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261.
BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling 总被引:21,自引:0,他引:21
He XC Zhang J Tong WG Tawfik O Ross J Scoville DH Tian Q Zeng X He X Wiedemann LM Mishina Y Li L 《Nature genetics》2004,36(10):1117-1121
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. 相似文献
262.
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. 相似文献
263.
本文利用系统动力学的方法对安微省农户的生产、消费和积累三方面的经济行为进行研究。探讨了农户在现有的生产条件和政策环境下生产、消费和积累的特点及其发展趋势,并提出了应该采取的对策。 相似文献
264.
Multiple regulatory sites in large-conductance calcium-activated potassium channels 总被引:28,自引:0,他引:28
Large conductance, Ca(2+)- and voltage-activated K(+) channels (BK) respond to two distinct physiological signals -- membrane voltage and cytosolic Ca(2+) (refs 1, 2). Channel opening is regulated by changes in Ca(2+) concentration spanning 0.5 micro M to 50 mM (refs 2-5), a range of Ca(2+) sensitivity unusual among Ca(2+)-regulated proteins. Although voltage regulation arises from mechanisms shared with other voltage-gated channels, the mechanisms of Ca(2+) regulation remain largely unknown. One potential Ca(2+)-regulatory site, termed the 'Ca(2+) bowl', has been located to the large cytosolic carboxy terminus. Here we show that a second region of the C terminus, the RCK domain (regulator of conductance for K(+) (ref. 12)), contains residues that define two additional regulatory effects of divalent cations. One site, together with the Ca(2+) bowl, accounts for all physiological regulation of BK channels by Ca(2+); the other site contributes to effects of millimolar divalent cations that may mediate physiological regulation by cytosolic Mg(2+) (refs 5, 13). Independent regulation by multiple sites explains the large concentration range over which BK channels are regulated by Ca(2+). This allows BK channels to serve a variety of physiological roles contingent on the Ca(2+) concentration to which the channels are exposed. 相似文献
265.
The secreted protein Sonic hedgehog (Shh) exerts many of its patterning effects through a combination of short- and long-range signalling. Three distinct mechanisms, which are not necessarily mutually exclusive, have been proposed to account for the long-range effects of Shh: simple diffusion of Shh, a relay mechanism in which Shh activates secondary signals, and direct delivery of Shh through cytoplasmic extensions, termed cytonemes. Although there is much data (using soluble recombinant Shh (ShhN)) to support the simple diffusion model of long-range Shh signalling, there has been little evidence to date for a native form of Shh that is freely diffusible and not membrane-associated. Here we provide evidence for a freely diffusible form of Shh (s-ShhNp) that is cholesterol modified, multimeric and biologically potent. We further demonstrate that the availability of s-ShhNp is regulated by two functional antagonists of the Shh pathway, Patched (Ptc) and Hedgehog-interacting protein (Hip). Finally, we show a gradient of s-ShhNp across the anterior-posterior axis of the chick limb, demonstrating the physiological relevance of s-ShhNp. 相似文献
266.
267.
曾中辉 《东莞理工学院学报》2003,10(2):81-85
在《西游记》中,孙悟空是一个天才型人才。但是,这个天才型人才却在两种不同的用人制度下经历了两种不同的命运。《西游记》就是通过对孙悟空等人物形象的塑造,通过对玉皇大帝和观音菩萨两种不同用人方式以及产生的不同结果的对照,抒发了对封建时代的不合理的用人制度的不满,表达了一种对理想的用人制度的憧憬。 相似文献
268.
提出一种新的竖向弹簧—钢球隔震系统隔离水平地震作用的隔震方法,用势能不变值原理与“对号入座”法则建立该隔震系统的振动方程,分析各控制参数对该隔震系统地震反应的影响.研究结果表明,该隔震系统结构简单,隔离水平地震作用效果显著. 相似文献
269.
XUShandong LEIShengbin ZENGQingdao WANGChen WANLijun BAIChunli 《科学通报(英文版)》2003,48(8):742-745
An important precursor 4,5-didodecylthiolphthalonitrile (DCP) for synthesis of phthalocyanines (Pcs) and subphthalocyanines (SubPcs) was synthesized and the assembling structure of this molecule on the basal plane of highly oriented pyrolytic graphite (HOPG) surface was characterized using the scanning tunneling microscopy (STM) in ambient conditions. In high-resolution images of the molecules, we found that the arrangement of the cyano groups forms a “head-to-head” configuration to keep the stability of the entire system. The mismatch of the DCP molecules with the substrate lattice has also been observed in the experiment. 相似文献
270.
在校大学生消费情况分析及科学理财模式的构筑 总被引:1,自引:0,他引:1
通过问卷调查对在校大学生的消费结构现状进行了分析,指出目前大学生消费结构中存在的问题,提出从社会、家庭、学校、学生个人四个方面全方位构筑大学生科学的理财模式,以期对大学生合理消费模式的形成提供指导. 相似文献