Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Characterization of Systemic Disease Development and Paw Inflammation in a Susceptible Mouse Model of Mayaro Virus Infection and Validation Using X-ray Synchrotron Microtomography

Mayaro virus (MAYV) is an emerging arthropod-borne virus endemic in Latin America and the causative agent of arthritogenic febrile disease. Mayaro fever is poorly understood; thus, we established an in vivo model of infection in susceptible type-I interferon receptor-deficient mice (IFNAR−/−) to characterize the disease. MAYV inoculations in the hind paws of IFNAR−/− mice result in visible paw inflammation, evolve into a disseminated infection and involve the activation of immune responses and inflammation. The histological analysis of inflamed paws indicated edema at the dermis and between muscle fibers and ligaments. Paw edema affected multiple tissues and was associated with MAYV replication, the local production of CXCL1 and the recruitment of granulocytes and mononuclear leukocytes to muscle. We developed a semi-automated X-ray microtomography method to visualize both soft tissue and bone, allowing for the quantification of MAYV-induced paw edema in 3D with a voxel size of 69 µm3. The results confirmed early edema onset and spreading through multiple tissues in inoculated paws. In conclusion, we detailed features of MAYV-induced systemic disease and the manifestation of paw edema in a mouse model extensively used to study infection with alphaviruses. The participation of lymphocytes and neutrophils and expression of CXCL1 are key features in both systemic and local manifestations of MAYV disease

Data standardization of plant-pollinator interactions

Background: Animal pollination is an important ecosystem function and service, ensuring both the integrity of natural systems and human well-being. Although many knowledge shortfalls remain, some high-quality data sets on biological interactions are now available. The development and adoption of standards for biodiversity data and metadata has promoted great advances in biological data sharing and aggregation, supporting large-scale studies and science-based public policies. However, these standards are currently not suitable to fully support interaction data sharing. Results: Here we present a vocabulary of terms and a data model for sharing plant–pollinator interactions data based on the Darwin Core standard. The vocabulary introduces 48 new terms targeting several aspects of plant–pollinator interactions and can be used to capture information from different approaches and scales. Additionally, we provide solutions for data serialization using RDF, XML, and DwC-Archives and recommendations of existing controlled vocabularies for some of the terms. Our contribution supports open access to standardized data on plant–pollinator interactions. Conclusions: The adoption of the vocabulary would facilitate data sharing to support studies ranging from the spatial and temporal distribution of interactions to the taxonomic, phenological, functional, and phylogenetic aspects of plant–pollinator interactions. We expect to fill data and knowledge gaps, thus further enabling scientific research on the ecology and evolution of plant–pollinator communities, biodiversity conservation, ecosystem services, and the development of public policies. The proposed data model is flexible and can be adapted for sharing other types of interactions data by developing discipline-specific vocabularies of terms.Fil: Salim, José A. Universidade de Sao Paulo; BrasilFil: Saraiva, Antonio M.. Universidade de Sao Paulo; BrasilFil: Zermoglio, Paula Florencia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Recursos Naturales, Agroecologia y Desarrollo Rural. - Universidad Nacional de Rio Negro. Instituto de Investigaciones En Recursos Naturales, Agroecologia y Desarrollo Rural.; ArgentinaFil: Agostini, Kayna. Universidade Federal do São Carlos; BrasilFil: Wolowski, Marina. Universidade Federal de Alfenas; BrasilFil: Drucker, Debora P.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Soares, Filipi M.. Universidade de Sao Paulo; BrasilFil: Bergamo, Pedro J.. Jardim Botânico do Rio de Janeiro; BrasilFil: Varassin, Isabela G.. Universidade Federal do Paraná; BrasilFil: Freitas, Leandro. Jardim Botânico do Rio de Janeiro; BrasilFil: Maués, Márcia M.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Rech, Andre R.. Universidade Federal dos Vales do Jequitinhonha e Mucuri; BrasilFil: Veiga, Allan K.. Universidade de Sao Paulo; BrasilFil: Acosta, Andre L.. Instituto Tecnológico Vale; BrasilFil: Araujo, Andréa C. Universidade Federal do Mato Grosso do Sul; BrasilFil: Nogueira, Anselmo. Universidad Federal do Abc; BrasilFil: Blochtein, Betina. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Freitas, Breno M.. Universidade Estadual do Ceará; BrasilFil: Albertini, Bruno C.. Universidade de Sao Paulo; BrasilFil: Maia Silva, Camila. Universidade Federal Rural Do Semi Arido; BrasilFil: Nunes, Carlos E. P.. University of Stirling; BrasilFil: Pires, Carmen S. S.. Empresa Brasileira de Pesquisa Agropecuaria (embrapa);Fil: Dos Santos, Charles F.. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Queiroz, Elisa P.. Universidade de Sao Paulo; BrasilFil: Cartolano, Etienne A.. Universidade de Sao Paulo; BrasilFil: de Oliveira, Favízia F. Universidade Federal da Bahia; BrasilFil: Amorim, Felipe W.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Fontúrbel, Francisco E.. Pontificia Universidad Católica de Valparaíso; ChileFil: da Silva, Gleycon V.. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Consolaro, Hélder. Universidade Federal de Catalão; Brasi

Data standardization of plant–pollinator interactions

Background: Animal pollination is an important ecosystem function and service, ensuring both the integrity of natural systems and human well-being. Although many knowledge shortfalls remain, some high-quality data sets on biological interactions are now available. The development and adoption of standards for biodiversity data and metadata has promoted great advances in biological data sharing and aggregation, supporting large-scale studies and science-based public policies. However, these standards are currently not suitable to fully support interaction data sharing. Results: Here we present a vocabulary of terms and a data model for sharing plant–pollinator interactions data based on the Darwin Core standard. The vocabulary introduces 48 new terms targeting several aspects of plant–pollinator interactions and can be used to capture information from different approaches and scales. Additionally, we provide solutions for data serialization using RDF, XML, and DwC-Archives and recommendations of existing controlled vocabularies for some of the terms. Our contribution supports open access to standardized data on plant–pollinator interactions. Conclusions: The adoption of the vocabulary would facilitate data sharing to support studies ranging from the spatial and temporal distribution of interactions to the taxonomic, phenological, functional, and phylogenetic aspects of plant–pollinator interactions. We expect to fill data and knowledge gaps, thus further enabling scientific research on the ecology and evolution of plant–pollinator communities, biodiversity conservation, ecosystem services, and the development of public policies. The proposed data model is flexible and can be adapted for sharing other types of interactions data by developing discipline-specific vocabularies of termsinfo:eu-repo/semantics/publishedVersio

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC₅₀ values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective

Madagascar’s extraordinary biodiversity: Evolution, distribution, and use

Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique living laboratory for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity

Madagascar’s extraordinary biodiversity: Threats and opportunities

Madagascar's unique biota is heavily affected by human activity and is under intense threat. Here, we review the current state of knowledge on the conservation status of Madagascar's terrestrial and freshwater biodiversity by presenting data and analyses on documented and predicted species-level conservation statuses, the most prevalent and relevant threats, ex situ collections and programs, and the coverage and comprehensiveness of protected areas. The existing terrestrial protected area network in Madagascar covers 10.4% of its land area and includes at least part of the range of the majority of described native species of vertebrates with known distributions (97.1% of freshwater fishes, amphibians, reptiles, birds, and mammals combined) and plants (67.7%). The overall figures are higher for threatened species (97.7% of threatened vertebrates and 79.6% of threatened plants occurring within at least one protected area). International Union for Conservation of Nature (IUCN) Red List assessments and Bayesian neural network analyses for plants identify overexploitation of biological resources and unsustainable agriculture as themost prominent threats to biodiversity. We highlight five opportunities for action at multiple levels to ensure that conservation and ecological restoration objectives, programs, and activities take account of complex underlying and interacting factors and produce tangible benefits for the biodiversity and people of Madagascar