《基因Ⅺ》

<正>出版日期:2014年5月定价:398.00元字数:180万内容简介分子生物学是一门发展迅速的学科,其知识更新之快及前沿的蓬勃发展,对人类生活产生了持久而深入的影响。Lewin的《基因》自问世以来,一     

Coordinate Regulation of the Cyclic AMP System with Firing Rate and Expression of Tyrosine Hydroxylase in the Rat Locus Coeruleus: Effects of Chronic Stress and Drug Treatments

Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels of protein kinase activity. Other treatments known to either increase (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also found to increase or decrease, respectively, levels of cAMP-dependent protein kinase activity in this brain region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hierarchic organization of domains in globular proteins

An automatic procedure is developed for the identification of domains in globular proteins from X-ray elucidated co-ordinates. Using this tool, domains are shown to be iteratively decomposable into subdomains, leading to a hierarchic molecular architecture.There is no convenient geometry that will fully characterize the atom by atom interdigitation at an interface between domains, and the strategy adopted here was devised to reduce this unwieldy three-dimensional problem to a closely approximating companion analysis in a plane. These analytically derived domain choices can be used subsequently to construct computer-generated, space-filling, color-coded views of the domains; and when this is done, the derived domains are seen to be completely resolved.The number of domains in a protein is a mathematically well-behaved function of the chain length, lending support to the supposition that the domains are an implicit structural consequence of the folding process. A spectrum of domains ranging in size from whole protein monomers to the individual units of secondary structure is apparent in each of the 22 proteins analyzed here.The hierarchic organization of structural domains is evidence in favor of an underlying protein folding process that proceeds by hierarchic condensation. In this highly constrained model, every pathway leading to the native state can be described by a tree of local folding interactions.     

An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation

Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal differentiation to cell cycle arrest. Using macrophages as a model, we provide evidence that METS/PE1 blocks Ras-dependent proliferation without inhibiting Ras-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Antiproliferative effects of METS require its interaction with DP103, a DEAD box-containing protein that assembles a novel corepressor complex. Functional interactions between the METS/DP103 complex and E2F/ pRB family proteins are also necessary for inhibition of cellular proliferation, suggesting a combinatorial code that directs permanent cell cycle exit during terminal differentiation.     

Development of homogeneous luminescence assays for histone demethylase catalysis and binding

Covalent modifications to histones play important roles in chromatin dynamics and the regulation of gene expression. The JumonjiC (JmjC)-containing histone demethylases (HDMs) catalyze the demethylation of methylated lysine residues on histone tails. Here we report the development of homogeneous luminescence-based assay methods for measuring the catalytic activity and the binding affinities of peptides to HDMs. The assays use amplified luminescent proximity homogeneous assay (ALPHA) technology, are sensitive and robust, and can be used for small molecule inhibitor screening of HDMs. We have profiled known inhibitors of JMJD2E and demonstrate a correlation between the inhibitor potencies determined by the ALPHA and other types of assays. Although this study focuses on the JMJD2E isoform, the catalytic turnover and binding assays described here can be used in studies on other HDMs. The assays should be useful for the development of small molecule inhibitors selective for HDM isoforms.     

Listening to Puns Elicits the Co-Activation of Alternative Homophone Meanings during Language Production

Recent evidence suggests that lexical-semantic activation spread during language production can be dynamically shaped by contextual factors. In this study we investigated whether semantic processing modes can also affect lexical-semantic activation during word production. Specifically, we tested whether the processing of linguistic ambiguities, presented in the form of puns, has an influence on the co-activation of unrelated meanings of homophones in a subsequent language production task. In a picture-word interference paradigm with word distractors that were semantically related or unrelated to the non-depicted meanings of homophones we found facilitation induced by related words only when participants listened to puns before object naming, but not when they heard jokes with unambiguous linguistic stimuli. This finding suggests that a semantic processing mode of ambiguity perception can induce the co-activation of alternative homophone meanings during speech planning.     

Purification and Characterization of A Human-Specific Esterase From Urine

Abstract

A human-specific esterase was isolated from urine and partially characterized by ammonium sulfate precipitation, starch block electrophoresis, and gel filtration. Its molecular weight was estimated to be 136,000 by polyacrylamide gel electrophoresis in 0.17. SDS. A diffusion coefficient of 8.6 X 10^?7 was determined by the L-plate method. Immunologic identity was shown between the urinary esterase and a human tissue esterase.