15 research outputs found

    Gibraltar Outflow and Mediterranean overturning circulation during the last 500 ky

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    20th Congress of the International Union for Quaternary Research (INQUA). Dublin, 25th and 31st July 2019, AbstractsIn order to explore past changes in the Mediterranean Outflow Water (MOW) we analyzed the fine sand content in the sediments together with some geochemical proxies and planktic and benthic stable isotopes at IODP site U1389. This site was recovered in the vicinity of the Strait of Gibraltar along the path of the main core of the MOW. The content of fine sand together with Zr/Al ratios were used to investigate the MOW speed variability along the past 500 ky. The MOW speed variability at this site was mainly driven by changes in the density contrast between the Inflow and Outflow, which was, in turn, governed by changes in the Mediterranean heat and freshwater budgets. Events of enhanced freshwater input to the Mediterranean associated to northward shifts of the Intertropical convergence Zone reduced the density contrast at Gibraltar and weakened the MOW at Gibraltar. Weak MOW events were recorded at times of sapropel deposition in the eastern Mediterranean. At millennial scale, the MOW intensified at times of Greenland stadials and weakened during interstadials. However, during Heinrich stadials typical three-phase events were observed, with a sandy contourite layer at the bottom and top and a phase of weak MOW in the middle of the stadial, coinciding with the arrival of icebergs to the Gulf of Cadiz. For Heinrich stadial 1 this weak MOW event occurred at the time of the massive release of icebergs from the Laurentian ice sheets. However, the inflow of less saline water to the Mediterranean should have increased not decreased the density contrast between the Inflow and Outflow, especially because freshwater discharge to the Mediterranean from the African monsoons was extremely low. We propose different scenarios to explain these weak MOW events in the middle of Heinrich stadials that were certainly triggered by prominent changes in the Mediterranean heat and freshwater budget.Universidad de Salamanca, EspañaUniversity of Cambridge, Reino UnidoLeibniz-Laboratory for Radiometric Dating and Isotope Research, AlemaniaJapan Agency for Marine-Earth Science and Technology, JapónInstitute of Earth Sciences, Heidelberg University, AlemaniaRoyal Holloway, University of London, Reino UnidoSchool of Environmental Sciences, University of Hull, Reino UnidoInstituto Geológico y Minero de España, Españ

    Causes of hOCT1-dependent cholangiocarcinoma resistance to sorafenib and sensitization by tumor-selective gene therapy

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    Although the multi-tyrosine kinase inhibitor sorafenib is useful in the treatment of several cancers, cholangiocarcinoma (CCA) is refractory to this drug. Among other mechanisms of chemoresistance, impaired uptake through human organic cation transporter type 1 (hOCT1) (gene SLC22A1) has been suggested. Here we have investigated the events accounting for this phenotypic characteristic and have evaluated the interest of selective gene therapy strategies to overcome this limitation. Gene expression and DNA methylation of SLC22A1 were analyzed using intrahepatic (iCCA) and extrahepatic (eCCA) biopsies (Copenhagen and Salamanca cohorts; n = 132) and The Cancer Genome Atlas (TCGA)-CHOL (n = 36). Decreased hOCT1 mRNA correlated with hypermethylation status of the SLC22A1 promoter. Treatment of CCA cells with decitabine (demethylating agent) or butyrate (histone deacetylase inhibitor) restored hOCT1 expression and increased sorafenib uptake. MicroRNAs able to induce hOCT1 mRNA decay were analyzed in paired samples of TCGA-CHOL (n = 9) and Copenhagen (n = 57) cohorts. Consistent up-regulation in tumor tissue was found for miR-141 and miR-330. High proportion of aberrant hOCT1 mRNA splicing in CCA was also seen. Lentiviral-mediated transduction of eCCA (EGI-1 and TFK-1) and iCCA (HuCCT1) cells with hOCT1 enhanced sorafenib uptake and cytotoxic effects. In chemically induced CCA in rats, reduced rOct1 expression was accompanied by impaired sorafenib uptake. In xenograft models of eCCA cells implanted in mouse liver, poor response to sorafenib was observed. However, tumor growth was markedly reduced by cotreatment with sorafenib and adenoviral vectors encoding hOCT1 under the control of the BIRC5 promoter, a gene highly up-regulated in CCA. Conclusion: The reason for impaired hOCT1-mediated sorafenib uptake by CCA is multifactorial. Gene therapy capable of selectively inducing hOCT1 in tumor cells can be considered a potentially useful chemosensitization strategy to improve the response of CCA to sorafenib

    Industrias audiovisuales: tendencias de producción y consumo

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    La digitalización de la creación cultural y su difusión online ha supuesto la entrada en los mercados de poderosos y novedosos agentes que se han convertido en los líderes no sólo de la industria tecnológica, sino de toda la producción cultural y de la economía. Dicha digitalización de los medios, además de la convergencia de las pantallas y la ruptura de la linealidad vertical y unidireccional de los medios convencionales ha conllevado un profundo cambio de paradigmas que atañe directamente a la creación audiovisual. Este volumen de la serie iniciada en el año 2012 a partir de las investigaciones de los estudiantes de la asignatura Estructura del mercado audiovisual del grado de Comunicación Audiovisual en la Universidad de Málaga nos lleva al análisis de la recepción y del consumo de diversas industrias del audiovisual, pero también al análisis de la producción condicionada por el contexto económico y por la demanda, así como a diversas cuestiones relacionadas con el marketing y los modelos de negocio de aquellas industrias. En una disciplina en la que no abundan los trabajos académicos actualizados, los autores y autoras de este volumen ofrecen con sus aportaciones estudios de casos significativos y paradigmáticos del estado de los diversos sectores de las industrias audiovisuales. Presentados aquí a modo de capítulos, estos textos suponen la iniciación en la investigación de estudiantes que combinan su formación académica e investigadora con su formación como profesionales en el área de la Comunicación Audiovisual. Ofrecemos aquí una selección de aquellas investigaciones que destacan por su interés, su capacidad analítica y crítica, su actualidad, su pertinencia y su disciplinada adecuación a una metodología de investigación apropiada para unos estudios que forman parte de las Ciencias Sociales. https://www.eumed.net/libros/1851/index.htm

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    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

    4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

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    Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

    Balance hídrico a través del Estrecho de Gibraltar (Golfo de Cádiz – Mar de Alborán) durante los últimos 18 Ka

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    Jornadas de Paleontología (33. 2017. Cádiz)El Golfo de Cádiz se comunica con el Mar Mediterráneo a través del Estrecho de Gibraltar, por lo que se considera un lugar clave para estudiar y comprender la dinámica de corrientes entre el Atlántico y el Mediterráneo. Con el objetivo de analizar los cambios ocurridos en el balance hídrico del Mediterráneo se ha llevado a cabo la caracterización isotópica de la masa de agua superficial atlántica mediante el análisis de la temperatura de la superficie del agua (SST=Sea Surface Temperature) a partir del porcentaje de las especies de foraminíferos planctónicos presentes en muestras pertenecientes al testigo U1389 situado en el Golfo de Cádiz.Instituto Geológico y Minero de España, EspañaDepartamento de Geología, Universidad de Salamanca, EspañaPeer reviewe

    Causes of hOCT1-dependent cholangiocarcinoma resistance to sorafenib and sensitization by tumor-selective gene therapy

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    Although the multi-tyrosine kinase inhibitor sorafenib is useful in the treatment of several cancers, cholangiocarcinoma (CCA) is refractory to this drug. Among other mechanisms of chemoresistance, impaired uptake through human organic cation transporter type 1 (hOCT1) (gene SLC22A1) has been suggested. Here we have investigated the events accounting for this phenotypic characteristic and have evaluated the interest of selective gene therapy strategies to overcome this limitation. Gene expression and DNA methylation of SLC22A1 were analyzed using intrahepatic (iCCA) and extrahepatic (eCCA) biopsies (Copenhagen and Salamanca cohorts; n = 132) and The Cancer Genome Atlas (TCGA)-CHOL (n = 36). Decreased hOCT1 mRNA correlated with hypermethylation status of the SLC22A1 promoter. Treatment of CCA cells with decitabine (demethylating agent) or butyrate (histone deacetylase inhibitor) restored hOCT1 expression and increased sorafenib uptake. MicroRNAs able to induce hOCT1 mRNA decay were analyzed in paired samples of TCGA-CHOL (n = 9) and Copenhagen (n = 57) cohorts. Consistent up-regulation in tumor tissue was found for miR-141 and miR-330. High proportion of aberrant hOCT1 mRNA splicing in CCA was also seen. Lentiviral-mediated transduction of eCCA (EGI-1 and TFK-1) and iCCA (HuCCT1) cells with hOCT1 enhanced sorafenib uptake and cytotoxic effects. In chemically induced CCA in rats, reduced rOct1 expression was accompanied by impaired sorafenib uptake. In xenograft models of eCCA cells implanted in mouse liver, poor response to sorafenib was observed. However, tumor growth was markedly reduced by cotreatment with sorafenib and adenoviral vectors encoding hOCT1 under the control of the BIRC5 promoter, a gene highly up-regulated in CCA. Conclusion: The reason for impaired hOCT1-mediated sorafenib uptake by CCA is multifactorial. Gene therapy capable of selectively inducing hOCT1 in tumor cells can be considered a potentially useful chemosensitization strategy to improve the response of CCA to sorafenib

    Tinta purpura: historias y relatos desde la crónica

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    Esta publicación es el resultado de las dos primeras ediciones del concurso Tinta púrpura: historias y relatos desde la crónica, promovido por el Programa de Ciencias Humanas y Sociales de UNIMINUTO Virtual y a Distancia, en los años 2015 y 2016, para el desarrollo y fortalecimiento de las competencias escriturales, creativas y de producción audiovisual y radiofónica de los estudiantes de UNIMINUTO. Las crónicas que se presentan en este libro corresponden a las propuestas ganadoras y finalistas de las ediciones de 2015 y 2016 arbitradas por los jurados designados para estas ediciones: 2015, Marisol Esperanza Cipagauta, Miguel Fernando Mendoza Luna y Alejandro Cuervo; 2016, Cristian Sebastián Hernández Jiménez, Sandra Milena Gutiérrez Zambrano y David Arnulfo Nieto Castillo
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