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Golubchik T Brueggemann AB Street T Gertz RE Spencer CC Ho T Giannoulatou E Link-Gelles R Harding RM Beall B Peto TE Moore MR Donnelly P Crook DW Bowden R 《Nature genetics》2012,44(3):352-355
Streptococcus pneumoniae ('pneumococcus') causes an estimated 14.5 million cases of serious disease and 826,000 deaths annually in children under 5 years of age(1). The highly effective introduction of the PCV7 pneumococcal vaccine in 2000 in the United States(2,3) provided an unprecedented opportunity to investigate the response of an important pathogen to widespread, vaccine-induced selective pressure. Here, we use array-based sequencing of 62 isolates from a US national monitoring program to study five independent instances of vaccine escape recombination(4), showing the simultaneous transfer of multiple and often large (up to at least 44 kb) DNA fragments. We show that one such new strain quickly became established, spreading from east to west across the United States. These observations clarify the roles of recombination and selection in the population genomics of pneumococcus and provide proof of principle of the considerable value of combining genomic and epidemiological information in the surveillance and enhanced understanding of infectious diseases. 相似文献
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The genome sequence of the rice blast fungus Magnaporthe grisea 总被引:8,自引:0,他引:8
Dean RA Talbot NJ Ebbole DJ Farman ML Mitchell TK Orbach MJ Thon M Kulkarni R Xu JR Pan H Read ND Lee YH Carbone I Brown D Oh YY Donofrio N Jeong JS Soanes DM Djonovic S Kolomiets E Rehmeyer C Li W Harding M Kim S Lebrun MH Bohnert H Coughlan S Butler J Calvo S Ma LJ Nicol R Purcell S Nusbaum C Galagan JE Birren BW 《Nature》2005,434(7036):980-986
Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation. 相似文献
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In vitro studies of muscle mitochondrial metabolism in patients with mitochondrial myopathy have identified a variety of functional defects of the mitochondrial respiratory chain, predominantly affecting complex I (NADH-CoQ reductase) or complex III (ubiquinol-cytochrome c reductase) in adult cases. These two enzymes consist of approximately 36 subunits, eight of which are encoded by mitochondrial DNA (mtDNA). The increased incidence of maternal, as opposed to paternal, transmission in familial mitochondrial myopathy suggests that these disorders may be caused by mutations of mtDNA. Multiple restriction endonuclease analysis of leukocyte mtDNA from patients with the disease, and their relatives, showed no differences in cleavage patterns between affected and unaffected individuals in any single maternal line. When muscle mtDNA was studied, nine of 25 patients were found to have two populations of muscle mtDNA, one of which had deletions of up to 7 kilobases in length. These observations demonstrate that mtDNA heteroplasmy can occur in man and that human disease may be associated with defects of the mitochondrial genome. 相似文献
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Miscunica Platica W. Harding V. P. Hollander 《Cellular and molecular life sciences : CMLS》1978,34(9):1154-1155
Summary Dithiothreitol, dithioerythritol and bacterial lipopolysaccharides increase optical absorbance and clotLimulus lysate. Purification of dithiothreitol from possible endotoxin contamination by vacuum sublimation or chromatography does not abolish the reaction with lysate. The dithiols reported active here represent the smallest molecules capable of simulating endotoxin in theLimulus test.Acknowledgments. This investigation was supported by grant No. P30 14194 and CA 12635, awarded by the National Cancer Institute, Dhew. 相似文献
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Lizarralde D Axen GJ Brown HE Fletcher JM González-Fernández A Harding AJ Holbrook WS Kent GM Paramo P Sutherland F Umhoefer PJ 《Nature》2007,448(7152):466-469
Constraints on the structure of rifted continental margins and the magmatism resulting from such rifting can help refine our understanding of the strength of the lithosphere, the state of the underlying mantle and the transition from rifting to seafloor spreading. An important structural classification of rifts is by width, with narrow rifts thought to form as necking instabilities (where extension rates outpace thermal diffusion) and wide rifts thought to require a mechanism to inhibit localization, such as lower-crustal flow in high heat-flow settings. Observations of the magmatism that results from rifting range from volcanic margins with two to three times the magmatism predicted from melting models to non-volcanic margins with almost no rift or post-rift magmatism. Such variations in magmatic activity are commonly attributed to variations in mantle temperature. Here we describe results from the PESCADOR seismic experiment in the southern Gulf of California and present crustal-scale images across three rift segments. Over short lateral distances, we observe large differences in rifting style and magmatism--from wide rifting with minor synchronous magmatism to narrow rifting in magmatically robust segments. But many of the factors believed to control structural evolution and magmatism during rifting (extension rate, mantle potential temperature and heat flow) tend to vary over larger length scales. We conclude instead that mantle depletion, rather than low mantle temperature, accounts for the observed wide, magma-poor margins, and that mantle fertility and possibly sedimentary insulation, rather than high mantle temperature, account for the observed robust rift and post-rift magmatism. 相似文献
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