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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: InĂŞs Fontes; Hanna Hartikainen; Chris F. Williams; Beth Okamura;

    Background Persistent covert infections of the myxozoan, Tetracapsuloides bryosalmonae, in primary invertebrate hosts (the freshwater bryozoan, Fredericella sultana) have been proposed to represent a reservoir for proliferative kidney disease in secondary fish hosts. However, we have limited understanding of how covert infections persist and vary in bryozoan populations over time and space and how they may impact these populations. In addition, previous studies have likely underestimated covert infection prevalence. To improve our understanding of the dynamics, impacts and implications of covert infections we employed a highly sensitive polymerase chain reaction (PCR) assay and undertook the first investigation of covert infections in the field over an annual period by sampling bryozoans every 45 days from three populations within each of three rivers. Results Covert infections persisted throughout the year and prevalence varied within and between rivers, but were often > 50%. Variation in temperature and water chemistry were linked with changes in prevalence in a manner consistent with the maintenance of covert infections during periods of low productivity and thus poor growth conditions for both bryozoans and T. bryosalmonae. The presence and increased severity of covert infections reduced host growth but only when bryozoans were also investing in the production of overwintering propagules (statoblasts). However, because statoblast production is transitory, this effect is unlikely to greatly impact the capacity of bryozoan populations to act as persistent sources of infections and hence potential disease outbreaks in farmed and wild fish populations. Conclusions We demonstrate that covert infections are widespread and persist over space and time in bryozoan populations. To our knowledge, this is the first long-term study of covert infections in a field setting. Review of the results of this and previous studies enables us to identify key questions related to the ecology and evolution of covert infection strategies and associated host-parasite interactions. Parasites & Vectors, 10 (1) ISSN:1756-3305

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    Parasites & Vectors
    Article . 2017
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    Research Collection
    Article . 2017
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    DOAJ
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    Parasites & Vectors
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    Parasites & Vectors
    Article . 2017 . Peer-reviewed
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    ETH Zürich Research Collection
    Article . 2017
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      Parasites & Vectors
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      Parasites & Vectors
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      Parasites & Vectors
      Article . 2017 . Peer-reviewed
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      ETH Zürich Research Collection
      Article . 2017
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    Authors: Turqueti-Neves, Adriana; Otte, Manuel; Schwartz, Christian; Schmitt, Michaela Erika Renate; +4 Authors

    IgE-mediated activation of mast cells and basophils contributes to protective immunity against helminths but also causes allergic responses. The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells. Here, we used next generation sequencing to uncover a striking overlap between the IgE and IgG1 repertoires in helminth-infected or OVA/alum-immunized wild-type BALB/c mice. The memory IgE response after secondary infection induced a strong increase of IgE+ plasma cells in spleen and lymph nodes. In contrast, germinal center B cells did not increase during secondary infection. Unexpectedly, the memory IgE response was lost in mice where the extracellular part of IgG1 had been replaced with IgE sequences. Adoptive transfer studies revealed that IgG1+ B cells were required and sufficient to constitute the memory IgE response in recipient mice. T cell-derived IL-4/IL-13 was required for the memory IgE response but not for expansion of B cells from memory mice. Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells. Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders. Author Summary Allergic inflammation is initiated when IgE antibodies bind to high-affinity receptors on the cell surface of mast cells and basophils, thereby triggering the release of proinflammatory mediators. The development and persistence of IgE responses in vivo is poorly characterized because of the low number of IgE-producing B cells and plasma cells. Naïve mature B cells produce IgM antibodies. Upon activation, they “switch” class to produce IgG, IgA, or IgE antibodies. It is currently highly debated whether IgE-expressing B cells are generated by direct switching from IgM-expressing B cells or by sequential switching via IgG1-expressing B cells. Using next generation sequencing, we compared thousands of IgE, IgG1, and IgM sequences after immunization of mice with parasitic worms and found a striking overlap between the IgE and IgG1 repertoires. We further show that the memory IgE response to a secondary encounter with the same parasitic worms was dependent on T cell-derived cytokines. Genetically modified mice and adoptive transfers of B cells revealed that the memory IgE response is conserved at the level of IgG1-expressing B cells. These results favor the concept that bona fide IgE-expressing B cells do not exist, and memory IgE responses unfold from IgG1-expressing B cells, which undergo a secondary switch reaction and differentiation to plasma cells. This study reveals that repertoires of IgE—the class of antibody that mediates allergic reactions—closely resemble those of IgG1, suggesting that the memory IgE response unfolds from IgG1-switched B cells (and not from IgM-expressing B cells) in response to T cell-derived cytokines.

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    PLoS Biology
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    PLoS Biology
    Article . 2015 . Peer-reviewed
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    Article . 2015
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      Article . 2015 . Peer-reviewed
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      Article . 2015
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    Authors: Sanghamitra Pati; Subhashisa Swain; Mohammad Akhtar Hussain; Marjan van den Akker; +3 Authors

    OBJECTIVE: To systematically review the studies of prevalence, patterns and consequences of multimorbidity reported from South Asia.DESIGN: Systematic review.SETTING: South Asia.DATA SOURCES: Articles were retrieved from two electronic databases (PubMed and Embase) and from the relevant references lists. Methodical data extraction according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was followed. English-language studies published between 2000 and March 2015 were included.ELIGIBILITY CRITERIA: Studies addressing prevalence, consequences and patterns of multimorbidity in South Asia. Articles documenting presence of two or more chronic conditions were included in the review. The quality and risk of bias were assessed using STROBE criteria.DATA SELECTION: Two reviewers independently assessed studies for eligibility, extracted data and assessed study quality. Due to heterogeneity in methodologies among reported studies, only narrative synthesis of the results was carried out.RESULTS: Of 11 132, 61 abstracts were selected and 13 were included for final data synthesis. The number of health conditions analysed per study varied from 7 to 22, with prevalence of multimorbidity from 4.5% to 83%. The leading chronic conditions were hypertension, arthritis, diabetes, cardiac problems and skin diseases. The most frequently reported outcomes were increased healthcare utilisation, lowered physical functioning and quality of life, and psychological distress.CONCLUSIONS: Our study, a comprehensive mapping of multimorbidity research in South Asia, reveals the insufficient volume of work carried out in this domain. The published studies are inadequate to provide an indication of the magnitude of multimorbidity in these countries. Research into clinical and epidemiological aspects of multimorbidity is warranted to build up scientific evidence in this geographic region. The wide heterogeneity observed in the present review calls for greater methodological rigour while conducting these epidemiological studies.TRIAL REGISTRATION NUMBER: CRD42013005456.

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    Europe PubMed Central
    Article . 2015 . Peer-reviewed
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    BMJ Open
    Article . 2015 . Peer-reviewed
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      Europe PubMed Central
      Article . 2015 . Peer-reviewed
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    Authors: Kavousi, Javid; Goudarzi, Forough; Izadi, Mohammad; Gardner, Charlie J.;

    The conservation of biodiversity-and the vital ecosystem services it generates-is one of the greatest challenges humanity faces, yet the field faces drastic funding cuts as society realigns its priorities in the face of the COVID-19 pandemic. Here, we argue that diverting attention from conservation would, however, increase the risk of further global health crises because the emergence of novel infectious diseases is partially driven by global environmental change. As the discrepancy between conservation needs and society's willingness to pay for them grows, conservation will have to evolve to stay relevant in the age global change-induced human infectious disease. International audience

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    Authors: Felix Gremse; Marius Stärk; Josef Ehling; Jan Robert Menzel; +2 Authors

    Theranostics 6(3), 328-341 (2016). doi:10.7150/thno.13624 Published by Ivyspring, Wyoming, NSW

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    Theranostics
    Article . 2016 . Peer-reviewed
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      Theranostics
      Article . 2016 . Peer-reviewed
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    Authors: Dang, C.; Gonzalez, P.; Mesmer-dudons, N.; Bonami, J-r; +2 Authors

    AbstractRecently, Manila clam, Ruditapes philippinarum, populations have suffered mortalities in Arcachon Bay (SW France). Mortality was associated with extensive lesions of the posterior adductor muscle, which become progressively brown and calcified. Ultrastructural observations by transmission electron microscopy revealed tissue degradation with necrotized muscle fibres and granulocytomas. Unenveloped virus‐like particles (VLPs) were detected in muscle, granulocytic, epithelial and rectal cells. VLPs were abundant in the extracellular space, in the cytoplasm (free or enclosed in vesicles) and in the nucleoplasm of granulocytes. Nuclei and mitochondria of granulocytes displayed changes which suggested reactive oxygen species production and apoptosis induction. VLPs exhibited an icosahedral structure with a diameter of 25 to 35 nm. These observations suggest that the VLPs could belong to the family Picornaviridae or the Parvoviridae.

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    Journal of Fish Diseases
    Article . 2009 . Peer-reviewed
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      Journal of Fish Diseases
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    Authors: David Roquis; Julie M J Lepesant; Marion A L Picard; Michael Freitag; +5 Authors

    Background Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC). It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a similar developmental constraint (i.e. to quickly start development into a new phenotype) might use a similar system. Schistosomes are parasitic platyhelminthes that are characterized by passage through two hosts: a mollusk as intermediate host and humans or rodents as definitive host. During its development, the parasite undergoes drastic changes, most notable immediately after infection of the definitive host, i.e. during the transition from the free-swimming cercariae into adult worms. Methodology/Principal Findings We used Chromatin Immunoprecipitation followed by massive parallel sequencing (ChIP-Seq) to analyze genome-wide chromatin structure of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3, and H3K9ac) in cercariae, schistosomula and adults (available at http://genome.univ-perp.fr). We saw striking differences in chromatin structure between the developmental stages, but most importantly we found that cercariae possess a specific combination of marks at the transcription start sites (TSS) that has similarities to a structure found in ESC. We demonstrate that in cercariae no transcription occurs, and we provide evidences that cercariae do not possess large numbers of canonical stem cells. Conclusions/Significance We describe here a broad view on the epigenome of a metazoan parasite. Most notably, we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is removed during transformation into schistosomula (and stays absent in adults) and transcription is activated. In addition, shifts of H3K9 methylation and acetylation occur towards upstream and downstream of the transcriptional start site (TSS). We conclude that specific H3 modifications are a phylogenetically older and probably more general mechanism, i.e. not restricted to stem cells, to poise transcription. Since adult couples must form to cause the disease symptoms, changes in histone modifications appear to be crucial for pathogenesis and represent therefore a therapeutic target. Author Summary The blood fluke Schistosoma mansoni causes intestinal bilharzia. The parasite has a complex life cycle in which a freshwater snail serves as intermediate host from which the human infecting larvae hatch. These larvae will actively seek skin contact, penetrate through the epithelium and start developing straight away into adult worms. Development from larvae into adults needs thorough adjustment of gene expression through repositioning or modification of proteins that are associated with DNA (the chromatin). We decided to compare the chromatin of human infective larvae (cercariae), the first developmental stage after infection of the vertebrate host (schistosomula) and adults of S. mansoni. We found that cercariae possess chromatin structures (modifications of histone H3) around the beginning of genes that are very different from schistosomula and adults. We conclude that this structure serves to keep gene transcription in a poised state, i.e. transcription is initiated and can start immediately when the blocking histone modification is removed. A similar type of histone modification was found in embryonic stem cells of vertebrates and our data indicate that it is either a more ancient and/or more general means to poise transcription than previously assumed. Since many parasites possess infective stages that develop rapidly within the host, this particular chromatin structure could be a therapeutic target for a new class of antiparasitic drugs.

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    DOAJ
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    PLoS Neglected Tropical Diseases
    Article . 2015 . Peer-reviewed
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    PLoS Neglected Tropical Diseases
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      PLoS Neglected Tropical Diseases
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    Authors: Tim Schulte; Jonas Lofling; Cecilia Mikaelsson; Alexey Kikhney; +7 Authors

    Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR187-385) determined to 2.0 Å resolution. BR187-385 adopts a novel variant of the DEv-IgG fold, typical for microbial surface components recognizing adhesive matrix molecules adhesins, despite very low sequence identity. An extended β-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study also demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short β-strands, for interaction with KRT10. International audience

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    Open Biology
    Other literature type . Article . 2014 . Peer-reviewed
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    Authors: Christina Viegelmann; Lekha Menon Margassery; Jonathan Kennedy; Tong Zhang; +5 Authors

    Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge Haliclona simulans from Irish waters. Streptomyces strain SM8 extracts showed antibacterial and antifungal activity. NMR analysis of the active fractions proved that hydroxylated saturated fatty acids were the major components present in the antibacterial fractions. Antimycin compounds were initially putatively identified in the antifungal fractions using LC-Orbitrap. Their presence was later confirmed by comparison to a standard. Genomic analysis of Streptomyces sp. SM8 revealed the presence of multiple secondary metabolism gene clusters, including a gene cluster for the biosynthesis of the antifungal antimycin family of compounds. The antimycin gene cluster of Streptomyces sp. SM8 was inactivated by disruption of the antimycin biosynthesis gene antC. Extracts from this mutant strain showed loss of antimycin production and significantly less antifungal activity than the wild-type strain. Three butenolides, 4,10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (2), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (3) that had previously been reported from marine Streptomyces species were also isolated from SM8. Comparison of the extracts of Streptomyces strain SM8 and its host sponge, H. simulans, using LC-Orbitrap revealed the presence of metabolites common to both extracts, providing direct evidence linking sponge metabolites to a specific microbial symbiont.

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    Marine Drugs
    Other literature type . Article . 2014 . Peer-reviewed
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    Authors: Shrikant Patil; Moeys, Sara; Dassow, Peter Von; Huysman, Marie; +6 Authors

    Multiple sequence alignment of Spo11 proteins used in building the phylogenetic tree of Spo11, shown in Fig. 2 . (PDF 553 kb)

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    Authors: InĂŞs Fontes; Hanna Hartikainen; Chris F. Williams; Beth Okamura;

    Background Persistent covert infections of the myxozoan, Tetracapsuloides bryosalmonae, in primary invertebrate hosts (the freshwater bryozoan, Fredericella sultana) have been proposed to represent a reservoir for proliferative kidney disease in secondary fish hosts. However, we have limited understanding of how covert infections persist and vary in bryozoan populations over time and space and how they may impact these populations. In addition, previous studies have likely underestimated covert infection prevalence. To improve our understanding of the dynamics, impacts and implications of covert infections we employed a highly sensitive polymerase chain reaction (PCR) assay and undertook the first investigation of covert infections in the field over an annual period by sampling bryozoans every 45 days from three populations within each of three rivers. Results Covert infections persisted throughout the year and prevalence varied within and between rivers, but were often > 50%. Variation in temperature and water chemistry were linked with changes in prevalence in a manner consistent with the maintenance of covert infections during periods of low productivity and thus poor growth conditions for both bryozoans and T. bryosalmonae. The presence and increased severity of covert infections reduced host growth but only when bryozoans were also investing in the production of overwintering propagules (statoblasts). However, because statoblast production is transitory, this effect is unlikely to greatly impact the capacity of bryozoan populations to act as persistent sources of infections and hence potential disease outbreaks in farmed and wild fish populations. Conclusions We demonstrate that covert infections are widespread and persist over space and time in bryozoan populations. To our knowledge, this is the first long-term study of covert infections in a field setting. Review of the results of this and previous studies enables us to identify key questions related to the ecology and evolution of covert infection strategies and associated host-parasite interactions. Parasites & Vectors, 10 (1) ISSN:1756-3305

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      Parasites & Vectors
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      Article . 2017
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    Authors: Turqueti-Neves, Adriana; Otte, Manuel; Schwartz, Christian; Schmitt, Michaela Erika Renate; +4 Authors

    IgE-mediated activation of mast cells and basophils contributes to protective immunity against helminths but also causes allergic responses. The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells. Here, we used next generation sequencing to uncover a striking overlap between the IgE and IgG1 repertoires in helminth-infected or OVA/alum-immunized wild-type BALB/c mice. The memory IgE response after secondary infection induced a strong increase of IgE+ plasma cells in spleen and lymph nodes. In contrast, germinal center B cells did not increase during secondary infection. Unexpectedly, the memory IgE response was lost in mice where the extracellular part of IgG1 had been replaced with IgE sequences. Adoptive transfer studies revealed that IgG1+ B cells were required and sufficient to constitute the memory IgE response in recipient mice. T cell-derived IL-4/IL-13 was required for the memory IgE response but not for expansion of B cells from memory mice. Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells. Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders. Author Summary Allergic inflammation is initiated when IgE antibodies bind to high-affinity receptors on the cell surface of mast cells and basophils, thereby triggering the release of proinflammatory mediators. The development and persistence of IgE responses in vivo is poorly characterized because of the low number of IgE-producing B cells and plasma cells. Naïve mature B cells produce IgM antibodies. Upon activation, they “switch” class to produce IgG, IgA, or IgE antibodies. It is currently highly debated whether IgE-expressing B cells are generated by direct switching from IgM-expressing B cells or by sequential switching via IgG1-expressing B cells. Using next generation sequencing, we compared thousands of IgE, IgG1, and IgM sequences after immunization of mice with parasitic worms and found a striking overlap between the IgE and IgG1 repertoires. We further show that the memory IgE response to a secondary encounter with the same parasitic worms was dependent on T cell-derived cytokines. Genetically modified mice and adoptive transfers of B cells revealed that the memory IgE response is conserved at the level of IgG1-expressing B cells. These results favor the concept that bona fide IgE-expressing B cells do not exist, and memory IgE responses unfold from IgG1-expressing B cells, which undergo a secondary switch reaction and differentiation to plasma cells. This study reveals that repertoires of IgE—the class of antibody that mediates allergic reactions—closely resemble those of IgG1, suggesting that the memory IgE response unfolds from IgG1-switched B cells (and not from IgM-expressing B cells) in response to T cell-derived cytokines.

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    DOAJ
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    PLoS Biology
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      Article . 2015
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    Authors: Sanghamitra Pati; Subhashisa Swain; Mohammad Akhtar Hussain; Marjan van den Akker; +3 Authors

    OBJECTIVE: To systematically review the studies of prevalence, patterns and consequences of multimorbidity reported from South Asia.DESIGN: Systematic review.SETTING: South Asia.DATA SOURCES: Articles were retrieved from two electronic databases (PubMed and Embase) and from the relevant references lists. Methodical data extraction according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was followed. English-language studies published between 2000 and March 2015 were included.ELIGIBILITY CRITERIA: Studies addressing prevalence, consequences and patterns of multimorbidity in South Asia. Articles documenting presence of two or more chronic conditions were included in the review. The quality and risk of bias were assessed using STROBE criteria.DATA SELECTION: Two reviewers independently assessed studies for eligibility, extracted data and assessed study quality. Due to heterogeneity in methodologies among reported studies, only narrative synthesis of the results was carried out.RESULTS: Of 11 132, 61 abstracts were selected and 13 were included for final data synthesis. The number of health conditions analysed per study varied from 7 to 22, with prevalence of multimorbidity from 4.5% to 83%. The leading chronic conditions were hypertension, arthritis, diabetes, cardiac problems and skin diseases. The most frequently reported outcomes were increased healthcare utilisation, lowered physical functioning and quality of life, and psychological distress.CONCLUSIONS: Our study, a comprehensive mapping of multimorbidity research in South Asia, reveals the insufficient volume of work carried out in this domain. The published studies are inadequate to provide an indication of the magnitude of multimorbidity in these countries. Research into clinical and epidemiological aspects of multimorbidity is warranted to build up scientific evidence in this geographic region. The wide heterogeneity observed in the present review calls for greater methodological rigour while conducting these epidemiological studies.TRIAL REGISTRATION NUMBER: CRD42013005456.

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    Europe PubMed Central
    Article . 2015 . Peer-reviewed
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    BMJ Open
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    Authors: Kavousi, Javid; Goudarzi, Forough; Izadi, Mohammad; Gardner, Charlie J.;

    The conservation of biodiversity-and the vital ecosystem services it generates-is one of the greatest challenges humanity faces, yet the field faces drastic funding cuts as society realigns its priorities in the face of the COVID-19 pandemic. Here, we argue that diverting attention from conservation would, however, increase the risk of further global health crises because the emergence of novel infectious diseases is partially driven by global environmental change. As the discrepancy between conservation needs and society's willingness to pay for them grows, conservation will have to evolve to stay relevant in the age global change-induced human infectious disease. International audience

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    Authors: Felix Gremse; Marius Stärk; Josef Ehling; Jan Robert Menzel; +2 Authors

    Theranostics 6(3), 328-341 (2016). doi:10.7150/thno.13624 Published by Ivyspring, Wyoming, NSW

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    Theranostics
    Article . 2016 . Peer-reviewed
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      Theranostics
      Article . 2016 . Peer-reviewed
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    Authors: Dang, C.; Gonzalez, P.; Mesmer-dudons, N.; Bonami, J-r; +2 Authors

    AbstractRecently, Manila clam, Ruditapes philippinarum, populations have suffered mortalities in Arcachon Bay (SW France). Mortality was associated with extensive lesions of the posterior adductor muscle, which become progressively brown and calcified. Ultrastructural observations by transmission electron microscopy revealed tissue degradation with necrotized muscle fibres and granulocytomas. Unenveloped virus‐like particles (VLPs) were detected in muscle, granulocytic, epithelial and rectal cells. VLPs were abundant in the extracellular space, in the cytoplasm (free or enclosed in vesicles) and in the nucleoplasm of granulocytes. Nuclei and mitochondria of granulocytes displayed changes which suggested reactive oxygen species production and apoptosis induction. VLPs exhibited an icosahedral structure with a diameter of 25 to 35 nm. These observations suggest that the VLPs could belong to the family Picornaviridae or the Parvoviridae.

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    Journal of Fish Diseases
    Article . 2009 . Peer-reviewed
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      Journal of Fish Diseases
      Article . 2009 . Peer-reviewed
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    Authors: David Roquis; Julie M J Lepesant; Marion A L Picard; Michael Freitag; +5 Authors

    Background Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC). It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a similar developmental constraint (i.e. to quickly start development into a new phenotype) might use a similar system. Schistosomes are parasitic platyhelminthes that are characterized by passage through two hosts: a mollusk as intermediate host and humans or rodents as definitive host. During its development, the parasite undergoes drastic changes, most notable immediately after infection of the definitive host, i.e. during the transition from the free-swimming cercariae into adult worms. Methodology/Principal Findings We used Chromatin Immunoprecipitation followed by massive parallel sequencing (ChIP-Seq) to analyze genome-wide chromatin structure of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3, and H3K9ac) in cercariae, schistosomula and adults (available at http://genome.univ-perp.fr). We saw striking differences in chromatin structure between the developmental stages, but most importantly we found that cercariae possess a specific combination of marks at the transcription start sites (TSS) that has similarities to a structure found in ESC. We demonstrate that in cercariae no transcription occurs, and we provide evidences that cercariae do not possess large numbers of canonical stem cells. Conclusions/Significance We describe here a broad view on the epigenome of a metazoan parasite. Most notably, we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is removed during transformation into schistosomula (and stays absent in adults) and transcription is activated. In addition, shifts of H3K9 methylation and acetylation occur towards upstream and downstream of the transcriptional start site (TSS). We conclude that specific H3 modifications are a phylogenetically older and probably more general mechanism, i.e. not restricted to stem cells, to poise transcription. Since adult couples must form to cause the disease symptoms, changes in histone modifications appear to be crucial for pathogenesis and represent therefore a therapeutic target. Author Summary The blood fluke Schistosoma mansoni causes intestinal bilharzia. The parasite has a complex life cycle in which a freshwater snail serves as intermediate host from which the human infecting larvae hatch. These larvae will actively seek skin contact, penetrate through the epithelium and start developing straight away into adult worms. Development from larvae into adults needs thorough adjustment of gene expression through repositioning or modification of proteins that are associated with DNA (the chromatin). We decided to compare the chromatin of human infective larvae (cercariae), the first developmental stage after infection of the vertebrate host (schistosomula) and adults of S. mansoni. We found that cercariae possess chromatin structures (modifications of histone H3) around the beginning of genes that are very different from schistosomula and adults. We conclude that this structure serves to keep gene transcription in a poised state, i.e. transcription is initiated and can start immediately when the blocking histone modification is removed. A similar type of histone modification was found in embryonic stem cells of vertebrates and our data indicate that it is either a more ancient and/or more general means to poise transcription than previously assumed. Since many parasites possess infective stages that develop rapidly within the host, this particular chromatin structure could be a therapeutic target for a new class of antiparasitic drugs.

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    DOAJ
    Article . 2015
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    PLoS Neglected Tropical Diseases
    Article . 2015 . Peer-reviewed
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    PLoS Neglected Tropical Diseases
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      Article . 2015
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      PLoS Neglected Tropical Diseases
      Article . 2015 . Peer-reviewed
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      PLoS Neglected Tropical Diseases
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    Authors: Tim Schulte; Jonas Lofling; Cecilia Mikaelsson; Alexey Kikhney; +7 Authors

    Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR187-385) determined to 2.0 Å resolution. BR187-385 adopts a novel variant of the DEv-IgG fold, typical for microbial surface components recognizing adhesive matrix molecules adhesins, despite very low sequence identity. An extended β-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study also demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short β-strands, for interaction with KRT10. International audience

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    Open Biology
    Other literature type . Article . 2014 . Peer-reviewed
    License: Royal Society Data Sharing and Accessibility
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    Article . 2014
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    Open Biology
    Article . 2014
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    HAL-INSA Toulouse
    Article . 2014
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      Other literature type . Article . 2014 . Peer-reviewed
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      Article . 2014
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    Authors: Christina Viegelmann; Lekha Menon Margassery; Jonathan Kennedy; Tong Zhang; +5 Authors

    Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge Haliclona simulans from Irish waters. Streptomyces strain SM8 extracts showed antibacterial and antifungal activity. NMR analysis of the active fractions proved that hydroxylated saturated fatty acids were the major components present in the antibacterial fractions. Antimycin compounds were initially putatively identified in the antifungal fractions using LC-Orbitrap. Their presence was later confirmed by comparison to a standard. Genomic analysis of Streptomyces sp. SM8 revealed the presence of multiple secondary metabolism gene clusters, including a gene cluster for the biosynthesis of the antifungal antimycin family of compounds. The antimycin gene cluster of Streptomyces sp. SM8 was inactivated by disruption of the antimycin biosynthesis gene antC. Extracts from this mutant strain showed loss of antimycin production and significantly less antifungal activity than the wild-type strain. Three butenolides, 4,10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (2), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (3) that had previously been reported from marine Streptomyces species were also isolated from SM8. Comparison of the extracts of Streptomyces strain SM8 and its host sponge, H. simulans, using LC-Orbitrap revealed the presence of metabolites common to both extracts, providing direct evidence linking sponge metabolites to a specific microbial symbiont.

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    Marine Drugs
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    Authors: Shrikant Patil; Moeys, Sara; Dassow, Peter Von; Huysman, Marie; +6 Authors

    Multiple sequence alignment of Spo11 proteins used in building the phylogenetic tree of Spo11, shown in Fig. 2 . (PDF 553 kb)

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