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951.
Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema 总被引:16,自引:0,他引:16
Morris DG Huang X Kaminski N Wang Y Shapiro SD Dolganov G Glick A Sheppard D 《Nature》2003,422(6928):169-173
Integrins are heterodimeric cell-surface proteins that regulate cell growth, migration and survival. We have shown previously that the epithelial-restricted integrin alpha(v)beta6 has another critical function; that is, it binds and activates latent transforming growth factor-beta (TGF-beta). Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)--a metalloproteinase that preferentially degrades elastin and has been implicated in the chronic lung disease emphysema. Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12. Furthermore, we show that the effects of Itgb6 deletion are overcome by simultaneous transgenic expression of active TGF-beta1. We have uncovered a pathway in which the loss of integrin-mediated activation of latent TGF-beta causes age-dependent pulmonary emphysema through alterations of macrophage Mmp12 expression. Furthermore, we show that a functional alteration in the TGF-beta activation pathway affects susceptibility to this disease. 相似文献
952.
Glycine binding primes NMDA receptor internalization 总被引:18,自引:0,他引:18
NMDA (N-methyl-d-aspartate) receptors (NMDARs) are a principal subtype of excitatory ligand-gated ion channel with prominent roles in physiological and disease processes in the central nervous system. Recognition that glycine potentiates NMDAR-mediated currents as well as being a requisite co-agonist of the NMDAR subtype of 'glutamate' receptor profoundly changed our understanding of chemical synaptic communication in the central nervous system. The binding of both glycine and glutamate is necessary to cause opening of the NMDAR conductance pore. Although binding of either agonist alone is insufficient to cause current flow through the channel, we report here that stimulation of the glycine site initiates signalling through the NMDAR complex, priming the receptors for clathrin-dependent endocytosis. Glycine binding alone does not cause the receptor to be endocytosed; this requires both glycine and glutamate site activation of NMDARs. The priming effect of glycine is mimicked by the NMDAR glycine site agonist d-serine, and is blocked by competitive glycine site antagonists. Synaptic as well as extrasynaptic NMDARs are primed for internalization by glycine site stimulation. Our results demonstrate transmembrane signal transduction through activating the glycine site of NMDARs, and elucidate a model for modulating cell-cell communication in the central nervous system. 相似文献
953.
西藏对外贸易的发展趋势与对策建议 总被引:2,自引:0,他引:2
本就十一届三中全会以来,西藏对外贸易规模不断扩大、对外开放程度不断提高和对外贸易商品结构不断改善的总体趋势,以及西藏对外贸易发展存在的一些突出的矛盾与问题加以分析,并针对这些矛盾和问题,根据西藏对外贸易发展所面临的机遇与挑战背景,提出了更新观念、实施以质取胜战略、实施市场多元化战略和加强外贸企业改革等促进西藏世外贸易发展的有效对策建议。 相似文献
954.
Huang E Ishida S Pittman J Dressman H Bild A Kloos M D'Amico M Pestell RG West M Nevins JR 《Nature genetics》2003,34(2):226-230
955.
Huang ZD 《浙江大学学报(自然科学英文版)》2003,4(1):80-85
A judgment criterion to guarantee a point to be a Chen's approximate zero of Newton method for solving nonlinear equation is sought by dominating sequence techniques. The criterion is based on the fact that the dominating function may have only one simple positive zero, assuming that the operator is weak Lipschitz continuous, which is much more relaxed and can be checked much more easily than Lipschitz continuous in practice. It is demonstrated that a Chen's approximate zero may not be a Smale's approximate zero. The error estimate obtained indicated the convergent order when we use /f(x)/ < epsilon to stop computation in software. The result can also be applied for solving partial derivative and integration equations. 相似文献
956.
Signal frequency based self-tuning fuzzy controller for semi-active suspension system 总被引:1,自引:0,他引:1
A new kind of fuzzy control scheme, based on the identification of the signal‘ s main frequency and the behavior of the ER damper, is proposed to control the semi-active suspension system. This method ad-justs the fuzzy controller to achieve the best isolation effect by analyzing the main frequency‘ s characters and inspecting the change of system parameters. The input of the fuzzy controller is the main frequency and the op-timal damping ratio is the output. Simulation results indicated that the proposed control method is very effec-tive in isolating the vibration. 相似文献
957.
TANG Zhiwen WANG Kemin TAN Weihong LI Jun LIU Lingfeng GUO Qiuping MENG Xiangxian HUANG Shasheng LI Du & LUO Weifang State Key Laboratory of Chemo/Biosensing Chemometrics Institute of Biological Technology College of Chemistry Chemical Engi-neering Hunan University Changsha China Correspondence should be addressed to Wang Kemin 《科学通报(英文版)》2003,48(12):1215-1218
The replication, ligation and repair of nucleic acids are essential life processes that based the survival, pro-creation and evolution of creatures. These interactions involving proteins (enzymes) and nucleic acids have fas-cinated great interest of scientists[1]. The nucleic acids ligation has been revealed that it is catalyzed by ligase and co-enzyme (ATP or NAD)[2—4]. Along with in-depth re-search, the nucleic acids ligation becomes a significant and common tool employed in bioengineerin… 相似文献
958.
FANGJianwu HUANGSiluo LIUHuisheng M.Crepin XUTao LIUJianfeng 《科学通报(英文版)》2003,48(15):1539-1547
Fibroblast growth factor-2 (FGF-2) is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. It has been proved that FGF-2 stimulates the growth and development of new blood vessels (angiogenesis) that contribute to the pathogenesis of several diseases (i.e. cancer, atherosclerosis). However, many of the biological activities of FGF-2 have been found to depend on its receptor抯 intrinsic tyrosine kinase activity and second messengers such as the mitogen activated protein kinases. This review will focus on the mechanism of FGF-2/FGFR induced signaling pathway in tumor and human breast cancer. 相似文献
959.
CAOWenxi YANGYuezhong XUXiaoqiang HUANGLiangmin ZHANGJianlin 《科学通报(英文版)》2003,48(21):2344-2351
Knowledge about the spectral absorption properties of marine particulate matters is of important signification for various goals of optical oceanography, among them the most concerns are the bio-optical algorithms for ocean color remote sensing[1], basic theory of light radiative transfer in water column[2], bio-optical models for estima-tion of primary productivity and simulation of the upper ocean ecological process[3,4]. The spectral absorption by marine particulate matter is combined influe… 相似文献
960.
Temperature trends over the past five centuries reconstructed from borehole temperatures 总被引:2,自引:0,他引:2
For an accurate assessment of the relative roles of natural variability and anthropogenic influence in the Earth's climate, reconstructions of past temperatures from the pre-industrial as well as the industrial period are essential. But instrumental records are typically available for no more than the past 150 years. Therefore reconstructions of pre-industrial climate rely principally on traditional climate proxy records, each with particular strengths and limitations in representing climatic variability. Subsurface temperatures comprise an independent archive of past surface temperature changes that is complementary to both the instrumental record and the climate proxies. Here we use present-day temperatures in 616 boreholes from all continents except Antarctica to reconstruct century-long trends in temperatures over the past 500 years at global, hemispheric and continental scales. The results confirm the unusual warming of the twentieth century revealed by the instrumental record, but suggest that the cumulative change over the past five centuries amounts to about 1 K, exceeding recent estimates from conventional climate proxies. The strength of temperature reconstructions from boreholes lies in the detection of long-term trends, complementary to conventional climate proxies, but to obtain a complete picture of past warming, the differences between the approaches need to be investigated in detail. 相似文献