1,071 research outputs found

    A gene-by-gene population genomics platform: de novo assembly, annotation and genealogical analysis of 108 representative Neisseria meningitidis genomes

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    Background: Highly parallel,‘second generation’ sequencing technologies have rapidly expanded the number of bacterial whole genome sequences available for study, permitting the emergence of the discipline of population genomics. Most of these data are publically available as unassembled short-read sequence files that require extensive processing before they can be used for analysis. The provision of data in a uniform format, which can be easily assessed for quality, linked to provenance and phenotype and used for analysis, is therefore necessary. Results: The performance of de novo short-read assembly followed by automatic annotation using the pubMLST. orgNeisseriadatabase was assessed and evaluated for 108 diverse, representative, and well-characterisedNeisseria meningitidisisolates. High-quality sequences were obtained for >99% of known meningococcal genes among the de novoassembled genomes and four resequenced genomes and less than 1% of reassembled genes had sequence discrepancies or misassembled sequences. A core genome of 1600 loci, present in at least 95% of the population, was determined using the Genome Comparator tool. Genealogical relationships compatible with, but at a higher resolution than, those identified by multilocus sequence typing were obtained with core genome comparisons and ribosomal protein gene analysis which revealed a genomic structure for a number of previously described phenotypes. This unified system for cataloguing Neisseria genetic variation in the genome was implemented and used for multiple analyses and the data are publically available in the PubMLST Neisseria database. Conclusions: The de novo assembly, combined with automated gene-by-gene annotation, generates high quality draft genomes in which the majority of protein-encoding genes are present with high accuracy. The approach catalogues diversity efficiently, permits analyses of a single genome or multiple genome comparisons, and is a practical approach to interpreting WGS data for large bacterial population samples. The method generates novel insights into the biology of the meningococcus and improves our understanding of the whole population structure, not just disease causing lineages.</p

    Bacteriocin-mediated competition in cystic fibrosis lung infections

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    Bacteriocins are toxins produced by bacteria to kill competitors of the same species. Theory and laboratory experiments suggest that bacteriocin production and immunity play a key role in the competitive dynamics of bacterial strains. The extent to which this is the case in natural populations, especially human pathogens, remains to be tested. We examined the role of bacteriocins in competition using Pseudomonas aeruginosa strains infecting lungs of humans with cystic fibrosis (CF). We assessed the ability of different strains to kill each other using phenotypic assays, and sequenced their genomes to determine what bacteriocins (pyocins) they carry. We found that (i) isolates from later infection stages inhibited earlier infecting strains less, but were more inhibited by pyocins produced by earlier infecting strains and carried fewer pyocin types; (ii) this difference between early and late infections appears to be caused by a difference in pyocin diversity between competing genotypes and not by loss of pyocin genes within a lineage over time; (iii) pyocin inhibition does not explain why certain strains outcompete others within lung infections; (iv) strains frequently carry the pyocin-killing gene, but not the immunity gene, suggesting resistance occurs via other unknown mechanisms. Our results show that, in contrast to patterns observed in experimental studies, pyocin production does not appear to have a major influence on strain competition during CF lung infections

    Multiple Sclerosis and the Implications of Anesthesia

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    Multiple Sclerosis (MS) is an autoimmune process characterized by inflammation and demyelination of axons in the brain and spinal cord (Schneider, 2005). According to Maclean (2010), MS is one of the most common debilitating neurological disorders in young adults. My intent of this research project is to explain the pathophysiological process and become familiar with the implications of anesthesia related to MS. This research will enable me to prepare a safe, individualized anesthetic plan, taking all essential precautions when caring for a patient with multiple sclerosis

    Statistics of selectively neutral genetic variation

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    Random models of evolution are instrumental in extracting rates of microscopic evolutionary mechanisms from empirical observations on genetic variation in genome sequences. In this context it is necessary to know the statistical properties of empirical observables (such as the local homozygosity for instance). Previous work relies on numerical results or assumes Gaussian approximations for the corresponding distributions. In this paper we give an analytical derivation of the statistical properties of the local homozygosity and other empirical observables assuming selective neutrality. We find that such distributions can be very non-Gaussian.Comment: 4 pages, 4 figure

    Exactly stable non-BPS spinors in heterotic string theory on tori

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    Considering SO(32) heterotic string theory compactified on a torus of dimension 4 and less, stability of non-supersymmetric states is studied. A non-supersymmetric state with robust stability is constructed, and its exact stability is proven in a large region of moduli space against all the possible decay mechanisms allowed by charge conservation. Using various T-duality transform matrices, we translate various selection rules about conserved charges into simpler problems resembling partition and parity of integers. For heterotic string on T^4, we give a complete list of BPS atoms with elementary excitations, and we study BPS and non-BPS molecules with various binding energies. Using string-string duality, the results are interpreted in terms of Dirichlet-branes in type IIA string theory compactified on an orbifold limit of a K3 surface.Comment: 47 pages, 14 figures, LaTe

    Gauge Thresholds and Kaehler Metrics for Rigid Intersecting D-brane Models

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    The gauge threshold corrections for globally consistent Z2 x Z2' orientifolds with rigid intersecting D6-branes are computed. The one-loop corrections to the holomorphic gauge kinetic function are extracted and the Kaehler metrics for the charged chiral multiplets are determined up to two constants.Comment: 22 pages, 1 figure; v2: minor modifications, version to appear in JHE

    Observational Signatures and Non-Gaussianities of General Single Field Inflation

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    We perform a general study of primordial scalar non-Gaussianities in single field inflationary models in Einstein gravity. We consider models where the inflaton Lagrangian is an arbitrary function of the scalar field and its first derivative, and the sound speed is arbitrary. We find that under reasonable assumptions, the non-Gaussianity is completely determined by 5 parameters. In special limits of the parameter space, one finds distinctive ``shapes'' of the non-Gaussianity. In models with a small sound speed, several of these shapes would become potentially observable in the near future. Different limits of our formulae recover various previously known results.Comment: 53 pages, 5 figures; v3, minor revision, JCAP version; v4, numerical coefficients corrected in Appendix B, discussion on consistency condition revise
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