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41.
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
42.
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
43.
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
44.
用正交试验法优化手性镍催化二乙基锌对α,β不饱和酮的不对称麦克尔加成反应条件,优化后的不对称麦克尔加成反应的一般条件为:低温(近反应溶剂冰点),常压,非质子非极性溶剂(环己烷). 相似文献
45.
46.
姚民雄 《无锡职业技术学院学报》2004,3(4):40-42
研究性学习是实施素质教育和创新教育的一种新型教学方式。在工科类课程的教学中 可采用引入一个工程项目,通过项目设计来学习研究新知识,完成教学计划。 相似文献
47.
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
48.
49.
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
50.
搪瓷釉的烧成过程是一种“液相烧结”过程,其传质有赖于熔体的粘性流动。根据玻璃态物质化学组成-结构-粘度-温度的一般关系,推导出计算瓷釉烧成温度(T烧)的经验公式。 相似文献