Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean

Members of the muscarinic acetylcholine receptor family (M1-M5) have central roles in the regulation of many fundamental physiological functions. Identifying the specific receptor subtype(s) that mediate the diverse muscarinic actions of acetylcholine is of considerable therapeutic interest, but has proved difficult primarily because of a lack of subtype-selective ligands. Here we show that mice deficient in the M3 muscarinic receptor (M3R-/- mice) display a significant decrease in food intake, reduced body weight and peripheral fat deposits, and very low levels of serum leptin and insulin. Paradoxically, hypothalamic messenger RNA levels of melanin-concentrating hormone (MCH), which are normally upregulated in fasted animals leading to an increase in food intake, are significantly reduced in M3R-/- mice. Intra-cerebroventricular injection studies show that an agouti-related peptide analogue lacked orexigenic (appetite-stimulating) activity in M3R-/- mice. However, M3R-/- mice remained responsive to the orexigenic effects of MCH. Our data indicate that there may be a cholinergic pathway that involves M3-receptor-mediated facilitation of food intake at a site downstream of the hypothalamic leptin/melanocortin system and upstream of the MCH system.     

燕山东段山前平原冬小麦高产栽培优化农艺措施组合的研究

以密度、氮肥、磷肥、氮肥施用期及灌水五项措施为决策变量。采用五因素二次回归旋转设计方案,经田间试验后进行计算机处理,建立了相应的数学模型。本文对因素效应和不同产量等级筛选出的优化农艺方案进行了总结分析。结果表明,本生态区以灌水及密度对产量的影响最为显著。≥300公斤/亩产量的优化方案有2274套出现频率为72.8％。相应的优化农艺组合为27～28万苗/亩,20.8公斤/亩尿素,21.0公斤/亩三料磷肥,氮肥底施和枝节期追施,灌水130米~3/亩。     

Debris Flow Monitoring System and Observed Event in Taiwan： A Case Study at Aiyuzi River

Since 2002,the Soil and Water Conservation Bureau,which is responsible for the conservation and administrative man-agement of hillside in Taiwan,has been cooperating with Feng Chia University. Together,they have successfully carried out the establishment and maintenance of 13 fixed debris flow monitoring stations over the island and 2 mobile debris flow monitoring sta-tions. During July 2004,a powerful southwest air current brought by Mindulle Typhoon caused serious flood in central and southern Taiwan. This paper aims to describe the establishment of debris flow monitoring systems in Taiwan and the observation of the debris flow event during Mindulle Typhoon at Aiyuzi River in Shenmu Village,Nantou County by the monitoring station.     

Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching

Mitochondrial uncoupling protein 2 (UCP2) is an integral membrane protein in the mitochondrial anion carrier protein family, the members of which facilitate the transport of small molecules across the mitochondrial inner membrane. When the mitochondrial respiratory complex pumps protons from the mitochondrial matrix to the intermembrane space, it builds up an electrochemical potential. A fraction of this electrochemical potential is dissipated as heat, in a process involving leakage of protons back to the matrix. This leakage, or 'uncoupling' of the proton electrochemical potential, is mediated primarily by uncoupling proteins. However, the mechanism of UCP-mediated proton translocation across the lipid bilayer is unknown. Here we describe a solution-NMR method for structural characterization of UCP2. The method, which overcomes some of the challenges associated with membrane-protein structure determination, combines orientation restraints derived from NMR residual dipolar couplings (RDCs) and semiquantitative distance restraints from paramagnetic relaxation enhancement (PRE) measurements. The local and secondary structures of the protein were determined by piecing together molecular fragments from the Protein Data Bank that best fit experimental RDCs from samples weakly aligned in a DNA nanotube liquid crystal. The RDCs also determine the relative orientation of the secondary structural segments, and the PRE restraints provide their spatial arrangement in the tertiary fold. UCP2 closely resembles the bovine ADP/ATP carrier (the only carrier protein of known structure), but the relative orientations of the helical segments are different, resulting in a wider opening on the matrix side of the inner membrane. Moreover, the nitroxide-labelled GDP binds inside the channel and seems to be closer to transmembrane helices 1-4. We believe that this biophysical approach can be applied to other membrane proteins and, in particular, to other mitochondrial carriers, not only for structure determination but also to characterize various conformational states of these proteins linked to substrate transport.     

The RAG2 C terminus suppresses genomic instability and lymphomagenesis

Misrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans and in mice. Defects in DNA damage response factors such as ataxia telangiectasia mutated (ATM) protein and combined deficiencies in classical non-homologous end joining and p53 predispose to RAG-initiated genomic rearrangements and lymphomagenesis. Although we showed previously that RAG1/RAG2 shepherd the broken DNA ends to classical non-homologous end joining for proper repair, roles for the RAG proteins in preserving genomic stability remain poorly defined. Here we show that the RAG2 carboxy (C) terminus, although dispensable for recombination, is critical for maintaining genomic stability. Thymocytes from 'core' Rag2 homozygotes (Rag2(c/c) mice) show dramatic disruption of Tcrα/δ locus integrity. Furthermore, all Rag2(c/c) p53(-/-) mice, unlike Rag1(c/c) p53(-/-) and p53(-/-) animals, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcrα/δ and Igh loci. We also find these features in lymphomas from Atm(-/-) mice. We show that, like ATM-deficiency, core RAG2 severely destabilizes the RAG post-cleavage complex. These results reveal a novel genome guardian role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2(c/c) p53(-/-) and Atm(-/-) mice.     

基于冻融作用的固化硫酸盐渍土-混凝土界面力学行为

冻融作用下固化盐渍土强度发生劣化并影响土体与结构的相互作用。鉴于此,开展了不同固化剂对硫酸盐渍土力学特性的影响研究并得知石灰+硅灰双掺改良效果显著;在此基础上,探索了石灰-硅灰双掺固化剂、含盐量、冻融次数等因素对非饱和固化硫酸盐渍土-混凝土接触面力学性能的影响。结果表明,石灰-硅灰固化硫酸盐渍土与混凝土界面内摩擦角随着冻融循环次数的增加先增大后减小再增大,黏聚力随着冻融次数的增加先增加后逐渐减小,接触面抗剪强度随着冻融次数的增加逐渐减小并趋于稳定;在相同的冻融次数下,接触面的内摩擦角及黏聚力均随着含盐量的增大先增大后减小,两者含盐量阈值分别为3%和2%。在本试验范围内,5%石灰+10%硅灰对含盐量为2%～3%的硫酸盐渍土改良效果较好;冻融前后,固化盐渍土-混凝土接触面剪应力-剪切位移曲线分为4个阶段：弹性变形阶段、强化阶段、软化阶段及流动阶段。     

液压振动步冲机液压系统动态仿真研究

本文叙述了一种液压振动步冲机,它是以回转式单循环液压脉冲发生器为“心脏””元件所组成的新型液压振动系统。利用功率键合图及状态空间方程对系统的动态特性进行了数字仿真,并优选了部分参数。通过实测与仿真,系统的应用是成功的,可供工业生产领域广泛使用。     

常用二元熔盐氯化物相图及其热力学性质的最优化

本文介绍了一种优化处理二元相图及热力学性质的方法。通过系统分析全部所获得的LiCl—KCl,LiCl—SrCl_2,NaCl—SrCl_2,NaCl—CaCl_2,NaCl—BaCl_2,KCl—BaCl_2,CaCl_2—BaCl_2,BaCl_2—SrCl_2等八个二元系热力学性质和相图的数据并进行优化处理,取得了热力学性质和相图自相一致的结果。