122 research outputs found

    Jackie mahu pecah rekod lagi

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    El objetivo fue analizar la incidencia de participar en diferentes tipos de juegos motores deportivos sobre la vivencia emocional de alumnos en formación de Ciencias de la Actividad Física y del Deporte y determinar el papel que la competición puede causar en la expresión emocional. Método: Se diseñó una experiencia pedagógica en la que se practicaron 8 juegos deportivos con y sin competición de cuatro familias de juegos. Los alumnos participaron de todos los juegos y valoraron las intensidades emocionales suscitadas al finalizar cada uno. Instrumentos: Se utilizó el Games Emotion Scale, validado en contextos universitarios, para medir la vivencia subjetiva de cada estudiante. Resultados: Se registró una vivencia emocional muy positiva, con valores muy bajos para emociones negativas. Competir resultó ser un factor influyente en la valoración de emociones

    Expanding the Clinical and Molecular Heterogeneity of Nonsyndromic Inherited Retinal Dystrophies

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    A cohort of 172 patients diagnosed clinically with nonsyndromic retinal dystrophies, from 110 families underwent full ophthalmologic examination, including retinal imaging, electrophysiology, and optical coherence tomography, when feasible. Molecular analysis was performed using targeted next-generation sequencing (NGS). Variants were filtered and prioritized according to the minimum allele frequency, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Multiplex ligation-dependent probe amplification and array comparative genomic hybridization were performed to validate copy number variations identified by NGS. The diagnostic yield of this study was 62% of studied families. Thirty novel mutations were identified. The study found phenotypic intra- and interfamilial variability in families with mutations in C1QTNF5, CERKL, and PROM1; biallelic mutations in PDE6B in a unilateral retinitis pigmentosa patient; interocular asymmetry RP in 50% of the symptomatic RPGR-mutated females; the first case with possible digenism between CNGA1 and CNGB1; and a ROM1 duplication in two unrelated retinitis pigmentosa families. Ten unrelated cases were reclassified. This study highlights the clinical utility of targeted NGS for nonsyndromic inherited retinal dystrophy cases and the importance of full ophthalmologic examination, which allows new genotypeephenotype associations and expands the knowledge of this group of disorders. Identifying the cause of disease is essential to improve patient management, provide accurate genetic counseling, and take advantage of gene therapyebased treatments. (J Mol Diagn 2020, 22: 532e543; https:// doi.org/10.1016/j.jmoldx.2020.01.003)Supported by grants from the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health, including the Center for Biomedical Research Network on Rare Diseases (CIBERER), Fondo de Investigacion Sanitaria grant PI16/00539; the Spanish National Organization for the Blind (Fundación ONCE); and Fundación Mutua Madrileña. G.G.-G. is sponsored by the CIBERER, and A.R.-M. is supported by the Río Hortega program from ISCIII.Medicin

    Análisis territorial de la Política Agraria Común (PAC) en el periodo 2014-2020. Estudio de caso: Extremadura

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    As Spain joined the European Union (EU), the Common Agricultural Policy (CAP) plays an important role in the agricultural sector in Extremadura with the intention of progressing a fundamental sector for the development of the regional economy and with sufficient capacity to maintain the population in rural areas. Hence, since Agenda 2000, there have been a series of reforms that have established decoupled aid by paying farmers for the environmental benefits they produce in the rural environment, as well as addressing the problems of Europe's rural areas through rural development aid. The aim of this study is to describe the latest CAP 2014-2020 budget framework in Extremadura, through a territorial analysis that has provided in-depth knowledge of the distribution of this aid. Thus, the results obtained show the concentration of the amounts in certain aids introduced in the last CAP reform, as well as how the total amounts of aid are located in the main municipalities of the region where the agricultural sector is more dynamic and concentrates a large number of farms

    Comparación del estado de ánimo en estudiantes de Educación Física: efecto de dos modelos de enseñanza

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    The main objective of this study was to analyze the acute effect of two teaching models on mood in university students. The sample used is made up of 112 students of the Degree in Physical Activity and Sport Sciences. The Profile of Mood States Questionnaire (Profile of Mood States) by McNair, Lorr and Droppleman (1971) was used in its adaptation to Spanish. Two sessions were conducted, a traditional one based on direct instruction (DI) and an alternative (AL) one based on search and discovery. The traditional model increased all negative factors with significant differences (p£0,05), while the alternative model improved positive mood. By gender, the effect of the teaching model on mood is different, and it does so with significant differences (p£0,05). The alternative model would be the most suitable for improving the positive of student’s mood.El objetivo principal de este estudio fue analizar el efecto agudo que tienen dos modelos de enseñanza sobre el estado de ánimo en alumnos universitarios. La muestra estuvo formada por 112 estudiantes del Grado en Ciencias de la Actividad Física y del Deporte. Se utilizó el Cuestionario de Perfil de los Estados de Ánimo (Profile of Mood States) de McNair, Lorr y Droppleman (1971) en su adaptación al español. Se realizaron dos sesiones, una tradicional basada en la instrucción directa (ID) y otra alternativa (AL) basado en la búsqueda y el descubrimiento. El modelo tradicional aumenta todos los factores negativos con diferencias significativas (p£0,05), mientras que el modelo alternativo mejora el estado de ánimo positivo. Por géneros, el efecto del modelo de enseñanza sobre el estado de ánimo es distinto, además lo hace con diferencias significativas (p£0,05). Por lo tanto, el modelo alternativo sería el más adecuado para la mejorar el estado de ánimo positivo de los alumnos

    Application of Multi-core and GPU Architectures on Signal Processing: Case Studies

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    In this article part of the techniques and developments we are carrying out within the INCO2 group are reported. Results follow the interdisciplinary approach with which we tackle signal processing applications. Chosen case studies show different stages of development: We present algorithms already completed which are being used in practical applications as well as new ideas that may represent a starting point, and which are expected to deliver good results in a short and medium term

    Paradigmatic de novo GRIN1 variants recapitulate pathophysiological mechanisms underlying GRIN1-related disorder clinical spectrum

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    Background: GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting GRIN genes (mostly GRIN1, GRIN2A and GRIN2B genes), which encode for the GluN subunit of the N-methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present. Methods: In this study, we aimed to delineate the structural and functional alterations of GRIN1 disease-associated variants, and their correlations with clinical symptoms in a Spanish cohort of 15 paediatric encephalopathy patients harbouring these variants. Results: Patients harbouring GRIN1 disease-associated variants have been clinically deeplyphenotyped. Further, using computational and in vitro approaches, we identified different critical checkpoints affecting GluN1 biogenesis (protein stability, subunit assembly and surface trafficking) and/or NMDAR biophysical properties, and their association with GRD clinical symptoms. Conclusions: Our findings show a strong correlation between GRIN1 variants-associated structural and functional outcomes. This structural-functional stratification provides relevant insights of genotypephenotype association, contributing to future precision medicine of GRIN1-related encephalo

    Analysis of the Interferon Gamma (rs2430561, +874T/A) Functional Gene Variant in Relation to the Presence of Cardiovascular Events in Rheumatoid Arthritis

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    OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. METHODS: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA. RESULTS: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not. CONCLUSION: Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients

    Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma

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    [Objective]: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models.[Design]: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2KO or KCL2KO and KPCL2KI or KCL2KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation.[Results]: Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment.[Conclusion]: Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.JCL-G received support from a 'la Caixa' Foundation (ID 100010434) fellowship (LCF/BQ/DR21/11880011). This study was supported by ISCIII FIS grants PI18/00757 and PI21/01110 (BSJ) and PI18/00267 (LG-B), and grants from the Spanish Ministry of Economy and Innovation SAF2016-76504-R (ACan and FP), PID2019-111052RB-I00 (FP), PID2019-104644RB-I00 (GM-B), a Ramón y Cajal Merit Award RYC-2012–12104 (BSJ) and ISCIII, CIBERONC, CB16/12/00446 (ACar) and CB16/12/00295 (ACan and GM-B), all of them co-financed through Fondo Europeo de Desarrollo Regional (FEDER) 'Una manera de hacer Europa'; a Fero Foundation Grant (BSJ); a Coordinated grant (GC16173694BARB) from the Fundación Científica Asociación Española Contra el Cáncer (FC-AECC) (BSJ); a Miguel Servet award (CP16/00121) (PS); a DFG, German Research Foundation Grant—Project no: 492 436 553 (KG); and a Max Eder Fellowship of the German Cancer Aid (111746) (PCH

    USH2A is a Meissner’s corpuscle protein necessary for normal vibration sensing in mice and humans

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    Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive, vibration-sensing neurons are associated with Meissner’s corpuscles in the skin. In the present study, we found that USH2A, a transmembrane protein with a very large extracellular domain, was found in terminal Schwann cells within Meissner’s corpuscles. Pathogenic USH2A mutations cause Usher’s syndrome, associated with hearing loss and visual impairment. We show that patients with biallelic pathogenic USH2A mutations also have clear and specific impairments in vibrotactile touch perception, as do mutant mice lacking USH2A. Forepaw rapidly adapting mechanoreceptors innervating Meissner’s corpuscles, recorded from Ush2a−/− mice, showed large reductions in vibration sensitivity. However, the USH2A protein was not found in sensory neurons. Thus, loss of USH2A in corpuscular end-organs reduced mechanoreceptor sensitivity as well as vibration perception. Thus, a tether-like protein is required to facilitate detection of small-amplitude vibrations essential for the perception of fine-grained tactile surfaces.The present study was funded by grants from the Deutsche Forschungsgemeinshaft (grant nos. SFB665-B6 to G.R.L., SFB1315 to J.F.A.P. and SFB1158-A01 to S.G.L.) and grants from the European Research Council (grant nos. 789128 to G.R.L. and ERC-2015-CoG-682422 to J.F.A.P.). Additional funding was from the Institute of Health Carlos III (Spanish Ministry of Science and Innovation, grant no. FIS PI16/00539 to J.M.).Peer reviewe
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