The fusogenic peptide HA2 impairs selectivity of CXCR4-targeted protein nanoparticles

Altres ajuts: CIBER de Bioingenierı'a, Biomateriales y Nanomedicina (project NANOPROTHER) to AV, Marato' deTV3 foundation (TV32013-3930) and ISCIII (PI15/00272, co-founding FEDER) to EV and ISCIII (PI15/00378 and PIE15/00028, co-founding FEDER), Marato' TV3 (2013-2030). UU received a Sara Borrell postdoctoral fellowship from ISCIII and AV an ICREA ACADEMIA.We demonstrate here that the genetic incorporation of the fusogenic peptide HA2 into a CXCR4-targeted protein nanoparticle dramatically reduces the specificity of the interaction between nanoparticles and cell receptors, a factor to be considered when designing tumor-homing drug vehicles displaying endosomal-escape agents. The loss of specificity is concomitant with enhanced cell penetrabilit

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Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

Funder: Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Ministry of Culture, Education and University Planning, Government of Galicia); doi: https://doi.org/10.13039/501100008425Funder: Ministerio de Educación, Cultura y Deporte (Ministry of Education, Culture and Sports, Spain); doi: https://doi.org/10.13039/501100003176Funder: EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council); doi: https://doi.org/10.13039/100010663Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Korea Health Industry Development Institute (KHIDI); doi: https://doi.org/10.13039/501100003710Funder: Danish Medical Research CouncilFunder: NIHFunder: Associazione Italiana Contro le Leucemie-Linfomi e MielomaFunder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Abstract: About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Conversational Agents for the Elderly, the Guardian Platform

ABSTRACTWith increasing of life expectancy innovative solutions that ensurewell-being of the seniors become most needed. In this context, inorder to deny the main difficulties reported by the senior public withthe use of mobile devices, we propose a technology entirely basedon voice interactions and we name this project of Guardian. Theessence of the project is to provide, through a mobile application, aplatform with a set of intelligent agents focused on the well-beingof the older adults. In this work the mains objectives to analyze andevaluate the usability of the Guardian and the cultural impacts ofthe technology. For the data collection, video recordings were used,a questionnaire that identifies the socio-technological profile of theresearch participants and the system usability scale (SUS)

Spreading the word -current status of VO tutorials and schools

With some telescopes standing still, now more than ever simple access to archival data is vital for astronomers and they need to know how to go about it. Within Eu- ropean Virtual Observatory (VO) projects, such as AIDA (2008-2010), ICE (2010- 2012), CoSADIE (2013-2015), ASTERICS (2015-2018) and ESCAPE (since 2019), we have been offering Virtual Observatory schools for many years. The aim of these schools are twofold: teaching (early career) researchers about the functionalities and possibilities within the Virtual Observatory and collecting feedback from the astronom- ical community. In addition to the VO schools on the European level, different national teams have also put effort into VO dissemination. The team at the Centre de Données astronomiques de Strasbourg (CDS) started to explore more and new ways to interact with the community: a series of blog posts on AstroBetter.com or a lunch time session at the virtual EAS meeting 2020. The Spanish VO has conducted virtual VO schools. GAVO has supported online archive workshops and maintains their Virtual Observatory Text Treasures. In this paper, we present the different formats in more detail, and report on the resulting interaction with the community as well as the estimated reach

Spreading the Word - Current Status of VO Tutorials and Schools

International audienceWith some telescopes standing still, now more than ever simple access to archival data is vital for astronomers, and they need to know how to go about it. Within European Virtual Observatory (VO) projects, such AIDA (2008-2010), ICE (2010- 2012), CoSADIE (2013-2015), ASTERICS (2015-2018) and ESCAPE (since 2019), we have been offering Virtual Observatory schools for many years. The aim of these schools are twofold: teaching (early career) researchers about the functionalities and possibilities within the Virtual Observatory and collecting feedback from the astronomical community. In addition to the VO schools on the European level, different national teams have also put effort into VO dissemination. The team at the Centre de Données astronomiques de Strasbourg (CDS) started to explore more and new ways to interact with the community: a series of blog posts on AstroBetter.com or a lunchtime session at the virtual EAS meeting 2020. The Spanish VO has conducted virtual VO schools. GAVO has supported online archive workshops and maintains their Virtual Observatory Text Treasures. In this paper, we present the different formats in more detail, and report on the resulting interaction with the community as well as the estimated reach