15 research outputs found
Evaluating face2gene as a tool to identify cornelia de lange syndrome by facial phenotypes
Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS.Spanish Ministry of Science, Innovation and Universities/State Research Agency RTC-2017-6494-1; RTI2018-094434-B-I00 (MCIU/AEI/FEDER, UE) to P.G.-P.; DiputaciĂłn General de AragĂłn - FEDER: European Social Fund [Grupo de Referencia B32_17R, to J.P.] as well as funds from the European
JPIAMR-VRI network âCONNECTâ to P.G.-P.; Medical Faculty of the University of LĂŒbeck J09-2017 to I. P.; German Federal Ministry of Education and Research (BMBF
Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6
The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity.This work is supported by the Spanish AIDS network âRed TemĂĄtica Cooperativa de InvestigaciĂłn en SIDAâ RD12/0017/0002, RD12/0017/0028, RD12/0017/0034, RD16/0025/0011, RDCIII16/0002/0005 and RD16/0025/0041 as part of the Plan Nacional R + D+I and co-funded by the Spanish âInstituto de Salud Carlos III (ISCIII)-SubdirecciĂłn General de EvaluaciĂłn y el Fondo Europeo de Desarrollo Regional (FEDER)â. J.B. is a researcher from âFundaciĂł Institut de Recerca en CiĂšncies de la Salut Germans Trias i Pujolâ supported by the Health Department of the Catalonian Government/Generalitat de Catalunya and ISCIII grant numbers PI17/01318 and PI20/00093 (to J.B.). Work in CC Lab was supported by grants SAF (2010-17226) and (2016-77894-R) from MINECO (Spain), FIS (PI 13/02269, ISCIII) and PI20/00093. Work in CF Lab was supported by the Cabildo Insular de Tenerife (grants CGIEU0000219140 and âApuestas cientĂficas del ITER para colaborar en la lucha contra la COVID-19â); the agreement with the Instituto TecnolĂłgico y de EnergĂas Renovables (ITER) to strengthen scientific and technological education, training research, development and innovation in Genomics, Personalized Medicine and Biotechnology (grant number OA17/008). A.V.-F.âs Lab is supported by the European Regional Development Fund (ERDF), RTI2018-093747-B-100 (âMinisterio de Ciencia e InnovaciĂłnâ, Spain), âMinisterio de Ciencia, InnovaciĂłn y Universidadesâ (Spain), ProID2020010093 (âAgencia Canaria de InvestigaciĂłn, InnovaciĂłn y Sociedad de la InformaciĂłnâ and European Social Fund), UNLL10-3E-783 (ERDF and âFundaciĂłn CajaCanariasâ) and âSEGAI-ULLâ. S.P-Y is funded by âFundaciĂłn Doctor Manuel Moralesâ (La Palma, Spain) and âContrato Predoctoral Ministerio-ULL FormaciĂłn de Doctoresâ (2019 Program) (âMinisterio de Ciencia, InnovaciĂłn y Universidadesâ, Spain). R.C.-R. is funded by RD16/0025/0011 and ProID2020010093 (âAgencia Canaria de InvestigaciĂłn, InnovaciĂłn y Sociedad de la InformaciĂłnâ and European Social Fund). J.G.-L. is funded by the âJuan de la Cierva de IncorporaciĂłnâ Spanish Program (IJC2019-038902-I) (âAyudas Juan de la Cierva de incorporaciĂłn; Agencia Estatal de InvestigaciĂłn. Ministerio de Ciencia e InnovaciĂłnâ).S
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Reinfection rate and disease severity of the BA.5 Omicron SARS-CoV-2 lineage compared to previously circulating variants of concern in the Canary Islands (Spain)
ABSTRACTThe emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisherâs exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta pâ=â2.89âĂâ10â25; vs. BA.1 pâ=â5.17âĂâ10â11; vs. BA.2 pâ=â0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR]â=â 0.45, 95% Confidence Interval [CI]â=â 0.23-0.87, pâ=â0.02), BA.2 (ORâ=â â0.38, 95% CIâ=â0.22-0.63, pâ=â1.91âĂâ10â4), and BA.5 (ORâ=â0.30, 95% CIâ=â0.16-0.55, pâ=â1.05âĂâ10â4) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern
Bioinformatic approaches to draft the viral genome sequence of Canary Islands cases related to the multicountry mpox virus 2022-outbreak
On July 23, 2022, monkeypox disease (mpox) was declared a Public Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to a multicountry outbreak. In Europe, several cases of mpox virus (MPXV) infection related to this outbreak were detected in the Canary Islands (Spain). Here we describe the combination of viral DNA sequencing and bioinformatic approaches, including methods for de novo genome assembly and short- and long-read technologies, used to reconstruct the first MPXV genome isolated in the Canary Islands on the 31st of May 2022 from a male adult patient with mild symptoms. The same sequencing and bioinformatic approaches were then validated with three other positive cases of MPXV infection from the same mpox outbreak. We obtained the best results using a reference-based approach with short reads, evidencing 46â79 nucleotide variants against viral sequences from the 2018â2019 mpox outbreak and placing the viral sequences in the new B.1 sublineage of clade IIb of the MPXV classification. This study of MPXV demonstrates the potential of metagenomics sequencing for rapid and precise pathogen identification
Ajedrez en la escuela
Convocatoria Proyectos de innovaciĂłn de Extremadura 2017/2018Se parte de la idea que el ajedrez es un juego-deporte atractivo para los niños y una herramienta potente para el profesorado por sus mĂșltiples posibilidades que permiten desarrollar la atenciĂłn, la memoria, la concentraciĂłn, el anĂĄlisis de problemas, la toma de decisiones, etc. Por ello se lleva a cabo un proyecto en el CEIP Conquistador Loaysa (Jarandilla de la Vera, CĂĄceres) que pretende fomentar el aprendizaje del ajedrez entre los alumnos del centro. Otros objetivos del proyecto fueron: promover el respeto al adversario en las prĂĄcticas realizadas; fomentar la actitud de investigaciĂłn acerca del ajedrez; conocer la historia de la ajedrez desde sus inicios, asĂ como los campeones del mundo y personajes destacados; saber transcribir una partida de ajedrez del tablero a la hoja de registro y viceversa; desarrollar habilidades estratĂ©gicas y tĂĄcticas en el juego, etc. AsĂ mismo se trabajaron otros objetivos propios de la etapa de EducaciĂłn Primaria como conocer y aprenciar los valores de la convivencia, desarrollar hĂĄbitos de trabajo individual y de equipo, conocer y utilizar de modo adecuado la lengua castellana, adquirir la competencia comunicativa bĂĄsica en al menos una lengua extranjera, desarrollar la competencia matemĂĄtica e iniciarse en la resoluciĂłn de problemas, etc.ExtremaduraES
Geodivulgar: GeologĂa y Sociedad
Depto. de GeodinĂĄmica, EstratigrafĂa y PaleontologĂaDepto. de QuĂmica InorgĂĄnicaDepto. de DidĂĄctica de las Ciencias Experimentales , Sociales y MatemĂĄticasFac. de Ciencias GeolĂłgicasFac. de Ciencias QuĂmicasFac. de EducaciĂłnFALSEsubmitte
Inborn errors of OASâRNase L in SARS-CoV-2ârelated multisystem inflammatory syndrome in children
International audienceMultisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)âsensing OAS1 and OAS2 generate 2âČ-5âČ-linked oligoadenylates (2-5A) that activate the single-stranded RNAâdegrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase Lâdeficient cells. Cytokine production in RNase Lâdeficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OASâRNase L deficiencies in these patients unleash the production of SARS-CoV-2âtriggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C