Utilidad de las queratinas séricas en el diagnóstico de las enfermedades hepáticas

A determinación de K18 (TPS) sérica engade información aos marcadores habituais de dano hepático. En contrapartida, o seu valor como marcador tumoral (o seu deseño orixinal como marcador sérico) verase comprometido nos pacientes con enfermidade hepática. Nesta tese estúdiase a súa utilidade no diagnóstico de pacientes nos pacientes con hepatite crónica por virus C, pacientes con abuso de alcohol, con fígado graxo non alcohólico, con hepatopatías autoinmunes e tamén nos pacientes con transplante hepático

SUMOylation regulates LKB1 localization and its oncogenic activity in liver cancer

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

Estudio de la intercara en materiales compuestos tipo cermet para el diseño de matrices metálicas alternativas

La ponencia presentada en: XI Congreso Nacional de Materiales Compuestos, celebrado los días 6, 7 y 8 de julio de 2015, en Móstoles (España).Uno de los grandes temas de investigación actual en el campo de los materiales compuestos tipo cermet base TiCN es la búsqueda de matrices metálicas alternativas a las convencionales las cuales cuentan en su composición Ni y/o Co de manera mayoritaria. El objetivo principal que debe cumplir el cermet con una matriz metálica alternativa es alcanzar propiedades similares e incluso superiores a las obtenidas con matrices convencionales utilizando materiales más económicos e inocuos. Además, siendo un material compuesto, a la hora de diseñar la composición de una nueva matriz metálica se debe tener en cuenta cómo es su interacción con el refuerzo cerámico. Este concepto cobra una mayor importancia en este tipo de materiales debido a que su fabricación se lleva a cabo mediante sinterización en fase líquida y las propiedades finales del material compuesto dependerán de la mojabilidad y solubilidad entre ambas fases. Algunas investigaciones sobre cermets reforzados con partículas de TiCN y matriz convencional han concluido que carburos como WC ó Mo2C tienen una gran influencia en la sinterabilidad de estos materiales compuestos porque mejoran la mojabilidad de la matriz metálica sobre el refuerzo cerámico. El objetivo principal de este trabajo es el estudio sistemático de la influencia de estos carburos en la sinterabilidad de un cermet base TiCN con Fe como matriz metálica. Para ello se ha estudiado la solubilidad entre ambas fases estudiando su intercara tanto de forma experimental como mediante herramientas de simulación termodinámica y cinética utilizando el software Dictra. Gracias a los resultados obtenidos se crea una metodología de trabajo que permite conocer la influencia de la composición en la solubilidad entre las dos fases siendo una herramienta útil en el diseño de nuevas matrices metálicas alternativas en cermets.Los autores agradecen la financiación recibida para la realización de este trabajo al MINECO (proyecto MAT2012-38650-C02-01) y a la Comunidad de Madrid por el programa MULTIMAT-CHALLENGE, ref. S2013/MIT-2862.Publicad

XII Congreso de didáctica de la Geografía. Madrid, octubre de 2018

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Notes for a didactic model of critical geography. Analysis and evaluation of a classroom experience with university students from Galicia (Spain)

This article presents a didactic model of critical geography, based on instruction recommendations for the teaching and learning of geography and social sciences. This is all with a very clear idea: to depart from a descriptive and reflective geography and move to an active and critical geography. Geography in which students participate in the construction of knowledge and increase their ability to reflect on geographical issues. The proposed didactic model drives active and critical geography in the classrooms. It starts with the analysis of territorial problems in Europe and makes them the object of research and reflection. The idea is not to dictate geography in classrooms but to introduce methodologies, resources and sources to carry out geographic research with students. With this idea in mind, the second part of the article examines the value of our didactic model through the analysis of fifteen research projects on European natural spaces carried out in the academic years of 2014-2015 and 2015-2016 with 74 university students in training to be geography teachers in secondary education. The results show that the students’ didactic expectations grow when given geographic research to do as teaching practice.This research has received funding from the Programme for Research, Development and Technological Innovation oriented to the Challenges of Society (CSO2016- 75236-C2-1-R) and the National Plan of R&D from the Spanish Government (EDU2015-65621-C3-1-R) co-financed with ERDF funds from the European UnionS

In-situ mechanical and microstructural characterization of miniaturized Al-Mg-Sc-Zr and AlSi10Mg specimens processed by laser powder-bed fusion (PBF-LB)

Manufacturing through powder-bed fusion laser-beam (PBF-LB) enables innovative part design strategies, facilitating weight reduction, and capitalizing on the metallurgical conditions developed during the manufacturing of designed alloys. Consequently, Al-based light alloys hold enormous potential for reducing fuel consumption in the transport industry. Fabricating such small features has a significant impact on heat dissipation, thereby affecting microstructure, porosity, and, consequently, mechanical properties. This study proposesthe use of near-net shape miniaturized tensile specimens in both horizontal and vertical orientations to characterize Al-Mg-Sc-Zr, commercially known as Scalmalloy®, and AlSi10Mg, two aluminum alloys typicallyemployed in PBF-LB. The size and distribution of both grains and pores were analyzed and compared, with Al-Mg-Sc-Zr exhibiting a more competitive set of properties compared to AlSi10Mg. This difference also influences mechanical properties. Al-Mg-Sc-Zr demonstrated double the Ultimate Tensile Strength (UTS) of AlSi10Mg (450MPa versus 225 MPa) and higher hardness values (142 HV30 versus 75 HV30), with similar elongation in both alloys (approximately 12–16%), owing to its fine microstructure and low porosity of the near-net shape miniaturized tensile specimens. Neither material exhibited any form of anisotropy. In-situ SEM tensile tests were conducted to monitor damage evolution, allowing continuous observation of crack nucleation and propagation through imperfections typically encountered in PBF-LB. Despite differences in static strength, the fracture sur-faces of the samples displayed a ductile behavior in both materials

Teaching and learning landscape in primary education in Spain: A necessary curricular review to educate citizens

The study of landscape is not new, nor is society’s concern for the environment. It occupies a central place in teaching geography and offers many opportunities for the integration of one’s own contents of geographic education. Landscape must be presented as a portion of space on the Earth's surface where natural elements and the actions of human beings interact, a complex reality where nature and culture mix. Knowing a landscape means more than knowing a portion of the territory, it also implies understanding the social groups and peoples that inhabit it. In this regard, and in addition to the study of exceptional, singular, or exotic landscapes, it is necessary to value the importance of ordinary landscapes close to schoolchildren. In this article, a curricular review of primary education in Galicia (Spain) is carried out with the aim of knowing how the study of landscape is approached, also taking into account the guidelines set out in the basic curricula at the national level

Effect of mechanical alloying on the microstructural evolution of a ferritic ODS steel with (Y-Ti-Al-Zr) addition processed by Spark Plasma Sintering (SPS)

The high-energy milling is one of the most extended techniques to produce Oxide dispersion strengthened (ODS) powder steels for nuclear applications. The consequences of the high energy mill process on the final powders can be measured by means of deformation level, size, morphology and alloying degree. In this work, an ODS ferritic steel, Fe-14Cr-5Al-3W-0.4Ti-0.25Y2O3-0.6Zr, was fabricated using two different mechanical alloying (MA) conditions (Mstd and Mact) and subsequently consolidated by Spark Plasma Sintering (SPS). Milling conditions were set to evidence the effectivity of milling by changing the revolutions per minute (rpm) and dwell milling time. Differences on the particle size distribution as well as on the stored plastic deformation were observed, determining the consolidation ability of the material and the achieved microstructure. Since recrystallization depends on the plastic deformation degree, the composition of each particle and the promoted oxide dispersion, a dual grain size distribution was attained after SPS consolidation. Mact showed the highest areas of ultrafine regions when the material is consolidated at 1100 degrees C. Microhardness and small punch tests were used to evaluate the material under room temperature and up to 500 degrees C. The produced materials have attained remarkable mechanical properties under high temperature conditions.Authors want to acknowledge Ferro-Ness project and Ferro- Genesys project funded by MINECO under National I + D + I program MAT2016-80875-C3-3-R and MAT2013-47460-C5-5-P

A novel efficient solver for Ampere's equation in general toroidal topologies based on singular value decomposition techniques

A new method is proposed to solve Ampere's equation in an arbitrary toroidal domain in which all currents are known, given proper boundary conditions for the magnetic vector potential. The novelty of the approach lies in the application of singular value decomposition (SVD) techniques to tackle the difficulties caused by the kernel associated by the curl operator. This kernel originates physically due to the magnetic field gauge. To increase the efficiency of the solver, the problem is represented by means of a dual finite difference-spectral scheme in arbitrary generalized toroidal coordinates, which permits to take advantage of the block structure exhibited by the matrices that describe the discretized problem. The result is a fast and efficient solver, up to three times faster than the double-curl method in some cases, that provides an accurate solution of the differential form of Ampere law while guaranteeing a zero divergence of the resulting magnetic field down to machine precision.This research has been sponsored in part by the Ministerio de Economía y Competitividad (MINECO) of Spain under Project No. ENE2015-68265-P. Use have also been made of Uranus, a supercomputer cluster located at Universidad Carlos III de Madrid (Spain) funded jointly by EU FEDER Project No. UNC313-4E-2361, by the Ministerio de Economía, Industria y Competitividad (MICINN) via the National Research Project No. ENE2009-12213-C03-03 and by the Ministerio de Economía y Competitividad (MINECO) via the National Research Project Nos. ENE2012-33219 and ENE2012-31753