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31.
Beatriz E. Nielsen Teresa Minguez Isabel Bermudez Cecilia Bouzat 《Cellular and molecular life sciences : CMLS》2018,75(13):2457-2471
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.
Laurence Canaple Aline Gréchez-Cassiau Franck Delaunay Ouria Dkhissi-Benyahya Jacques Samarut 《Cellular and molecular life sciences : CMLS》2018,75(21):3991-4005
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.
Danielle Kamato Muhamad Ashraf Rostam Rebekah Bernard Terrence J. Piva Nitin Mantri Daniel Guidone Wenhua Zheng Narin Osman Peter J. Little 《Cellular and molecular life sciences : CMLS》2015,72(4):799-808
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.
基于信噪比的投资组合策略研究 总被引:1,自引:0,他引:1
采用收益率的协方差矩阵的特征根刻划投资的风险;用主成分综合反映证券市场的信息;用主成分的信噪比反映投资组合的期望收益率与风险之间的均衡关系,并以此作为投资组合收益极大化的指标;得到了不同与H.Markowitz的投资组合模型,并给出了具体的投资组合策略-卖空与非卖空条件下的投资组合的比例,文章最后给出了一个实例. 相似文献
35.
LuJian-ke 《武汉大学学报:自然科学英文版》2004,9(1):1-5
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
36.
通过学科评估指标体系的比较分析与研究,阐述了评估指标体系的客观性、可行性,分析了《美国新闻与世界报道》中多元学科评估指标体系的特点及对我国大学学科评估的启示。 相似文献
37.
根据人工神经网络的结构特点和信息传输与处理特征,提出了利用物理神经网络作为通信信道的观点.在分析了现有通信信道物理模型之后,具体讨论了作为通信信道的神经网络的可能拓朴结构、神经网络学习要点、允许传输信号的模式特征,研究了神经网络信道的传输延时、通信带宽及信噪比,分析了神经网络信道处理多媒体信号的计算潜力,并着重剖析了神经网络信道固有的保密通信特征.最后给出了一个具体的神经网络信道设计实例. 相似文献
38.
39.
Abrupt climate change:Debate or action 总被引:4,自引:1,他引:3
CHENGHai 《科学通报(英文版)》2004,49(18):1997-2002
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.
RAOLan-lan CAIDong-han 《武汉大学学报:自然科学英文版》2004,9(4):404-406
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