36 research outputs found

    Identification and characterization of a novel non-structural protein of bluetongue virus

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    Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

    Genomic investigations of unexplained acute hepatitis in children

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    Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

    A Quantitative Analytical Method to Test for Salt Effects on Giant Unilamellar Vesicles

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    Today, free-standing membranes, i.e. liposomes and vesicles, are used in a multitude of applications, e.g. as drug delivery devices and artificial cell models. Because current laboratory techniques do not allow handling of large sample sizes, systematic and quantitative studies on the impact of different effectors, e.g. electrolytes, are limited. In this work, we evaluated the Hofmeister effects of ten alkali metal halides on giant unilamellar vesicles made of palmitoyloleoylphosphatidylcholine for a large sample size by combining the highly parallel water-in-oil emulsion transfer vesicle preparation method with automatic haemocytometry. We found that this new quantitative screening method is highly reliable and consistent with previously reported results. Thus, this method may provide a significant methodological advance in analysis of effects on free-standing model membranes

    A new macrofaunal limit in the deep biosphere revealed by extreme burrow depths in ancient sediments

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    Macrofauna is known to inhabit the top few 10s cm of marine sediments, with rare burrows up to two metres below the seabed. Here, we provide evidence from deep-water Permian strata for a previously unrecognised habitat up to at least 8 metres below the sediment-water interface. Infaunal organisms exploited networks of forcibly injected sand below the seabed, forming living traces and reworking sediment. This is the first record that shows sediment injections are responsible for hosting macrofaunal life metres below the contemporaneous seabed. In addition, given the widespread occurrence of thick sandy successions that accumulate in deep-water settings, macrofauna living in the deep biosphere are likely much more prevalent than considered previously. These findings should influence future sampling strategies to better constrain the depth range of infaunal animals living in modern deep-sea sands. One Sentence Summary: The living depth of infaunal macrofauna is shown to reach at least 8 metres in new habitats associated with sand injections

    Musical evolution in the lab exhibits rhythmic universals

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    Music exhibits some cross-cultural similarities, despite its variety across the world. Evidence from a broad range of human cultures suggests the existence of musical universals1, here defined as strong regularities emerging across cultures above chance. In particular, humans demonstrate a general proclivity for rhythm2, although little is known about why music is particularly rhythmic and why the same structural regularities are present in rhythms around the world. We empirically investigate the mechanisms underlying musical universals for rhythm, showing how music can evolve culturally from randomness. Human participants were asked to imitate sets of randomly generated drumming sequences and their imitation attempts became the training set for the next participants in independent transmission chains. By perceiving and imitating drumming sequences from each other, participants turned initially random sequences into rhythmically structured patterns. Drumming patterns developed into rhythms that are more structured, easier to learn, distinctive for each experimental cultural tradition and characterized by all six statistical universals found among world music1; the patterns appear to be adapted to human learning, memory and cognition. We conclude that musical rhythm partially arises from the influence of human cognitive and biological biases on the process of cultural evolution

    Enfermagem e Sindicalismo em Goiás: análise do período 1982-2004 Enfermería y Sindicalismo en Goiás: análisis del período 1982-2004 Nursing and Unionism in Goiás: analysis of the period from 1982 to 2004

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    Estudos sobre Sindicalismo e Enfermagem são bastante escassos no Brasil. Em Goiás, só encontramos uma monografia acerca do tema, o que nos levou a examinar a questão. Este trabalho tem como objetivo analisar o sindicalismo na área de enfermagem em Goiás, buscando reconstituir sua trajetória e evidenciar a ocorrência de articulações com outros sindicatos. A metodologia empregada (qualitativa) embasa-se na História Nova, com o emprego de fontes primárias (entrevistas e documentos originais) e secundárias. As respostas obtidas demonstraram que alguns sindicatos são mais atuantes que outros e que as diferentes possibilidades de afiliação contribuem para enfraquecer o Sindicato dos Enfermeiros de Goiás.<br>Estúdios con respecto al Sindicalismo y Enfermería son bastante raros en el Brasil. En Goiás, sólo encontramos una monografia acerca del tema, lo que nos llevou a examinar esta cuestión. Este trabajo tiene como objetivo analizar el sindicalismo en la área de la enfermería en Goiás, procurando reconstruir su trayectoria y evidenciar la ocurrencia de las articulaciones con otros sindicatos. La metodología utilzada basease en la Historia Nueva, con lo empleo de fuentes primarias y secundarias. Las respuestas obtenidas demonstráron que algunos sindicatos son más actuantes que otros y que las diferentes posibilidades de filiación contribuyen para debilitar el Sindicato de los Enfermeros de Goiás.<br>Studies about Unionism and Nursing are rare in Brazil. In Goiás, we just find out a monograph about the subject, which made us to analyze the question. The objective of this work is to analyze the Unionism of Nursing in Goiás, in search of rebuilt their trajectory and evidence the articulation with others syndicates. The methodology used called "qualitative" based on New History, using primary sources (interview and originals documents) and secondary. The answers we have got showed that some syndicates are much skilled than others and the different possibilities of membership helps to weaken the Union of Nurses in Goiás

    Large-scale stratigraphic architecture and sequence analysis of an early Pleistocene submarine canyon fill, Monte Ascensione succession (Peri-Adriatic basin, eastern central Italy)

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