901 research outputs found

    In the Wake of the Storm: Environment, Disaster, and Race After Katrina

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    Studies evidence of environmental disparities by which poor and minority communities are disproportionately exposed to disasters, are less prepared, and have less access to relief agencies. Makes recommendations for preparedness and environmental justice

    Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

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    Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

    An examination of business occupier relocation decision making : distinguishing small and large firm behaviour

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    This paper explores how business occupiers decide whether and where to relocate. It captures the experience and behaviour of a range of sizes and types of business occupier and subjects their decision-making processes to detailed scrutiny. A linear three-stage decision model is used to sequence and structure interviews with individuals who have intimate involvement with the relocation of 28 firms and organizations in Tyne and Wear, in the north-east of England. The 'constant comparative' method is used to analyse the interview data, from which emerges 18 key concepts, comprising 51 characteristic components. Using an axial approach, these are organized into 10 cross-cutting themes that represent the main areas of consideration or influence on the thinking of the people involved in determining whether a firm or organization should relocate and, if so, where to. The resulting analysis finds that organizations adopt varying degrees of sophistication when making relocation decisions; small firms are more inclined to make decisions based on constrained information; larger organizations adopt a more complex approach. Regardless of firm size, key individuals exert considerable influence over the decision-making process and its outcome

    Inhibitors of Leishmania mexicana phosphoglycerate mutase identified by virtual screening and verified by inhibition studies

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    Cofactor-independent phosphoglycerate mutase has been proposed as a therapeutic target for the treatment of trypanosomatid diseases. In this paper, we report the identification of compounds that could potentially be developed as selective inhibitors of cofactor-independent phosphoglycerate mutase from Leishmania mexicana (LmiPGAM). Virtual screening was used in this search, as well as compounds identified by high-throughput screening. A ligand-based virtual screen programme, ultra fast shape recognition with atom types (UFSRAT), was used to screen for compounds resembling the substrate/product, before a structure-based approach was applied using AutoDock 4 and AutoDock Vina in a consensus docking scheme. In this way eight selected compounds were identified. In addition, three compounds from the Library of Pharmacologically Active Compounds (LOPAC) were selected from the published results of high-throughput screening of this library. The inhibitory effects of these compounds were tested at a fixed concentration of 1 mM. The results showed that seven compounds inhibited LmiPGAM activity and of these, two compounds (one each from high-throughput and virtual screening) showed substantial inhibition (i.e. 14% and 49% remaining activity, respectively). Taken together, the findings from this study indicate that these compounds have potential as novel inhibitors that specifically target LmiPGAM
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