A synthetic biology approach for a vaccine platform against known and newly emerging serotypes of bluetongue virus

Bluetongue is one of the major infectious diseases of ruminants and is caused by Bluetongue virus (BTV), an arbovirus existing in nature in at least 26 distinct serotypes. Here, we describe the development of a vaccine platform for BTV. The advent of synthetic biology approaches and the development of reverse genetics systems, has allowed the rapid and reliable design and production of pathogen genomes which can be subsequently manipulated for vaccine production. We describe BTV vaccines based on “synthetic” viruses in which the outer core proteins of different BTV serotypes are incorporated into a common tissue-culture adapted backbone. As a means of validation for this approach, we selected two BTV-8 synthetic reassortants and demonstrated their ability to protect sheep against virulent BTV-8 challenge. In addition, to further highlight the possibilities of genome manipulation for vaccine production, we also designed and rescued a synthetic BTV chimera containing a VP2 protein including regions derived from both BTV-1 and BTV-8. Interestingly, while the parental viruses were neutralized only by homologous antisera, the chimeric proteins could be neutralized by both BTV-1 and BTV-8 antisera. These data suggest that neutralizing epitopes are present in different areas of the BTV VP2 and likely “bivalent” strains eliciting neutralizing antibodies for multiple strains can be obtained

Portugal e a defesa europeia

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A política comum de segurança e defesa e o Conselho Europeu de Dezembro de 2013

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

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

Estudos Luso-Hispanos de História do Direito II = Estudios Luso-Hispanos de Historia del Derecho II

This book brings together a set of studies that were presented and discussed at the III Spanish-Portuguese Meeting of Law Historians. They deal with central themes of the History of Law and Institutions in Modern and Contemporary eras, with special emphasis on the peninsular territories and also on the territories that made up, at different times, the Spanish and Portuguese empires. As a whole, they contribute to broaden and deepen the historical knowledge of aspects related to justice and the administration of the territories, the functioning of institutions (courts, universities, courts) and the discussion of legal concepts central to the knowledge of the legal-political doctrine produced at different times of a vast chronological period.Este libro reúne un conjunto de estudios que fueron presentados y discutidos en el III Encuentro hispano-luso de historiadores del Derecho. Tratan temas centrales de la historia del derecho y de las instituciones en la época moderna y contemporánea, con especial énfasis en los territorios peninsulares y también en los territorios que compusieron, en distintas épocas, los imperios español y portugués. En su conjunto, contribuyen a ampliar y profundizar el conocimiento histórico de aspectos relacionados con la justicia y la administración de los territorios, el funcionamiento de las instituciones (tribunales, universidades, Cortes) y la discusión de conceptos jurídicos centrales para el conocimiento de la doctrina jurídico-política producida en distintos momentos de un vasto período cronológico. = Neste livro reúne-se um conjunto de estudos que foram apresentados e discutidos no III Encontro hispano-luso de historiadores do Direito. Neles são abordados temas centrais da história do direito e das instituições na época moderna e contemporânea, com especial incidência nos territórios peninsulares e também nos territórios que integraram, em momentos diversos, os impérios espanhol e português. No seu conjunto, contribuem para o alargamento e o aprofundamento do conhecimento histórico de aspectos ligados à justiça e à administração dos territórios, ao funcionamento das instituições (tribunais, universidades, Cortes) e à discussão de conceitos jurídicos centrais para o conhecimento da doutrina jurídico-política produzida em momentos diferentes de um vasto período cronológico

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Custos e índices econômicos de povoamentos de eucalipto do Programa Produtor Florestal no Espírito Santo

Com o objetivo de analisar a atividade de produção de madeira proveniente do Programa Produtor Florestal como alternativa econômica de investimento, foram coletados dados de custos de implantação de povoamentos de eucalipto, bem como os custos referentes à colheita e ao transporte. Os custos das atividades na fase de implantação, além dos preços da madeira (m³), foram obtidos junto à empresa Fibria S.A. Os custos de colheita e transporte foram obtidos por meio de aplicação de questionários em seis propriedades, em municípios do Sul do Estado do Espírito Santo. Todos os valores de custos e preços foram corrigidos pelo IPCA para 2014. A avaliação compreendeu a análise dos custos referentes ao processo de produção, colheita e transporte e sua participação no custo total da atividade. Também foram calculados os índices econômicos renda bruta, margem bruta, margem líquida, lucratividade e rentabilidade da atividade. Os custos com maior participação na produção foram custo da terra (34,90%), implantação (23,34%), transporte (21,09%) e colheita (20,67%). De acordo com os índices econômicos aplicados, o investimento em reflorestamento mostrou-se como uma alternativa viável economicamente para os produtores, considerando a produtividade obtida e o preço do m³ da madeira praticado pela empresa