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21.
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   
22.
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   
23.
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   
24.
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   
25.
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   
26.
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   
27.
井下抽油泵柱塞与泵筒运动规律的研究   总被引:1,自引:0,他引:1  
用三元振动模型,综合考虑油柱、抽油杆柱和油管柱的振动.建立起数学模型并离散化,然后用微机编程求解微分方程组.对不同工况下的抽油泵运动规律和抽油机示功图进行分析研究,得出了油管应予锚定的结论,并给出了不同抽油机的适用范围.为进一步研究抽油泵的井下工作机理和故障原因打下了基础.  相似文献   
28.
This paper formulates a robust stage-structured SI eco-epidemiological model with periodic constant pulse releasing of infectious pests with pathogens. The authors show that the conditions for global attractivity of the 'pest-eradication' periodic solution and permanence of the system depend on time delay, hence, the authors call it "profitless". Further, the authors present a pest management strategy in which the pest population is kept under the economic threshold level (ETL) when the pest population is uniformly persistent. By numerical analysis, the authors also show that constant maturation time delay for the susceptible pests and pulse releasing of the infectious pests can bring obvious effects on the dynamics of system.  相似文献   
29.
采用文献资料法、数理统计法、比较法对吉林省民办高校和公立高校体育教师的科研现状进行比较分析,比较二者不同年龄、学历、职称的教师发表论文状况,分析二者的科研学术氛围及科研条件,旨在了解长春市两类高校的体育科研的现状,为长春市高校体育科研水平的提高提供参考。  相似文献   
30.
The method of extracting and describing the intended behavior of software precisely has become one of the key points in the fields of software behavior's dynamic and trusted authentication. In this paper, the author proposes a specified measure of extracting SIBDS (software intended behaviors describing sets) statically from the binary executable using the software's API functions invoking, and also introduces the definition of the structure used to store the SIBDS in detail. Experimental results demonstrate that the extracting method and the storage structure definition offers three strong properties: (i) it can describe the software's intended behavior accurately; (ii) it demands a small storage expense; (iii) it provides strong capability to defend against mimicry attack.  相似文献   
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