120 research outputs found

    Los grabados paleolíticos del techo policromo de Altamira. Estudio, revisión y elaboración del mapa de los grabados a partir de la fotografía de alta resolución

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    En esta tesis doctoral se presenta la revisión de los grabados paleolíticos del techo policromo de Altamira. Se muestran los resultados obtenidos a la vez que se realiza una comparativa con los publicados por los prehistoriadores Henri Breuil y Hugo Obermaier en su obra La cueva de Altamira en Santillana del Mar, teniendo en cuenta, además, los datos aportados por las sucesivas investigaciones realizadas hasta la fecha. En última instancia, se presenta el mapa completo de los grabados del techo policromo de Altamira. METODOLOGÍA Esta investigación se ha acometido mediante una metodología de carácter indirecto, basada en la fotografía de alta resolución, debido a las circunstancias en las que se halla este yacimiento que, por motivos de conservación, permanece cerrado desde el año 2002, viéndose sometido a un permanente y rígido control ambiental. Para ello, se ha recurrido al valioso archivo fotográfico del catedrático de la facultad de Bellas Artes de la Universidad Complutense de Madrid, D. Pedro Saura Ramos, que desde hace más de tres décadas viene realizando sobre la cueva Altamira en sucesivas sesiones. A partir de este archivo y aplicando programas digitales de tratamiento de imágenes, se ha llevado a cabo la revisión, análisis y registro de los grabados paleolíticos del techo policromo de Altamira..

    Decoding protein methylation function with thermal stability analysis

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    Methylation; ProteomicsMetilació; ProteòmicaMetilación; ProteómicaProtein methylation is an important modification beyond epigenetics. However, systems analyses of protein methylation lag behind compared to other modifications. Recently, thermal stability analyses have been developed which provide a proxy of a protein functional status. Here, we show that molecular and functional events closely linked to protein methylation can be revealed by the analysis of thermal stability. Using mouse embryonic stem cells as a model, we show that Prmt5 regulates mRNA binding proteins that are enriched in intrinsically disordered regions and involved in liquid-liquid phase separation mechanisms, including the formation of stress granules. Moreover, we reveal a non-canonical function of Ezh2 in mitotic chromosomes and the perichromosomal layer, and identify Mki67 as a putative Ezh2 substrate. Our approach provides an opportunity to systematically explore protein methylation function and represents a rich resource for understanding its role in pluripotency.We thank all members of the CNIO Proteomics Unit for discussions, the CNIO Flow Cytometry Unit for flow cytometry support, Cyan Lynch for sharing reagents and Ana Martinez-Val for support with data analysis. This work was supported by SAF2016-74962-R (MINECO) and the European Union Horizon 2020 program INFRAIA project EPIC-XS (project 823839). The CNIO Proteomics Unit belongs to ProteoRed, PRB3- ISCIII, supported by grant PT17/0019/0005. J.M. is supported by the Ikerbasque Programme, Basque Foundation for Science. O.F-C. is supported by grants from the Spanish Ministry of Science, Innovation and Universities (PID2021-128722OB-I00, co-financed with European FEDER funds) and the Spanish Association Against Cancer (AECC; PROYE20101FERN). M.M. lab was supported by grants from MINECO (PID2021-128726 and PDC2022-133408-I00), and Comunidad de Madrid (Y2020/BIO-6519 and S2022/BMD-7437)

    Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

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    INTRODUCTION: Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. METHODS: Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. RESULTS: Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. CONCLUSIONS: The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE

    Recycling Bio-BasedWastes into Road-Base Binder: Mechanical, Leaching, and Radiological Implications

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    This work presents a physical, mechanical, durability, leaching, and radiological assay of three wastes (egg and scallop shells and olive pomace ash) as road-base binders. Two different waste/Portland-cement ratios (7.5/92.5 and 80/20) were studied. Density and compressive strength decreased when different wastes were added in every proportion. Additions of 7.5% of both shells reduce the density to about 2.5% and the compressive strength to 20%, while 80% reduces the density to 20% and the compressive strength to 90%, while the addition of biomass fly ash decreases the density and compressive strength in a higher proportion than shells. The durability against acid attack is increased when the three wastes are used, and this increase is higher when the waste dosage is increased (up to 15 times more when 80% biomass ash is used). With respect to leaching, scallop and eggshells can be used as a component of hydraulic road binder, but olive pomace ash presents leaching values higher than the limits of different regulations (Se, Pb, Ni, Mo, Cu, and As). From a radiological perspective, all road-base binders present an activity concentration index lower than 1, except when olive pomace ash was used, and the binders showed higher values of 40K due to the high potassium content of fly ash

    Functional characterization of twelve natural PROS1 mutations associated with anticoagulant protein S deficiency

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    Background The molecular mechanisms by which PROS1 mutations result in protein S deficiency are still unknown for many of the mutations, particularly for those that result in a premature termination codon. The aim of this study was to analyze the functional relevance on mRNA and protein expression of 12 natural PROS1 mutations associated with protein S deficiency. Design and Methods Five mutations were nonsense, three were small frameshift deletions, one was c.258,259AG>GT at the 3' end of exon 3, one was p.M640T and the last two were c.-7C>G and p.L15H, found in double heterozygosis as [c.-7C>G;44T>A].The apparently neutral variant p.R233K was also analyzed. PROS1 cDNA was assessed by reverse transcriptase polymerase chain reaction of platelet mRNA. Expression of mutant proteins was determined by site-directed mutagenesis and analyses of transiently transfected PROS1 mutants in COS-7 cells. Results Only cDNA from the normal allele was observed from the five nonsense mutations, the frameshift deletion c.1731delT and from c.258,259AG>GT. Both the normal and the mutated alleles were observed from [c.-7C>G;44T>Aj, c.187,188delTG and p.M640T Transient expression analyses of PROS1 mutants whose mRNA was normally expressed revealed greatly reduced secretion of p.L15H and c.1272delA, mild secretion values of p.M640T and normal secretion levels of c.7C>G and, as expected, p.R233K. Conclusions Whereas the main cause of quantitative protein S deficiency associated with missense mutations is defective synthesis, stability or secretion of the mutated protein, the main mechanism for the deficiency associated with mutations that generate a premature termination codon is not the synthesis of a truncated protein, but the exclusion of the mutated allele, probably by nonsense-mediated mRNA decay

    Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

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    Introduction: Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. Methods: Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. Results: Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. Conclusions: The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE

    Dimensiones y principios para el diseño de espacios educativos desde la investigación

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    Podeu consultar el llibre complet a: http://hdl.handle.net/2445/164579[spa] Los avances experimentados en el ámbito de la educación requieren poner atención preeminente en la investigación sobre cuáles son los cambios que debería experimentar la configuración y la organización del espacio de aprendizaje), así como las condiciones, las dinámicas y las metodologías que en estos espacios se desarrollan. Este paper presenta los primeros resultados y diseños del proyecto: “SMART CLASSROOM Codiseño de entornos de aprendizaje innovadores: investigando nuevos modelos de aula”. De este modo, se ha llevado a cabo un proceso de codiseño aplicando el diseño basado en la investigación.[eng] The advances in the field of education require a preeminent attention in what changes should be done in the configuration and organization of the learning space, as well as the conditions, dynamics and methodologies that should take place inside the spaces designed. This paper presents the first results and designs of the project: SMART CLASSROOM, Co-design of innovative learning environments: researching new classroom models. A co-design process has been carried out following the steps of a research-based design

    The alhambra survey: evolution of galaxy spectral segregation

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    We study the clustering of galaxies as a function of spectral type and redshift in the range 0.35 <z <1.1 using data from the Advanced Large Homogeneous Area Medium Band Redshift Astronomical (ALHAMBRA) survey. The data cover 2.381 deg2 in 7 fields, after applying a detailed angular selection mask, with accurate photometric redshifts down to IAB <24. From this catalog we draw five fixed number density redshift-limited bins. We estimate the clustering evolution for two different spectral populations selected using the ALHAMBRA-based photometric templates: quiescent and star-forming galaxies. For each sample we measure the real-space clustering using the projected correlation function. Our calculations are performed over the range [0.03, 10.0] h-1 Mpc, allowing us to find a steeper trend for Mpc, which is especially clear for star-forming galaxies. Our analysis also shows a clear early differentiation in the clustering properties of both populations: star-forming galaxies show weaker clustering with evolution in the correlation length over the analyzed redshift range, while quiescent galaxies show stronger clustering already at high redshifts and no appreciable evolution. We also perform the bias calculation where similar segregation is found, but now it is among the quiescent galaxies where a growing evolution with redshift is clearer (abrigatted). These findings clearly corroborate the well-known color-density relation, confirming that quiescent galaxies are mainly located in dark matter halos that are more massive than those typically populated by star-forming galaxies.Ministerio de Economía y Competitividad y FEDER AYA2010-22111-C03-02 AYA2013-48623-C2-2 AYA2012-39620 AYA2013-40611-P AYA2013-42227-P AYA2013-43188-P AYA2013-48623-C2-1 ESP2013-48274 AYA2014-58861-C3-1Junta de Andalucía TIC114 JA2828 P10-FQM-644
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