29 research outputs found

    Proyecto de Innovación y Mejora de la Calidad para la sostenibilización curricular en el Trabajo de Fin de Grado en Educación Social. Diseño y creación de una herramienta para la acción tutorial

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    El proyecto pretende, mediante el diseño de tutoriales, contribuir a la mejora de los métodos, espacios y el seguimiento del aprendizaje en el TFG de Educación Social. La sostenibilización aparece como factor clave para el desarrollo académico

    Fluorizoline-induced apoptosis requires prohibitins in nematodes and human cells

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    We previously showed that fluorizoline, a fluorinated thiazoline compound, binds to both subunits of the mitochondrial prohibitin (PHB) complex, PHB1 and PHB2, being the expression of these proteins required for fluorizoline-induced apoptosis in mouse embryonic fibroblasts. To investigate the conservation of this apoptotic mechanism, we studied the effect of PHB downregulation on fluorizoline activity on two human cell lines, HEK293T and U2OS. Then, we asked whether PHBs mediate the effect of fluorizoline in a multicellular organism. Interestingly, reduced levels of PHBs in the human cells impaired the induction of apoptosis by fluorizoline. We observed that fluorizoline has a detrimental dose-dependent effect on the development and survival of the nematode model Caenorhabditis elegans. Besides, such effects of fluorizoline treatment in living nematodes were absent in PHB mutants. Finally, we further explored the apoptotic pathway triggered by fluorizoline in human cell lines. We found that the BH3-only proteins NOXA, BIM and PUMA participate in fluorizoline-induced apoptosis and that the induction of NOXA and PUMA is dependent on PHB expression.This work was supported by grants from the Agencia Estatal de Investigación (Ministerio de Ciencia e Innovación), European Regional Development Fund (ERDF), the European Research Council, the Junta de Andalucía and the Instituto de Salud Carlos III (ISCIII) (SAF2017-83178-R to J.G.; PID2019-107991RB-I00 to R.L.; ERC-2011-StG-281691 and C2A ID: 42571/Exp: 70806 to M.A-S; PI15-00895 to J.C.). J.S-E and I.S-V are recipients of research fellowships from the Ministerio de Ciencia e Innovación. S.N-V is recipient of a research fellowship from Universitat de Barcelona. MD.M-B was supported by the Plan de Empleo Juvenil (EJP09) from the Junta de Anadalucía. D.K has a FI AGAUR fellowship from Generalitat de Catalunya

    Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines

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    The prohibitin (PHB)-binding compound fluorizoline as well as PHB-downregulation activate the integrated stress response (ISR) in HEK293T and U2OS human cell lines. This activation is denoted by phosphorylation of eIF2 alpha and increases in ATF4, ATF3, and CHOP protein levels. The blockage of the activation of the ISR by overexpression of GRP78, as well as an increase in IRE1 activity, indicate the presence of ER stress after fluorizoline treatment. The inhibition of the ER stress response in HEK293T and U2OS led to increased sensitivity to fluorizoline-induced apoptosis, indicating a pro-survival role of this pathway after fluorizoline treatment in these cell lines. Fluorizoline induced an increase in calcium concentration in the cytosol and the mitochondria. Finally, two different calcium chelators reduced fluorizoline-induced apoptosis in U2OS cells. Thus, we have found that fluorizoline causes increased ER stress and activation of the integrated stress response, which in HEK293T and U2OS cells are protective against fluorizoline-induced apoptosis

    Nanosystems as Quorum Quenchers Targeting Foodborne Pathogens: Understanding the Inhibition Mechanisms and Their Docking Predictions

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    Food poisoning is one of the main problems affecting public health. Bacterial adhesion on surfaces has been documented for decades, and it is known that biofilm-forming bacteria are much more resistant than planktonic cells. Typically, nanosystems are studied regarding their antimicrobial activity (i.e., pathogenic bacteria such as Campylobacter, Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, Staphylococcus aureus, Clostridium perfringens, Bacillus cereus, and Yersinia enterocolitica), but not for antibiofilm activity and their associated genes. Some studies established protein-ligand prediction concerning quorum sensing suppression, commonly called quorum quenching. This chapter focuses on nanosystems or functionalized nanomaterials that have demonstrated antibiofilm or quorum quenching activity and, thus, establishes perspectives in modeling specific nanosystems to eradicate biofilms produced by foodborne pathogens

    Dissecting the role of the NADPH oxidase NOX4 in TGF-beta signaling in hepatocellular carcinoma

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    The NADPH oxidase NOX4 has been proposed as necessary for the apoptosis induced by the Transforming Growth Factor-beta (TGF-I3) in hepatocytes and hepatocellular carcinoma (HCC) cells. However, whether NOX4 is required for TGF-I3-induced canonical (SMADs) or non-canonical signals is not fully understood yet, neither its potential involvement in other parallel actions induced by TGF-I3. In this work we have used CRISPR Cas9 technology to stable attenuate NOX4 expression in HCC cells. Results have indicated that NOX4 is required for an efficient SMAD2/3 phosphorylation in response to TGF-I3, whereas non-canonical signals, such as the phos-phorylation of the Epidermal Growth Receptor or AKT, are higher in NOX4 silenced cells. TGF-I3-mediated in-hibition of cell proliferation and viability is attenuated in NOX4 silenced cells, correlating with decreased response in terms of apoptosis, and maintenance of high expression of MYC and CYCLIN D1. These results would indicate that NOX4 is required for all the tumor suppressor actions of TGF-I3 in HCC. However, analysis in human HCC tumors has revealed a worse prognosis for patients showing high expression of TGF-I31-related genes concomitant with high expression of NOX4. Deepening into other tumorigenic actions of TGF-I3 that may contribute to tumor progression, we found that NOX4 is also required for TGF-I3-induced migratory effects. The Epithelial-Mesenchymal transition (EMT) program does not appear to be affected by attenuation of NOX4 levels. However, TGF-I3-mediated regulation of cytoskeleton dynamics and focal adhesions require NOX4, which is necessary for TGF-I3-induced increase in the chaperone Hsp27 and correct subcellular localization of Hic-5 within focal adhesions, as well for upregulation of the metalloprotease MMP9. All these results together point to NOX4 as a key element in the whole TGF-I3 signaling in HCC cells, revealing an unknown role for NOX4 as tumor promoter in HCC patients presenting activation of the TGF-I3 pathway

    Búsqueda de empleo activo y mejora de la empleabilidad en el Grado en Educación Social

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    El desarrollo de este trabajo tiene como objetivo mejorar la tasa de empleabilidad de los egresados en el Grado en Educación Social de la Universidad Complutense de Madrid, así como la búsqueda de empleo activo, al proporcionar diferentes recursos y estrategias y crear redes y espacios de diálogo con las asociaciones profesionales del sector. Parte de la necesidad del fomento de la inserción laboral y el emprendimiento entre los estudiantes, el desarrollo de la orientación laboral como una herramienta básica para el estudio y el análisis del fortalecimiento del empleo para educadores sociales y la búsqueda activa del mismo. Igualmente, se apoya en postulados y paradigmas como el de educación para el bien común y sostenible, en un marco de educación permanente, humanista y con vocación para la transformación social

    Data sources for drug utilization research in Latin American countries—A cross-national study: DASDUR-LATAM study

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    Purpose: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. Methods: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. Results: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. Conclusions: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.Fil: Lopes, Luciane C.. University Of Sorocaba; BrasilFil: Salas, Daiana Maribel. University of Pennsylvania; Estados UnidosFil: Osorio de Castro, Claudia Garcia Serpa. Fundación Oswaldo Cruz; BrasilFil: Freitas Leal, Lisiane. McGill University; CanadáFil: Doubova, Svetlana V.. Mexican Institute of Social Security; MéxicoFil: Cañás, Martín. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; ArgentinaFil: Dreser, Anahi. Instituto Nacional de Salud Pública; MéxicoFil: Acosta, Angela. Universidad ICESI; ColombiaFil: Oliveira Baldoni, Andre. Federal University of São João Del-Rei; BrasilFil: de Cássia Bergamaschi, Cristiane. University of Sorocaba; BrasilFil: Marques Mota, Daniel. Brazilian Health Regulatory Agency; BrasilFil: Gómez Galicia, Diana L.. Universidad Autónoma del Estado de Morelos; MéxicoFil: Sepúlveda Viveros, Dino. Universidad de Chile; ChileFil: Narvaez Delgado, Edgard. No especifíca;Fil: da Costa Lima, Elisangela. Universidade Federal do Rio de Janeiro; BrasilFil: Chandia, Felipe Vera. Pontificia Universidad Católica de Chile; ChileFil: Ferre, Felipe. Universidade Federal de Minas Gerais; BrasilFil: Marin, Gustavo Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Olmos, Ismael. State Health Services Administration; UruguayFil: Zimmermann, Ivan R.. Universidade do Brasília; BrasilFil: Fulone, Izabela. University of Sorocaba; BrasilFil: Roldán Saelzer, Juan. Instituto de Salud Pública; ChileFil: Sánchez Salgado, Juan Carlos. No especifíca;Fil: Castro Pastrana, Lucila I.. Universidad de Las Américas de Puebla; MéxicoFil: de Souza, Luiz Jupiter Carneiro. Fundación Oswaldo Cruz; BrasilFil: Machado Beltrán, Manuel. Universidad Nacional de Colombia; ColombiaFil: Tolentino Silva, Marcus. University of Sorocaba; BrasilFil: Mena, María Belén. Universidad Central del Ecuador; EcuadorFil: de França Fonteles, Marta Maria. Universidade Federal do Ceara; BrasilFil: Urtasun, Martín Alejandro. Universidad Nacional Arturo Jauretche; Argentina. Federación Médica de la Provincia de Buenos Aires; Argentin
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