Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with ...SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14. These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. In contrast, infection of K18-hACE2 transgenic mice resulted in pneumocyte damage, with viral particles and replication complexes in both type I and type II pneumocytes together with the presence of convoluted or cubic membranes; however, there was no evidence of virus replication in the conducting airways. The Syrian hamster is a useful model for the study of SARS-CoV-2 transmission and vaccination strategies, whereas infection of the K18-hCE2 transgenic mouse results in lethal disease with fatal neuroinvasion but with sparing of conducting airways.
Aim: Our aim was to evaluate the extent to which we can predict and map tree alpha diversity across broad spatial scales either by using climate and remote sensing data or by exploiting spatial ...autocorrelation patterns. Location: Tropical rain forest, West Africa and Atlantic Central Africa. Methods: Alpha diversity estimates were compiled for trees with diameter at breast height ≥ 10 cm in 573 inventory plots. Linear regression (ordinary least squares, OLS) and random forest (RF) statistical techniques were used to project alpha diversity estimates at unsampled locations using climate data and remote sensing data Moderate Resolution Imaging Spectroradiometer (MODIS), normalized difference vegetation index (NDVI), Quick Scatterometer (QSCAT), tree cover, elevation. The prediction reliabilities of OLS and RF models were evaluated using a novel approach and compared to that of a kriging model based on geographic location alone. Results: The predictive power of the kriging model was comparable to that of OLS and RF models based on climatic and remote sensing data. The three models provided congruent predictions of alpha diversity in well-sampled areas but not in poorly inventoried locations. The reliability of the predictions of all three models declined markedly with distance from points with inventory data, becoming very low at distances > 50 km. According to inventory data, Atlantic Central African forests display a higher mean alpha diversity than do West African forests. Main conclusions: The lower tree alpha diversity in West Africa than in Atlantic Central Africa may reflect a richer regional species pool in the latter. Our results emphasize and illustrate the need to test model predictions in a spatially explicit manner. Good OLS or RF model predictions from inventory data at short distance largely result from the strong spatial autocorrelation displayed by both the alpha diversity and the predictive variables rather than necessarily from causal relationships. Our results suggest that alpha diversity is driven by history rather than by the contemporary environment. Given the low predictive power of models, we call for a major effort to broaden the geographical extent and intensity of forest assessments to expand our knowledge of African rain forest diversity.
Abstract
Immunodominant T cell responses are important for virus clearance. However, the identification of immunodominant T cell peptide+HLA glycoprotein epitopes has been hindered by the extent of ...HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for new, immunodominant CD8+ T cell epitopes. The analysis targeted healthy HLA-A2+ and HLA-A2- donors. While M158A2 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three out of eight while, for the other five, prominent CD8+ T cell responses tended to focus on various peptides from the influenza nucleoprotein (NP) that were not presented by HLA-A2. In all the tested 7 A2- individuals, immunodominant responses all focused on NP. Importantly, most novel, immunodominant T cell epitopes identified by our study would not have been predicted by the current prediction programs as they are either too long or lacking typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8+ T cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.
Immunodominant T-cell responses are important for virus clearance. However, the identification of immunodominant T-cell peptide + HLA glycoprotein epitopes has been hindered by the extent of HLA ...polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for immunodominant CD8⺠T-cell specificities. The analysis targeted healthy HLA-A2⺠donors to allow comparison with responses to the well-studied influenza matrix protein 1 epitope. Although influenza matrix protein 1 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three of eight, whereas for the other five, prominent CD8⺠T-cell responses tended to focus on various peptides from the influenza nucleoprotein that were not presented by HLA-A2. Importantly, with the four immunodominant T-cell epitopes identified here, only one would have been detected by the current prediction programs. The other three peptides would have been either considered too long or classified as not containing typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8⺠T-cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.
There is no sign of saturation in accumulation of alien species (AS) introductions worldwide, additionally the rate of spread for some species has also been shown to be increasing. However, the ...challenges of gathering information on AS are recognized. Recent developments in citizen science (CS) provide an opportunity to improve data flow and knowledge on AS while ensuring effective and high quality societal engagement with the issue of IAS (Invasive Alien Species). Advances in technology, particularly on-line recording and smartphone apps, along with the development of social media, have revolutionized CS and increased connectivity while new and innovative analysis techniques are emerging to ensure appropriate management, visualization, interpretation and use and sharing of the data. In early July 2018 we launched a European CO-operation in Science and Technology (COST) Action to address multidisciplinary research questions in relation to developing and implementing CS, advancing scientific understanding of AS dynamics while informing decision-making specifically implementation of technical requirements of relevant legislation such as the EU Regulation 1143/2014 on IAS. It will also support the EU biodiversity goals and embedding science within society. The Action will explore and document approaches to establishing a European-wide CS AS network. It will embrace relevant innovations for data gathering and reporting to support the implementation of monitoring and surveillance measures, while ensuring benefits for society and citizens, through an AS CS European network. The Action will, therefore, increase levels of participation and quality of engagement with current CS initiatives, ensuring and evaluating educational value, and improve the value outcomes for potential users including citizens, scientists, alien species managers, policy-makers, local authorities, industry and other stakeholders.
Abstract
Expression of the Aire molecule is thought to be important for self-tolerance through promoting ectopic expression of tissue-specific antigens in the thymus. In the absence of Aire, animals ...develop a variety of autoimmune conditions. It is unclear whether the absence of self-peptides in the thymus effects the selection of all T cells in the thymus (because they see a different mix of self-peptides), or only allows through a few self-specific cells, without perturbing selection of other cells. Here we study the CD8+ T cell responses to two well characterized influenza virus epitopes (DbNP366 and DbPA224) in AIRE +/+ and AIRE -/- mice using single cell sequencing of T cell receptors (TCR). Studying a total of approximately 1500 TCR Vbeta sequences from 25 mice, we find no differences between the responses in the presence or absence of Aire. This suggests that the absence of Aire does not perturb selection of the majority of T cells, but instead opens a small window allowing survival of a few self-specific cells.
PDF
