951 resultados para MAP KINASES


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Background: Increasing concentrations of atmospheric greenhouse gases (GHG) and its impact on the climate has resulted in many international governments committing to reduce their GHG emissions. The UK, for example, has committed to reducing its carbon emissions by 80% by 2050. Suggested ways of reaching such a target are to increase dependency on offshore wind, offshore gas and nuclear. It is not clear, however, how the construction, operation and decommissioning of these energy systems will impact marine ecosystem services, i.e. the services obtained by people from the natural environment such as food provisioning, climate regulation and cultural inspiration. Research on ecosystem service impacts associated with offshore energy technologies is still in its infancy. The objective of this review is to bolster the evidence base by firstly, recording and describing the impacts of energy technologies at the marine ecosystems and human level in a consistent and transparent way; secondly, to translate these ecosystem and human impacts into ecosystem service impacts by using a framework to ensure consistency and comparability. The output of this process will be an objective synthesis of ecosystem service impacts comprehensive enough to cover different types of energy under the same analysis and to assist in informing how the provision of ecosystem services will change under different energy provisioning scenarios. Methods: Relevant studies will be sourced using publication databases and selected using a set of selection criteria including the identification of: (i) relevant subject populations such as marine and coastal species, marine habitat types and the general public; (ii) relevant exposure types including offshore wind farms, offshore oil and gas platforms and offshore structures connected with nuclear; (iii) relevant outcomes including changes in species structure and diversity; changes in benthic, demersal and pelagic habitats; and changes in cultural services. The impacts will be synthesised and described using a systematic map. To translate these findings into ecosystem service impacts, the Common International Classification of Ecosystem Services (CICES) and Millennium Ecosystem Assessment (MEA) frameworks are used and a detailed description of the steps taken provided to ensure transparency and replicability.

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While protein tyrosine kinases (PTKs) have been extensively characterized in eukaryotes, far less is known about their emerging counterparts in prokaryotes. Studies of close to 20 homologs of bacterial protein tyrosine (BY) kinases have inaugurated a blooming new field of research, all since just the end of the last decade. These kinases are key regulators in the polymerization and exportation of the virulence-determining polysaccharides which shield the bacterial from the non-specific defenses of the host. This research is aimed at furthering our understanding of the BY kinases through the use of X-ray crystallography and various in vitro and in vivo experiments. We reported the first crystal structure of a bacterial PTK, the C-terminal kinase domain of E. coli tyrosine kinase (Etk) at 2.5Å resolution. The fold of the Etk kinase domain differs markedly from that of eukaryotic PTKs. Based on the observed structure and supporting evidences, we proposed a unique activation mechanism for BY kinases in Gram-negative bacteria. The phosphorylation of tyrosine residue Y574 at the active site and the specific interaction of P-Y574 with a previously unidentified key arginine residue, R614, unblock the Etk active site and activate the kinase. Both in vitro kinase activity and in vivo antibiotics resistance studies utilizing structure-guided mutants further support the novel activation mechanism. In addition, the level of phosphorylation of their C-terminal Tyr cluster is known to regulate the translocation of extracellular polysaccharides. Our studies have significantly clarified our understanding of how the phosphorylation status on the C-terminal tyrosine cluster of BY kinases affects the oligomerization state of the protein, which is likely the machinery of polysaccharide export regulation. In summary, this research makes a substantial contribution to the rapidly progressing research of bacterial tyrosine kinases.

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Reality shows are TV programs which represent a format used in television nowadays; however, the observation practices of individual and/or group intimacy dates from thousands years ago. Sometimes this was driven by voyeurism or morbid fascination, some others, by the purpose of guarding, supervising and maintaining status quo. This work offers an alternative answer to the explanation of this type of TV program emergence and relates this appearance to a government procedure bound up with modern State terrorism which began at the end of the eighteenth century and has been recalled by different regimes until present days.

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Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal inflammation. This study investigated the mechanisms underlying the synergistic upregulation of preproET-1 gene expression in human mesangial cells after co-stimulation with thrombin and tumor necrosis factor alpha (TNFalpha). Whereas thrombin induced a moderate upregulation of preproET-1 mRNA, co-stimulation with TNFalpha resulted in a strong and protracted upregulation of this mRNA species. Thrombin+TNFalpha-induced upregulation of preproET-1 expression was found to require p38 mitogen-activated protein kinase and protein kinases C, whereas activation of extracellular signal-regulated kinase, c-Jun-N-terminal kinase, or intracellular Ca(2+) release were not required. Actinomycin D chase experiments suggested that enhanced stability of preproET-1 mRNA did not account for the increase in transcript levels. PreproET-1 promoter analysis demonstrated that the 5'-flanking region of preproET-1 encompassed positive regulatory elements engaged by thrombin. Negative modulation of thrombin-induced activation exerted by the distal 5' portion of preproET-1 promoter (-4.4 kbp to 204 bp) was overcome by co-stimulation with TNFalpha, providing a possible mechanism underlying the synergistic upregulation of preproET-1 expression by these two agonists. In conclusion, human mesangial cell expression of preproET-1 may be increased potently in the presence of two common proinflammatory mediators, thereby providing a potential mechanism for ET-1 production in inflammatory renal disease.

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A new universal flow map has been developed for two-phase co-current flow. The map has been successfully tested against wide variety of data. Flow regime transition predictors suggested by other authors have been shown to be useful. New transitional models are proposed for the stratified to annular regimes, blow through slug and intermittent regimes.