Implicación de los polimorfismos genéticos en la farmacocinéticaa y farmacodinamia de antipsicóticos:: estudio farmacogénetico en voluntarios sanos

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Farmacología y Terapéutica. Fecha de lectura: 24 de Septiembre 201

Los permisos ordinarios de salida: antecedentes, regulación vigente y reflexiones críticas

[RESUMEN] Los permisos ordinarios de salida persiguen la preparación del interno para la vida en libertad, constituyendo una herramienta esencial del tratamiento penitenciario, al poner en contacto a la persona presa con la libertad de la que carece. En este trabajo se parte de un paso por su historia, para continuar con el análisis de su naturaleza, finalidad y regulación vigente, para luego abordar una posición crítica al respecto. Su concesión está condicionada al cumplimiento de unos requisitos no sólo objetivos sino también subjetivos que están relacionados con la “conveniencia” de concederlos, lo que es valorado por el Equipo Técnico y la Junta de Tratamiento a partir de una Tablas e Informes en los que se tienen en cuenta variables que resultan, algunas, imprecisas, inadecuadas, injustas e incluso discriminatorias[ABSTRACT]Regular furloughs pursue internal preparation for life in freedom, constituting an essential tool of prison treatment, by contacting the person prey to the freedom that lacks. This work begins with a step for its history, to continue the analysis of its nature, purpose and current regulations, and then address a critical position. Its concession is conditional on fulfillment of not only objective but also subjective conditions that are related to the “convenience” licensed, what is valued by the Task Force and the Treatment Board from a tables and reports in which they take into account some variables that are some inaccurate, inappropriate, unfair and even discriminator

PAMP-triggered immunity against Pseudomonas syringae involves microRNA-mediated regulation of several uncharacterized R genes

Two main types of noncoding small RNA molecules have been found in plants: microRNAs (miRNAs) and small interfering RNAs (siRNAs). They differ in their biogenesis and mode of action, but share similar sizes (20-24 nt). Their precursors are processed by Dicer-Like RNase III (dcl) proteins present in Arabidopsis thaliana, and in their mature form can act as negative regulators of gene expression, being involved in a vast array of plant processes, including plant development, genomic integrity or response to stress. Small-RNA mediated regulation can occurs at transcriptional level (TGS) or at post-transcriptional level (PTGS). In recent years, the role of gene silencing in the regulation of expression of genes related to plant defence responses against bacterial pathogens is becoming clearer. Comparisons carried out in our lab between the expression profiles of different mutants affected in gene silencing, and plants challenged with Pseudomonas syringae pathovar tomato DC3000, led us to identify a set of uncharacterized R genes, belonging to the TIR-NBS-LRR gene family, differentially expressed in these conditions. Through the use of bioinformatics tools, we found a miRNA* of 22 nt putatively responsible for down-regulating expression of these R genes through the generation of siRNAs. We have also found that the corresponding pri-miRNA is down-regulated after PAMP-perception in a SA-dependent manner. We also demonstrate that plants with altered levels of miRNA* (knockdown lines or overexpression lines) exhibit altered PTI-associated phenotypes, suggesting a role for this miRNA* in this defence response against bacteria. In addition we identify one of the target genes as a negative regulator of defence response against Pseudomonas syringae.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. MINECO, FEDE

Effector-mediated suppression of plant defense against biotrophs through activation of antagonistic defense against necrotrophs

Plant hormones are small molecules involved in the regulation of plant growth, development, reproduction and stress responses. Salicylic acid (SA) and jasmonates (JA) are essential for the activation of defence responses against pathogens. SA signaling is involved in triggering immunity against biotrophic pathogens while JA activates resistance against necrotrophic pathogens. The SA and JA pathways are mostly antagonistic: elevated biotroph resistance correlates with increased necrotroph susceptibility, and vice versa. Using transcriptomics to look for a functional overlap between plant gene silencing and type III-mediated plant responses we found that genes associated to JA signaling were overrepresented in the overlapping set, more so than SA-related genes. We present here the results of the ensuing analysis, showing effector-mediated activation of the JA pathway as a virulence mechanism, and establishing a novel role for gene silencing in the regulation of the JA pathway.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech - See more at: http://riuma.uma.es/xmlui/handle/10630/5393/submit/12176e8e39815b4d6112192a6815221718868c2f.continue#sthash.RYCQTkwy.dpu

Androgen receptor polyQ alleles and COVID-19 severity in men: A replication study.

Background Ample evidence indicates a sex-related difference in severity of COVID-19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity. Objective To test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients. Materials and methods This study included 1136 male patients infected with SARS-CoV-2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID-19 severity was assessed by Chi-squared (Chi2) and logistic regression analysis. Results The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis). Discussion Androgen sensitivity may be a critical factor in COVID-19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID-19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID-19 outcome. Conclusions The results obtained in our study do not support the role of this polymorphism as biomarker of COVID-19 severity.post-print253 K

Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID‑19.

Rare variants afecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n= 44). To this end, diferent etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodefciencies or blood coagulation were studied. We detected 44 diferent variants of interest, in 29 diferent patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially infuence COVID-19 outcome in our cohort of patients. Further studies are needed to confrm the ultimate role of the genetic variants described in the present study on COVID-19 severitypost-print2807 K

Conodont content and stratigraphy of the Llessui Formation from the south central Pyrenees

A synthetic stratigraphic succession of the Upper Silurian Llessui Formation is established according to partial sections and conodont sampling. The lower part of the formation is considered Ludlow, while the uppermost Přídolí conodont O. e. detortus Zone is recognised at the top. Above, the shales, with some limestones of the Aneto Formation, range from the Přídolí to the middle Lochkovian L. omoalpha-A. trigonicus Zone, where the limestones of the Rueda Formation begin. The carbonate facies of the Llessui Fm are similar to the Ockerkalk facies from the Northern Gondwana. The succession is compared with other Pyrenean sequences and related with some Mediterranean neighbouring areas.Ministerio de Educación y Cultura; Project PB98-155

The school direction to the development of the autonomy of the centers

This study focuses on knowledge of the difficulties to achieve the autonomy of the schools and to advance in their capacity of management, from the perspective of school principals. The research presented has employed a qualitative methodology in which 20 directors have collaborated, 70% are men and the remaining 30% are women. The data collection was carried out through semi-structured interviews, which had a flexible script of open questions written based on the development of the autonomy of the centers. The content analysis of the different interviews carried out established a system of categories, codes and frequencies that allowed us to establish the weight of each of the categories. In the results, consequences are deduced in the four dimensions studied: planning, methodology, evaluation and improvements for the daily work in the centers.Este estudio se centra, en conocer, desde el punto de vista de los directivos, las problemáticas fundamentales que encuentran en su práctica sobre el desarrollo de la autonomía en los centros y, su capacidad de gestión. La investigación presentada ha empleado una metodología cualitativa en la que han colaborado 20 directores/as, el 70% son hombres y el 30% restante mujeres. La recogida de los datos se ha realizado a través de entrevistas semiestructuradas, que contaron con un guion flexible de preguntas abiertas redactadas en base al desarrollo de la autonomía de los centros. Se ha desarrollado un análisis de contenido de las distintas entrevistas realizadas y se ha establecido un sistema de categorías, códigos y frecuencias que nos ha permitido establecer el peso de cada una de las categorías. Del análisis de los resultados se deducen consecuencias en las cuatro categorías estudiadas como son planificación, metodología, evaluación y mejoras para el trabajo diario en los centros

A ringed pole-on outflow from DO Tauri revealed by ALMA

We present new ALMA Band 6 observations including the CO (2-1) line and 1.3 mmcontinuum emission from the surroundings of the young stellar object DO Tauri. TheALMA CO molecular data show three different series of rings at different radial ve-locities. These rings have radii around 220 au and 800 au. We make individual fits tothe rings and note that their centers are aligned with DO Tauri and its optical high-velocity jet. In addition, we notice that the velocity of these structures increases withthe separation from the young star. We discuss the data under the hypothesis that therings represent velocity cuts through three outflowing shells that are possibly drivenby a wide-angle wind, dragging the environment material along a direction close to theline of sight (i= 19◦). We estimate the dynamical ages, the mass, the momentum andthe energy of each individual outflow shell and those of the whole outflow. The resultsare in agreement with those found in outflows from Class II sources. We make a roughestimate for the size of the jet/wind launching region, which needs to be of.15 au.We report the physical characteristics of DO Tauri?s disk continuum emission (almostface-on and with a projected major axis in the north-south direction) and its velocitygradient orientation (north-south), indicative of disk rotation for a 1-2 Mcentral star.Finally we show an HST [SII] image of the optical jet and report a measurement of itsorientation in the plane of the sky.Fil: Fernandez Lopez, Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Zapata Gonzalez, Luis Alberto. Universidad Nacional Autonoma de Mexico. Instituto de Astronomia; MéxicoFil: Rodríguez, Luis F.. Universidad Nacional Autonoma de Mexico. Instituto de Astronomia; MéxicoFil: Vazzano, María Mercedes. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Guzman, Andrés E.. National Astronomical Observatory Of Japan; JapónFil: López, Rosario. Universidad Autónoma de Barcelona. Facultad de Física. Departamento Astronomía y Meteorología; Españ

Diseño y evaluación de un programa de informática aplicada a la investigación educativa

Este artículo presenta un estudio empírico de carácter evaluativo sobre el programa de la asignatura "Informática Aplicada a la Investigación Educativa". Esta materia surge en los nuevos planes de estudio de la Facultad de Ciencias de la Educación, concretamente como parte de la Licenciatura Pedagogía, y supone una respuesta del plan a la necesidad de formación científica en la actual Sociedad del Conocimiento, un aspecto que tiene escasa tradición en cuanto a propuestas curriculares. Ello justifica que abordemos tanto el contexto curricular y científico en que surge la materia, como la propuesta de programa de formación y su evaluación.This article presents an empiric study of evaluative character about the program proposed in Informática Aplicada a la Investigación Educativa. This matter arises on new sillabi of the ability of Sciences of the Education, specifically like part of the Licentiate of Pedagogy. It supposes an answer from the plan to the necessity of scientific formation in the current Society of the Knowledge, and it lacking tradition as for previous curricular proposals in this sense. This is justified that we approach the evaluative and scientific context, the proposal of formation and, its evaluation