42 research outputs found

    The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

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    Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica; ArgentinaFil: Assis, Juliana. FundaciĂłn Oswaldo Cruz; BrasilFil: Gomes AraĂșjo, FlĂĄvio M.. FundaciĂłn Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. FundaciĂłn Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica; ArgentinaFil: Oliveira, Guilherme. Instituto TecnolĂłgico Vale; Brasil. FundaciĂłn Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂ­a y ParasitologĂ­a MĂ©dica; Argentin

    Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro

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    Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host

    Polymorphisms in the Mitochondrial Ribosome Recycling Factor EF-G2mt/MEF2 Compromise Cell Respiratory Function and Increase Atorvastatin Toxicity

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    Mitochondrial translation, essential for synthesis of the electron transport chain complexes in the mitochondria, is governed by nuclear encoded genes. Polymorphisms within these genes are increasingly being implicated in disease and may also trigger adverse drug reactions. Statins, a class of HMG-CoA reductase inhibitors used to treat hypercholesterolemia, are among the most widely prescribed drugs in the world. However, a significant proportion of users suffer side effects of varying severity that commonly affect skeletal muscle. The mitochondria are one of the molecular targets of statins, and these drugs have been known to uncover otherwise silent mitochondrial mutations. Based on yeast genetic studies, we identify the mitochondrial translation factor MEF2 as a mediator of atorvastatin toxicity. The human ortholog of MEF2 is the Elongation Factor Gene (EF-G) 2, which has previously been shown to play a specific role in mitochondrial ribosome recycling. Using small interfering RNA (siRNA) silencing of expression in human cell lines, we demonstrate that the EF-G2mt gene is required for cell growth on galactose medium, signifying an essential role for this gene in aerobic respiration. Furthermore, EF-G2mt silenced cell lines have increased susceptibility to cell death in the presence of atorvastatin. Using yeast as a model, conserved amino acid variants, which arise from non-synonymous single nucleotide polymorphisms (SNPs) in the EF-G2mt gene, were generated in the yeast MEF2 gene. Although these mutations do not produce an obvious growth phenotype, three mutations reveal an atorvastatin-sensitive phenotype and further analysis uncovers a decreased respiratory capacity. These findings constitute the first reported phenotype associated with SNPs in the EF-G2mt gene and implicate the human EF-G2mt gene as a pharmacogenetic candidate gene for statin toxicity in humans

    State of the world’s plants and fungi 2020

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    Kew’s State of the World’s Plants and Fungi project provides assessments of our current knowledge of the diversity of plants and fungi on Earth, the global threats that they face, and the policies to safeguard them. Produced in conjunction with an international scientific symposium, Kew’s State of the World’s Plants and Fungi sets an important international standard from which we can annually track trends in the global status of plant and fungal diversity

    Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015)

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    As pesquisas sobre professores iniciantes: algumas aproximaçÔes Researches about inexperienced teachers: some approaches

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    O presente texto tem como foco as investigaçÔes sobre professores iniciantes e faz um balanço do tema a partir de pesquisas realizadas no Brasil, tendo em vista a atual tendĂȘncia dos estudos sobre essa etapa do desenvolvimento profissional do professor. Para tanto, sĂŁo analisados os trabalhos apresentados nas reuniĂ”es da ANPEd, nos anos de 2005, 2006 e 2007, e as pesquisas disponĂ­veis no banco de teses da CAPES - 2000 a 2007 (mestrado e doutorado). TambĂ©m Ă© analisada a pesquisa de Brzezinski (2006), em que foi apresentado o estado do conhecimento sobre a formação de profissionais da educação. O estudo evidencia que a maioria das pesquisas analisa o professor, focando sua prĂĄtica pedagĂłgica, a construção de sua identidade, a socialização profissional e as dificuldades encontradas. Demonstra tambĂ©m a quase inexistĂȘncia de açÔes de formação para esses professores e a necessidade das pesquisas brasileiras se dedicarem mais ao tema, que Ă© pouco explorado, se considerada a relevĂąncia dessa etapa profissional.<br>The following text focuses on the investigation into "Inexperienced Teachers" and ponders on the theme based on researches conducted in Brazil, regarding current trends about this stage of the teacher's professional development. In order to accomplish this objective, we analyzed the work presented at the ANPEd meetings in the years of 2005, 2006 and 2007 and the researches available at the CAPES Thesis Bank from 2000 to 2007 (for mastering and doctorate degrees). The research carried out by Brzezinski (2006) was also taken as an object of analysis In this research, the state of knowledge on the development of professionals working with education was presented. The study reveals that most of the researchers analyzed the teachers, focusing on their pedagogic practice, identity construction, and professional socialization, as well as on the difficulties found. It also demonstrates the nearly inexistence of development actions for those teachers and the need for further research by Brazilian specialists, since this issue has been poorly explored considering its relevance
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