Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects

Hermansky Pudlak type 2 syndrome (HPS2) is a rare autosomal recessive primary immune deficiency caused by mutations on b3A gene (AP3B1 gene). The defect results in the impairment of the adaptor protein 3 (AP-3) complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL) in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf) + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56brightCD162 Natural Killer (NK) cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-c production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.peer-reviewe

Genome Analyses of an Aggressive and Invasive Lineage of the Irish Potato Famine Pathogen

Pest and pathogen losses jeopardise global food security and ever since the 19th century Irish famine, potato late blight has exemplified this threat. The causal oomycete pathogen, Phytophthora infestans, undergoes major population shifts in agricultural systems via the successive emergence and migration of asexual lineages. The phenotypic and genotypic bases of these selective sweeps are largely unknown but management strategies need to adapt to reflect the changing pathogen population. Here, we used molecular markers to document the emergence of a lineage, termed 13_A2, in the European P. infestans population, and its rapid displacement of other lineages to exceed 75% of the pathogen population across Great Britain in less than three years. We show that isolates of the 13_A2 lineage are among the most aggressive on cultivated potatoes, outcompete other aggressive lineages in the field, and overcome previously effective forms of plant host resistance. Genome analyses of a 13_A2 isolate revealed extensive genetic and expression polymorphisms particularly in effector genes. Copy number variations, gene gains and losses, amino-acid replacements and changes in expression patterns of disease effector genes within the 13_A2 isolate likely contribute to enhanced virulence and aggressiveness to drive this population displacement. Importantly, 13_A2 isolates carry intact and in planta induced Avrblb1, Avrblb2 and Avrvnt1 effector genes that trigger resistance in potato lines carrying the corresponding R immune receptor genes Rpi-blb1, Rpi-blb2, and Rpi-vnt1.1. These findings point towards a strategy for deploying genetic resistance to mitigate the impact of the 13_A2 lineage and illustrate how pathogen population monitoring, combined with genome analysis, informs the management of devastating disease epidemic

Genome sequence of the necrotrophic plant pathogen Pythium ultimum reveals original pathogenicity mechanisms and effector repertoire

Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae

Analyses of genome architecture and gene expression reveal novel candidate virulence factors in the secretome of Phytophthora infestans

<p>Abstract</p> <p>Background</p> <p><it>Phytophthora infestans </it>is the most devastating pathogen of potato and a model organism for the oomycetes. It exhibits high evolutionary potential and rapidly adapts to host plants. The <it>P. infestans </it>genome experienced a repeat-driven expansion relative to the genomes of <it>Phytophthora sojae </it>and <it>Phytophthora ramorum </it>and shows a discontinuous distribution of gene density. Effector genes, such as members of the RXLR and Crinkler (CRN) families, localize to expanded, repeat-rich and gene-sparse regions of the genome. This distinct genomic environment is thought to contribute to genome plasticity and host adaptation.</p> <p>Results</p> <p>We used <it>in silico </it>approaches to predict and describe the repertoire of <it>P. infestans </it>secreted proteins (the secretome). We defined the "plastic secretome" as a subset of the genome that (i) encodes predicted secreted proteins, (ii) is excluded from genome segments orthologous to the <it>P. sojae </it>and <it>P. ramorum </it>genomes and (iii) is encoded by genes residing in gene sparse regions of <it>P. infestans </it>genome. Although including only ~3% <it>of P. infestans </it>genes, the plastic secretome contains ~62% of known effector genes and shows >2 fold enrichment in genes induced <it>in planta</it>. We highlight 19 plastic secretome genes induced <it>in planta </it>but distinct from previously described effectors. This list includes a trypsin-like serine protease, secreted oxidoreductases, small cysteine-rich proteins and repeat containing proteins that we propose to be novel candidate virulence factors.</p> <p>Conclusions</p> <p>This work revealed a remarkably diverse plastic secretome. It illustrates the value of combining genome architecture with comparative genomics to identify novel candidate virulence factors from pathogen genomes.</p

Strategic Research & Innovation Agenda for Organics and agroecology

TP Organics is one of the 40 European Technology Platforms recognized by the European Commission. Since 2007, TP Organics has been shaping research and innovation agendas to advocate for more sustainable food and farming systems in Europe based on organic and agroecological principles. The research priorities outlined in this publication are the result of intensive discussions, workshops and consultations that TP Organics held in 2018–2019. The priorities are the reflection of the knowledge and innovation needs of farmers, processors, companies, and civil society groups. They are eager to work with researchers and transform the food and farming systems of Europe. Our food and farming systems need to be climate-neutral, circular, diverse and fair. They need to be prepared for the rapid digitalisation of our economies, which brings new opportunities but also comes with risks. To achieve this, all actors need to change the way we produce and consume our food. Policy makers have a crucial role to play in this transformation. Their role is to ensure a common, integrated and holistic approach to food policy. An approach that has a long-term vision for the future, harmonizes goals, strategies and actions across sectors1, prioritizes investment for public goods and engages diverse actors in making this happen. TP Organics is convinced that research and innovation on organics and agroecology can enable the transition of our food systems towards a more sustainable future for all. The Strategic Research and Innovation Agenda shows concrete research areas and priorities that need to receive proper support at EU level, in particular through Horizon Europe, the European Partnerships and Missions as well as EIP-AGRI, in order to leverage the potential of organics and agroecology

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic.Peer reviewe