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121.
Placental expression of the alpha subunit gene of the human glycoprotein hormones requires a multicomponent enhancer composed of tandem cAMP-response elements and an adjacent upstream regulatory element. Based on recent studies indicating that the upstream regulatory element includes binding sites for more than one protein, we investigated how functional activity correlated with these binding sites. Through extensive replacement mutagenesis of the native promoter regulatory region, we provide the first functional map of the upstream regulatory element. Within this region, we find that distinct proteins interact with three overlapping binding sites. While each site is functionally significant, no single site is essential or displays clear dominance. This is surprising since one of the sites binds a placenta-specific protein that heretofore has been regarded as essential for activity of the human alpha subunit placenta-specific enhancer. Consequently, our refined functional map of the upstream regulatory element reveals a complex combinatorial code that directs expression of the human alpha subunit gene to placenta. 相似文献
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为了加深对盆地深部和浅部高自然伽马异常特征综合分析研究,揭示高自然伽马异常地质成因,从而
促进盆地多种能源矿产协同开发研究,针对收集大量的地球物理测井资料、地质资料及其他相关成果,绘制并分
析了相关成果图。研究中遵循从单孔测井曲线特征分析到典型剖面研究,并按层对高自然伽马的平面分布特征
进行分析研究。化验测试结果和自然伽马能谱测井成果研究表明,在本区,自然伽马异常增大主要是由于铀的
活化和聚集,导致铀元素增加而引起。相关研究表明,盆地深部和浅部的铀异常具有一定的关系,盆地历经的沉
积环境变迁是铀元素富集的主导因素。 相似文献
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Wall shear stress in postcapillary venules varies widely within and between tissues and in response to inflammation and exercise. However, the speed at which leukocytes roll in vivo has been shown to be almost constant within a wide range of wall shear stress, i.e., force on the cell. Similarly, rolling velocities on purified selectins and their ligands in vitro tend to plateau. This may be important to enable rolling leukocytes to be exposed uniformly to activating stimuli on endothelium, independent of local hemodynamic conditions. Wall shear stress increases the rate of dissociation of individual selectin-ligand tether bonds exponentially (, ) thereby destabilizing rolling. We find that this is compensated by a shear-dependent increase in the number of bonds per rolling step. We also find an increase in the number of microvillous tethers to the substrate. This explains (a) the lack of firm adhesion through selectins at low shear stress or high ligand density, and (b) the stability of rolling on selectins to wide variation in wall shear stress and ligand density, in contrast to rolling on antibodies (). Furthermore, our data successfully predict the threshold wall shear stress below which rolling does not occur. This is a special case of the more general regulation by shear of the number of bonds, in which the number of bonds falls below one. 相似文献
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GH Posner MH Parker J Northrop JS Elias P Ploypradith S Xie TA Shapiro 《Canadian Metallurgical Quarterly》1999,42(2):300-304
In only three chemical operations, natural trioxane lactone artemisinin (1) was converted into a series of C-10 carbon-substituted 10-deoxoartemisinin compounds 4-9. The three steps involved lactone reduction, replacement of the anomeric lactol OH by F using diethylaminosulfur trifluoride, and finally boron trifluoride-promoted substitution of F by aryl, heteroaryl, and acetylide nucleophiles. All of these C-10 nonacetal, chemically robust, enantiomerically pure compounds 4-9 have high antimalarial potencies in vitro against Plasmodium falciparum malaria parasites, and furans 5a and 5b and pyrrole 7a are antimalarially potent also in vivo even when administered to rodents orally. 相似文献
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Through the high-resolution structure of the gramicidin A channel in lamellar phase lipids and the characterization of specific ion peptide interactions, fundamental principles for ion channel selectivity and conductance efficiency are illustrated with atomic resolution detail. Delocalized cation binding in the first turn of the helix reduces the unfavorable entropy contribution upon binding. Stepwise dehydration minimizes the energy barrier for cation entry and provides valence selectivity in this channel. Three or more water molecules in the monovalent cation binding site result in flexibility in the cation solvation environment causing weak cation size selectivity. Lack of cation induced structural modification avoids the formation of a significant energy barrier, thus permitting efficient cation transport. 相似文献