161 research outputs found

    PRS17 COSTS TO TREAT COMMUNITY-ACQUIRED PNEUMONIA EPISODES IN US ADULTS AGED 50 YEARS AND OLDER BY AGE AND RISK

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    Satellite observations of chlorophyll, phytoplankton biomass, and Ekman pumping in nonlinear mesoscale eddies

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    Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 118 (2013): 6349–6370, doi:10.1002/2013JC009027.Nonlinear mesoscale eddies can influence biogeochemical cycles in the upper ocean through vertical and horizontal advection of nutrients and marine organisms. The relative importance of these two processes depends on the polarity of an eddy (cyclones versus anticyclones) and the initial biological conditions of the fluid trapped in the core of the eddy at the time of formation. Eddies originating in the eastern South Indian Ocean are unique in that anticyclones, typically associated with downwelling, contain elevated levels of chlorophyll-a, enhanced primary production and phytoplankton communities generally associated with nutrient-replete environments. From analysis of 9 years of concurrent satellite measurements of sea surface height, chlorophyll, phytoplankton carbon, and surface stress, we present observations that suggest eddy-induced Ekman upwelling as a mechanism that is at least partly responsible for sustaining positive phytoplankton anomalies in anticyclones of the South Indian Ocean. The biological response to this eddy-induced Ekman upwelling is evident only during the Austral winter. During the Austral summer, the biological response to eddy-induced Ekman pumping occurs deep in the euphotic zone, beyond the reach of satellite observations of ocean color.This work was funded by NASA grants NNX08AI80G, NNX08AR37G, NNX10AO98G, and NNX13AD78G.2014-06-0

    Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism

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    Zymoseptoria tritici is the causative agent of Septoria tritici blotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide classes, and the rate of discovery and development of new fungicides has stalled, demanding new approaches and insights. Here we investigate a potential mechanism of targeting an important wheat pathogen Z. tritici via inhibition of N-myristoyltransferase (NMT). We characterize Z. tritici NMT biochemically for the first time, profile the in vivo Z. tritici myristoylated proteome and identify and validate the first Z. tritici NMT inhibitors. Proteomic investigation of the downstream effects of NMT inhibition identified an unusual and novel mechanism of defense against chemical toxicity in Z. tritici through the application of comparative bioinformatics to deconvolute function from the previously largely unannotated Z. tritici proteome. Research into novel fungicidal modes-of-action is essential to satisfy an urgent unmet need for novel fungicide targets, and we anticipate that this study will serve as a useful proteomics and bioinformatics resource for researchers studying Z. tritici

    Regional variations in the influence of mesoscale eddies on near-surface chlorophyll

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    Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 119 (2014): 8195–8220, doi:10.1002/2014JC010111.Eddies can influence biogeochemical cycles through a variety of mechanisms, including the excitation of vertical velocities and the horizontal advection of nutrients and ecosystems, both around the eddy periphery by rotational currents and by the trapping of fluid and subsequent transport by the eddy. In this study, we present an analysis of the influence of mesoscale ocean eddies on near-surface chlorophyll (CHL) estimated from satellite measurements of ocean color. The influences of horizontal advection, trapping, and upwelling/downwelling on CHL are analyzed in an eddy-centric frame of reference by collocating satellite observations to eddy interiors, as defined by their sea surface height signatures. The influence of mesoscale eddies on CHL varies regionally. In most boundary current regions, cyclonic eddies exhibit positive CHL anomalies and anticyclonic eddies contain negative CHL anomalies. In the interior of the South Indian Ocean, however, the opposite occurs. The various mechanisms by which eddies can influence phytoplankton communities are summarized and regions where the observed CHL response to eddies is consistent with one or more of the mechanisms are discussed. This study does not attempt to link the observed regional variability definitively to any particular mechanism but provides a global overview of how eddies influence CHL anomalies.This work was funded by NASA grants NNX08AI80G, NNX08AR37G, and NNX10AO98G. DJM gratefully acknowledges NASA grant NNX13AE47G and NSF grant OCE-1048897.2015-06-0

    Generation of Recombinant N-Linked Glycoproteins in E. coli

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    The production of N-linked recombinant glycoproteins is possible in a variety of biotechnology host cells, and more recently in the bacterial workhorse, Escherichia coli. This methods chapter will outline the components and procedures needed to produce N-linked glycoproteins in E. coli, utilizing Campylobacter jejuni glycosylation machinery, although other related genes can be used with minimal tweaks to this methodology. To ensure a successful outcome, various methods will be highlighted that can confirm glycoprotein production to a high degree of confidence, including the gold standard of mass spectrometry analysis

    Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales

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    England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000–62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch

    The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

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    Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

    Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.

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    Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation. The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones. Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b. Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed
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