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排序方式: 共有111条查询结果,搜索用时 15 毫秒
1.
Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency 总被引:13,自引:0,他引:13
Irwin WA Bergamin N Sabatelli P Reggiani C Megighian A Merlini L Braghetta P Columbaro M Volpin D Bressan GM Bernardi P Bonaldo P 《Nature genetics》2003,35(4):367-371
Collagen VI is an extracellular matrix protein that forms a microfilamentous network in skeletal muscles and other organs. Inherited mutations in genes encoding collagen VI in humans cause two muscle diseases, Bethlem myopathy and Ullrich congenital muscular dystrophy. We previously generated collagen VI-deficient (Col6a1-/-) mice and showed that they have a muscle phenotype that strongly resembles Bethlem myopathy. The pathophysiological defects and mechanisms leading to the myopathic disorder were not known. Here we show that Col6a1-/- muscles have a loss of contractile strength associated with ultrastructural alterations of sarcoplasmic reticulum (SR) and mitochondria and spontaneous apoptosis. We found a latent mitochondrial dysfunction in myofibers of Col6a1-/- mice on incubation with the selective F1F(O)-ATPase inhibitor oligomycin, which caused mitochondrial depolarization, Ca2+ deregulation and increased apoptosis. These defects were reversible, as they could be normalized by plating Col6a1-/- myofibers on collagen VI or by addition of cyclosporin A (CsA), the inhibitor of mitochondrial permeability transition pore (PTP). Treatment of Col6a1-/- mice with CsA rescued the muscle ultrastructural defects and markedly decreased the number of apoptotic nuclei in vivo. These findings indicate that collagen VI myopathies have an unexpected mitochondrial pathogenesis that could be exploited for therapeutic intervention. 相似文献
2.
运用8对微卫星引物对新疆3个地方驴群体的遗传多样性进行检测,统计并计算了等位基因频率,群体多态信息含量,有效等值基因数,杂合度和遗传距离。根据Nei氏标准遗传距离利用PHYLIP3.6软件采用NJ法构建系统发生树。结果表明:8个微卫星基因座在3个地方驴群体中均表现高度多态,可用于遗传连锁及进化分析。同时,分析了不同微卫星座位与体尺性状间的相关性,等位基因190与体长和胸围呈显著负相关。 相似文献
3.
基于智能卡和数字信封的电子文档安全认证模型 总被引:1,自引:0,他引:1
马乐 《东北师大学报(自然科学版)》2009,41(2)
设计并实现了基于PKI/CA的安全电子文档传输系统.以PKI体系作为基础,利用CA颁发的数字证书进行安全认证和文档签名,将数字证书的私钥存放于USB型智能卡中,对于电子文档首先进行对称加密,然后利用数字信封原理加密对称密钥,确保密钥传递中的安全性以及只有指定的人才能解密得到对称密钥.此系统克服了单纯使用PKI体系的不足,有效地保证了电子文档的保密性、完整性、不可否认性,同时保证了用户私钥的安全性. 相似文献
4.
Houlden H Johnson J Gardner-Thorpe C Lashley T Hernandez D Worth P Singleton AB Hilton DA Holton J Revesz T Davis MB Giunti P Giunti P Wood NW 《Nature genetics》2007,39(12):1434-1436
The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration. 相似文献
5.
Carette JE Raaben M Wong AC Herbert AS Obernosterer G Mulherkar N Kuehne AI Kranzusch PJ Griffin AM Ruthel G Dal Cin P Dye JM Whelan SP Chandran K Brummelkamp TR 《Nature》2011,477(7364):340-343
Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents. 相似文献
6.
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma 总被引:1,自引:0,他引:1
Bertolotto C Lesueur F Giuliano S Strub T de Lichy M Bille K Dessen P d'Hayer B Mohamdi H Remenieras A Maubec E de la Fouchardière A Molinié V Vabres P Dalle S Poulalhon N Martin-Denavit T Thomas L Andry-Benzaquen P Dupin N Boitier F Rossi A Perrot JL Labeille B Robert C Escudier B Caron O Brugières L Saule S Gardie B Gad S Richard S Couturier J Teh BT Ghiorzo P Pastorino L Puig S Badenas C Olsson H Ingvar C Rouleau E Lidereau R Bahadoran P Vielh P Corda E Blanché H Zelenika D 《Nature》2011,480(7375):94-98
7.
ARTC1-mediated ADP-ribosylation of GRP78/BiP: a new player in endoplasmic-reticulum stress responses
8.
9.
van der Meijden PE Feijge MA Swieringa F Gilio K Nergiz-Unal R Hamulyák K Heemskerk JW 《Cellular and molecular life sciences : CMLS》2012,69(20):3481-3492
The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation. 相似文献
10.
本文探讨了三十烷醇对春小麦品种赛洛斯的生理效应,试验研究说明:三十烷醇对春小麦的生长量、叶绿素含量、硝酸还原酶和性细胞透性方面,均有明显的生理效应,为在大田应用三十烷醇提供了一定的理论依据。从试验选定的三个处理浓度试验结果比较来看,以0.5ppm为最佳。 相似文献