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41.
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   
42.
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   
43.
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   
44.
 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   
45.
工业用PET及PA纤维模量-应变曲线的分析   总被引:2,自引:0,他引:2  
通过拉伸试验数据得到应力—应变曲线和模量-应变曲线可以更全面地反映纤维的力学性能。PET及PA的模量—应变曲线都是明显的双峰曲线。结合拉伸过程中PET纤维内部结构的变化解释PET纤维的特征模量—应变曲线,并讨论如何提高持续使用应变范围的模量问题。PET模量—应变曲线上的第一个模量峰为初始模量,标志着无定形区缠结网的破坏;无定形区蜷曲大分子伸直时模量较低,导致出现模量低谷;由于伸直的缚结大分子模量较高,出现了第二个模量峰。  相似文献   
46.
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   
47.
“数字电路与系统”具有实践性和离散性等特点;采用多媒体与板书相结合的方法克服多媒体的局限性,发扬板书的优势,取长补短;加强与学生的交流,创建和谐、有序、兴趣盎然的教学氛围。  相似文献   
48.
In this paper,the new development of three basic theories of Extenics,incluing basic-element theory,extension set theory and extension logic theory ,has been introduced.And the new theoretical frame of Extenics has also been set forth.  相似文献   
49.
高校图书馆数字化与现代化服务   总被引:1,自引:0,他引:1  
互联网改变了图书馆的运作方式,网络已成为高校图书馆信息采集、存储和传播的主要途径。介绍了高校图书馆数字化与现代化服务的主要内容,对高校图书馆数字化与现代化服务的功能与特点、技术关键、对策与措施及发展趋势进行了深入的探讨。  相似文献   
50.
Abrupt climate change:Debate or action   总被引:4,自引:1,他引:3  
Global abrupt climate changes have been documented by various climate records, including ice cores, ocean sediment cores, lake sediment cores, cave deposits, loess deposits and pollen records. The climate system prefers to be in one of two stable states, i.e. interstadial or stadial conditions, but not in between. The transition between two states has an abrupt character. Abrupt climate changes are, in general, synchronous in the northern hemisphere and tropical regions. The timescale for abrupt climate changes can be as short as a decade. As the impacts may be potentially serious, we need to take actions such as reducing CO2 emissions to the atmosphere.  相似文献   
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