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Papers by Victor gonzalez rumayor
European Journal of Pharmaceutics and Biopharmaceutics
Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic op... more Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. Here, we present ADEx (https://adex.genyo.es), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis.
Bioinformatics, 2019
Motivation The identification of differentially methylated regions (DMRs) among phenotypes is one... more Motivation The identification of differentially methylated regions (DMRs) among phenotypes is one of the main goals of epigenetic analysis. Although there are several methods developed to detect DMRs, most of them are focused on detecting relatively large differences in methylation levels and fail to detect moderate, but consistent, methylation changes that might be associated to complex disorders. Results We present mCSEA, an R package that implements a Gene Set Enrichment Analysis method to identify DMRs from Illumina450K and EPIC array data. It is especially useful for detecting subtle, but consistent, methylation differences in complex phenotypes. mCSEA also implements functions to integrate gene expression data and to detect genes with significant correlations among methylation and gene expression patterns. Using simulated datasets we show that mCSEA outperforms other tools in detecting DMRs. In addition, we applied mCSEA to a previously published dataset of sibling pairs disco...
Arthritis & Rheumatology, 2017
Objective. Granzyme A (GzmA) levels are elevated in the plasma and synovium of patients with rheu... more Objective. Granzyme A (GzmA) levels are elevated in the plasma and synovium of patients with rheumatoid arthritis (RA), suggesting involvement of this protease in the pathogenesis of the disease. GzmA contributes to sepsis by regulating the production of proinflammatory cytokines. The purpose of this study was to evaluate the contribution of GzmA to the pathogenesis of RA in vivo and to examine the possibility that GzmA acting via tumor necrosis factor (TNF) stimulates osteoclastogenesis. Methods. Inflammatory arthritis induced by type II collagen was evaluated in wild-type, GzmA-deficient, and perforin-deficient mice. The osteoclastogenic potential of GzmA was examined in vitro using bone marrow cells and colony-forming unit-granulocyte-macrophage (CFU-GM) cells and in vivo using GzmA-deficient mice. Results. Gene deletion of GzmA attenuated collagen-induced arthritis, including serum levels of proinflammatory cytokines, joint damage, and bone erosion in affected mice, suggesting that osteoclast activity is reduced in the absence of GzmA. Accordingly, GzmAtreated bone marrow cells produced multinucleated cells that fulfilled the criteria for mature osteoclasts: tartrateresistant acid phosphatase (TRAP) activity, b integrin expression, calcitonin receptor expression, and resorptive activity on dentin slices. GzmA appeared to act without accessory cells, and its activity was not affected by osteoprotegerin, suggesting a minor contribution of RANKL. It also induced the expression and secretion of TNF. Neutralization of TNF or stimulation of CFU-GM cells from TNF-/mice prevented GzmA-induced osteoclastogenesis. GzmA-deficient mice had reduced osteoclastogenesis in vivo (fewer calcitonin receptor-positive multinucleated cells and fewer transcripts for cathepsin K, matrix metalloproteinase 9, and TRAP in joints) and reduced serum levels of C-terminal telopeptide of type I collagen. Conclusion. GzmA contributes to the joint destruction of RA partly by promoting osteoclast differentiation.
Se han puesto a punto tecnicas de cultivo de tejidos de Crocus sativus L. encaminadas a la produc... more Se han puesto a punto tecnicas de cultivo de tejidos de Crocus sativus L. encaminadas a la produccionde azafran in vitro. Para ello se han seguido dos estrategias. Por una parte se ha procedido al estudio de los factores que afectan a la regeneracion de estigmas, evaluando la productividad del sistema en cada una de las condiciones analizadas. En segundo lugar se ha procedido a la obtencion de callos con el objetivo de establecer suspensiones celulares con capacidad biosintetica, de los compuestos cruciales del azafran (croacina, picrocroacina y safranal) que sirven de base para la produccion de azafran molido. En este caso se han estudiado tambien las condiciones de cultivo que conducen tanto a la mayor produccion de biosoma como a los mayores niveles de produccion de metabolitos secundarios. En todos los casos se han analizado las caracteristicas organolepticas del azafran obtenido in vitro.
European Journal of Pharmaceutics and Biopharmaceutics
Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic op... more Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. Here, we present ADEx (https://adex.genyo.es), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis.
Bioinformatics, 2019
Motivation The identification of differentially methylated regions (DMRs) among phenotypes is one... more Motivation The identification of differentially methylated regions (DMRs) among phenotypes is one of the main goals of epigenetic analysis. Although there are several methods developed to detect DMRs, most of them are focused on detecting relatively large differences in methylation levels and fail to detect moderate, but consistent, methylation changes that might be associated to complex disorders. Results We present mCSEA, an R package that implements a Gene Set Enrichment Analysis method to identify DMRs from Illumina450K and EPIC array data. It is especially useful for detecting subtle, but consistent, methylation differences in complex phenotypes. mCSEA also implements functions to integrate gene expression data and to detect genes with significant correlations among methylation and gene expression patterns. Using simulated datasets we show that mCSEA outperforms other tools in detecting DMRs. In addition, we applied mCSEA to a previously published dataset of sibling pairs disco...
Arthritis & Rheumatology, 2017
Objective. Granzyme A (GzmA) levels are elevated in the plasma and synovium of patients with rheu... more Objective. Granzyme A (GzmA) levels are elevated in the plasma and synovium of patients with rheumatoid arthritis (RA), suggesting involvement of this protease in the pathogenesis of the disease. GzmA contributes to sepsis by regulating the production of proinflammatory cytokines. The purpose of this study was to evaluate the contribution of GzmA to the pathogenesis of RA in vivo and to examine the possibility that GzmA acting via tumor necrosis factor (TNF) stimulates osteoclastogenesis. Methods. Inflammatory arthritis induced by type II collagen was evaluated in wild-type, GzmA-deficient, and perforin-deficient mice. The osteoclastogenic potential of GzmA was examined in vitro using bone marrow cells and colony-forming unit-granulocyte-macrophage (CFU-GM) cells and in vivo using GzmA-deficient mice. Results. Gene deletion of GzmA attenuated collagen-induced arthritis, including serum levels of proinflammatory cytokines, joint damage, and bone erosion in affected mice, suggesting that osteoclast activity is reduced in the absence of GzmA. Accordingly, GzmAtreated bone marrow cells produced multinucleated cells that fulfilled the criteria for mature osteoclasts: tartrateresistant acid phosphatase (TRAP) activity, b integrin expression, calcitonin receptor expression, and resorptive activity on dentin slices. GzmA appeared to act without accessory cells, and its activity was not affected by osteoprotegerin, suggesting a minor contribution of RANKL. It also induced the expression and secretion of TNF. Neutralization of TNF or stimulation of CFU-GM cells from TNF-/mice prevented GzmA-induced osteoclastogenesis. GzmA-deficient mice had reduced osteoclastogenesis in vivo (fewer calcitonin receptor-positive multinucleated cells and fewer transcripts for cathepsin K, matrix metalloproteinase 9, and TRAP in joints) and reduced serum levels of C-terminal telopeptide of type I collagen. Conclusion. GzmA contributes to the joint destruction of RA partly by promoting osteoclast differentiation.
Se han puesto a punto tecnicas de cultivo de tejidos de Crocus sativus L. encaminadas a la produc... more Se han puesto a punto tecnicas de cultivo de tejidos de Crocus sativus L. encaminadas a la produccionde azafran in vitro. Para ello se han seguido dos estrategias. Por una parte se ha procedido al estudio de los factores que afectan a la regeneracion de estigmas, evaluando la productividad del sistema en cada una de las condiciones analizadas. En segundo lugar se ha procedido a la obtencion de callos con el objetivo de establecer suspensiones celulares con capacidad biosintetica, de los compuestos cruciales del azafran (croacina, picrocroacina y safranal) que sirven de base para la produccion de azafran molido. En este caso se han estudiado tambien las condiciones de cultivo que conducen tanto a la mayor produccion de biosoma como a los mayores niveles de produccion de metabolitos secundarios. En todos los casos se han analizado las caracteristicas organolepticas del azafran obtenido in vitro.