Molecular function of the novel α7β2 nicotinic receptor

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.     

Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice

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.     

The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier

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.     

环境规制政策与公共健康——基于环境污染的中介效应检验

为了探究环境规制政策对于环境污染及公共健康的影响,本文基于我国1978至2013年颁布的976条环境规制政策,利用从政策属性力度、政策内容力度两个维度对我国环境规制政策进行量化的数据,构建了针对环境规制政策效果的计量模型,通过将中介效应检验方法引入环境健康经济学分析,检验了环境污染对环境规制政策与公共健康的中介效应.研究结果表明:环境规制政策对公共健康具有促进作用;我国总体的环境规制政策对于防治环境污染产生了一定程度的积极效果;环境规制政策通过对环境污染显著的部分中介效应进而对公共健康产生了促进作用.本研究基于总体环境规制政策文献量化角度考察的"政策-环境-健康"三维动态关系结果,阐明了环境规制政策、环境污染以及公共健康三者的影响传输路径,对于有效评估环境规制政策效果,保障环境质量以及公共健康的可持续提升具有理论借鉴价值.     

塔东热液地质作用机制及对储层的改造意义

塔东地区断裂发育，早期发育的断裂与晚期断裂之间存在相互改造、叠加、复合的过程，深大断裂沟通多套地层，断裂活动期形成的挤压破碎带和断裂裂缝带作为岩浆热液上升通道，为热液溶蚀作用改造储层提供了有利条件，因此，识别出热液期次对塔东白云岩储层成因机制具有重要意义。通过对钻井岩芯、岩屑及岩石薄片、铸体薄片观察鉴定分析，在区内下古生界碳酸盐岩中识别和发现了钠长石化作用和自生羽毛状伊利石沉淀，也是塔里木盆地内的首次发现，并通过对包裹体均一温度，碳氧同位素等地化特征研究，揭示其成岩流体源于岩浆热液，丰富了区内热液作用的矿物学标志，进一步识别出区内存在3期热液作用，通过对3期热液作用的机制及其储渗空间意义的研究，总结出第I期热液作用对于储层形成意义不大，第Ⅱ期热液作用主要发育在局限的沉积环境，第Ⅲ期热液溶蚀形成溶蚀缝孔洞，与天然气运移聚集匹配良好，构成了区内天然气聚集成藏的主要储渗空间。     

黄冈公铁两用长江大桥维修通道施工

维修通道专为桥梁竣工后接收管养单位而设。本文以黄冈桥维修通道为例,从下部基础到上部主体框架乃至附属,全面地叙述了各部位的施工情况及工序控制要点,为以后类似施工提供一定经验。     

基于模糊证据推理的突发事件风险分析模型

突发事件发生、发展和演化过程中的风险属性来源复杂,且相关信息具有不确定、不完备的特点.为准确分析这一特点下的突发事件运行风险问题,引入模糊证据推理构建分析模型.首先根据突发事件的结构化描述框架和故障模式影响危害分析(FMECA)方法构建突发事件风险属性识别框架,获取信息作为风险分析证据并对其进行规范化处理;然后以模糊证据推理构建突发事件风险分析的模型,通过计算,给出事件风险程度的合理判断;最后选取CRH某型动车组行车安全事件进行实例分析.分析结果表明,在分析突发事件风险时,针对信息不确定、不完备特点构建的模糊证据推理模型具有可行性与有效性,同时该模型能够为突发事件风险分析和风险应对决策的制定提供辅助参考.     

Reconsideration on Homogeneous Quadratic Riemann Boundary Value Problem

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.     

一种有效的网格综合优化算法

提出一种有效的网格综合优化算法。给定一定数量的三维散乱点和一个初始三角网格,使用Hoppe提出的能量函数对网格顶点位置优化,使网格更好的逼近三维散乱点。同时通过分裂网格中度数特别大的节点,使网格的空间形状更加平滑。计算机仿真实验表明,使用该算法能够获得形状良好的网格。     

New Develoopment of the Basic Theory of Extenics

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.