7 research outputs found

    Conocimiento didáctico de maestros en formación sobre objetivos de aprendizaje

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    El proceso de formación de los maestros incluye la familiarización con objetivos específicos de aprendizaje, puesto que su empleo forma parte de la futura labor profesional. Identificar qué objetivos se pueden planificar con una tarea matemática escolar pertenece al ámbito del conocimiento didáctico. En esta comunicación describimos cómo expresan los estudiantes del grado de Educación Primaria de último curso objetivos a partir de una tarea matemática escolar. Los resultados muestran diferencias en las capacidades identificadas, el nivel cognitivo de los contenidos mencionados y la ausencia de consideración de contextos

    Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation

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    Androgen deprivation therapy (ADT) and novel hormonal agents (NHAs) (Abiraterone and Enzalutamide) are the goal standard for metastatic prostate cancer (PCa) treatment. Although ADT is initially effective, a subsequent castration resistance status (CRPC) is commonly developed. The expression of androgen receptor (AR) alternative splicing isoforms (AR-V7 and AR-V9) has been associated to CRPC. However, resistance mechanisms to novel NHAs are not yet well understood. Androgen-dependent PCa cell lines were used to generate resistant models to ADT only or in combination with Abiraterone and/or Enzalutamide (concomitant models). Functional and genetic analyses were performed for each resistance model by real-time cell monitoring assays, flow cytometry and RT-qPCR. In androgen-dependent PCa cells, the administration of Abiraterone and/or Enzalutamide as first-line treatment involved a critical inhibition of AR activity associated with a significant cell growth inhibition. Genetic analyses on ADT-resistant PCa cell lines showed that the CRPC phenotype was accompanied by overexpression of AR full-length and AR target genes, but not necessarily AR-V7 and/or AR-V9 isoforms. These ADT resistant cell lines showed higher proliferation rates, migration and invasion abilities. Importantly, ADT resistance induced cross-resistance to Abiraterone and/or Enzalutamide. Similarly, concomitant models possessed an elevated expression of AR full-length and proliferation rates and acquired cross-resistance to its alternative NHA as second-line treatment.Instituto de Salud Carlos III PI17/00989European Regional Development Fund "A way to build Europe"Ramon y Cajal - Ministry of Economy and Competitiveness RYC-2015-18382Ministry of Education, Culture and Sport FPU14/05461University of Granad

    Lentiviral gene therapy reverts GPIX expression and phenotype in Bernard-Soulier syndrome type C

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    Bernard-Soulier syndrome (BSS) is a rare congenital disease characterized by macrothrombocytopenia and frequent bleeding. It is caused by pathogenic variants in three genes (GP1BA, GP1BB, or GP9) that encode for the GPIbα, GPIbβ, and GPIX subunits of the GPIb-V-IX complex, the main platelet surface receptor for von Willebrand factor, being essential for platelet adhesion and aggregation. According to the affected gene, we distinguish BSS type A1 (GP1BA), type B (GP1BB), or type C (GP9). Pathogenic variants in these genes cause absent, incomplete, or dysfunctional GPIb-V-IX receptor and, consequently, a hemorrhagic phenotype. Using gene-editing tools, we generated knockout (KO) human cellular models that helped us to better understand GPIb-V-IX complex assembly. Furthermore, we developed novel lentiviral vectors capable of correcting GPIX expression, localization, and functionality in human GP9-KO megakaryoblastic cell lines. Generated GP9-KO induced pluripotent stem cells produced platelets that recapitulated the BSS phenotype: absence of GPIX on the membrane surface and large size. Importantly, gene therapy tools reverted both characteristics. Finally, hematopoietic stem cells from two unrelated BSS type C patients were transduced with the gene therapy vectors and differentiated to produce GPIX-expressing megakaryocytes and platelets with a reduced size. These results demonstrate the potential of lentiviral-based gene therapy to rescue BSS type C

    The reference site collaborative network of the european innovation partnership on active and healthy ageing

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    Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs

    Impacto educativo en un Proyecto de Innovación Docente con Instagram: @Guíaporundía

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    This paper reports the design and results of an activity implemented by the students of the master’s degree in Social Developments in Artistic Culture at the University of Málaga during the 2019-2020 academic year. The objective of the project was to design an educational innovation practice, whose purpose was to improve the acquisition of skills and abilities of the students, taking cultural heritage as the focus, a brief note or critical commentary as proof of the acquisition of skills related to written expression, and the use of the social network Instagram as a demonstration of the acquisition of digital skills and competences. We show the initial idea, the methodology used, the results, and the evaluation. We draw conclusions through a survey, as well as showing the key elements that have led us to continue implementing activities on social networks in other subjects during the 2020-2021 academic year.Este artículo recoge el diseño y los resultados de una actividad desarrollada por el alumnado del título de Máster en Desarrollos Sociales de la Cultura Artística de la Universidad de Málaga durante el curso 2019-2020. El objetivo del proyecto era el diseño de una práctica en innovación educativa cuyo fin era mejorar la adquisición de competencias y habilidades del alumno tomando como eje vertebrador el patrimonio cultural, una breve nota o comentario crítico como prueba de adquisición de competencias relacionadas con la expresión escrita y el uso de la red social Instagram como demostración de adquisición de habilidades y competencias digitales. Se muestra la idea inicial, la metodología empleada, los resultados y la evaluación. Extraemos conclusiones a través de una encuesta, además de mostrar los elementos clave que nos han llevado a seguir implementando actividades en redes sociales en otras asignaturas durante el curso 2020-2021

    Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients

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    © Springer Nature Limited 2018The aim of this case-control study was to evaluate whether 47 single-nucleotide polymorphisms (SNPs) in steroid hormone-related genes are associated with the risk of RA and anti-TNF drug response. We conducted a case-control study in 3 European populations including 2936 RA patients and 2197 healthy controls. Of those, a total of 1985 RA patients were treated with anti-TNF blockers. The association of potentially interesting markers in the discovery population was validated through meta-analysis with data from DREAM and DANBIO registries. Although none of the selected variants had a relevant role in modulating RA risk, the meta-analysis of the linear regression data with those from the DREAM and DANBIO registries showed a significant correlation of the CYP3A4rs11773597 and CYP2C9rs1799853 variants with changes in DAS28 after the administration of anti-TNF drugs (P = 0.00074 and P = 0.006, respectively). An overall haplotype analysis also showed that the ESR2GGG haplotype significantly associated with a reduced chance of having poor response to anti-TNF drugs (P = 0.0009). Finally, a ROC curve analysis confirmed that a model built with eight steroid hormone-related variants significantly improved the ability to predict drug response compared with the reference model including demographic and clinical variables (AUC = 0.633 vs. AUC = 0.556; PLR_test = 1.52 × 10-6). These data together with those reporting that the CYP3A4 and ESR2 SNPs correlate with the expression of TRIM4 and ESR2 mRNAs in PBMCs (ranging from P = 1.98 × 10-6 to P = 2.0 × 10-35), and that the CYP2C9rs1799853 SNP modulates the efficiency of multiple drugs, suggest that steroid hormone-related genes may have a role in determining the response to anti-TNF drugs.KEY POINTS• Polymorphisms within the CYP3A4 and CYP2C9 loci correlate with changes in DAS28 after treatment with anti-TNF drugs.• A haplotype including eQTL SNPs within the ESR2 gene associates with better response to anti-TNF drugs.• A genetic model built with eight steroid hormone-related variants significantly improved the ability to predict drug response.This work was supported by grants from FIBAO foundation (Granada, Spain), Novo Nordisk Fonden (NNF15OC0016932), Knud og Edith Eriksens Mindefond and Gigtforeningen (A2037, A3570).info:eu-repo/semantics/publishedVersio
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