Calcineurin expression and activity is regulated by the intracellular redox status and under hypertension in human neutrophils

Calcineurin (protein phosphatase 2B) (CN) comprises a family of serine/threonine phosphatases that play a pivotal role in signal transduction cascades in a variety of cells, including neutrophils. Angiotensin II (Ang II) increases both activity and de novo synthesis of CN in human neutrophils. This study focuses on the role that intracellular redox status plays in the induction of CN activity by Ang II. Both de novo synthesis of CN and activity increase promoted by Ang II were downregulated when cells were treated with l-buthionine-(S,R)-sulfoximine, an inhibitor of synthesis of the antioxidant glutathione. We have also investigated the effect of pyrrolidine dithiocarbamate and phenazine methosulfate, which are antioxidant and oxidant compounds, respectively, and concluded that the intracellular redox status of neutrophils is highly critical for Ang II-induced increase of CN expression and activity. Results obtained in neutrophils from hypertensive patients were very similar to those obtained in these cells on treatment with Ang II. We have also addressed the possible functional implication of CN activation in the development of hypertension. Present findings indicate that downregulation of hemoxygenase-1 expression in neutrophils from hypertensive subjects is likely mediated by CN, which acts by hindering translocation to the nucleus of the transcription factor NRF2. These data support and extend our previous results and those from other authors on modulation of CN expression and activity levels by the intracellular redox status.

Transcription of liver X receptor is down-regulated by 15-deoxy-Δ12,14-prostaglandin J2 through oxidative stress in human neutrophils

Liver X receptors (LXRs) are ligand-activated transcription factors of the nuclear receptor superfamily. They play important roles in controlling cholesterol homeostasis and as regulators of inflammatory gene expression and innate immunity, by blunting the induction of classical pro-inflammatory genes. However, opposite data have also been reported on the consequences of LXR activation by oxysterols, resulting in the specific production of potent pro-inflammatory cytokines and reactive oxygen species (ROS). The effect of the inflammatory state on the expression of LXRs has not been studied in human cells, and constitutes the main aim of the present work. Our data show that when human neutrophils are triggered with synthetic ligands, the synthesis of LXRα mRNA became activated together with transcription of the LXR target genes ABCA1, ABCG1 and SREBP1c. An inflammatory mediator, 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), hindered T0901317-promoted induction of LXRα mRNA expression together with transcription of its target genes in both neutrophils and human macrophages. This down-regulatory effect was dependent on the release of reactive oxygen species elicited by 15dPGJ2, since it was enhanced by pro-oxidant treatment and reversed by antioxidants, and was also mediated by ERK1/2 activation. Present data also support that the 15dPGJ2-induced serine phosphorylation of the LXRα molecule is mediated by ERK1/2. These results allow to postulate that down-regulation of LXR cellular levels by pro-inflammatory stimuli might be involved in the development of different vascular diseases, such as atherosclerosis.

Análisis de encuestas como herramienta de gestión sostenible de especies cinegéticas en agrosistemas del este de la provincia de Alicante (Marina Baja): estudio del caso del jabalí Sus scrofa Linnaeus, 1758

El trabajo ha sido desarrollado en un agrosistema tradicional del NE de la provincia de Alicante (SE España). La superficie total del área de estudio es de aproximadamente 59.000 ha. La zona presenta grandes contrastes, con un área interior de morfología montañosa, con pequeñas cuencas dedicadas a la agricultura de secano, mientras que la zona litoral se caracteriza por un relieve menos abrupto, con núcleos de población y explotaciones agrícolas de regadío. El estudio se basa en la información extraída a partir de encuestas realizadas a los gestores cinegéticos, obteniendo datos acerca de las abundancias y la evolución de las poblaciones de jabalí entre los años 1980 y la actualidad. Se construye una base de datos SIG con un total de 15 cotos de caza. La base de datos incluye las siguientes variables: usos del suelo a nivel de coto, abundancias y evolución temporal de la especie. Los resultados muestran que dos de los cotos presentan densidades de jabalí elevadas (15-25 ind/ha), dos cotos presentan densidades medias (10-15 ind/ha), cinco cotos muestran densidades bajas (5-10 ind/ha) y otros seis cotos densidades muy bajas (0-5 ind/ha). Los valores máximos se encuentran en cotos de interior y de montaña donde todavía se mantienen en activo cultivos de secano y se intercalan con cultivos abandonados y áreas naturales. También se observan densidades elevadas en el único coto de todos los analizados que se encuentra en la costa, donde la disponibilidad de hábitat es menor y, por lo tanto, hay una mayor concentración de individuos. Finalmente, el jabalí ha aumentado sus poblaciones desde la década de los años 1980 en la totalidad de los cotos estudiados.

Hybrid simulation-optimization based approach for the optimal design of single-product biotechnological processes

In this work, we present a systematic method for the optimal development of bioprocesses that relies on the combined use of simulation packages and optimization tools. One of the main advantages of our method is that it allows for the simultaneous optimization of all the individual components of a bioprocess, including the main upstream and downstream units. The design task is mathematically formulated as a mixed-integer dynamic optimization (MIDO) problem, which is solved by a decomposition method that iterates between primal and master sub-problems. The primal dynamic optimization problem optimizes the operating conditions, bioreactor kinetics and equipment sizes, whereas the master levels entails the solution of a tailored mixed-integer linear programming (MILP) model that decides on the values of the integer variables (i.e., number of equipments in parallel and topological decisions). The dynamic optimization primal sub-problems are solved via a sequential approach that integrates the process simulator SuperPro Designer® with an external NLP solver implemented in Matlab®. The capabilities of the proposed methodology are illustrated through its application to a typical fermentation process and to the production of the amino acid L-lysine.

Platelet-activating factor downregulates the expression of liver X receptor-α and its target genes in human neutrophils

Liver X receptors (LXRs) are ligand-activated members of the nuclear receptor superfamily that regulate the expression of genes involved in lipid metabolism and inflammation, although their role in inflammation and immunity is less well known. It has been reported that oxysterols/LXRs may act as anti-inflammatory molecules, although opposite actions have also been reported. In this study, we investigated the effect of platelet-activating factor (PAF), a proinflammatory molecule, on LXRα signalling in human neutrophils. We found that PAF exerted an inhibitory effect on mRNA expression of TO901317-induced LXRα, ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and sterol response element binding protein 1c. This negative action was mediated by the PAF receptor, and was dependent on the release of reactive oxygen species elicited by PAF, as it was enhanced by pro-oxidant treatment and reversed by antioxidants. Current data also support the idea that PAF induces phosphorylation of the LXRα molecule in an extracellular signal-regulated kinase 1/2-mediated fashion. These results suggest that a possible mechanism by which PAF exerts its proinflammatory effect is through the downregulation of LXRα and its related genes, which supports the notion that LXRα ligands exert a modulatory role in the neutrophil-mediated inflammatory response.

Changes in the Photoreceptor Mosaic of P23H-1 Rats During Retinal Degeneration: Implications for Rod-Cone Dependent Survival

Purpose. To investigate the spatiotemporal relationship between rod and cone degeneration in the P23H-1 rat. Methods. Control Sprague-Dawley (SD) and P23H-1 rats of ages ranging from P30 to P365 were used. Retinas were processed for whole mounts or cross sections and rods and cones were immunodetected. We used newly developed image analysis techniques to quantify the total population of L/M cones (the most abundant cones in the rat) and analyzed the rings of rod-cone degeneration. Results. In P23H-1 rats, rod degeneration occurs rapidly: first the rod outer segment shortens, at P30 there is extensive rod loss, and by P180 rod loss is almost complete except for the most peripheral retina. The numbers of L/M cones are, at all postnatal ages, lower in P23H-1 rats than in control SD rats, and decrease significantly with age (by P180). Rod and cone degeneration is spatiotemporally related and occurs in rings that appear already at P90 and spread throughout the entire retina. At P180, the rings of rod-cone degeneration are more abundant in the equatorial retina and are larger in the dorsal retina. Conclusions. This work describes for the first time that in the P23H-1 rat, rod and cone degeneration is spatiotemporally related and occurs in rings. Cone loss follows rod loss and starts very soon, even before P30, the first age analyzed here. The characteristics of the rings suggest that secondary cone degeneration is influenced by retinal position and/or other intrinsic or extrinsic factors.

Equidad de género en españa. Determinante social de la salud sigue desfavorable a las mujeres en 2011

Antecedentes/Objetivos: La distancia de la equidad de género entre los países mejor y peor posicionados ha crecido. España ha empeorado relativamente. La evidencia sugiere que la situación social de las mujeres influye en la salud de ambos sexos y varía al interior de los países. Objetivo: determinar la evolución de la equidad de género en España entre 2006 y 2011. Métodos: Estudio ecológico sobre la equidad de género en España y CC.AA, mediante el cálculo del Índice de Equidad de Género modificado (IEGm) en 2006 y 2011: Diferencias entre las proporciones en hombres (H) y mujeres (M) en educación, economía y empoderamiento (–1: inequidad para las M, 0: equidad y 1: inequidad para los H). Cálculo convergencia beta (): –1: convergencia, 1: no convergencia, mediante correlación de Spearman () entre el valor del IEGm de las CC.AA para 2006 y sus Tasas de crecimiento (TC). Convergencia cuando las CCAA con menor IEGm mejoran más rápido que las más equitativas, en 2011 respecto a 2006. Cálculo convergencia sigma (): 0: convergencia, 1: no convergencia, mediante resta de las desviaciones medianas de las CC.AA en 2006 y 2011. Indica la dispersión de los valores de equidad de género de las CC.AA en 2011 respecto a 2006. Convergencia: valor de 2011 < que en 2006. Resultados: Todas las CC.AA han mejorado su IEGm en 2011 excepto País Vasco (TC = –0,007 × año), Extremadura y Murcia: –0,003 y Canarias: –0,001. No se detecta que las CC.AA. de menor IEGm tengan mayor crecimiento o viceversa (= –0,345, p = 0,2). Pero País Vasco pasa de ocupar la 1ª posición en 2006 a la 11ª, y Navarra que era quien menor IEGm tenía en 2006 (–0,184), en 2011 es la que más mejora (0,018): de 17ª a 5ª posición. En 2011, Galicia, que estaba en la 5ª posición (–0,120), es la CC.AA más paritaria (–0,049), y Murcia la menos (–0,184). En todo caso, la dispersión de los valores del IEGm de las CC.AA no ha variado en 2011 respecto a 2006 (= 2,6 en ambos años). La brecha de género de empoderamiento marca el patrón del IEGm de España en ambos años, en 2011 desfavorable a las M en todas las CC.AA. Aquellas con mejor brecha de género en empoderamiento en 2006 han empeorado en 2011, y las de mayor la han reducido (: –0,574 p = 0,02), implicando reducción en la dispersión entre CC.AA. (= 0,2). Conclusiones: Pese a que la equidad de género no ha crecido en España como en otros países en 2011 respecto a antes de la crisis económica, ésta es alta, al ser sus valores próximos a 0. Tiene un patrón coincidente con el del empoderamiento político, lo que explica el descenso del País Vasco, modelo de desarrollo de género en España, y lo que es importante: la inequidad sigue desfavorable a las mujeres.

Braquiópodos del Jurásico Inferior del norte de España en la colección Jiménez de Cisneros

Se actualizan sistemáticamente las especies de braquiópodos del Jurásico Inferior procedentes de varias localidades del N y NE de España alojados en la colección Jiménez de Cisneros, refiriéndolas a contextos actualmente contrastados, dotándolas así de un conveniente marco lito- y cronoestratigráfico. Se encuentran representados especímenes de la Rama Castellana y Aragonesa de la Cordillera Ibérica, Asturias, Pirineos y la Cordillera costera Catalana. La actualización ha permitido identificar 18 especies distintas desde el Sinemuriense al Aaleniense basal, contextualizándolas y comparándolas paleobiogeográficamente con el conjunto de plataformas que ocupaban los paleomárgenes de la Subplaca Ibérica durante el Jurásico Inferior.

Oleic acid modulates mRNA expression of liver X receptor (LXR) and its target genes ABCA1 and SREBP1c in human neutrophils

Purpose: Regulation of liver X receptors (LXRs) is essential for cholesterol homeostasis and inflammation. The present study was conducted to determine whether oleic acid (OA) could regulate mRNA expression of LXRα and LXRα-regulated genes and to assess the potential promotion of oxidative stress by OA in neutrophils. Methods: Human neutrophils were treated with OA at different doses and LXR target gene expression, oxidative stress production, lipid efflux and inflammation state were analyzed. Results: We describe that mRNA synthesis of both LXRα and ABCA1 (a reverse cholesterol transporter) was induced by OA in human neutrophils. This fatty acid enhanced the effects of LXR ligands on ABCA1 and LXR expression, but it decreased the mRNA levels of sterol regulatory element-binding protein 1c (a transcription factor that regulates the synthesis of triglycerides). Although OA elicited a slight oxidative stress in the short term (15–30 min) in neutrophils, it is unlikely that this is relevant for the modulation of transcription in our experimental conditions, which involve longer incubation time (i.e., 6 h). Of physiological importance is our finding that OA depresses intracellular lipid levels and that markers of inflammation, such as ERK1/2 and p38 mitogen-activated protein kinase phosphorylation, were decreased by OA treatment. In addition, 200 μM OA reduced the migration of human neutrophils, another marker of the inflammatory state. However, OA did not affect lipid peroxidation induced by pro-oxidant agents. Conclusions: This work presents for the first time evidence that human neutrophils are highly sensitive to OA and provides novel data in support of a protective role of this monounsaturated acid against the activation of neutrophils during inflammation.

Brackish groundwater desalination by reverse osmosis in southeastern Spain. Presence of emerging contaminants and potential impacts on soil-aquifer media

Desalinated brackish groundwater is becoming a new source of water supply to comply with growing water demands, especially in (semi-) arid countries. Recent publications show that some chemical compounds may persist in an unaltered form after the desalination processes and that there is an associated risk of mixing waters with different salinity for irrigation. At the university of Alicante campus (Spain), a mix of desalinated brackish groundwater and water from the existing aquifer is currently applied for landscape irrigation. The presence of 209 emerging compounds, surfactants, priority substances according to the 2008/105/EC Directive, 11 heavy metals and microbiological organisms in blended water and aquifer samples was investigated. Thirty-five compounds were detected (pesticides, pharmaceuticals and surfactants) among them two priority substances α-endosulfan and Ni were found above the permitted maximum concentration. Blended water used for landscape irrigation during the summer period is supersaturated with respect to carbonates, which may ultimately lead to mineral precipitation in the soil-aquifer media and changes in hydraulic parameters.

GPLSI Compendium App

GPLSI Compendium App se trata de una aplicación móvil que hará las veces de un sistema de gestión y difusión de contenidos digitales, en la que el usuario podrá realizar resúmenes de textos de diferentes webs, tales como artículos o noticias, y posteriormente compartir esos resúmenes en sus redes sociales o a través del correo. Se le proporcionarán varios métodos de resumen, así como las descripciones y un pequeño tutorial de cómo utilizar la aplicación.

Mecanismos de coordinación docente en la Facultad de Derecho

El trabajo de esta Red docente ha consistido en recopilar y proponer nuevos mecanismos de coordinación docente aplicables a las cuatro titulaciones de Grado de la Facultad de Derecho. Los resultados de los Informes de Seguimiento de cada titulación de la Facultad, muestran la necesidad de establecer instrumentos de coordinación del profesorado de cada titulación para unificar y armonizar criterios en lo relativo al volumen total del trabajo exigido al estudiante, la distribución temporal adecuada del mismo y el trabajo colectivo de todos los profesores para conseguir los objetivos plasmados en la Memoria Verificada por ANECA para cada título. El objetivo de esta Red ha sido recopilar los mecanismos de coordinación ya existentes y proponer otros nuevos que puedan plantearse en las correspondientes Comisiones de titulación y aplicarse en cursos sucesivos en nuestra Facultad.

Red de Docencia Introducción en Geografía del Turismo

La red docente de la asignatura Introducción a la Geografía del Turismo, ha intentado coordinar la asignatura para poner en común las experiencias desarrolladas por el profesorado de la asignatura. Tras varios cursos impartiendo la misma en el primer curso del Grado en Turismo, es necesario revisar la asignatura para la búsqueda de los problemas y cuestiones más conflictivas, para intentar mejorar para los próximos cursos. Por este motivo se ha trabajado para trabajar en común y establecer un dialogo sobre los aspectos que cada profesor ha considerado como más importantes. En el caso de esta asignatura la dificultad ha estado en el elevado número de alumnos y en coordinar a tantos grupos de prácticas, por lo que la opinión de cada uno de los siete profesores de la asignatura será clave para establecer las cuestiones más importantes para el futuro.