140 research outputs found

    Complacent media fails debate over ‘empire’ wars

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    Reviewed book by Nicky Hager Publication date: October, 2011 Nicky Hager's main charge in Other People’s Wars is that New Zealand’s defence and foreign affairs establishment has developed a culture where some senior officers ‘wanted to obey the government only when they agreed with it’, and otherwise ‘quietly undermined’ its policies and decisions. They believed they could ‘go to war without telling the public most of what they did’—and Hager provides convincing evidence that, for most of the last decade, they have been successful

    Macroinvertebrate responses to flow and stream temperature variability across regulated and non-regulated rivers

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    Flow regulation via impoundments threatens lotic ecosystems and the services they provide globally. Impoundments drastically alter flow and stream temperature variability within fluvial environments, but efforts to quantify ecohydrological and ecothermal responses to flow regulation in conjunction have been sparsely explored to date. This study examined macroinvertebrate community responses to river flow (discharge) and stream temperature variability across paired regulated and non-regulated systems associated with three reservoirs located in adjacent catchments. Community abundances, functional traits and biomonitoring indices were examined and ecological differences between non-regulated and regulated sites were quantified, with the most sensitive faunal response being correlated against a suite of flow and thermal indices. Regulated sites exhibited reduced low-flow variability and rapid increases in discharge during peak flows that regularly exceeded those conveyed by non-regulated sites, whilst stream temperature variability was highly congruent between sites. Macroinvertebrate functional traits were particularly sensitive to flow regulation and incorporating biomonitoring indices marginally improved the ecological discrimination between regulated and non-regulated sites. Unlike community abundances, functional traits did not vary spatially between catchments, highlighting that such information could guide the implementation of regionally uniform environmental flows. Macroinvertebrate communities responded significantly to various hydrological parameters, particularly those associated with the timing of extreme flows, but were less sensitive to thermal controls. Future research should explore ecological responses to antecedent hydrological and stream temperature variability associated with flow regulation to provide a better understanding of the underlying mechanisms driving biotic alterations, which could guide future environmental flow methodologies

    Insights into a Multidrug Resistant Escherichia coli Pathogen of the Globally Disseminated ST131 Lineage: Genome Analysis and Virulence Mechanisms

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    Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI

    Identification of IncA/C plasmid replication and maintenance genes and development of a plasmid multilocus sequence typing scheme

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    Plasmids of incompatibility group A/C (IncA/C) are becoming increasingly prevalent within pathogenic Enterobacteriaceae. They are associated with the dissemination of multiple clinically relevant resistance genes, including blaCMY and blaNDM. Current typing methods for IncA/C plasmids offer limited resolution. In this study, we present the complete sequence of a blaNDM-1-positive IncA/C plasmid, pMS6198A, isolated from a multidrug-resistant uropathogenic Escherichia coli strain. Hypersaturated transposon mutagenesis, coupled with transposon-directed insertion site sequencing (TraDIS), was employed to identify conserved genetic elements required for replication and maintenance of pMS6198A. Our analysis of TraDIS data identified roles for the replicon, including repA, a toxin-antitoxin system; two putative partitioning genes, parAB; and a putative gene, 053. Construction of mini-IncA/C plasmids and examination of their stability within E. coli confirmed that the region encompassing 053 contributes to the stable maintenance of IncA/C plasmids. Subsequently, the four major maintenance genes (repA, parAB, and 053) were used to construct a new plasmid multilocus sequence typing (PMLST) scheme for IncA/C plasmids. Application of this scheme to a database of 82 IncA/C plasmids identified 11 unique sequence types (STs), with two dominant STs. The majority of blaNDM-positive plasmids examined (15/17; 88%) fall into ST1, suggesting acquisition and subsequent expansion of this blaNDM-containing plasmid lineage. The IncA/C PMLST scheme represents a standardized tool to identify, track, and analyze the dissemination of important IncA/C plasmid lineages, particularly in the context of epidemiological studies

    Mechanisms involved in acquisition of blaNDM genes by IncA/C2 and IncFIIY plasmids

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    blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family

    Subjective and objective outcome in congenital clubfoot; a comparative study of 204 children

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    <p>Abstract</p> <p>Background</p> <p>Outcome following management of congenital talipes equinovarus (clubfoot) can be assessed in a number of ways. Bjonness stated simply that <it>"the patient is the final judge of whether he has a good foot</it>"; a purely subjective assessment. Others have employed objective measures. Combining subjective evaluation with a more objective assessment of movement and position of the foot, is likely to give a more comprehensive picture of the final result of clubfoot. The purpose of this study was to compare subjective and objective outcome following management of clubfoot, and evaluate sex differences in outcome.</p> <p>Methods</p> <p>We used a patient-administered subjective assessment of outcome following treatment of clubfoot and compared it with objective anthropometry and range of movement of the ankle to assess and compare subjective and objective outcome in clubfoot. Statistical analysis was performed using Pearson correlation coefficients. Significance was tested using Student's t-test test.</p> <p>Results</p> <p>Objective outcome can be assessed using length of the foot, calf circumference and range of movement at the ankle. These are easy to measure, reproducible, and correlate well with subjective outcome. Objective outcome is comparable for boys and girls. However, subjectively, female patients and their parents are less happy with the results of management of clubfoot.</p> <p>Conclusion</p> <p>There is a correlation between the anthropometric measures and the subjective outcome and an objective grading can be designed using foot length, calf muscle bulk and range of movement at the ankle.</p

    The host metabolite D-serine contributes to bacterial niche specificity through gene selection

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    Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

    LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer

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    Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular “nest” structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1+ TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1+ TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8+ T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy
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