Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis

Long runs of homozygosity are associated with Alzheimer's disease

Altres ajuts: The Genome Research at Fundació ACE project (GR@ACE) is supported by Fundación bancaria "La Caixa," Grifols SA and Fundació ACE. L.M.R. is supported by Consejería de Salud de la Junta de Andalucía (Grant PI-0001/2017).Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer's disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [ β (CI 95%) = 0.070 (0.037-0.104); P = 3.91 × 10 −5 ; β (CI95%) = 0.043 (0.009-0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10 −16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10 −4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability

Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis.P.G.-G. (Pablo García-González) is supported by CIBERNED employment plan CNV-304-PRF-866. CIBERNED is integrated into ISCIII (Instituto de Salud Carlos III). I.d.R is supported by a national grant from the Instituto de Salud Carlos III FI20/00215. A.C. (Amanda Cano) acknowledges the support of the Spanish Ministry of Science, Innovation, and Universities under the grant Juan de la Cierva (FJC2018-036012-I). M.B. (Mercé Boada) and A.R. (Agustín Ruiz) are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240, and PI19/01301. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación—and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de hacer Europa”). Genotyping of the ACE MCI-EADB samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND). Partial funding for open access charge: Universidad de Málag

Evaluación del perfil competencial del estudiantado UCM por nivel de iniciativa emprendedora y género. Validación del Modelo Entrecomp de competencias emprendedoras

Examinar la relación entre las competencias emprendedoras propuestas por el Marco Europeo de Competencias Emprendedoras (Entrecomp) y el nivel de intención emprendedora. Se consideran las siguientes variables: sexo, estudios que realiza, si compagina trabajo y estudio, y Universidad en la que estudia

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Design and implementation of the SiSo Scale to measure situations of social difficulty. Diagnostic Tool for Social Work

Objetivo. Diseñar una escala de valoración de las situaciones de dificultad social para su aplicación en el diagnóstico profesional de los y las trabajadoras sociales. Métodos. El diseño se basa en un proceso participativo a través de una estructura de anillos concéntricos. A partir de la revisión bibliográfica se ha elaborado una escala compuesta por 6 dimensiones y 25 items, graduados en función de la intensidad de las situaciones de dificultad social. Resultados. Se presentan los aspectos que explican el alto grado de utilización de la escala: diseño conceptual y validación; co-construcción centrada en el servicio a los y las profesionales; decisiones de gestión. Conclusiones. La Escala no sustituye el diagnóstico profesional, lo complementa; permite armonizar los criterios de valoración, focalizar las áreas de intervención y valorar los procesos de cambio. El uso de escalas en el proceso de intervención contribuye al refuerzo del Trabajo Social como disciplina científica y práctica profesional.Aim. To design an assessment scale of situations of social difficulty to support social workers’ professional diagnosis. Methods. The design followed a participatory process according to a concentric ring structure. Based on a literature review, a scale was developed composed of 6 dimensions and 25 items graded according to the intensity of situations of social difficulty. Results. Aspects explaining the high level of use of the scale are presented: conceptual design and validation; co-construction focusing on service to professionals; and management decisions. Conclusions. The designed scale does not replace a professional diagnosis, it complements it; it allows harmonising the evaluation criteria, focalising on intervention areas and assessing the change processes. The use of scales during interventions contributes to reinforcing Social Work as a scientific discipline and professional practice.La Escala SiSo se ha elaborado en el marco de las convocatorias de proyectos de inclusión social del Consejería de Bienestar Social de Castilla-La Mancha, desarrolladas dentro de la ESTRATEGIA EUROPEA 2020: Programa operativo del Fondo Social Europeo 2014-2020, mediante convenio de colaboración entre la citada Consejería y la Universidad de La Rioja Social, durante los años 2017, 2018 y 2019

Estudio socio-laboral para un diseño de la formación profesional específica en la Rioja Baja

Elaborar una propuesta de formación profesional específica para los centros de enseñanza media en La Rioja Baja: determinar los ciclos formativos de grado medio y superior en función de las necesidades reales de la estructura socioeconómica comarcal y prever futuras adaptaciones curriculares. 69 empresarios de la comarca; organismos oficiales; instituciones privadas; miembros del equipo. Conocimiento de la estructura socioeconómica de la comarca; tipos de empleados; categorías profesionales actuales; previsiones de las empresas respecto a la evolución curricular. 1.- Censos de población, actualizaciones de los padrones municipales de habitantes y censos agrarios, renta de los municipios riojanos, cuestionario 1-t de cámaras agrarias locales, catalogo de la industria riojana, censo de establecimientos comerciales de La Rioja, listados de empresas, sondeos de contrataciones. 2.- Encuesta elaborada por el equipo investigador. 3.- Curso actualización científico-didáctica. Estudio comparativo de los resultados estadísticos; análisis de las implicaciones de la Logse; análisis de la estructura económica de la comarca. La Rioja Baja tiene una estructura económica muy diversificada debido a un proceso de desarrollo endógeno y con un tejido productivo de pequeñas y medianas empresas: agricultura , hortofruticultura, industria, calzado, conservas, madera, caucho, envases metálicos, construcción, comercio minorista, transporte, hosteleria. Las necesidades de las empresas se concretan en empleos comunes a varias ramas productivas y otros específicos, con tendencia a desaparecer los puestos de menor cualificación. Se propone la implantación en los centros de formación profesional específica de la comarca, una serie de ciclos formativos correspondientes a las siguientes familias profesionales: administración y gestión, agricultura y ganadería, automoción, comercio y marketing, electricidad y electrónica, mecánica industrial, química, piel y confección. Se describe el perfil profesional de los puestos de trabajo para cuyo desempeño capacita cada ciclo formativo y se plantean las lineas generales de su currículo. Se completa con el desarrollo completo de dos de ellos.La RiojaES

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains