454 research outputs found

    Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds.

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    Previously, we only apply a traditional Chinese medicine (TCM) Danshen-Chuanxiong-Honghua (DCH) for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA) for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO). We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg) and FA (100 mg/kg) improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds

    Normative-legal mechanism of state management of vocational (voation-and-technical) education’s development: historical retrospective

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    У статті наведено періодизацію розвитку професійної (професійно-технічної) освіти в Україні, визначено особливості використання інструментарію державного управління на кожному з етапів її розвитку; розглянуто потенціали нормативно-правового механізму державного управління у формуванні сучасної системи професійної (професійно-технічної) освіти незалежної України.The article contains periodization of vocational (vocation-and-technical) educa-tion’s development in Ukraine, there are determined peculiarities of applying state man-agement instruments on each stage in its development; potential of normative-legal mechanism of state management in respect of forming a modern system of vocational (vocation-and-technical) education of independent Ukraine is viewed

    Insights into distinct regulatory modes of nucleosome positioning

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    <p>Abstract</p> <p>Background</p> <p>The nucleosome is the fundamental unit of eukaryotic genomes. Experimental evidence suggests that the genomic DNA sequence and a variety of protein factors contribute to nucleosome positioning <it>in vivo</it>. However, how nucleosome positioning is determined locally is still largely unknown.</p> <p>Results</p> <p>We found that transcription factor binding sites (TFBSs) with particular nucleosomal contexts show a preference to reside on specific chromosomes. We identified four typical gene classes associated with distinct regulatory modes of nucleosome positioning, and further showed that they are distinguished by transcriptional regulation patterns. The first mode involves the cooperativity between chromatin remodeling and stable transcription factor (TF)-DNA binding that is linked to high intrinsic DNA binding affinities, evicting nucleosomes from favorable DNA sequences. The second is the DNA-encoded low nucleosome occupancy that is associated with high gene activity. The third is through chromatin remodeling and histone acetylation, sliding nucleosomes along DNA. This mode is linked to more cryptic sites for TF binding. The last consists of the nucleosome-enriched organization driven by other factors that overrides nucleosome sequence preferences. In addition, we showed that high polymerase II (Pol II) occupancy is associated with high nucleosome occupancy around the transcription start site (TSS).</p> <p>Conclusions</p> <p>We identified four different regulatory modes of nucleosome positioning and gave insights into mechanisms that specify promoter nucleosome location. We suggest two distinct modes of recruitment of Pol II, which are selectively employed by different genes.</p

    Two distinct modes of nucleosome modulation associated with different degrees of dependence of nucleosome positioning on the underlying DNA sequence

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    <p>Abstract</p> <p>Background</p> <p>The nucleosome is the fundamental unit of eukaryotic genomes. Its positioning plays a central role in diverse cellular processes that rely on access to genomic DNA. Experimental evidence suggests that the genomic DNA sequence is one important determinant of nucleosome positioning. Yet it is less clear whether the role of the underlying DNA sequence in nucleosome positioning varies across different promoters. Whether different determinants of nucleosome positioning have characteristic influences on nucleosome modulation also remains to be elucidated.</p> <p>Results</p> <p>We identified two typical promoter classes in yeast associated with high or low dependence of nucleosome positioning on the underlying DNA sequence, respectively. Importantly, the two classes have low or high intrinsic sequence preferences for nucleosomes, respectively. The two classes are further distinguished by multiple promoter features, including nucleosome occupancy, nucleosome fuzziness, H2A.Z occupancy, changes in nucleosome positions before and after transcriptional perturbation, and gene activity. Both classes have significantly high turnover rates of histone H3, but employ distinct modes of nucleosome modulation: The first class is characterized by hyperacetylation, whereas the second class is highly regulated by ATP-dependent chromatin remodelling.</p> <p>Conclusion</p> <p>Our results, coupled with the known features of nucleosome modulation, suggest that the two distinct modes of nucleosome modulation selectively employed by different genes are linked with the intrinsic sequence preferences for nucleosomes. The difference in modes of nucleosome modulation can account for the difference in the contribution of DNA sequence to nucleosome positioning between both promoter classes.</p

    Genome-wide analysis of the effect of histone modifications on the coexpression of neighboring genes in Saccharomyces cerevisiae

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    <p>Abstract</p> <p>Background</p> <p>Neighboring gene pairs in the genome of <it>Saccharomyces cerevisiae </it>have a tendency to be expressed at the same time. The distribution of histone modifications along chromatin fibers is suggested to be an important mechanism responsible for such coexpression. However, the extent of the contribution of histone modifications to the coexpression of neighboring genes is unclear.</p> <p>Results</p> <p>We investigated the similarity of histone modification between neighboring genes using autocorrelation analysis and composite profiles. Our analysis showed that neighboring genes had similar levels or changes of histone modifications, especially those transcribed in the same direction. The similarities, however, were restricted to 1 or 2 neighboring genes. Moreover, the expression of a gene was significantly correlated with histone modification of its neighboring gene(s), but this was limited to only 1 or 2 neighbors. Using a hidden Markov model (HMM), we found more than 2000 chromatin domains with similar acetylation changes as the cultures changed and a considerable number of these domains covered 2-4 genes. Gene pairs within domains exhibited a higher level of coexpression than random pairs and shared similar functions.</p> <p>Conclusions</p> <p>The results of this study suggest that similar histone modifications occur within only a small local chromatin region in yeast. The modifications generally have an effect on coexpression with only 1 or 2 neighboring genes. Some blocking mechanism(s) might strictly restrain the distribution of histone modifications in yeast.</p

    Petrogenesis of the Northwest Africa 4734 basaltic lunar meteorite

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    We report the petrography, mineralogy, trace element abundance geochemistry, and Pb–Pb geochronology of the lunar meteorite Northwest Africa (NWA) 4734 and make a comparison with the LaPaz Icefield (LAP) 02205/02224 low-Ti lunar basaltic meteorites. NWA 4734 is an unbrecciated low-Ti mare basalt composed mainly of subophitic-textured pyroxene (60 vol%) and plagioclase (30%). Pyroxene, plagioclase, and olivine exhibit large compositional variations and intra-grain chemical zoning. Pyroxene and plagioclase in NWA 4734 have rare earth element (REE) concentrations and patterns similar to those of the LAPs. The crystallization age of NWA 4734, determined in situ in baddeleyite, is 3073 ± 15 Ma (2σ), nearly identical to that of the LAPs (3039 ± 12 Ma). NWA 4734 and the LAPs have similar textures, modal abundances, mineral chemistry, and crystallization ages, and are most likely source-crater paired on the Moon. One baddeleyite grain in LAP 02224 displays distinctively older and spatially variable ages, from 3349 ± 62 to 3611 ± 62 Ma (2σ), similar to another baddeleyite grain (3109 ± 29 to 3547 ± 21 Ma) reported by Zhang et al. (2010) for the same meteorite. Raman spectra, cathodoluminescence, and stoichiometric studies of the baddeleyite suggest that the two older grains were not endogenic but were trapped by the parental magma. Equilibrium partition calculation shows that the parental melt from which the NWA 4734 plagioclase crystallized has much lower REE contents than its whole rock, indicating an open system during magma evolution. NWA 4734 could have originated from a parental melt with REE concentrations similar to that of the Apollo 12 olivine basalt. The magma likely assimilated a small amount (∼4 wt%) of KREEP-rich material during its ascent through the lunar crust

    Genome-wide analysis of interactions between ATP-dependent chromatin remodeling and histone modifications

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    <p>Abstract</p> <p>Background</p> <p>ATP-dependent chromatin remodeling and the covalent modification of histones play central roles in determining chromatin structure and function. Although several specific interactions between these two activities have been elaborated, the global landscape remains to be elucidated.</p> <p>Results</p> <p>In this paper, we have developed a computational method to generate the first genome-wide landscape of interactions between ATP-dependent chromatin remodeling and the covalent modification of histones in <it>Saccharomyces cerevisiae</it>. Our method succeeds in identifying known interactions and uncovers many previously unknown interactions between these two activities. Analysis of the genome-wide picture revealed that transcription-related modifications tend to interact with more chromatin remodelers. Our results also demonstrate that most chromatin remodeling-modification interactions act via interactions of remodelers with both histone-modifying enzymes and histone residues. We also found that the co-occurrence of both modification and remodeling has significantly different influences on multiple gene features (e.g. nucleosome occupancy) compared with the presence of either one.</p> <p>Conclusion</p> <p>We gave the first genome-wide picture of ATP-dependent chromatin remodeling-histone modification interactions. We also revealed how these two activities work together to regulate chromatin structure and function. Our results suggest that distinct strategies for regulating chromatin activity are selectively employed by genes with different properties.</p
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