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61.
Synapsin I bundles F-actin in a phosphorylation-dependent manner 总被引:12,自引:0,他引:12
Synapsin I is a neuron-specific phosphoprotein localized to the cytoplasmic surface of synaptic vesicles. This phosphoprotein is a major substrate for cyclic AMP-dependent and calcium/calmodulin-dependent protein kinases. Its state of phosphorylation can be altered both in vivo and in vitro by a variety of physiological and pharmacological manipulations known to affect synaptic function. Recent direct evidence suggests that it may be involved in the regulation of neurotransmitter release from the nerve terminal. In the nerve terminal, synaptic vesicles are embedded in a cytoskeletal network, consisting in part of actin. We report here the ability of the dephospho-form of synapsin I to bundle F-actin. This bundling activity is reduced when synapsin I is phosphorylated by cAMP-dependent protein kinase and virtually abolished when it is phosphorylated by calcium/calmodulin-dependent protein kinase II or by both kinases. These results, demonstrating an interaction of synapsin I with actin in vitro, support the possibility that synapsin I is involved in clustering of synaptic vesicles at the presynaptic terminal and that the phosphorylation of synapsin I may be involved in regulating the translocation of synaptic vesicles to their sites of release. 相似文献
62.
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
63.
A thermal gravimetric method is described for evaluating the kinetics of cell size-dependent decomposition and lifetime estima- tion for microcellular tissue engineering scaffolds made of biodegradable polylactic acid(PLA)foams.PLA foam cell sizes from 550 to 20?m were fabricated experimentally using a solvent-free solid-state foaming technique under saturation pressures from 1 to 5 MPa.The thermal properties of the PLA foams with respect to the cell sizes were measured using thermal gravimetric analy- sis in a nitrogen atmosphere and the activation energy and pre-exponential factor were derived to evaluate the decomposition ki- netics and estimate lifetime.It was found that small cell sizes can be achieved under high saturation pressures and that the thermal stability of PLA decreases after the fabrication process.The cell size-dependent thermal stability and degradation rate indicate that a PLA foam of larger cell sizes has a shorter degradation time,a few tenths that of the PLA raw material,at a temperature of 37°C. The results suggest that it is feasible to optimize fabrication parameters to obtain appropriate cell sizes and lifetimes that satisfy the application requirements for various organs.This study provides the basis for precise scaffold design and quantitative analysis of PLA foams in tissue engineering applications. 相似文献
64.
A new method based on the combining of the wavelet theory with the fractal theory and named wavelet fractal peak position method (WFPPM) is introduced to extract the number of the components and the relevant peak positions from overlapping signals in chemistry .The overlapping signal is first transformed into continuous wavelet transform value of time domain in certain dilation range via continuous wavelet transform (CWT),and then changed into capacity dimensions (Dc),The number of the components and the relevant positions of overlapping peaks can be identified easily according to the change of Dc.An investigation concerning the influence of different dilation ranges on the peak positions extracted by WFPPM is also provided .Studies show that the WFPPM is an efficient tool for extracting the peak positions and identifying the number of peaks from unresoloved signals,even when this kind of overlapping is significantly serious,Relative errors of lless than 1.0% in peak positions are found when WFPPM is used in the processing of the cadmium (Ⅱ)-indium(Ⅲ) mixture system .The analytical results demonstrate that the desired peak positions can be extracted conveniently ,accurately and rapidly from an unresoled signal via WFPPM,Tremendous developing and applications based on currently reported WFPPM in extracting overlapping signals would be expected in the near future. 相似文献
65.
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
66.
Fluid inclusions evidence for differential exhumation of ultrahigh pressure metamorphic rocks in the Sulu terrane 总被引:6,自引:0,他引:6
FAN Hongrui GUO Jinghui HU Fangfang CHU Xuelei CHEN Fukun & JIN Chengwei State Key Laboratory of Lithosphere Tectonic Evolution Key Labo- ratory of Mineral Resources Institute of Geology Geophysics Chi- nese Academy of Sciences Beijing China Correspondence should be addressed to Fan Hongrui 《科学通报(英文版)》2005,50(11):1139-1148
Since the discovery of coesite and diamond inclusions in eclogites from the Dabie-Sulu orogen, east-central China[1―3], this largest ultrahigh pressure (UHP) metamor- phic terrane in the world has attracted extensive scientific interests. A number of hydrous minerals such as zoisite, phengite, magnesite and talc have been found in the UHP rocks, showing that fluids have played an important role in this type of extreme metamorphic evolution[4―8]. Sev-eral techniques have been applied to th… 相似文献
67.
HUAHong CHENZhe ZHANGLuyi 《科学通报(英文版)》2004,49(5):487-490
Marine invertebrate animal embryos and their early developmental products are of great significance to the study of taxonomy and phylogeny of early animals. A great number of phosphatized globular fossils were collected fromthe early Cambrian Kuanchuanpu Member (upper Dengying Formation), southern Shaanxi, and a nearly complete develo-pmental sequence—from a fertilized egg, via blastodisc formation, blastula development, blastodisc enlargement toward gastrulae, to tissue differentiation—can be discerned in this collection. This discovery provides unmatchable material for studies on the origin, taxonomy, radiation, and ontogeny of early metazoans. 相似文献
68.
PENGJin ZHAOYuanlong WUYishan YUANJinliang TAITongshu 《科学通报(英文版)》2005,50(11):1159-1162
In April 2004, Wu Yishan, a teacher from Kaili No. 4 Middle School, took his students to Wenglingtang to conduct popular science activities. They found fossils of trilobites and eocrinoids in gray and gray-greenish silty shale, and calcareous, silty mudrock in the upper part of the lower Cambrian Balang Formation. In May 2004, we were invited to investigate the new discovery. 相似文献
69.
基于结构状态方程进行结构参数和荷载的共同识别。以结构参数修正因子为优化变量,由测得的结构动态响应结构和构造的系统矩阵计算相应的未知荷载。通过最小化实测结构响应与给定的修正因子下的计算结构响应间的距离来识别未知量。其中给定修正因子的系统矩阵由虚拟变形方法构造,并通过一个桁架结构的数值算例验证了该方法的有效性。 相似文献
70.
南京市不同功能区路域表土重金属
污染评价及相关性分析 总被引:2,自引:0,他引:2
为调查南京市路域表土重金属污染状况,在南京市5个功能区布设了1 500个监测点,分析测定重金属Cr、Cd、Ni、Pb、Zn的含量,并对其进行评价和相关性分析。结果表明,5个功能区均有不同程度的重金属富集。按照南京市土壤环境背景值标准进行单项污染指数法评价得出:5个功能区均存在Cd重度污染; Cr、Zn轻度污染(在风景名胜区不存在Zn污染); 无Ni污染; 在交通枢纽区、工业区及科教生活区均存在Pb轻度污染,其他功能区无Pb污染。各区域内梅罗综合污染指数、潜在生态危害指数由高到低依次为:交通枢纽区、工业区、科教生活区、商业区、风景名胜区。5个功能区综合污染均达重度,且除Cd生态危害水平极强外,Cr、Ni、Pb、Zn均为轻微危害水平。不同功能区5种重金属元素彼此间相关性程度不同,表明各区重金属污染来源不同。 相似文献