473 research outputs found

    SUMOylation regulates LKB1 localization and its oncogenic activity in liver cancer

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    BACKGROUND: Even though liver kinase B1 (LKB1) is usually described as a tumor suppressor in a wide variety of tissues, it has been shown that LKB1 aberrant expression is associated with bad prognosis in Hepatocellular Carcinoma (HCC). METHODS: Herein we have overexpressed LKB1 in human hepatoma cells and by using histidine pull-down assay we have investigated the role of the hypoxia-related post-translational modification of Small Ubiquitin-related Modifier (SUMO)ylation in the regulation of LKB1 oncogenic role. Molecular modelling between LKB1 and its interactors, involved in regulation of LKB1 nucleocytoplasmic shuttling and LKB1 activity, was performed. Finally, high affinity SUMO binding entities-based technology were used to validate our findings in a pre-clinical mouse model and in clinical HCC. FINDINGS: We found that in human hepatoma cells under hypoxic stress, LKB1 overexpression increases cell viability and aggressiveness in association with changes in LKB1 cellular localization. Moreover, by using site-directed mutagenesis, we have shown that LKB1 is SUMOylated by SUMO-2 at Lys178 hampering LKB1 nucleocytoplasmic shuttling and fueling hepatoma cell growth. Molecular modelling of SUMO modified LKB1 further confirmed steric impedance between SUMOylated LKB1 and the STe20-Related ADaptor cofactor (STRADα), involved in LKB1 export from the nucleus. Finally, we provide evidence that endogenous LKB1 is modified by SUMO in pre-clinical mouse models of HCC and clinical HCC, where LKB1 SUMOylation is higher in fast growing tumors. INTERPRETATION: Overall, SUMO-2 modification of LKB1 at Lys178 mediates LKB1 cellular localization and its oncogenic role in liver cancer. FUND: This work was supported by grants from NIH (US Department of Health and Human services)-R01AR001576-11A1 (J.M.M and M.L.M-C.), Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M.-C), MINECO: SAF2017-87301-R and SAF2014-52097-R integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M., respectively), BFU2015-71017/BMC MINECO/FEDER, EU (to A.D.Q. and I.D.M.), BIOEF (Basque Foundation for Innovation and Health Research): EITB Maratoia BIO15/CA/014; Instituto de Salud Carlos III:PIE14/00031, integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovacion 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M), Asociación Española contra el Cáncer (T.C.D, P·F-T and M.L.M-C), Daniel Alagille award from EASL (to T.C.D), Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M and M.A), La Caixa Foundation Program (to M.L.M), Programma di Ricerca Regione-Università 2007-2009 and 2011-2012, Regione Emilia-Romagna (to E.V.), Ramón Areces Foundation and the Andalusian Government (BIO-198) (A.D.Q. and I.D.M.), ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.), MINECO:SAF2015-64352-R (P.A.), Institut National du Cancer, FRANCE, INCa grant PLBIO16-251 (M.S.R.), MINECO - BFU2016-76872-R to (E.B.). Work produced with the support of a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (M.V-R). Finally, Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). Funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

    Catalytic production of jet fuels from biomass

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    Concerns about depleting fossil fuels and global warming e ects are pushing our society to search for new renewable sources of energy with the potential to substitute coal, natural gas, and petroleum. In this sense, biomass, the only renewable source of carbon available on Earth, is the perfect replacement for petroleum in producing renewable fuels. The aviation sector is responsible for a significant fraction of greenhouse gas emissions, and two billion barrels of petroleum are being consumed annually to produce the jet fuels required to transport people and goods around the world. Governments are pushing directives to replace fossil fuel-derived jet fuels with those derived from biomass. The present mini review is aimed to summarize the main technologies available today for converting biomass into liquid hydrocarbon fuels with a molecular weight and structure suitable for being used as aviation fuels. Particular emphasis will be placed on those routes involving heterogeneous catalysts

    Hacia una visión antropológica como una identidad funcional, en niños y jóvenes en condición de discapacidad visual, en santa marta. Mitos, estigmas y contradicciones de dicha población.

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    La investigación etnográfica no tiene como primer plano, pretensiones universales, lo cual no la exime de estudiar, conocer y servir a una comunidad en este caso la población en situación de discapacidad sensorial visual, a mediano tiempo, se utilizará el teatro antropológico y la representación del mito en el espacio, como desarrollo psicosocial y por ende mejorar la calidad de vida de dicha unidad de análisis, por ultimo su fin remoto a largo tiempo es llegar a descubrir y establecer teorías generales. La discapacidad está considerada como un problema de la salud pública, puesto que afecta millones de personas en el mundo y les impide el acceso a una vida plena y su integración adecuada a la vida social. Esta situación agrupa un complicado conjunto de condiciones, muchas de las cuales emerge del complejo contexto entorno social. La investigación parcial, muestra como en Santa Marta, solo existen 2 organizaciones acreditadas, para atender a la población en situación de discapacidad visual

    Hacia una visión antropológica como identidad funcional, en niños y jóvenes en condición de discapacidad sensorial visual en Santa Marta

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    La Biblioteca Cajamag forma parte de la comunidad y propende por el bienestar y desarrollo formativo, cultural, social y económico del Dpto. del Magdalena, para satisfacer las necesidades de Información y conocimiento, involucrando en la prestación de sus servicios toda clase de herramientas que contribuyan al desarrollo intelectual de nuestros usuarios, afiliados y comunidad en general. Cajamag a través de la biblioteca promueve el programa “Oídos para Ver “el cual va dirigido a niños, niñas, jóvenes y adultos que presentan discapacidad visual y tiene como fin, fortalecer las capacidades cognitivas, e intelectuales relacionadas con la informática a través del empleo de herramientas tecnológicas, que les permitirán afrontar los retos del mundo actual, además les brindad la oportunidad de integrarse con personas de su misma condición de discapacidad

    A Study on the Parametric Design Parameters That Influence Environmental Ergonomics and Sustainability

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    The publication is part of Grant FJC2021-047711-I, funded by MCIN/AEI/10.13039/5011000 11033 and by the European Union NextGenerationEU/PRTR awarded to Carmen Díaz-López through contract reference USE-23442-MThe parametric design applied to the built environment is critical to creating sustainable and resilient spaces. However, this research field involves a vast and complex amount of disconnected information. Therefore, this paper aims to analyse research trends in applying parametric design to optimise sustainability and environmental ergonomics parameters in built environments. The following specific objectives are identified to meet this objective: (i) a quantitative analysis based on a systematic literature review; (ii) a qualitative review based on a performance analysis and scientific mapping; and (iii) a comparative analysis of case studies applying parametric language for the optimisation of sustainability and environmental ergonomics parameters. The 1045 research records covering 1974 to 2021 illustrate a field in development that evolves from early digital advances to climate change adaptations, the circular economy and resilience. It highlights the importance of applying bioclimatic techniques in the built environment, identifying the most optimised measures and encouraging the creation of guidelines to serve as a protocol for future studies, contributing to the existing body of knowledge by highlighting trends, establishing research themes, outlining research networks and suggesting areas for further studies.MCIN/AEI FJC2021-047711-IEuropean Commission USE-23442-

    Promoting Sustainable and Resilient Constructive Patterns in Vulnerable Communities: Habitat for Humanity’s Sustainable Housing Prototypes in El Salvador

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    The global challenges regarding sustainability and the guarantee of minimum habitability requirements have led to the transformation of construction practices, where research has failed to achieve sufficient dissemination and findings. The purpose of this research is to promote sustainable and resilient patterns in construction in vulnerable neighbourhoods in emerging countries by disseminating techniques and mechanisms through in situ transfer workshops and by raising awareness of the environmental importance of construction. Regarding materials and methods, this paper contributes innovative insights by combining training workshops and awareness-raising sessions to promote both environmental education and sustainable and optimised habits in construction. These methods are applied and tested in a real case study in El Salvador. Subsequent to carrying out a multi-disciplinary assessment analysis, the outcomes and results have led to the design of prototypes that have obtained a global EDGE certificate on sustainable construction and efficient use of resources once the users’ testimonies, weaknesses, and strengths have been addressed. The conclusions indicate that families, volunteers, and technical workers need to be trained by promoting environmental awareness in social housing and establishing a plan for dissemination to communicate across universities and public and private institutions in order to replicate guidelines across American dry-corridor countries.University of Seville US-AYP/18/2022 US-2020UI003 US-d07/201

    Electrochemical reduction of CO2: overcoming chemical inertness at ambient conditions

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    Electroreduction allows for the transformation of a chemically inert molecule such as CO2 into a wide variety of useful carbon products. Unlike other approaches operating at higher temperatures, electrochemical reduction holds great promise since it achieves reduction under ambient conditions, thereby providing more control over the reaction selectivity. By controlling basic parameters such as the potential and the composition of the electrode, CO2 can be transformed into a variety of products including carbon monoxide, syngas (CO/H2), methane, and methanol. This reduction process takes place without external hydrogen, since water can be used as a source of both electrons and protons. Furthermore, this technology, when combined with renewable wind- or solar-derived electricity, has the potential to serve as a storage system for excess electricity. Despite these advantages, a number of challenges need to be overcome before reaching commercialization. New (and cheaper) electrocatalyst formulations with high faradaic selectivities are required. Impressive progress has been made on carbon-doped materials, which, in certain cases, have outperformed expensive noble metal-based materials. Research is also needed on new electrochemical reactor configurations able to overcome kinetic/mass transport limitations, which are crucial to reduce overpotentials. Fine control over the nature of the active sites and the reaction conditions is important to avoid parasitic reactions such as the hydrogen evolution reaction (HER), and therefore increases the faradaic e ciency towards the desired products

    Recent advances in the electroreduction of CO2 over heteroatom-doped carbon materials

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    Ever-growing anthropogenic activity has increased global energy demands, resulting in growing concentrations of greenhouse gases such as CO2 in the atmosphere. The electroreduction of CO2 has been proposed as a potential solution for reducing anthropogenic CO2 emissions. Despite the promising results obtained so far, some limitations hinder large-scale applications, especially those associated with the activity and selectivity of electrocatalysts. A good number of metal catalysts have been studied to overcome this limitation, but the high cost and low earth abundance of some of these materials are important barriers. In this sense, carbon materials doped with heteroatoms such as N, B, S, and F have been proposed as cheaper and widely available alternatives to metal catalysts. This review summarizes the latest advances in the utilization of carbon-doped materials for the electroreduction of CO2, with a particular emphasis on the synthesis procedures and the electrochemical performance of the resulting materials

    Multi-criteria assessment model on environmental ergonomics for decision-making in schoolyards based on remote-sensing and GIS resources

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    The consequences of global warming have led to an acceleration of action strategies towards efficient and passive renovation work in the building stock. Most existing schoolyards are becoming obsolete with respect to current bioclimatic design patterns, for which a lack of methodological studies and diagnosis mechanisms in outdoor spaces has been identified. This research aims to design a multi-criteria assessment model on environmental ergonomics for the identification of feasible and passive measures that improve comfort conditions in schoolyards. The innovation of this system lies in its basis on weighting data that combines 12 qualitative, quantitative, and graphical parameters by using remote-sensing algorithms and GIS resources, leading to major insights regarding remote information acquisition capabilities for the promotion of bioclimatic actions in schools. The model is applied and tested in 6 representative pilot schools to demonstrate its operation and replicability. An innovative graphic output of results provides a significant research outcome, which contributes towards the visualisation of the diagnosis on environmental ergonomics and identifies potentials and weaknesses for decision-making. The conclusions focus on methodological insights and implications from an integral diagnosis for schoolyards, thereby serving as a decision-support system to identify optimal interventions that would ensure a more appropriate environmental performance.European Commission US-15547Andalusian Government US.20-06 POSTDOC_21_00575Spanish Government PID2021-124539OB-I00European project Horizon 2020-10103650
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