Efecto de la proteína presentadora de antígenos Tap en la infección IN VIVO del virus Herpes Simplex tipo 1 y generación de modelos transgénicos para su estudio

Tesis doctoral inédita de la Universidad Autónoma de Madrid. Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura : 21-06-200

DMRT Transcription Factors in the Control of Nervous System Sexual Differentiation

Sexual phenotypic differences in the nervous system are one of the most prevalent features across the animal kingdom. The molecular mechanisms responsible for sexual dimorphism throughout metazoan nervous systems are extremely diverse, ranging from intrinsic cell autonomous mechanisms to gonad-dependent endocrine control of sexual traits, or even extrinsic environmental cues. In recent years, the DMRT ancient family of transcription factors has emerged as being central in the development of sex-specific differentiation in all animals in which they have been studied. In this review, we provide an overview of the function of Dmrt genes in nervous system sexual regulation from an evolutionary perspective

Modular Organization of Cis-regulatory Control Information of Neurotransmitter Pathway Genes in Caenorhabditis elegans

Here, Serrano-Saiz et al. describe the cis-regulatory logic of how neurotransmitter identity is imposed onto individual, distinct neuron types... We explore here the cis-regulatory logic that dictates gene expression in specific cell types in the nervous system. We focus on a set of eight genes involved in the synthesis, transport, and breakdown of three neurotransmitter systems: acetylcholine (unc-17/VAChT, cha-1/ChAT, cho-1/ChT, and ace-2/AChE), glutamate (eat-4/VGluT), and γ-aminobutyric acid (unc-25/GAD, unc-46/LAMP, and unc-47/VGAT). These genes are specifically expressed in defined subsets of cells in the nervous system. Through transgenic reporter gene assays, we find that the cellular specificity of expression of all of these genes is controlled in a modular manner through distinct cis-regulatory elements, corroborating the previously inferred piecemeal nature of specification of neurotransmitter identity. This modularity provides the mechanistic basis for the phenomenon of “phenotypic convergence,” in which distinct regulatory pathways can generate similar phenotypic outcomes (i.e., the acquisition of a specific neurotransmitter identity) in different neuron classes. We also identify cases of enhancer pleiotropy, in which the same cis-regulatory element is utilized to control gene expression in distinct neuron types. We engineered a cis-regulatory allele of the vesicular acetylcholine transporter, unc-17/VAChT, to assess the functional contribution of a “shadowed” enhancer. We observed a selective loss of unc-17/VAChT expression in one cholinergic pharyngeal pacemaker motor neuron class and a behavioral phenotype that matches microsurgical removal of this neuron. Our analysis illustrates the value of understanding cis-regulatory information to manipulate gene expression and control animal behavior.This work was supported by the Howard Hughes Medical Institute. E.S.-S. has been supported by the Ramon y Cajal program (RYC-2016-20537), and M.G. was supported by the European Molecular Biology Organization and Human Frontier Science Program postdoctoral fellowships.Peer reviewe

White Paper 5: Brain, Mind & Behaviour

© CSICThe study of the brain will tell us what makes us humans and how our social behavior generates. Increasing our understanding of how the brain functions and interacts with the ecosystem to interpret the world will not only help to find effective means to treat and/or cure neurological and psychiatric disorders but will also change our vision on questions pertaining to philosophy and humanities and transform other fields such as economy and law. Neurosciences research at the CSIC is already valuable and should be intensified mainly focused on the eight major challenges described in this volume

Intranasal Delivery of Caspase-9 Inhibitor Reduces Caspase-6-Dependent Axon/Neuron Loss and Improves Neurological Function after Stroke

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke.C.M.T.wassupported bythe American Heart Association and National Institutes of Health (NIH)GrantsNS035933 and NS43089. G.S.S. and S.J.S. were supported by NIH Grant CA69381. E.S.C. was supported by NIH Grant NS40409.Peer reviewe

Assessment of Pablo de Olavide University's Alignment with the 2030 Agenda. A Diagnosis from Seville, Spain

Document compiled by staff from Pablo de Olavide University of Seville (UPO), with technical assistance from Periferia Consultoría Social. This project has been funded with support from the European Commission.Versión española del documento en: https://dx.doi.org/10.46661/rio.20230630_1Recognizing the crucial role of universities in implementing the 2030 Agenda, the Pablo de Olavide University (UPO) has conducted a comprehensive assessment to evaluate its alignment and contribution towards achieving the Targets defined within the 17 Sustainable Development Goals (SDGs). The 2030 Agenda presents a dual mandate for universities. Firstly, they are tasked with integrating the SDGs into their educational and research programs. Secondly, they are expected to act as catalysts for societal transformation and promote a governance model in higher education that aligns with the Agenda's objectives. In light of these responsibilities, UPO has recognized the need to equip itself with the necessary tools to effectively assess the fulfillment of these mandates. This accountability is crucial for demonstrating UPO's commitment to the SDGs and for enhancing the effectiveness of its actions within the framework of the Agenda. This document provides a summary of the process undertaken by UPO, in collaboration with Periferia Social Consulting, between November 2022 and May 2023. The objective was to design a set of indicators that can measure UPO's contribution to the 2030 Agenda. The first section describes the methodology and various phases involved in the process. Following that, the document presents the system of indicators developed and provides information on UPO's contribution to the 2030 Agenda for the academic year 2021-2022. In the annexes, two posters are included, displaying the complete set of indicators and the measurements made for the 2021-2022 academic year.Universidad Pablo de Olavid

Diagnóstico sobre alineamiento de la Universidad Pablo de Olavide de Sevilla con la Agenda 2030

Documento elaborado por el Grupo Interno de la UPO, con la asistencia técnica de Periferia Consultoría Social, y la financiación de la Agencia Andaluza de Cooperación Internacional.Versión inglesa del documento en: https://dx.doi.org/10.46661/rio.20230718_1Consciente del papel clave que juegan la universidades en la implementación de la Agenda 2030, la Universidad Pablo de Olavide (UPO) plantea realizar un diagnóstico para conocer el grado de alineamiento y contribución a la consecución de las metas englobadas en los 17 ODS que conforman dicha Agenda. La Agenda 2030 marca un doble mandato a las Universidades; por un lado, incorporar los ODS en el ámbito de la formación y la investigación y por otro, como agente transformador de la sociedad y modelo de gobernanza en Educación Superior. En este sentido, la UPO necesita dotarse de las herramientas necesarias con las que poder determinar cómo se están cumpliendo efectivamente estos mandatos, con la finalidad tanto de rendir cuentas sobre su contribución al cumplimiento de los ODS y de mejorar la eficacia de sus actuaciones en el marco de dicha Agenda. Este documento es un resumen del proceso que desde la UPO con el apoyo de Periferia Consultoría Social se ha llevado a cabo entre los meses de noviembre 2022 y mayo 2023 para la construcción de un Sistema de Indicadores que permite medir la contribución de la UPO a la Agenda 2030. En un primer apartado, se describe la metodología y distintas fases llevadas a cabo; a continuación, se presenta el sistema de indicadores construido y la información sobre la contribución de la UPO a la Agenda 2030 para el curso 2021-2022. En anexos, se pueden encontrar las fichas metodológicas de cada uno de los indicadores que conforman el sistema; así como, dos poster donde visualizar el conjunto de indicadores y la medición realizada para el curso 2021-2022.Universidad Pablo de Olavid

Libro Blanco Volumen 5: Cerebro, mente y comportamiento

Llegar a entender cómo funciona el cerebro y cómo este interacciona con el ecosistema para interpretar el mundo que nos rodea sin duda facilitará el desarrollo de estrategias más eficaces para tratar o curar los trastornos neurológicos y psiquiátricos. Además, la comprensión de los principios fundamentales que controlan el funcionamiento del sistema nervioso transformará nuestra visión sobre muchas cuestiones que han sido tradicionalmente enmarcadas en el campo de la filosofía, repercutiendo en áreas como la economía o el derecho. Las neurociencias nos ayudarán, en definitiva, a entender qué nos hace humanos. Este es un campo en el que los investigadores del CSIC destacan internacionalmente y así debe seguir siendo en los próximos años. Para lograrlo, deberíamos potenciar y reforzar nuestras investigaciones en los ocho desafíos que describimos en este volumen.Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

TFG 2012/2013

Amb aquesta publicació, EINA, Centre universitari de Disseny i Art adscrit a la Universitat Autònoma de Barcelona, dóna a conèixer el recull dels Treballs de Fi de Grau presentats durant el curs 2012-2013. Voldríem que un recull com aquest donés una idea més precisa de la tasca que es realitza a EINA per tal de formar nous dissenyadors amb capacitat de respondre professionalment i intel·lectualment a les necessitats i exigències de la nostra societat. El treball formatiu s’orienta a oferir resultats que responguin tant a paràmetres de rigor acadèmic i capacitat d’anàlisi del context com a l’experimentació i la creació de nous llenguatges, tot fomentant el potencial innovador del disseny.Con esta publicación, EINA, Centro universitario de diseño y arte adscrito a la Universidad Autónoma de Barcelona, da a conocer la recopilación de los Trabajos de Fin de Grado presentados durante el curso 2012-2013. Querríamos que una recopilación como ésta diera una idea más precisa del trabajo que se realiza en EINA para formar nuevos diseñadores con capacidad de responder profesional e intelectualmente a las necesidades y exigencias de nuestra sociedad. El trabajo formativo se orienta a ofrecer resultados que respondan tanto a parámetros de rigor académico y capacidad de análisis, como a la experimentación y la creación de nuevos lenguajes, al tiempo que se fomenta el potencial innovador del diseño.With this publication, EINA, University School of Design and Art, ascribed to the Autonomous University of Barcelona, brings to the public eye the Final Degree Projects presented during the 2012-2013 academic year. Our hope is that this volume might offer a more precise idea of the task performed by EINA in training new designers, able to speak both professionally and intellectually to the needs and demands of our society. The educational task is oriented towards results that might respond to the parameters of academic rigour and the capacity for contextual analysis, as well as to considerations of experimentation and the creation of new languages, all the while reinforcing design’s innovative potential