10,536 research outputs found

    The genome of Spraguea lophii and the basis of host-microsporidian interactions

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    This is the final version of the article. Available from the publisher via the DOI in this record.Microsporidia are obligate intracellular parasites with the smallest known eukaryotic genomes. Although they are increasingly recognized as economically and medically important parasites, the molecular basis of microsporidian pathogenicity is almost completely unknown and no genetic manipulation system is currently available. The fish-infecting microsporidian Spraguea lophii shows one of the most striking host cell manipulations known for these parasites, converting host nervous tissue into swollen spore factories known as xenomas. In order to investigate the basis of these interactions between microsporidian and host, we sequenced and analyzed the S. lophii genome. Although, like other microsporidia, S. lophii has lost many of the protein families typical of model eukaryotes, we identified a number of gene family expansions including a family of leucine-rich repeat proteins that may represent pathogenicity factors. Building on our comparative genomic analyses, we exploited the large numbers of spores that can be obtained from xenomas to identify potential effector proteins experimentally. We used complex-mix proteomics to identify proteins released by the parasite upon germination, resulting in the first experimental isolation of putative secreted effector proteins in a microsporidian. Many of these proteins are not related to characterized pathogenicity factors or indeed any other sequences from outside the Microsporidia. However, two of the secreted proteins are members of a family of RICIN B-lectin-like proteins broadly conserved across the phylum. These proteins form syntenic clusters arising from tandem duplications in several microsporidian genomes and may represent a novel family of conserved effector proteins. These computational and experimental analyses establish S. lophii as an attractive model system for understanding the evolution of host-parasite interactions in microsporidia and suggest an important role for lineage-specific innovations and fast evolving proteins in the evolution of the parasitic microsporidian lifecycle.This work was supported by a BBSRC studentship to SEC (http://www.bbsrc.ac.uk), a Marie Curie postdoctoral fellowship to TAW (http://cordis.europa.eu/fp7/home_en.html) and a Royal Society University Research Fellowship to BAPW (http://royalsociety.org)

    Emissions from the combustion of torrefied and raw biomass fuels in a domestic heating stove

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    Biomass (pellets, briquettes, logs) are a key contributor to many countries' strategies for decarbonising heat, particularly in domestic applications. The emissions from these small devices can be high and severely impact air quality, but their levels depend on the design, control, abatement and fuel options. This paper is concerned with the last case. A comparative study shows the emissions from a domestic wood stove for three biomass fuels and their torrefied counterparts. The fuels were burned in a multi-fuel stove along with two reload batches creating continuous combustion cycles: the initial cold start data is presented but not included in averaging and calculation of emission factors. Measurements were made using an FTIR instrument for carbon and nitrogen based gaseous emissions, particulates were measured using a smoke meter with micro-quartz filters as well as a size-selective impactor to obtain the particle size distribution. Particulate emissions were significantly reduced from the torrefied fuels and this is thought to be related to their pyrolysis fingerprint, which was investigated by pyrolysis-GC–MS. NOx was slightly reduced, despite increased fuel-N after torrefaction. In addition, the reduced moisture in the torrefied fuels decreases emissions of CO and CH4 because of increased time of flaming combustion

    Perceptions of Powerlessness Are Negatively Associated with Taking Action on Climate Change: A Preregistered Replication

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    “Final publication is available from Mary Ann Liebert, Inc., publishers https://www.liebertpub.com/doi/10.1089/eco.2020.0012]”Despite segments of skepticism, the majority of the general public in most countries believe that climate change is occurring and caused by human activities. Behavior changes by individuals can reduce greenhouse gas emissions to at least some extent, but a range of psychological and economic barriers can prevent individuals from taking action. A survey of New Zealanders by Aitken, Chapman, and McClure (2011) reported that belief in human influence on climate change and the risks of climate change were positively correlated with taking action on climate change. Conversely, perceptions of powerlessness and the commons dilemma were negatively correlated with taking action on climate change. Feeling powerless was associated with placing less importance on climate change as an influence on actions. Although the study by Aitken et al. has been influential, it was exploratory in nature, had a moderate sample size, was not preregistered, and has not previously been replicated. In this study, we report a preregistered replication with a sample of 352 Australians testing four hypotheses based on Aitken et al.'s findings (as summarized above). All four hypotheses were supported, reproducing Aitken et al.'s key findingsfals

    Country planning for health interventions under development: lessons from the malaria vaccine decision-making framework and implications for other new interventions

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    Traditionally it has taken years or decades for new public health interventions targeting diseases found in developing countries to be accessible to those most in need. One reason for the delay has been insufficient anticipation of the eventual processes and evidence required for decision making by countries. This paper describes research into the anticipated processes and data needed to inform decision making on malaria vaccines, the most advanced of which is still in phase 3 trials. From 2006 to 2008, a series of country consultations in Africa led to the development of a guide to assist countries in preparing their malaria vaccine decision-making frameworks. The guide builds upon the World Health Organization’s Vaccine Introduction Guidelines. It identifies the processes and data for decisions, when they would be needed relative to the development timelines of the intervention, and where they will come from. Policy development will be supported by data (e.g. malaria disease burden; roles of other malaria interventions; malaria vaccine impact; economic and financial issues; malaria vaccine efficacy, quality and safety) as will implementation decisions (e.g. programmatic issues and socio-cultural environment). This generic guide can now be applied to any future malaria vaccine. The paper discusses the opportunities and challenges to early planning for country decision-making—from the potential for timely, evidence-informed decisions to the risks of over-promising around an intervention still under development. Careful and well-structured planning by countries is an important way to ensure that new interventions do not remain unused for years or decades after they become available

    Development of the Carers’ Alert Thermometer (CAT) to identify family carers struggling with caring for someone dying at home: a mixed method consensus study

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    Background: There is an increasing international policy direction to promote home death for dying patients which will impact on the demands placed on family carers. The early identification of carer needs and appropriate intervention can help avoid crisis situations for the carer and avoidable hospital admissions which are reported to be a global concern. The aim of the study was to explore what professionals and carers of patients with cancer and advanced progressive illness, in their last year of life, find burdensome and to develop an alert system for use by non-specialist staff. Methods: A mixed-method, multi-phased, consensus study sequentially utilising qualitative and quantitative data to develop and pilot the Carers’ Alert Thermometer (CAT). 245 people (117 carers and 128 professionals) participated in the study across a range of health and social care settings in the North West of England (2011–2014). Results: A number of key domains were identified and prioritised by consensus for inclusion in the CAT. The 8 domains fit within two overarching themes of the reported carer experience; the support needed by the carer to provide care and the support needed for the carer’s own health and well-being. The resultant CAT is an evidence-based alert thermometer consisting of 10 questions, guidance on the possible actions for each alert and space for an action plan to be jointly agreed by the assessor and carer. Preliminary piloting of the CAT has shown it to be valued, fit for purpose and it can be administered by a range of personnel. Conclusions: The CAT enables the identification of current and potential future needs so a proactive approach can be taken to supporting the carer as their role develops over time, with a view to enhancing their well-being and preventing avoidable hospital admissions; ultimately supporting patient choice to remain in their own home

    A broad distribution of the alternative oxidase in microsporidian parasites

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    Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome
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