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      Molecular epidemiology of meningococcal disease in England and Wales 1975–1995, before the introduction of serogroup C conjugate vaccines

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          Abstract

          A comprehensive meningococcal vaccine is yet to be developed. In the absence of a vaccine that immunizes against the serogroup B capsular polysaccharide, this can only be achieved by targeting subcapsular antigens, and a number of outer-membrane proteins (OMPs) are under consideration as candidates. A major obstacle to the development of such a vaccine is the antigenic diversity of these OMPs, and obtaining population data that accurately identify and catalogue these variants is an important component of vaccine design. The recently proposed meningococcal molecular strain-typing scheme indexes the diversity of two OMPs, PorA and FetA, that are vaccine candidates, as well as the capsule and multilocus sequence type. This scheme was employed to survey 323 meningococci isolated from invasive disease in England and Wales from 1975 to 1995, before the introduction of meningococcal conjugated serogroup C polysaccharide vaccines in 1999. The eight-locus typing scheme provided high typeability (99.4 %) and discrimination (Simpson's diversity index 0.94–0.99). The data showed cycling of meningococcal genotypes and antigenic types in the absence of planned interventions. Notwithstanding high genetic and antigenic diversity, most of the isolates belonged to one of seven clonal complexes, with 11 predominant strain types. Combinations of PorA and FetA, chosen on the basis of their prevalence over time, generated vaccine recipes that included protein variants found in 80 % or more of the disease isolates for this time period. If adequate immune responses can be generated, these results suggest that control of meningococcal disease with relatively simple protein component vaccines may be possible.

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          Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms.

          Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms. To evaluate MLST, we determined the sequences of approximately 470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers. For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis. The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis. A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci. Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus. MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease. MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate. The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.
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            Principles that Govern the Folding of Protein Chains

            C ANFINSEN (1973)
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              A relativistic jetted outburst from a massive black hole fed by a tidally disrupted star

              While gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, the vast majority of MBHs are considered dormant. Occasionally, a star passing too near a MBH is torn apart by gravitational forces, leading to a bright panchromatic tidal disruption flare (TDF). While the high-energy transient Swift J164449.3+573451 ("Sw 1644+57") initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that the observations (Levan et al. 2011) suggest a sudden accretion event onto a central MBH of mass ~10^6-10^7 solar masses. We find evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 with a smaller-scale blazar. The phenomenologically novel Sw 1644+57 thus connects the study of TDFs and active galaxies, opening a new vista on disk-jet interactions in BHs and magnetic field generation and transport in accretion systems.
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                Author and article information

                Journal
                Microbiology
                mic
                Microbiology
                Society for General Microbiology
                1350-0872
                1465-2080
                April 2008
                April 2008
                : 154
                : Pt 4
                : 1170-1177
                Affiliations
                [1 ]Peter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, OX1 3SY, UK
                [2 ]Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Herts EN6 3QG, UK
                [3 ]Department of Biology, Pennsylvania State University, University Park, PA 16802, USA
                [4 ]Meningococcal Reference Unit, Health Protection Agency, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WZ, UK
                Author notes
                Correspondence: Martin C. J. Maiden: martin.maiden@ 123456zoo.ox.ac.uk

                Present address: Department of Medical Microbiology, University of Maastricht, Maastricht, The Netherlands.

                Article
                1170
                10.1099/mic.0.2007/014761-0
                2885627
                18375809
                39cb226b-63d5-4701-94b7-50fde8e8954f
                Copyright © 2008, SGM

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 November 2007
                : 15 January 2008
                : 16 January 2008
                Categories
                Pathogens and Pathogenicity

                Microbiology & Virology
                Microbiology & Virology

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