gene enriched in CTCs. Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 (also known as TAK1) kinase. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes, and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer.  相似文献   

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利用高速显微摄像系统对环锭细纱机的加捻三角区进行在线动态观察对比研究了加入芯丝前后环锭纺和环锭包芯纺加捻三角区的形态变化和纤维转移状况.试验结果表明,加入芯丝后,环锭包芯纺加捻三角区长度和宽度均发生不同程度的缩小,对称性大大降低;此外,在环锭纺和环锭包芯纺加捻三角区的上部区域,纤维转移现象并不明显.  相似文献   

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A vertebrate neurotoxin, alpha-latrotoxin, from black widow spider venom causes synaptic vesicle exocytosis and neurotransmitter release from presynaptic nerve terminals. Although the mechanism of action of alpha-latrotoxin is not known, it does require binding of alpha-latrotoxin to a high-affinity receptor on the presynaptic plasma membrane. The alpha-latrotoxin receptor seems to be exclusively at the presynaptic plasmamembrane. Here we report that the alpha-latrotoxin receptor specifically binds to a synaptic vesicle protein, synaptotagmin, and modulates its phosphorylation. Synaptotagmin is a synaptic vesicle-specific membrane protein that binds negatively charged phospholipids and contains two copies of a putative Ca(2+)-binding domain from protein kinase C (the C2-domain), suggesting a regulatory role in synaptic vesicle fusion. Our findings suggest that a physiological role of the alpha-latrotoxin receptor may be the docking of synaptic vesicles at the active zone. The direct interaction of the alpha-latrotoxin receptor with a synaptic vesicle protein also suggests a mechanism of action for this toxin in causing neurotransmitter release.  相似文献   

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论述了一种微机测量转矩和转速的原理与方法,利用微机的时钟脉冲研制出一种精度达微秒级的时种,用此时钟测量转矩的误差小于1%,测量转速的误差小于1‰;在实际应用中提出了解决现场信号不稳定的两种测量方法,即周期计数和定时截取的测量方法。  相似文献   

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Results of thermoluminescence (TL) measurement of quartz sandstone before and after impact using a two-stage light gas gun pressure apparatus indicate that, the TL of quartz sandstone decreases as the impact pressure increases, there exists a TL gradient from the outside to the inside around the impacted area, and the induced TL at the same location also has a TL gradient. Impact experiments were conducted under pressures of 12.4, 28.9, 37.8, 51.8, 64.6 and 77.6 GPa, respectively, and fission track density and fission track length before and after the impact were measured. Results demonstrate that the fission track density is decreased and the fission track length is shortened as the impact pressure is increased.  相似文献   

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Cell cycle is a programmed process, during which a cell proliferates to two daughter cells. The eukaryotic or-ganisms share the same characters, such as four cycle phases G1, S, G2 and M, the evolutionally conserved cell cycle proteins and its dependent kinases, and the check-points mechanism[1,2]. Due to the different functions and the complicated interactions of these proteins involved in cell cycle, it is very difficult to understand the regulatory mechanism of cell cycle in a whole sense …  相似文献   

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Dynamin was discovered in bovine brain tissue as a nucleotide-sensitive microtubule-binding protein of relative molecular mass 100,000. It was found to cross-link microtubules into highly ordered bundles, and appeared to have a role in intermicrotubule sliding in vitro. Cloning and sequencing of rat brain dynamin complementary DNA identified an N-terminal region of about 300 amino acids which contained the three consensus elements characteristic of GTP-binding proteins. Extensive homology was found between this domain and the mammalian Mx proteins which are involved in interferon-induced viral resistance, and with the product of the VPS1 locus in Saccharomyces cerevisiae, which has been implicated both in membrane protein sorting, and in meiotic spindle pole separation. Dynamin-containing microtubule bundles were not observed in an immunofluorescence study of cultured mammalian cells, but a role for a GTP-requiring protein in intermicrotubule sliding during mitosis in plants has been reported. We report here that Drosophila melanogaster contains multiple tissue-specific and developmentally-regulated forms of dynamin, which are products of the shibire locus previously implicated in endocytic protein sorting.  相似文献   

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由于曲线梁桥的外边梁受力较内梁显著增大 ,在曲线梁桥的设计过程中 ,采用具有大边梁的曲线梁桥将使结构受力更为合理。文章考虑到结构翘曲扭转的影响 ,利用多余刚度的弹簧系数法 ,同时结合曲梁的符拉索夫方程 ,对具有大边梁的曲线梁桥进行分析 ,推导出弹性支承反力的计算公式 ,据此求得荷载横向分布影响线 ,为此类结构的受力分析和内力计算提供了理论依据  相似文献   

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根据纺织厂信息化建设的实际需求,结合生产实践,利用计算机网络技术、串口通信技术、数据库技术开发了一种基于C/S模式的生产信息监测与管理系统.对系统的网络拓扑结构、管理功能、数据库的逻辑和物理结构、以及数据采集技术进行了设计,并对数据采集技术进行了优化,同时对系统实现过程中遇到的技术难点,应用相关技术提出了解决方案.实践证明,该系统提高了车间的工作效率,降低了企业的劳动力成本,实现了机台运转状态和生产数据的远程在线监测.  相似文献   

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Fantes P 《Nature》1979,279(5712):428-430
THERE is currently much interest in the mechanism which controls the timing of cell division. Certain features of the control have been found to be common to a variety of eukaryotes. In particular, the importance of cell size as a parameter affecting cell cycle progress has been reported for mammalian cells(1,2) and for several single-celled eukaryotes(3-6). Another feature common to several systems is that growth conditions have a direct effect on the timing of division cycle events(7-9), and on cell size(9,10). In the fission yeast Schizosaccharomyces pombe, both cell size(6) and nutritional conditions(9) have been shown to affect cycle kinetics. The organism has been used extensively as a model eukaryotic system, largely because of the ease of measuring cell size and because division occurs by binary fission(11). More recently, its genetic tractability has led to the isolation of cell division cycle (cdc) mutants(12), and also of wee mutants altered in the control coordinating growth with the division cycle(13-15). The existence of such control mutants allows a more direct approach to the investigation of the molecular basis of division control, in contrast to the indirect methods used in other systems(4,16-18). wee mutants are so far unique to S. pombe. The most conspicuous property of wee mutants is their reduced cell size(13,14). Analysis of these mutants(15,19) and other evidence(9) has shown that control over cell division timing normally acts at entry to mitosis. As the function of a number of cdc genes is specifically required for mitosis(12), interactions between wee and cdc mutants which affect mitosis might be expected. I report here that the mitotic defect caused by a defective cdc25 allele is suppressed in wee mutants. Suppression by wee1 mutants is almost complete, while the wee2.1 mutation is a less effective suppressor. The significance of these findings for genetic models of the control of mitosis is considered.  相似文献   

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G B Koudelka  P Carlson 《Nature》1992,355(6355):89-91
The bacteriophage 434 repressor regulates gene expression by binding with differing affinities to the six operator sites on the phage chromosome. The symmetrically arrayed outer eight base pairs (four in each half-site) of these 14-base-pair operators are highly conserved but the middle four bases are divergent. Although these four base pairs are not in contact with repressor, operators with A.T or T.A base pairs at these positions bind repressor more strongly than those bearing C.G or G.C, suggesting that these bases are important for the repressor's ability to discriminate between operators. There is evidence that the central base pairs influence operator function by constraining the twisting and/or bending of DNA. Here we show that there is a relationship between the intrinsic twist of an operator, as determined by the sequence of its central bases, and its affinity for repressor; an operator with a lower affinity is undertwisted relative to an operator with higher affinity. In complex with repressor, the twist of both high- and low-affinity operators is the same. These results indicate that the intrinsic twist of DNA and its twisting flexibility both affect the affinity of 434 operator for repressor.  相似文献   

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