95 research outputs found

    Cloning and sequence analysis of brain cDNA encoding a Xenopus D2 dopamine receptor

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    AbstractA D2 dopamine receptor pharmacologically different from the mammalian D2 receptor has previously been characterized in the amphibian Xenopus laevis. Here we report the cloning of a Xenopus D2 receptor which revealed about 75% amino acid sequence identity with its mammalian counterpart and the presence of an additional 33 amino acid sequence in the 3rd cytoplasmic loop instead of the additional 29 residues in the large form of the mammalian D2 receptor, All 7 predicted transmembrane domains are highly conserved between the Xenopus and mammalian D2 receptors, as are the 1st and 2nd intracellular loop, the 1st and 3rd extracellular loop and the carboxy-terminal portion of the receptors. The amino-terminal portion, the 2nd extracellular loop and the middle portion of the 3rd intracellular loop of these receptors, however, differ considerably, Knowledge of the locations of these regions of conservation and divergence within the D2 receptors or Xenopus and mammals will help to delineate portions of the receptor molecule that are functionally important. Interestingly, the 5-untranslated region of the Xenopus D2 receptor mRNA contains 4 small open reading frames which may affect translational efficiency

    The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease

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    Secretory leukocyte proteinase inhibitor and elafin are two low-molecular-mass elastase inhibitors that are mainly synthesized locally at mucosal sites. It is thought that their physicochemical properties allow them to efficiently inhibit target enzymes, such as neutrophil elastase, released into the interstitium. Historically, in the lung, these inhibitors were first purified from secretions of patients with chronic obstructive pulmonary disease and cystic fibrosis. This suggested that they might be important in controlling excessive neutrophil elastase release in these pathologies. They are upregulated by 'alarm signals' such as bacterial lipopolysaccharides, and cytokines such as interleukin-1 and tumor necrosis factor and have been shown to be active against Gram-positive and Gram-negative bacteria, so that they have joined the growing list of antimicrobial 'defensin-like' peptides produced by the lung. Their site of synthesis and presumed functions make them very attractive candidates as potential therapeutic agents under conditions in which the excessive release of elastase by neutrophils might be detrimental. Because of its natural tropism for the lung, the use of adenovirus-mediated gene transfer is extremely promising in such applications

    Clonality and Micro-Diversity of a Nationwide Spreading Genotype of Mycobacterium tuberculosis in Japan

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    Mycobacterium tuberculosis transmission routes can be estimated from genotypic analysis of clinical isolates from patients. In Japan, still a middle-incidence country of TB, a unique genotype strain designated as \u27M-strain\u27 has been isolated nationwide recently. To ascertain the history of the wide spread of the strain, 10 clinical isolates from different areas were subjected to genome-wide analysis based on deep sequencers. Results show that all isolates possessed common mutations to those of referential strains. The greatest number of accumulated single nucleotide variants (SNVs) from the oldest coalescence was 13 nucleotides, indicating high clonality of these isolates. When an SNV common to the isolates was used as a surrogate marker of the clone, authentic clonal isolates with variation in a reliable subset of variable number of tandem repeat (VNTR) genotyping method can be selected successfully from clinical isolates populations of M. tuberculosis. When the authentic clones can also be assigned to sub-clonal groups by SNVs derived from the genomic comparison, they are classifiable into three sub-clonal groups with a bias of geographical origins. Feedback from genomic analysis of clinical isolates of M. tuberculosis to genotypicmarkers will be an efficient strategy for the big data in various settings for public health actions against TB

    Structural, biochemical, and cell biological aspects of the serine proteinase inhibitor SKALP/Elafin/ESI

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    Contains fulltext : 21200___.PDF (publisher's version ) (Open Access

    Comparative Social Life Cycle Assessment between Battery Electric Vehicles and Internal Combustion Engine Vehicles

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    Battery electric vehicles (BEV) as opposed to internal combustion engine vehicles (ICEV) are seen as a viable solution for reducing transportation related environmental impacts. There are however advantages and disadvantages to both alternatives. Environmental life cycle assessments (LCA) are used to quantify the environmental lifecycle impact of these vehicles. The social impact for people in the value chain of these alternatives has not yet been tested. For this purpose, a social lifecycle assessment (S-LCA) can be conducted. This paper compares BEVs and ICEVs in a S-LCA according to the UNEP/SETAC guidelines, using the Product Social Impact Life Cycle Assessment database (PSILCA). It was found that overall, the ICEV seems to have lower levels of social risk related to the life cycle than the BEV has. These differences are smaller or opposite when the lifetime of both vehicles is assumed to be longer. The raw material extraction seems to be a hotspot for social risks, especially the extraction of cobalt in the Democratic Republic of Congo has high risk levels. The paper includes the assessment of a future end of life scenario where BEV batteries are recycled. Recycling could reduce the amount of social risk related to the BEV. The utility of the PSILCA for this case and the general cost sensitivity of this method was discussed. It was concluded that while the PSILCA is useful to provide insights in social risks related to a products lifecycle and uncovering hotspots, it is not very suitable to compare product systems where a high number of assumptions are made. The results of this study should therefore not be used for generalisations.Industrial Ecolog
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