Exogenous WNT5A and WNT11 proteins rescue CITED2 dysfunction in mouse embryonic stem cells and zebrafish morphants

Mutations and inadequate methylation profiles of CITED2 are associated with human congenital heart disease (CHD). In mouse, Cited2 is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that Cited2 depletion in ESC affects the expression of transcription factors and cardiopoietic genes involved in early mesoderm and cardiac specification. Interestingly, the supplementation of the secretome prepared from ESC overexpressing CITED2, during the onset of differentiation, rescued the cardiogenic defects of Cited2-depleted ESC. In addition, we demonstrate that the proteins WNT5A and WNT11 held the potential for rescue. We also validated the zebrafish as a model to investigate cited2 function during development. Indeed, the microinjection of morpholinos targeting cited2 transcripts caused developmental defects recapitulating those of mice knockout models, including the increased propensity for cardiac defects and severe death rate. Importantly, the co-injection of anti-cited2 morpholinos with either CITED2 or WNT5A and WNT11 recombinant proteins corrected the developmental defects of Cited2-morphants. This study argues that defects caused by the dysfunction of Cited2 at early stages of development, including heart anomalies, may be remediable by supplementation of exogenous molecules, offering the opportunity to develop novel therapeutic strategies aiming to prevent CHD.Agência financiadora: Fundação para a Ciência e a Tecnologia (FCT) Comissão de Coordenação e Desenvolvimento Regional do Algarve (CCDR Algarve) ALG-01-0145-FEDER-28044; DFG 568/17-2 Algarve Biomedical Center (ABC) Municipio de Louléinfo:eu-repo/semantics/publishedVersio

The TRUST Principles for digital repositories.

As information and communication technology has become pervasive in our society, we are increasingly dependent on both digital data and repositories that provide access to and enable the use of such resources. Repositories must earn the trust of the communities they intend to serve and demonstrate that they are reliable and capable of appropriately managing the data they hold. Following a year-long public discussion and building on existing community consensus1, several stakeholders, representing various segments of the digital repository community, have collaboratively developed and endorsed a set of guiding principles to demonstrate digital repository trustworthiness. Transparency, Responsibility, User focus, Sustainability and Technology: the TRUST Principles provide a common framework to facilitate discussion and implementation of best practice in digital preservation by all stakeholders.Proyecto de Enlace de Biblioteca

Los principios TRUST en los repositorios digitales

Con la adopción cada vez más generalizada de las TICs en nuestra sociedad, dependemos cada vez más de los datos digitales y de los repositorios que brindan acceso a ese tipo de recursos y nos permiten utilizarlos. Los repositorios deben ganarse la confianza de las comunidades a las que pretenden brindar servicios y demostrar que son confiables y capaces de administrar adecuadamente los datos que contienen. Tras un debate público que se prolongó durante un año y en función del consenso actual de la comunidad, varias partes interesadas, que representan diversos segmentos de la comunidad de los repositorios digitales, han colaborado para desarrollar y avalar un conjunto de principios rectores, para demostrar que el repositorio digital es confiable. Estos principios abarcan la Transparencia, la Responsabilidad, el Foco en el Usuario, la Sostenibilidad y la Tecnología, y presentan un marco común para facilitar el debate y la implementación de las mejores prácticas en cuanto a preservación digital en beneficio de todas las partes interesadas.Este artículo es una traducción de: Lin, D., Crabtree, J., Dillo, I., Downs, R. R., Edmunds, R., Giaretta, D., De Giusti, M., L’Hours, H., Hugo, W., Jenkyns, R., Khodiyar, V., Martone, M. E., Mokrane, M., Navale, V., Petters, J., Sierman, B., Sokolova, D. V., Stockhause, M., & Westbrook, J. (2020). The TRUST Principles for digital repositories. Scientific Data, 7(1), 144. https://doi.org/10.1038/s41597-020-0486-7Servicio de Difusión de la Creación Intelectua

Los principios TRUST en los repositorios digitales

Con la adopción cada vez más generalizada de las TICs en nuestra sociedad, dependemos cada vez más de los datos digitales y de los repositorios que brindan acceso a ese tipo de recursos y nos permiten utilizarlos. Los repositorios deben ganarse la confianza de las comunidades a las que pretenden brindar servicios y demostrar que son confiables y capaces de administrar adecuadamente los datos que contienen. Tras un debate público que se prolongó durante un año y en función del consenso actual de la comunidad, varias partes interesadas, que representan diversos segmentos de la comunidad de los repositorios digitales, han colaborado para desarrollar y avalar un conjunto de principios rectores, para demostrar que el repositorio digital es confiable. Estos principios abarcan la Transparencia, la Responsabilidad, el Foco en el Usuario, la Sostenibilidad y la Tecnología, y presentan un marco común para facilitar el debate y la implementación de las mejores prácticas en cuanto a preservación digital en beneficio de todas las partes interesadas.Este artículo es una traducción de: Lin, D., Crabtree, J., Dillo, I., Downs, R. R., Edmunds, R., Giaretta, D., De Giusti, M., L’Hours, H., Hugo, W., Jenkyns, R., Khodiyar, V., Martone, M. E., Mokrane, M., Navale, V., Petters, J., Sierman, B., Sokolova, D. V., Stockhause, M., & Westbrook, J. (2020). The TRUST Principles for digital repositories. Scientific Data, 7(1), 144. https://doi.org/10.1038/s41597-020-0486-7Servicio de Difusión de la Creación Intelectua

Los principios TRUST en los repositorios digitales

Con la adopción cada vez más generalizada de las TICs en nuestra sociedad, dependemos cada vez más de los datos digitales y de los repositorios que brindan acceso a ese tipo de recursos y nos permiten utilizarlos. Los repositorios deben ganarse la confianza de las comunidades a las que pretenden brindar servicios y demostrar que son confiables y capaces de administrar adecuadamente los datos que contienen. Tras un debate público que se prolongó durante un año y en función del consenso actual de la comunidad, varias partes interesadas, que representan diversos segmentos de la comunidad de los repositorios digitales, han colaborado para desarrollar y avalar un conjunto de principios rectores, para demostrar que el repositorio digital es confiable. Estos principios abarcan la Transparencia, la Responsabilidad, el Foco en el Usuario, la Sostenibilidad y la Tecnología, y presentan un marco común para facilitar el debate y la implementación de las mejores prácticas en cuanto a preservación digital en beneficio de todas las partes interesadas.Este artículo es una traducción de: Lin, D., Crabtree, J., Dillo, I., Downs, R. R., Edmunds, R., Giaretta, D., De Giusti, M., L’Hours, H., Hugo, W., Jenkyns, R., Khodiyar, V., Martone, M. E., Mokrane, M., Navale, V., Petters, J., Sierman, B., Sokolova, D. V., Stockhause, M., & Westbrook, J. (2020). The TRUST Principles for digital repositories. Scientific Data, 7(1), 144. https://doi.org/10.1038/s41597-020-0486-7Servicio de Difusión de la Creación Intelectua

The Gene Ontology's Reference Genome Project: A Unified Framework for Functional Annotation across Species

The Gene Ontology (GO) is a collaborative effort that provides structured vocabularies for annotating the molecular function, biological role, and cellular location of gene products in a highly systematic way and in a species-neutral manner with the aim of unifying the representation of gene function across different organisms. Each contributing member of the GO Consortium independently associates GO terms to gene products from the organism(s) they are annotating. Here we introduce the Reference Genome project, which brings together those independent efforts into a unified framework based on the evolutionary relationships between genes in these different organisms. The Reference Genome project has two primary goals: to increase the depth and breadth of annotations for genes in each of the organisms in the project, and to create data sets and tools that enable other genome annotation efforts to infer GO annotations for homologous genes in their organisms. In addition, the project has several important incidental benefits, such as increasing annotation consistency across genome databases, and providing important improvements to the GO's logical structure and biological content

Gene Ontology annotations and resources.

The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources

The Gene Ontology: enhancements for 2011

The Gene Ontology (GO) (http://www.geneontology.org) is a community bioinformatics resource that represents gene product function through the use of structured, controlled vocabularies. The number of GO annotations of gene products has increased due to curation efforts among GO Consortium (GOC) groups, including focused literature-based annotation and ortholog-based functional inference. The GO ontologies continue to expand and improve as a result of targeted ontology development, including the introduction of computable logical definitions and development of new tools for the streamlined addition of terms to the ontology. The GOC continues to support its user community through the use of e-mail lists, social media and web-based resources

The representation of heart development in the gene ontology.

An understanding of heart development is critical in any systems biology approach to cardiovascular disease. The interpretation of data generated from high-throughput technologies (such as microarray and proteomics) is also essential to this approach. However, characterizing the role of genes in the processes underlying heart development and cardiovascular disease involves the non-trivial task of data analysis and integration of previous knowledge. The Gene Ontology (GO) Consortium provides structured controlled biological vocabularies that are used to summarize previous functional knowledge for gene products across all species. One aspect of GO describes biological processes, such as development and signaling. In order to support high-throughput cardiovascular research, we have initiated an effort to fully describe heart development in GO; expanding the number of GO terms describing heart development from 12 to over 280. This new ontology describes heart morphogenesis, the differentiation of specific cardiac cell types, and the involvement of signaling pathways in heart development. This work also aligns GO with the current views of the heart development research community and its representation in the literature. This extension of GO allows gene product annotators to comprehensively capture the genetic program leading to the developmental progression of the heart. This will enable users to integrate heart development data across species, resulting in the comprehensive retrieval of information about this subject. The revised GO structure, combined with gene product annotations, should improve the interpretation of data from high-throughput methods in a variety of cardiovascular research areas, including heart development, congenital cardiac disease, and cardiac stem cell research. Additionally, we invite the heart development community to contribute to the expansion of this important dataset for the benefit of future research in this area