Borderline personality traits mediate the relationship between low perceived social support and non-suicidal self-injury in a clinical sample of adolescents

Altres ajuts: Acord transformatiu CRUE-CSICNon-suicidal self-injury (NSSI) is a serious public health concern among adolescents, especially in clinical settings. Social support plays a critical role in the onset and maintenance of NSSI in adolescence. NSSI is closely associated with borderline personality disorder (BPD), yet no previous work has analyzed the mediating role of borderline traits in the relationship between perceived social support (PSS) and NSSI. This study aimed to address this gap

Conservation of aging and cancer epigenetic signatures across human and mouse

Aging and cancer are two interrelated processes, with aging being a major risk factor for the development of cancer. Parallel epigenetic alterations have been described for both, although differences, especially within the DNA hypomethylation scenario, have also been recently reported. While many of these observations arise from the use of mouse models, there is a lack of systematic comparisons of human and mouse epigenetic patterns in the context of disease. However, such comparisons are significant as they allow to establish the extent to which some of the observed similarities or differences arise from pre-existing species-specific epigenetic traits. Here, we have used reduced representation bisulfite sequencing to profile the brain methylomes of young and old, tumoral and non-tumoral brain samples from human and mouse. We first characterized the baseline epigenomic patterns of the species and subsequently focused on the DNA methylation alterations associated with cancer and aging. Next, we described the functional genomic and epigenomic context associated with the alterations, and finally we integrated our data to study interspecies DNA methylation levels at orthologous CpG sites. Globally, we found considerable differences between the characteristics of DNA methylation alterations in cancer and aging in both species. Moreover, we describe robust evidence for the conservation of the specific cancer and aging epigenomic signatures in human and mouse. Our observations point towards the preservation of the functional consequences of these alterations at multiple levels of genomic regulation. Finally, our analyses reveal a role for the genomic context in explaining disease- and species-specific epigenetic traits.© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution

Enhanced detection of viral RNA species using fokI-assisted digestion of DNA duplexes and DNA/RNA hybrids

The accurate detection of nucleic acids from certain biological pathogens is critical for the diagnosis of human diseases. However, amplified detection of RNA molecules from a complex sample by direct detection of RNA/DNA hybrids remains a challenge. Here, we show that type IIS endonuclease FokI is able to digest DNA duplexes and DNA/RNA hybrids when assisted by a dumbbell-like fluorescent sensing oligonucleotide. As proof of concept, we designed a battery of sensing oligonucleotides against specific regions of the SARS-CoV-2 genome and interrogated the role of FokI relaxation as a potential nicking enzyme for fluorescence signal amplification. FokI-assisted digestion of SARS-CoV-2 probes increases the detection signal of ssDNA and RNA molecules and decreases the limit of detection more than 3.5-fold as compared to conventional molecular beacon approaches. This cleavage reaction is highly specific to its target molecules, and no detection of other highly related B-coronaviruses was observed in the presence of complex RNA mixtures. In addition, the FokI-assisted reaction has a high multiplexing potential, as the combined detection of different viral RNAs, including different SARS-CoV-2 variants, was achieved in the presence of multiple combinations of fluorophores and sensing oligonucleotides. When combined with isothermal rolling circle amplification technologies, FokI-assisted digestion reduced the detection time of SARS-CoV-2 in COVID-19-positive human samples with adequate sensitivity and specificity compared to conventional reverse transcription polymerase chain reaction approaches, highlighting the potential of FokI-assisted signal amplification as a valuable sensing mechanism for the detection of human pathogens.Funding was provided by the ISCIII (COV00624 to J.R.T. andM.F.F., PI18/01527 and PI21/01067 to M.F.F.), CSIC (202020E092 to M.F.F), the European Commission NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global) and the Spanish Ministry of Science and Innovation through the Recovery, Transformation and Resilience Plan (GL2021-03-39 and GL2021-03-040), the PCTI from the Asturias Government, co-funded by 2018−2022/FEDER (IDI/2018/146 to M.F.F.), the AECC (PROYE18061FERN to M.F.F), ISPA-Janssen (048-Intramural Nov-Tevar to J.R.T.) and the IUOPA. J.R.T is supported by a JdC fellowship from the Spanish Ministry of Science and Innovation (IJC2018-36825-I). R.F.P. and P.S.O. are supported by the Severo Ochoa program (BP17-114 and BP17-165). A.P. is supported by the PFIS program (ISCIII, FI19/ 00085). J.J.A.L. is supported by the AECC fellowship. C.M. and V.L. are supported by IUOPA, and R.G.U. is supported by CIBERER.Peer reviewe

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

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Recomendaciones para la práctica de ejercicio físico en pacientes cardiópatas en edad escolar

As cardiopatías conxénitas constitúen o defecto conxénito máis frecuente, e nas últimas décadas asistimos a un importante avance no tratamento das mesmas. Este documento consiste nunha recompilación de recomendacións para a práctica da actividade física, no ámbito escolar galego, para os nenos/as entre 6 e 16 anos, portadores da maioría das cardiopatías conxénitas e familiares.Las cardiopatías congénitas constituyen el defecto congénito más frecuente, y en las últimas décadas asistimos a un importante avance en el tratamiento de las mismas. Este documento consiste en una recopilación de recomendacións para la práctica de la actividade física, en el ámbito escolar gallego, para los niños y niñas entre 6 y 16 años, portadores de la mayoría de las cardiopatías congénitas y familiares

Loss of 5hmC identifies a new type of aberrant DNA hypermethylation in glioma

Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC and 5-methylcytosine (5mC) in human primary samples from 12 non-tumoral brains and 53 gliomas. We found that the levels of 5hmC identified in non-tumoral samples were significantly reduced in gliomas. Strikingly, hypo-hydroxymethylation at 4627 (9.3%) CpG sites was associated with aberrant DNA hypermethylation and was strongly enriched in CpG island shores. The DNA regions containing these CpG sites were enriched in H3K4me2 and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. As this 5mC gain is inversely correlated with loss of 5hmC and has not been identified with classical sodium bisulfite-based technologies, we conclude that our data identifies a novel 5hmC-dependent type of aberrant DNA hypermethylation in glioma.This work has been financially supported by: the Plan Nacional de I+D+I 2013–2016/FEDER (PI15/00892 to M.F.F. and A.F.F.; RTC-2015-3393-1 to A.F.F.); the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, and the Plan Nacional de I+D+I 2008–2011/FEDER (CP11/00131 to A.F.F.); IUOPA (to G.F.B. and M.S); the Fundación Científica de la AECC (to R.G.U.); the Fundación Ramón Areces (to M.F.F); FICYT (to E.G.T., M.G.G. and A.C.); and the Asturias Regional Government (GRUPIN14-052 to M.F.F.). Work in P.M. laboratory is supported by the European Research Council (CoG-2014-646903), the Spanish Ministry of Economy-Competitiveness (SAF-SAF2013-43065), the Obra Social La Caixa-Fundaciò Josep Carreras, and the Generalitat de Catalunya. P.M. is an investigator in the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain.Peer reviewe

La gamificación en el proceso de enseñanza-aprendizaje del Derecho

Esta propuesta busca introducir la gamificación (gamification, en inglés) en el proceso de enseñanza-aprendizaje del Derecho. Su objetivo es ejecutar mecánicas de juego clásicas (sopas de letras, crucigramas, anagramas, jeroglíficos, ruletas de las palabras, criptogramas...) en un entorno no lúdico que permita a los estudiantes dirigir su propio aprendizaje y superar su desmotivación. El reto es que sus principales protagonistas, los alumnos, aprendan disfrutando. Esta gamificación se basa en una planificación pedagógica y una sistematización adecuadas de dinámicas, mecánicas y estéticas que, definiendo claramente los objetivos del aprendizaje, lo "camuflan" en un entorno imaginativo atractivo y conforme con un desafío que se ajusta a la edad y los conocimientos previos de sus destinatarios. Esta metodología innovadora es útil en la educación presencial, semi-presencial (blended), virtual (E-Learning), en aplicaciones móviles educativas de gran éxito como ClassDojo, o en reconocidas experiencias de educación online como KhanAcademy. Su epicentro es el diseño de la actividad gamificada. A este respecto, la labor de los profesores se centra en planificar bloques temáticos, compuestos cada uno entre cinco y ocho juegos inmediatos distintos (crucigramas, sopas de letras, ruletas de las palabras, anagramas, criptogramas, jeroglíficos...) que repasan los sectores más relevantes de distintas materias jurídicas, ajustándose a sus respectivos Programas, de conformidad con sus correlativas Guías Docentes. Cada uno de esos juegos, formado normalmente por diez definiciones sobre las cuestiones más importantes de cada tema, se valorará sobre un total de diez puntos (un punto por cada definición). En los juegos más complejos, de cinco definiciones, cada una tendrá un valor de dos puntos. Más en concreto, lo primero que debe hacer cada profesor es explicar al alumnado el funcionamiento y la utilización que se le va a dar a esta técnica de aprendizaje. De esta suerte, seleccionada cada una de las actividades objetivo, el docente presentará las respectivas "reglas del juego", explicando la modalidad de ejecución, su cronograma y la fecha de retroalimentación o feedback. En cuanto a la forma de ejecución, estos desafíos pueden realizarse bien presencialmente en el último cuarto hora de clase, para verificar la comprensión de conocimientos bien a modo de repaso, al final de cada unidad, para comprobar el afianzamiento de los conceptos; incluso pueden ser utilizados por el profesor a modo de práctica evaluable en el propio aula o en el campus virtual, fijando un plazo de entrega. Más aún, también es posible colgar varios juegos en el campus virtual para que los estudiantes simplemente "se entrenen" (técnica dinámica) o busquen mejorar su expediente académico (técnica mecánica recompensa). Lo básico es que el alumnado se responsabilice de su propio aprendizaje, haciendo eficaz la gamificación que aquí se presenta. Profesores y alumnos son, en esta técnica, vasos comunicantes de un mismo proyecto: la enseñanza-aprendizaje rentable y eficaz

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

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research