2,888 research outputs found

    Movement of IS26-Associated Antibiotic Resistance Genes Occurs via a Translocatable Unit That Includes a Single IS26 and Preferentially Inserts Adjacent to Another IS26

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    TheinsertionsequenceIS26playsakeyroleindisseminatingantibioticresistancegenesinGram-negativebacteria, forming regions containing more than one antibiotic resistance gene that are flanked by and interspersed with copies of IS26. A model presented for a second mode of IS26 movement that explains the structure of these regions involves a translocatable unit consisting of a unique DNA segment carrying an antibiotic resistance (or other) gene and a single IS copy. Structures resembling class I transposons are generated via RecA-independent incorporation of a translocatable unit next to a second IS26 such that the ISs are in direct orientation. Repeating this process would lead to arrays of resistance genes with directly oriented copies of IS26 at each end and between each unique segment. This model requires that IS26 recognizes another IS26 as a target, and in transpo- sition experiments, the frequency of cointegrate formation was 60-fold higher when the target plasmid contained IS26. This re- action was conservative, with no additional IS26 or target site duplication generated, and orientation specific as the IS26s in the cointegrates were always in the same orientation. Consequently, the cointegrates were identical to those formed via the known mode of IS26 movement when a target IS26 was not present. Intact transposase genes in both IS26s were required for high- frequency cointegrate formation as inactivation of either one reduced the frequency 30-fold. However, the IS26 target specificity was retained. Conversion of each residue in the DDE motif of the Tnp26 transposase also reduced the cointegration frequency

    Evolutionary responses to acquiring a multidrug resistance plasmid are dominated by metabolic functions across diverse <i>Escherichia coli</i> lineages

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    Multidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ~700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions. IMPORTANCE Plasmids drive the spread of antimicrobial resistance genes between bacterial genomes. However, the evolutionary processes allowing plasmids to be assimilated by diverse bacterial genomes are poorly understood, especially in clinical pathogens. Using experimental evolution with diverse E. coli lineages and a clinical multidrug resistance plasmid, we show that although plasmids drove unique evolutionary paths per lineage, there was a surprising degree of convergence in the functions targeted by mutations across lineages, dominated by metabolic functions. Remarkably, these same metabolic functions show higher evolutionary rates in MDR-lineages in nature and in some cases, like anaerobic metabolism, their expression is directly manipulated by the plasmid. Interactions with other mobile elements resident in the genomes accelerated adaptation by disrupting genes and regulatory sequences that they inserted into. Beyond their role in horizontal gene transfer, plasmids are an important selective force driving the evolution of bacterial genomes and core cellular functions

    Genetic influence on East African running success

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    East African athletes now dominate international distance running events from the 800 m to the marathon. Explanations for their phenomenal success have included optimal environmental conditions for developing distance running performance, psychological advantage and advantageous physiological characteristics. It is well established that genetics plays a role in determining inter-individual differences in exercise performance and adaptation to training stimuli. It is not known, however, to what extent inter-population differences (i.e. between &lsquo;races&rsquo; and/or ethnic groups) in exercise performance can be attributed to genetics. There have been considerations that &lsquo;black&rsquo; athletes are genetically adapted towards performance, given the concurrent success of athletes of West African ancestry in sprint events. However, the current notion of &lsquo;race&rsquo; is not universally accepted, and genetic differences within and between populations are not clearly delineated by geographical or ethnic categorizations. Recent findings from mitochondrial DNA show that the populations from which Ethiopian athletes are drawn have not been isolated populations and are not genetically distinct from other Ethiopians. Y-chromosome analysis of the same population shows concurrent results, although some differences are present between athletes and the general Ethiopian population, suggesting an influence of the Y chromosome on athlete status in Ethiopia. It is concluded that there may be a role for genetics in the success of East African athletes; however, any genetic component to their success is unlikely to be limited to East Africans and is more likely to be found in other populations. At present it is unjustified to implicate a role for genetics in the success of East African runners when no genes have been identified as being important to their performance

    Introducción : cultivando los aspectos culturales al hacer investigación

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    El objetivo de esta introducción es enmarcar dentro de la complejidad cultural de nuestro mundo contemporáneo, las 14 contribuciones incluidas en este volumen especial. No debe descuidarse la particularidad de hacer investigación cualitativa en específicos contextos locales, nacionales o de lenguaje. Se brinda una breve descripción de cada artículo para presentar este nuevo volumen sobre las prácticas cualitativas de investigación en algunas de las periferias de nuestro globalizado mundo académicoFraming the 14 contributions included in this special issue on "Advances in Qualitative Research in Ibero America" within the cultural complexity of our current world is the objective of this introduction. The particularity of doing qualitative research in specific local, national, and even language contexts should not be overlooked. A brief description of each article is provided to introduce this new issue on qualitative research practices in some of the peripheries of our globalized academic worl

    Passive solid state microdosimeter with electronic readout

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    Apparatus and method for qualitatively and quantitatively analyzing a complex radiation field are provided. A passive microdosimetry detector device records the energy deposition of incident radiation using an array of microstructure non-volatile memory devices. Each microstructure non-volatile memory device is capable of storing a predetermined initial charge without requiring a power source. A radiation particle incident to a microstructure non-volatile memory device is termed an event . Each such event may generate a charge within a sensitive volume defined by the microstructure non-volatile memory device. The charge generated within the sensitive volume alters the stored initial charge by an amount falling within a range corresponding to the energy deposited by certain particle types. Data corresponding to such charge alterations for a plurality of microstructure non-volatile memory devices within an array of such devices are presented to a qualitative analyzing device. The qualitative analyzing device converts the data to a spectral analysis of the incident radiation field by applying ICRP-recommended weighting factors to individual events or approximations thereof

    Neurocysticercosis in Radiographically Imaged Seizure Patients in U.S. Emergency Departments1

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    Neurocysticercosis appears to be on the rise in the United States, based on immigration patterns and published cases series, including reports of domestic acquisition. We used a collaborative network of U.S. emergency departments to characterize the epidemiology of neurocysticercosis in seizure patients. Data were collected prospectively at 11 university-affiliated, geographically diverse, urban U.S. emergency departments from July 1996 to September 1998. Patients with a seizure who underwent neuroimaging were included. Of the 1,801 patients enrolled in the study, 38 (2.1%) had seizures attributable to neurocysticercosis. The disease was detected in 9 of the 11 sites and was associated with Hispanic ethnicity, immigrant status, and exposure to areas where neurocysticercosis is endemic. This disease appears to be widely distributed and highly prevalent in certain populations (e.g., Hispanic patients) and areas (e.g., Southwest)
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