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31.
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   
32.
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   
33.
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   
34.
以玉林高中生物教师为研究对象,通过问卷调查法和个人访谈法对高中生物教师队伍的基本结构、生物教师配备、工作量、任职、收入、科研水平和进修培训等情况进行了调查,分析得出了影响高中生物教师发展的不利因素:(1)教师队伍结构不合理;(2)公立和私立学校、城市和乡镇学校,在师资配备、教师培养、待遇等方面的投入存在着较大的差距;(3)高中生物教师工作量较大、得到发展的机会较少;(4)教学资金投入不足,不利于教学工作的开展.文中结合新形势下对高中生物教师的要求,提出了一些促进高中生物教师发展的对策,以求为有关部门有效地优化高中生物教师队伍、合理利用和分配教师资源提供理论依据和实践参考.  相似文献   
35.
三门峡水库电站运行调度的优化研究   总被引:2,自引:0,他引:2  
三门峡水库泥沙淤积严重,使其枢纽的各项技术指标经常变化,为其调度运行带来极大困难。为此,充分考虑三门峡水电站运行过程中的各种约束条件,分别采用动态规划和遗传算法给出了电站优化调度模型,建立了该电站的运行调度系统。经过水库1991年—2000年实际来水和控制运行的月报资料的模拟验证,结果表明,该系统可平均增加发电量约12.9%,使电站能更合理地进行管理调度。而且,通过对随机模拟的长序列入库月径流过程的模拟调度,建议了三门峡水电站具体的管理调度运行方式。  相似文献   
36.
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   
37.
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   
38.
《医疗事故处理条例》颁布实施后,在医患纠纷诉讼方面仍存在一些问题.文章就其在医疗事故分级、医疗纠纷诉讼仍未设置行政裁决前置、鉴定方面、病历资料的封存和启封及医疗保险赔偿机制方面存在的问题作一阐述,并提出建议性的解决办法。  相似文献   
39.
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   
40.
We prove that the model with physical and human capital adjustment costs has optimal solution when the production function is increasing return and the structure of vetor fields of the model changes substantially when the prodution function from decreasing return turns to increasing return. And it is shown that the economy is improved when the coefficients of adjustment costs become small.  相似文献   
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