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51.
The α7 nicotinic receptor is a promising drug target for neurological and inflammatory disorders. Although it is the homomeric member of the family, a novel α7β2 heteromeric receptor has been discovered. To decipher the functional contribution of the β2 subunit, we generated heteromeric receptors with fixed stoichiometry by two different approaches comprising concatenated and unlinked subunits. Receptors containing up to three β2 subunits are functional. As the number of β2 subunits increases in the pentameric arrangement, the durations of channel openings and activation episodes increase progressively probably due to decreased desensitization. The prolonged activation episodes conform the kinetic signature of α7β2 and may have an impact on neuronal excitability. For activation of α7β2 receptors, an α7/α7 binding-site interface is required, thus indicating that the three β2 subunits are located consecutively in the pentameric arrangement. α7-positive allosteric modulators (PAMs) are emerging as novel therapeutic drugs. The presence of β2 in the pentamer affects neither type II PAM potentiation nor activation by an allosteric agonist whereas it impairs type I PAM potentiation. This first single-channel study provides fundamental basis required to decipher the role and function of the novel α7β2 receptor and opens doors to develop selective therapeutic drugs.  相似文献   
52.
Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging. We found in vitro and in vivo a robust diurnal rhythm of Rev-Luc, mainly in liver, intestine, kidney and adipose tissues. We further confirmed in vivo that Rev-Luc peripheral tissues are food-entrainable oscillators, not affected by age or sex. These data strongly support the relevance of the Rev-Luc model for circadian studies, especially to investigate in vivo the establishment and the entrainment of the rhythm throughout ontogenesis. We then showed that Rev-Luc expression develops dynamically and gradually, both in amplitude and in phase, during fetal and postnatal development. We also demonstrate for the first time that the immature peripheral circadian system of offspring in utero is mainly entrained by maternal cues from feeding regimen. The prenatal entrainment will also differentially determine the Rev-Luc expression in pups before weaning underlining the importance of the maternal chrononutrition on the circadian system entrainment of the offspring.  相似文献   
53.
针对目前乌兹别克语、哈萨克语等中亚语种急缺专业领域词典、术语库及知识本体库的问题,文章以安全领域为例,利用现有术语作为种子词,自动采集维基百科及双语专业词典中的术语对,人工校对后构建了中型中、俄、乌、哈多语种专业领域术语库。以此术语库为基础,搭建了包含人员、组织、地域、技术、设备、活动、文件7大类及35个子类的领域本体,最后讨论了该专业术语库及领域本体库的扩展潜力和应用前景。本成果是一项重要的基础性工作,对中亚语种的术语词典编撰、术语学、自然语言处理和语言教学研究均有较大现实意义。  相似文献   
54.
G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the “triple membrane bypass” pathway and the generation of reactive oxygen species. The recent recognition of GPCR transactivation of serine/threonine kinase receptors enormously broadens the GPCR signalling paradigm. It may be predicted that the transactivation of serine/threonine kinase receptors would have mechanistic similarities with transactivation of tyrosine kinase pathways; however, initial studies suggest that these two transactivation pathways are mechanistically distinct. Important questions are the relative importance of tyrosine and serine/threonine transactivation pathways, the contribution of transactivation to overall GPCR signalling, mechanisms of transactivation and the range of cell types in which this phenomenon occurs. The ultimate significance of transactivation-dependent signalling remains to be defined but it appears to be prominent and if so will represent a new cell signalling frontier.  相似文献   
55.
 室外空气污染和污染空气中的颗粒物是一类致癌物,而近年中国的大气颗粒物污染仍然维持在较高浓度水平。通过综述中国近年大气颗粒物污染现状和开展的颗粒物致癌机制研究,分析中国研究中颗粒物有关实验动物致癌性的证据和颗粒物致癌的人群流行病学线索,阐述大气颗粒物与癌症的关系,提出中国亟需开展相关研究。  相似文献   
56.
57.
智能高速罐身电阻焊机数字化控制系统   总被引:1,自引:0,他引:1  
提出了以国产MCT80 0 0F8运动控制器为核心的智能高速罐身电阻焊机数字化控制系统 ,并介绍了系统的组成、工作原理、硬件接口、电机控制方法以及伺服电机的运动关系数学模型 .新的系统有利于提高罐身电阻焊机的制罐生产速度 ,并具有功能全面、可靠性高、控制精确、开放性好以及成本较低等优点  相似文献   
58.
Reconsideration on Homogeneous Quadratic Riemann Boundary Value Problem   总被引:1,自引:0,他引:1  
The homogeneous quadratic Riemann boundary value problem (1) with Hoelder continuous coefficients for the normal case was considered by the author in 1997. But the solutions obtained there are incomplete. Here its general method of solution is obtained.  相似文献   
59.
提高实验人员素质,加强实验队伍建设   总被引:3,自引:1,他引:2  
本文阐述了实验队伍建设的重要性,分析了目前高校实验技术队伍中存在的问题,并提出了解决问题的若干措施和对策.  相似文献   
60.
文章介绍了桩基工程旁站监理的过程和实效及保证监理目标实现的具体措施。  相似文献   
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