New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

16 páginas, 8 figuras. Disponoble información suplementaria en: http://www.nature.com/srepNew strategies are needed to develop better tools to control TB, including identification of novel antigens for vaccination. Such Mtb antigens must be expressed during Mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. Using genome-wide transcriptomics of Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo expressed Mtb) antigens expressed in the lung. Quantitative expression analysis of 2,068 Mtb genes from the predicted first operons identified the most upregulated IVE-TB genes during in-vivo pulmonary infection. By further analysing high-level conservation among whole-genome sequenced Mtb-complex strains (n = 219) and algorithms predicting HLA-class-Ia and II presented epitopes, we selected the most promising IVE-TB candidate antigens. Several of these were recognized by T-cells from in-vitro Mtb-PPD and ESAT6/CFP10-positive donors by proliferation and multi-cytokine production. This was validated in an independent cohort of latently Mtb-infected individuals. Significant T-cell responses were observed in the absence of IFN-γ-production. Collectively, the results underscore the power of our novel antigen discovery approach in identifying Mtb antigens, including those that induce unconventional T-cell responses, which may provide important novel tools for TB vaccination and biomarker profiling. Our generic approach is applicable to other infectious diseases.We acknowledge funding by EC HORIZON2020 TBVAC2020 (Grant Agreement No. 643381); EC ITN FP7 VACTRAIN project (the text represents the authors’ views and does not necessarily represent a position of the Commission who will not be liable for the use made of such information), The Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038); European Research Council (ERC TB-ACCELERATE Grant Agreement No. 638553). Funding was also supplied by the Ministerio de Economía y Competitividad (Spanish Government) research grant SAF2013-43521-R, and the European Research Council (ERC) (638553-TB-ACCELERATE) (to IC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

English didactics in Norway - 30 years of doctoral research

This edited volume presents 30 years of English didactics research (1988-2017) in Norway. As a collection of chapters, each representing a doctoral study, the book is a complete overview of all doctoral research within the field. Each study discusses empirical, methodological and theoretical contributions, and implications for teaching English as a second or later language (L2) today. The chapters provide models and insight to master students and doctoral students about to embark on English didactics research projects. All chapters present suggestions for future research, and offer a detailed presentation of the methodology and theoretical framing of each study, as well as reviews of other research in each particular field. For the first time, research from English didactics in Norway is collected in one volume. The book is therefore invaluable to researchers of English as a school subject, to teacher educators looking to provide future teachers of English with research-based insight, and to experienced English teachers looking to develop their teaching practice in ways that are research-based and relevant. Editors are Ulrikke Rindal and Lisbeth M. Brevik at the Department of Teacher Education and School Research at the University of Oslo. Both work as teacher educators and conduct research within English didactics

Assessment of the European Climate Projections as Simulated by the Large EURO-CORDEX Regional and Global Climate Model Ensemble

This paper analyzes the ensemble of regional climate model (RCM) projections for Europe completed within the EURO-CORDEX project. Projections are available for the two greenhouse gas concentration scenarios RCP2.6 (22 members) and RCP8.5 (55 members) at 0.11° resolution from 11 RCMs driven by eight global climate models (GCMs). The RCM ensemble results are compared with the driving CMIP5 global models but also with a subset of available last generation CMIP6 projections. Maximum warming is projected by all ensembles in Northern Europe in winter, along with a maximum precipitation increase there; in summer, maximum warming occurs in the Mediterranean and Southern European regions associated with a maximum precipitation decrease. The CMIP6 ensemble shows the largest signals, both for temperature and precipitation, along with the largest inter-model spread. There is a high model consensus across the ensembles on an increase of extreme precipitation and drought frequency in the Mediterranean region. Extreme temperature indices show an increase of heat extremes and a decrease of cold extremes, with CMIP6 showing the highest values and EURO-CORDEX the finest spatial details. This data set of unprecedented size and quality will provide the basis for impact assessment and climate service activities for the European region

Assessment of the European Climate Projections as Simulated by the Large EURO-CORDEX Regional and Global Climate Model Ensemble

International audienceThis paper analyzes the ensemble of regional climate model (RCM) projections for Europe completed within the EURO CORDEX project. Projections are available for the two greenhouse gas concentration scenarios RCP2.6 (22 members) and RCP8.5 (55 members) at 0.11° resolution from 11 RCMs driven by eight global climate models (GCMs). The RCM ensemble results are compared with the driving CMIP5 global models but also with a subset of available last generation CMIP6 projections. Maximum warming is projected by all ensembles in Northern Europe in winter, along with a maximum precipitation increase there; in summer, maximum warming occurs in the Mediterranean and Southern European regions associated with a maximum precipitation decrease. The CMIP6 ensemble shows the largest signals, both for temperature and precipitation, along with the largest inter model spread. There is a high model consensus across the ensembles on an increase of extreme precipitation and drought frequency in the Mediterranean region. Extreme temperature indices show an increase of heat extremes and a decrease of cold extremes, with CMIP6 showing the highest values and EURO CORDEX the finest spatial details. This data set of unprecedented size and quality will provide the basis for impact assessment and climate service activities for the European region

Persistent pulmonary pathology after COVID‑19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase‑9

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome

Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome

Evaluation of the Large EURO-CORDEX Regional Climate Model Ensemble

International audienceThe use of regional climate model (RCM)-based projections for providing regional climate information in a research and climate service contexts is currently expanding very fast. This has been possible thanks to a considerable effort in developing comprehensive ensembles of RCM projections, especially for Europe, in the EURO-CORDEX community (Jacob et al., 2014, 2020). As of end of 2019, EURO-CORDEX has developed a set of 55 historical and scenario projections (RCP8.5) using 8 driving global climate models (GCMs) and 11 RCMs. This article presents the ensemble including its design. We target the analysis to better characterize the quality of the RCMs by providing an evaluation of these RCM simulations over a number of classical climate variables and extreme and impact-oriented indices for the period 1981-2010. For the main variables, the model simulations generally agree with observations and reanalyses. However, several systematic biases are found as well, with shared responsibilities among RCMs and GCMs: Simulations are overall too cold, too wet, and too windy compared to available observations or reanalyses. Some simulations show strong systematic biases on temperature, others on precipitation or dynamical variables, but none of the models/simulations can be defined as the best or the worst on all criteria. The article aims at supporting a proper use of these simulations within a climate services context

Evaluation of the Large EURO-CORDEX Regional Climate Model Ensemble

The use of regional climate model (RCM)-based projections for providing regional climate information in a research and climate service contexts is currently expanding very fast. This has been possible thanks to a considerable effort in developing comprehensive ensembles of RCM projections, especially for Europe, in the EURO-CORDEX community (Jacob et al., 2014, 2020). As of end of 2019, EURO-CORDEX has developed a set of 55 historical and scenario projections (RCP8.5) using 8 driving global climate models (GCMs) and 11 RCMs. This article presents the ensemble including its design. We target the analysis to better characterize the quality of the RCMs by providing an evaluation of these RCM simulations over a number of classical climate variables and extreme and impact-oriented indices for the period 1981–2010. For the main variables, the model simulations generally agree with observations and reanalyses. However, several systematic biases are found as well, with shared responsibilities among RCMs and GCMs: Simulations are overall too cold, too wet, and too windy compared to available observations or reanalyses. Some simulations show strong systematic biases on temperature, others on precipitation or dynamical variables, but none of the models/simulations can be defined as the best or the worst on all criteria. The article aims at supporting a proper use of these simulations within a climate services context