BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling

In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.     

Immunogenicity of recombinant fowl-pox virus co-expressing structural protein precursor P1-2A and proteinase 3C of FMDV

Two recombinant plasmids, pUTA2P1 and pUTAL3CP1, were constructed by inserting structural protein precursor P1-2A and proteinase 3C of foot-and-mouth disease virus (FMDV) into fowl-pox virus (FPV) recombinant vectors pUTA-2 and pUTA-16-LacZ respectively, and two recombinant FPVs (vUTA2P1 and vUTAL3CP1) screened by the RT-PCR, IFA assay and Western blotting assay were obtained successfully. Mice injected respectively with rFPVs were induced high level specific anti-FMDV antibodies, increasing of T subtypes, and higher cytotoxicities of splenocytes than those of control groups. These results indicated that a new method was used to construct a potential candidate vaccine of FMDV.     

Fast dating of Yongzheng copper coins in tsing empire by SEM-EDS

Twenty Yongzheng copper coins were fast dat-ing by X-ray energy dispersive spectrometer with scanning electron microscope (SEM-EDS) according to official ingredient. The 20 coins were classified in two groups according to the results. Group 1 represents the coins minted before AD 1 728 and group 2 represents the coins minted after AD 1 728. At concentration range (0.00%-5.13%), the distribution of lead is not homogeneous in the coins, and the largest diameter of lead inclusion is less than 15 μm. The official fineness degrade is supported.     

A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm

Oestrogen receptor (ER) is a good prognostic marker for the treatment of breast cancers. Upregulation of metastatic tumour antigen 1 (MTA1) is associated with the invasiveness and metastatic potential of several human cancers and acts as a co-repressor of nuclear ER-alpha. Here we identify a naturally occurring short form of MTA1 (MTA1s) that contains a previously unknown sequence of 33 amino acids with an ER-binding motif, Leu-Arg-Ile-Leu-Leu (LRILL). MTA1s localizes in the cytoplasm, sequesters ER in the cytoplasm, and enhances non-genomic responses of ER. Deleting the LRILL motif in MTA1s abolishes its co-repressor function and its interaction with ER, and restores nuclear localization of ER. Dysregulation of human epidermal growth factor receptor-2 in breast cancer cells enhances the expression of MTA1s and the cytoplasmic sequestration of ER. Expression of MTA1s in breast cancer cells prevents ligand-induced nuclear translocation of ER and stimulates malignant phenotypes. MTA1s expression is increased in human breast tumours with no or low nuclear ER. The regulation of the cellular localization of ER by MTA1s represents a mechanism for redirecting nuclear receptor signalling by nuclear exclusion.     

Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits

The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) serves critical functions in physiological and pathological processes in the central nervous system, including neuronal development, plasticity and neurodegeneration. Conventional heteromeric NMDARs composed of NR1 and NR2A-D subunits require dual agonists, glutamate and glycine, for activation. They are also highly permeable to Ca2+, and exhibit voltage-dependent inhibition by Mg2+. Coexpression of NR3A with NR1 and NR2 subunits modulates NMDAR activity. Here we report the cloning and characterization of the final member of the NMDAR family, NR3B, which shares high sequence homology with NR3A. From in situ and immunocytochemical analyses, NR3B is expressed predominantly in motor neurons, whereas NR3A is more widely distributed. Remarkably, when co-expressed in Xenopus oocytes, NR3A or NR3B co-assembles with NR1 to form excitatory glycine receptors that are unaffected by glutamate or NMDA, and inhibited by D-serine, a co-activator of conventional NMDARs. Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable cation channels that are resistant to Mg2+, MK-801, memantine and competitive antagonists. In cerebrocortical neurons containing NR3 family members, glycine triggers a burst of firing, and membrane patches manifest glycine-responsive single channels that are suppressible by D-serine. By itself, glycine is normally thought of as an inhibitory neurotransmitter. In contrast, these NR1/NR3A or -3B 'NMDARs' constitute a type of excitatory glycine receptor.     

“雅”译观的历史与现实

本文探讨了严氏“雅”译观产生的历史、社会、教育背景和哲学基础。从辩证历史观的角度看 ,“雅”译观作为译事中宏观的指导理论和译文评鉴标准 ,与西学的“等值论”相得益彰 ,仍不失具有重要的现实意义和指导作用     

Heterogeneous reactions on the surface of fine particles in the atmosphere

Fine particles play an important role in the atmosphere. Research on heterogeneous reactions on the surface of fine particles is one of the frontier areas of atmospheric science. In this paper, physical and chemical characteristics of fine particles in the atmosphere and the interactions between trace gases and fine particles are described, methods used in heterogeneous reactions research are discussed in detail, progress in the study of heterogeneous reactions on the surface of fine particles in the atmosphere is summarized, existing important questions are pointed out and future research directions are suggested.     

面向武器装备系列研制的灵境仿真研究

首先阐明面向武器装备系列研制的灵境仿真研究的重要性及其学科归属.根据实施约束条件,将本项研究定位于应用基础研究.基于90年代的计算技术基础设施,将VR仿真开发系统的技术目标设定为自学习、自优化、目标驱动的自产生式建模与仿真环境.在1995年已实现的人工智能嵌入面向对象编程AI+OOP形式化体系中,通过知识封装赋予对象以知识禀赋和似人的精神属性.把AIOOM开发平台提升到面向智能体层次.文章给出Agent设计及实现的形式化描述,并通过二个实例说明该系统的可行性和优势.最后,展望系统发展方向并指出待努力解决和问题.     

张力减径机传动系统分析与比较

文章介绍了张力减径机的几种传动方式,并对其进行了分析与比较.     

加强企业思想政治工作的思考

在我国企业改制和建立现代企业制度的不断深入下,笔者通过多年工作实践对思想政治工作中的问题进行思考.