1,830 research outputs found

    Molecular characterization of 'Candidatus Borrelia tachyglossi' (family Spirochaetaceae) in echidna ticks, Bothriocroton concolor

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    Recently, a novel species of the genus Borreliawas identified in Bothriocroton concolor and Ixodes holocyclus ticks from echidnas. Analyses of 16S rRNA and flaB genes identified three closely related genotypes of this bacterium (Borrelia sp. Aus A-C) that were unique and distinct from previously described borreliae. Phylogenetic analyses of flaB (763 bp), groEL (1537 bp), gyrB (1702 bp) and glpQ (874 bp) gene sequences and concatenated sequences (3585 bp) of three gene loci (16S rRNA, flaB and gyrB) were consistent with previous findings and confirm that this novel species of the genus Borrelia is more closely related to, yet distinct from, the Reptile-associated (REP) and Relapsing Fever (RF) groups. At the flaB locus, genotypes A, B and C shared the highest percentage sequence similarities (87.9, 88 and 87.9 %, respectively) with B.orrelia turcica (REP), whereas at the groEL and gyrB loci, these genotypes were most similar (88.2-89.4 %) to B.orrelia hermsii (RF). At the glpQ locus, genotypes A and B were most similar (85.7 and 85.4 % respectively) to Borrelia sp. Tortoise14H1 (REP). The presence of the glpQ gene, which is absent in the Lyme Borreliosis group spirochaetes, further emphasises that the novel species of the genus Borrelia characterized in the present study does not belong to this group. Phylogenetic analyses at multiple loci produced consistent topographies revealing the monophyletic grouping of this bacterium, therefore providing strong support for its species status. We propose the name 'CandidatusBorrelia tachyglossi', and hypothesize that this species of the genus Borrelia may be endemic to Australia. The pathogenic potential of this bacterium is not yet known

    Assessing the Potential Return on Investment of the Proposed UK NHS Diabetes Prevention Programme in Different Population Subgroups: An Economic Evaluation

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    Objectives: To evaluate potential return on investment of the NHS Diabetes Prevention Programme (DPP) in England, and estimate which population subgroups are likely to benefit most in terms of cost-effectiveness, cost-savings and health benefits. Design: Economic Analysis using the School for Public Health Research Diabetes Prevention Model Setting: England 2015-16 Population: Adults aged 16 or over with high risk of type 2 diabetes (HbA1c 6-6.4%). Population subgroups defined by age, sex, ethnicity, socioeconomic deprivation, baseline BMI, baseline HbA1c and working status. Interventions: The proposed NHS DPP: An intensive lifestyle intervention focussing on dietary advice, physical activity and weight loss. Comparator: No diabetes prevention intervention. Main outcome measures: Incremental costs, savings and return on investment, quality adjusted life years (QALYs), diabetes cases, cardiovascular cases and net monetary benefit from an NHS perspective. Results: Intervention costs will be recouped through NHS savings within 12 years, with net NHS saving of £1.28 over 20 years for each £1 invested. Per 100,000 DPP interventions given, 3,552 QALYs are gained. The DPP is most cost-effective and cost-saving in obese individuals, those with baseline HbA1c 6.2-6.4% and those aged 40-74. QALY gains are lower in minority ethnic and low socioeconomic status subgroups. Probabilistic sensitivity analysis suggests that there is 97% probability that the DPP will be cost-effective within 20 years. NHS savings are highly sensitive to intervention cost, effectiveness and duration of effect. Conclusions: The DPP is likely to be cost-effective and cost-saving under current assumptions. Prioritising obese individuals could create the most value for money and obtain the greatest health benefits per individual targeted. Low socioeconomic status or ethnic minority groups may gain fewer QALYs per intervention, so targeting strategies should ensure the DPP does not contribute to widening health inequalities. Further evidence is needed around the differential responsiveness of population subgroups to the DPP.

    Spindle checkpoint proteins and chromosome–microtubule attachment in budding yeast

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    Accurate chromosome segregation depends on precise regulation of mitosis by the spindle checkpoint. This checkpoint monitors the status of kinetochore–microtubule attachment and delays the metaphase to anaphase transition until all kinetochores have formed stable bipolar connections to the mitotic spindle. Components of the spindle checkpoint include the mitotic arrest defective (MAD) genes MAD1–3, and the budding uninhibited by benzimidazole (BUB) genes BUB1 and BUB3. In animal cells, all known spindle checkpoint proteins are recruited to kinetochores during normal mitoses. In contrast, we show that whereas Saccharomyces cerevisiae Bub1p and Bub3p are bound to kinetochores early in mitosis as part of the normal cell cycle, Mad1p and Mad2p are kinetochore bound only in the presence of spindle damage or kinetochore lesions that interfere with chromosome–microtubule attachment. Moreover, although Mad1p and Mad2p perform essential mitotic functions during every division cycle in mammalian cells, they are required in budding yeast only when mitosis goes awry. We propose that differences in the behavior of spindle checkpoint proteins in animal cells and budding yeast result primarily from evolutionary divergence in spindle assembly pathways

    The spindle checkpoint : Bubs, Mads, and chromosome-microtubule attachment in budding yeast

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    Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2005.Includes bibliographical references.(cont.) DNA damage response, we hypothesize that the perinuclear pool of Mad proteins may be required for spindle checkpoint-independent functions such as invoking metaphase arrest following DNA damage.The high fidelity of chromosome transmission in eukaryotes is achieved, in part, by the activity of the spindle checkpoint. This checkpoint monitors the status of chromosome-microtubule attachments and delays the onset of anaphase until all kinetochores have formed stable bipolar connections to the mitotic spindle. We have characterized the localization of the Bub and Mad spindle checkpoint proteins in Saccharomyces cerevisiae. In metazoan cells, all known spindle checkpoint proteins are recruited to kinetochores during normal mitoses. In contrast, we show that whereas S. cerevisiae Bublp and Bub3p are bound to kinetochores early in mitosis as part of the normal cell cycle, Madlp and Mad2p are kinetochore-bound only in the presence of spindle damage or kinetochore lesions that interfere with chromosome-microtubule attachment. We propose that differences in the behavior of spindle checkpoint proteins in metazoan cells and budding yeast are due primarily to evolutionary divergence in spindle assembly pathways. The spindle checkpoint proteins Madlp and Mad2p exhibit perinuclear localization in both budding yeast and metazoans. We find that the perinuclear localization of Madlp is dependent on Myosin-like proteins Mlplp and Mlp2p, two proteins that link nuclear pore complexes to the interior of the nucleus. Deletion of either MLPI or MLP2 releases Mad proteins from the nuclear periphery and allows them to associate with kinetochores during early mitosis. Ectopic binding of Madlp to kinetochores does not dramatically alter cell cycle progression, nor does loss of Madlp from the nuclear periphery appear to impair spindle checkpoint activation. However, as the Mlps have been implicated in several cellular processes, such as theby Emily S. Gillett.Ph.D

    Modeling the climate impact of Southern Hemisphere ozone depletion:the importance of the ozone dataset

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    The ozone hole is an important driver of recent Southern Hemisphere (SH) climate change, and capturing these changes is a goal of climate modeling. Most climate models are driven by off-line ozone data sets. Previous studies have shown that there is a substantial range in estimates of SH ozone depletion, but the implications of this range have not been examined systematically. We use a climate model to evaluate the difference between using the ozone forcing (Stratospheric Processes and their Role in Climate (SPARC)) used by many Intergovernmental Panel on Climate Change Fifth Assessment Report (Coupled Model Intercomparison Project) models and one at the upper end of the observed depletion estimates (Binary Database of Profiles (BDBP)). In the stratosphere, we find that austral spring/summer polar cap cooling, geopotential height decreases, and zonal wind increases in the BDBP simulations are all doubled compared to the SPARC simulations, while tropospheric responses are 20–100% larger. These results are important for studies attempting to diagnose the climate fingerprints of ozone depletion
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