排序方式: 共有107条查询结果,搜索用时 125 毫秒
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Peter DA Alemu Y Xenos M Weisberg O Avneri I Eshkol M Oren T Elazar M Assaf Y Bluestein D 《Journal of biomechanical engineering》2012,134(4):041001
Drug-resistant hypertensive patients may be treated by mechanical stimulation of stretch-sensitive baroreceptors located in the sinus of carotid arteries. To evaluate the efficacy of endovascular devices to stretch the carotid sinus such that the induced strain might trigger baroreceptors to increase action potential firing rate and thereby reduce systemic blood pressure, numerical simulations were conducted of devices deployed in subject-specific carotid models. Two models were chosen--a typical physiologic carotid and a diminutive atypical physiologic model representing a clinically worst case scenario--to evaluate the effects of device deployment in normal and extreme cases, respectively. Based on the anatomical dimensions of the carotids, two different device sizes were chosen out of five total device sizes available. A fluid structure interaction (FSI) simulation methodology with contact surface between the device and the arterial wall was implemented for resolving the stresses and strains induced by device deployment. Results indicate that device deployment in the carotid sinus of the physiologic model induces an increase of 2.5% and 7.5% in circumferential and longitudinal wall stretch, respectively, and a maximum of 54% increase in von Mises arterial stress at the sinus wall baroreceptor region. The second device, deployed in the diminutive carotid model, induces an increase of 6% in both circumferential and longitudinal stretch and a 50% maximum increase in von Mises stress at the sinus wall baroreceptor region. Device deployment has a minimal effect on blood-flow patterns, indicating that it does not adversely affect carotid bifurcation hemodynamics in the physiologic model. In the smaller carotid model, deployment of the device lowers wall shear stress at sinus by 16% while accelerating flow entering the external carotid artery branch. Our FSI simulations of carotid arteries with deployed device show that the device induces localized increase in wall stretch at the sinus, suggesting that this will activate baroreceptors and subsequently may control hypertension in drug-resistant hypertensive patients, with no consequential deleterious effects on the carotid sinus hemodynamics. 相似文献
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Hilla Weidberg Elena Shvets Tomer Shpilka Frida Shimron Vera Shinder Zvulun Elazar 《The EMBO journal》2010,29(11):1792-1802
Autophagy, a critical process for bulk degradation of proteins and organelles, requires conjugation of Atg8 proteins to phosphatidylethanolamine on the autophagic membrane. At least eight different Atg8 orthologs belonging to two subfamilies (LC3 and GATE‐16/GABARAP) occur in mammalian cells, but their individual roles and modes of action are largely unknown. In this study, we dissect the activity of each subfamily and show that both are indispensable for the autophagic process in mammalian cells. We further show that both subfamilies act differently at early stages of autophagosome biogenesis. Accordingly, our results indicate that LC3s are involved in elongation of the phagophore membrane whereas the GABARAP/GATE‐16 subfamily is essential for a later stage in autophagosome maturation. 相似文献
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Vladimir Kirkin Trond Lamark Yu-Shin Sou Geir Bjørkøy Jennifer L. Nunn Jack-Ansgar Bruun Elena Shvets David G. McEwan Terje H. Clausen Philipp Wild Ivana Bilusic Jean-Philippe Theurillat Aud Øvervatn Tetsuro Ishii Zvulun Elazar Masaaki Komatsu Ivan Dikic Terje Johansen 《Molecular cell》2009,33(4):505-516
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It was reported that systemic administration of nicotine in rats potentiated the cataleptogenic effect of haloperidol. Moreover, addition of nicotine to the treatment with haloperidol in patients suffering from the Gilles de la Tourette's syndrome resulted in reduction in frequency and severity of tics. In the present article we report results of experiments aimed at investigating the role of striatum and pontine reticular formation in the synergistic relations between the two drugs. Nicotine was microinjected directly into the striatum or pontine reticular formation of rats and its cataleptogenic effects were studied when given alone or in combination with systemical injections of haloperidol. It was found that nicotine has cataleptogenic effects when microinjected both into the striatum and pontine reticular formation. The synergism between the two drugs occurred both after microinjections into the striatum and pontine reticular formation. 相似文献
97.
Einav S Gerber D Bryson PD Sklan EH Elazar M Maerkl SJ Glenn JS Quake SR 《Nature biotechnology》2008,26(9):1019-1027
More effective therapies are urgently needed against hepatitis C virus (HCV), a major cause of viral hepatitis. We used in vitro protein expression and microfluidic affinity analysis to study RNA binding by the HCV transmembrane protein NS4B, which plays an essential role in HCV RNA replication. We show that HCV NS4B binds RNA and that this binding is specific for the 3' terminus of the negative strand of the viral genome with a dissociation constant (Kd) of approximately 3.4 nM. A high-throughput microfluidic screen of a compound library identified 18 compounds that substantially inhibited binding of RNA by NS4B. One of these compounds, clemizole hydrochloride, was found to inhibit HCV RNA replication in cell culture that was mediated by its suppression of NS4B's RNA binding, with little toxicity for the host cell. These results yield new insight into the HCV life cycle and provide a candidate compound for pharmaceutical development. 相似文献
98.
LC3 is a widely used marker of autophagosomes in mammalian cells. However, in addition to its autophagosomal localization, GFP-LC3 is often found associated with protein aggregates that are formed in an autophagy-independent manner. In addition, LC3 directly interacts with p62/SQSTM1 (hereafter named p62), a common constituent of protein aggregates. In our recent report, we mapped the regions in LC3 involved in its binding to p62 and showed that this binding is essential for the incorporation of p62 into autophagosomes. Here we demonstrate that the autophagy-unrelated association of GFP-LC3 with protein aggregates is dependent on its interaction with p62. 相似文献
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Pathogenic Escherichia coli can be classified into several pathotypes, and it is believed that each pathotype carries one or more specific gene repertoire (or virulence factors combination) that distinguishes them from non-pathogenic E. coli strains and from other pathotypes. In contrast to this notion, it was proposed that this is not the case for E. coli mastitis, a common disease in farm animals and that any given E. coli isolate can cause this disease, even strains that are considered non-pathogenic. In this review we will re-examine this latter concept and recent advances in the study E. coli mastitis. 相似文献
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Muller JM Shorter J Newman R Deinhardt K Sagiv Y Elazar Z Warren G Shima DT 《The Journal of cell biology》2002,157(7):1161-1173
Characterization of mammalian NSF (G274E) and Drosophila NSF (comatose) mutants revealed an evolutionarily conserved NSF activity distinct from ATPase-dependent SNARE disassembly that was essential for Golgi membrane fusion. Analysis of mammalian NSF function during cell-free assembly of Golgi cisternae from mitotic Golgi fragments revealed that NSF disassembles Golgi SNAREs during mitotic Golgi fragmentation. A subsequent ATPase-independent NSF activity restricted to the reassembly phase is essential for membrane fusion. NSF/alpha-SNAP catalyze the binding of GATE-16 to GOS-28, a Golgi v-SNARE, in a manner that requires ATP but not ATP hydrolysis. GATE-16 is essential for NSF-driven Golgi reassembly and precludes GOS-28 from binding to its cognate t-SNARE, syntaxin-5. We suggest that this occurs at the inception of Golgi reassembly to protect the v-SNARE and regulate SNARE function. 相似文献