17 research outputs found

    Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts

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    Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray. We found widespread DNA hypomethylation concomitant with focal gain of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the TGF-β pathway. The latter included promoter hypermethylation-associated SMAD3 silencing, which was associated with hyperresponsiveness to exogenous TGF-β1 in terms of contractility and extracellular matrix deposition. In turn, activation of CFs with exogenous TGF-β1 partially mimicked the epigenetic alterations observed in TAFs, suggesting that TGF-β1 may be necessary but not sufficient to elicit such alterations. Moreover, integrated pathway-enrichment analyses of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the EDARADD promoter sequence as a prognostic factor in non-small cell lung cancer patients. Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance

    Impacts of Use and Abuse of Nature in Catalonia with Proposals for Sustainable Management

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    This paper provides an overview of the last 40 years of use, and in many cases abuse, of the natural resources in Catalonia, a country that is representative of European countries in general, and especially those in the Mediterranean region. It analyses the use of natural resources made by mining, agriculture, livestock, logging, fishing, nature tourism, and energy production and consumption. This use results in an ecological footprint, i.e., the productive land and sea surface required to generate the consumed resources and absorb the resulting waste, which is about seven times the amount available, a very high number but very similar to other European countries. This overexploitation of natural resources has a huge impact on land and its different forms of cover, air, and water. For the last 25 years, forests and urban areas have each gained almost 3% more of the territory at the expense of agricultural land; those municipalities bordering the sea have increased their number of inhabitants and activity, and although they only occupy 6.7% of the total surface area, they account for 43.3% of the population; air quality has stabilized since the turn of the century, and there has been some improvement in the state of aquatic ecosystems, but still only 36% are in good condition, while the remainder have suffered morphological changes and different forms of nonpoint source pollution; meanwhile the biodiversity of flora and fauna remains still under threat. Environmental policies do not go far enough so there is a need for revision of the legislation related to environmental impact and the protection of natural areas, flora, and fauna. The promotion of environmental research must be accompanied by environmental education to foster a society which is more knowledgeable, has more control and influence over the decisions that deeply affect it. Indeed, nature conservation goes hand in hand with other social and economic challenges that require a more sustainable vision. Today's problems with nature derive from the current economic model, which is environmentally unsustainable in that it does not take into account environmental impacts. Lastly, we propose a series of reasonable and feasible priority measures and actions related to each use made of the country's natural resources, to the impacts they have had, and to their management, in the hope that these can contribute to improving the conservation and management of the environment and biodiversity and move towards sustainability

    Impacts of Use and Abuse of Nature in Catalonia with Proposals for Sustainable Management

    Get PDF
    This paper provides an overview of the last 40 years of use, and in many cases abuse, of the natural resources in Catalonia, a country that is representative of European countries in general, and especially those in the Mediterranean region. It analyses the use of natural resources made by mining, agriculture, livestock, logging, fishing, nature tourism, and energy production and consumption. This use results in an ecological footprint, i.e., the productive land and sea surface required to generate the consumed resources and absorb the resulting waste, which is about seven times the amount available, a very high number but very similar to other European countries. This overexploitation of natural resources has a huge impact on land and its different forms of cover, air, and water. For the last 25 years, forests and urban areas have each gained almost 3% more of the territory at the expense of agricultural land; those municipalities bordering the sea have increased their number of inhabitants and activity, and although they only occupy 6.7% of the total surface area, they account for 43.3% of the population; air quality has stabilized since the turn of the century, and there has been some improvement in the state of aquatic ecosystems, but still only 36% are in good condition, while the remainder have suffered morphological changes and different forms of nonpoint source pollution; meanwhile the biodiversity of flora and fauna remains still under threat. Environmental policies do not go far enough so there is a need for revision of the legislation related to environmental impact and the protection of natural areas, flora, and fauna. The promotion of environmental research must be accompanied by environmental education to foster a society which is Land 2021, 10, 144 3 of 53 more knowledgeable, has more control and influence over the decisions that deeply affect it. Indeed, nature conservation goes hand in hand with other social and economic challenges that require a more sustainable vision. Today’s problems with nature derive from the current economic model, which is environmentally unsustainable in that it does not take into account environmental impacts. Lastly, we propose a series of reasonable and feasible priority measures and actions related to each use made of the country’s natural resources, to the impacts they have had, and to their management, in the hope that these can contribute to improving the conservation and management of the environment and biodiversity and move towards sustainability.info:eu-repo/semantics/publishedVersio

    Proyecto de ampliación del puerto de Marbella "la Bajadilla" (Málaga)

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    En el presente documento se definirá la ampliación del puerto de Marbella "La Bajadilla" (Málaga). Los objetivos del proyecto serán aumentar el número de amarres y crear un atraque para cruceros

    Modelaje físico aplicable a aerogeneradores marinos offshore

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    El presente documento tiene como objetivo final explicar la construcción de un modelo de aerogenerador offshore tipo SPAR y describir los ensayos a realizar en las instalaciones del laboratorio del Departamento de Ingeniería Marítima, para que los resultados puedan ser extrapolados al prototipo. Para ello se analizaran las opciones que se describen de prototipo, se propondrá un modelaje físico del mismo y unas condiciones ambientales para la realización de los ensayos. Para la correcta ejecución de los ensayos se expone también una instrumentación y diferentes técnicas para salvar las dificultades de modelización que van surgiendo

    Proyecto de ampliación del puerto de Marbella "la Bajadilla" (Málaga)

    No full text
    En el presente documento se definirá la ampliación del puerto de Marbella "La Bajadilla" (Málaga). Los objetivos del proyecto serán aumentar el número de amarres y crear un atraque para cruceros

    Modelaje físico aplicable a aerogeneradores marinos offshore

    No full text
    El presente documento tiene como objetivo final explicar la construcción de un modelo de aerogenerador offshore tipo SPAR y describir los ensayos a realizar en las instalaciones del laboratorio del Departamento de Ingeniería Marítima, para que los resultados puedan ser extrapolados al prototipo. Para ello se analizaran las opciones que se describen de prototipo, se propondrá un modelaje físico del mismo y unas condiciones ambientales para la realización de los ensayos. Para la correcta ejecución de los ensayos se expone también una instrumentación y diferentes técnicas para salvar las dificultades de modelización que van surgiendo
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