Interrelación entre proteínas asociadas a uniones intercelulares estrechas, polaridad de los hepatocitos y el virus de la hepatitis C

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 17 de Junio de 201

Progeria: a perspective on potential drug targets and treatment strategies.

Work in the V.A. laboratory is supported by the Spanish Ministerio de Ciencia e Innovación (MCIN)/Agencia Estatal de Investigación (AEI)/ 10.13039/501100011033 (grant PID2019-108489RB-I00) with co-funding from the European Regional Development Fund (‘A way to build Europe’), Fundació la Marató TV3 (grant 202033), the Progeria Research Foundation (PRF) (award PRF 2019–77), and Asociación Progeria Alexandra Peraut. Work in the M.O.B. lab is supported by grants from the PRF, Center for Innovative Medicine (Karolinska Institutet), and the Swedish Research Council. I.B. is supported by the Comunidad Autónoma de Madrid (grant 2017-T1/BMD-5247). The CNIC is supported by the MCIN, the Instituto de Salud Carlos III, and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MCIN/AEI/ 10.13039/501100011033).S

Coronary and carotid artery dysfunction and KV7 overexpression in a mouse model of Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease caused by expression of progerin, a lamin A variant that is also expressed at low levels in non-HGPS individuals. Although HGPS patients die predominantly from myocardial infarction and stroke, the mechanisms that provoke pathological alterations in the coronary and cerebral arteries in HGPS remain ill defined. Here, we assessed vascular function in the coronary arteries (CorAs) and carotid arteries (CarAs) of progerin-expressing LmnaG609G/G609G mice (G609G), both in resting conditions and after hypoxic stimulus. Wire myography, pharmacological screening, and gene expression studies demonstrated vascular atony and stenosis, as well as other functional alterations in progeroid CorAs and CarAs and aorta. These defects were associated with loss of vascular smooth muscle cells and overexpression of the KV7 family of voltage-dependent potassium channels. Compared with wild-type controls, G609G mice showed reduced median survival upon chronic isoproterenol exposure, a baseline state of chronic cardiac hypoxia characterized by overexpression of hypoxia-inducible factor 1α and 3α genes, and increased cardiac vascularization. Our results shed light on the mechanisms underlying progerin-induced coronary and carotid artery disease and identify KV7 channels as a candidate target for the treatment of HGPS.Work supported by Ministerio de Ciencia e Innovación (MCIN) and Agencia Estatal de Investigación (AEI) (MCIN/AEI/https:// doi. org/ 10. 13039/ 50110 00110 33 grants SAF2016-79490-R and PID2019-108489RB-I00), with cofunding from Fondo Social Europeo (“El FSE invierte en tu futuro”), and a donation from Asociación Progeria Alexandra Peraut. Microscopy was conducted at the Microscopy & Dynamic Imaging Unit, CNIC, ICTS-ReDib, co-funded by MCIN/AEI/https:// doi. org/ 10. 13039/ 50110 00110 33. R.M.N was supported by the Ministerio de Educación, Cultura y Deporte (pre-doctoral contract FPU16/05027), and I.B. is supported by the Comunidad Autónoma de Madrid (grants 2017- T1/BMD-5247 and 2021-5A/BMD-20944), and the Ramón y Cajal contract (RYC2021-033805-I) funded by MCIN/ AEI/10.13039/501100011033 and the European Union “Next- GenerationEU”/PRTR. The CNIC is supported by the MCIN, the Instituto de Salud Carlos III, the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant number CEX2020-001041-S funded by MCIN/AEI/https:// doi. org/ 10. 13039/ 50110 00110 33).N

Mejora del clima de clase y resolución de conflictos raciales y étnicos a través de la intervención en la organización y la metodología de las sesiones de Educación Física

Este trabajo de investigación se ha realizado en Zaragoza capital, concretamente en el Instituto de Enseñanza Secundaria María Moliner, centro al que acuden alumnos con importantes problemas de marginación social e inmigración. Mediante el desarrollo del Proyecto “Mejora del clima de clase y resolución de conflictos raciales y étnicos a través de la intervención en la organización y la metodología de las sesiones de Educación Física” se ha pretendido optimizar los procesos organizativos y metodológicos del área de Educación Física en aras de una mejora del nivel de convivencia y clima de clase, así como estrategias de resolución de conflictos específicos. En este sentido, se ha intervenido sobre el tratamiento de los contenidos del área de la Educación Física, tanto en el aula como en los recreos, para un mejor desarrollo de la competencia básica social y ciudadana y de los contenidos transversales. Los resultados obtenidos son optimistas e indican que es posible modificar ciertas conductas nocivas, aunque se hace necesario continuar con las intervenciones para consolidar actitudes positivas de respeto y convivencia, así como saludables

Evaluación sobre la caracterización de distintos tipos de cimentaciones superficiales por medio de georradar

En la rehabilitación de edificaciones o en el estudio de patologías constructivas la identificación de las características de los elementos portantes es de alto interés. La aplicación del georradar para la caracterización de la extensión y profundidad de dichos elementos es habitual por poderse realizar de forma no invasiva y con relativa rapidez. En este trabajo se aborda la caracterización de 3 tipos de cimentaciones superficiales habituales: una losa de cimentación, zapatas aisladas y zapatas aisladas sobre pozos de cimentación. El objetivo del análisis realizado es evaluar la potencial identificación de dichos elementos, pero sobre todo, dado que se conocen sus características constructivas, evaluar la capacidad de identificación de su base (cota de apoyo). La presencia de contrastes inversos de velocidad en la base de dichos elementos, el desfase producido por la presencia de medios de mayor reflectividad, la generación de reflexiones múltiples o los cambios de velocidad de propagación asociados a dichos elementos pueden definir problemas en su identificación exacta

Childhood abuse in the etiological continuum underlying psychosis from first-episode psychosis to psychotic experiences

GOAL: The present study aimed to examine the prevalence of child abuse across the continuum of psychosis. PATIENTS AND METHODS: The sample consisted of 198 individuals divided in three groups: (1) 48 FEP patients, (2) 77 individuals scoring high in Community Assessment of Psychic Experiences (CAPE), classified as 'High CAPE' group and (3) 73 individuals scoring low, classified as 'Low CAPE' group. Childhood abuse was assessed using self-report instruments. Chi(2) tests and logistic regression models controlling by sex, age and cannabis were used to perform three comparisons: (i) FEP vs. Low CAPE; (ii) FEP vs. High CAPE and (iii) High CAPE vs. Low CAPE. RESULTS: The frequency of individuals exposed to childhood abuse for FEP, High CAPE and Low CAPE groups were 52.1%, 41.6% and 11%, respectively. FEP and High CAPE group presented significantly higher rates of childhood abuse compared to Low CAPE group, however, no significant differences were found between FEP and High CAPE groups regarding the frequency of childhood abuse. CONCLUSION: There is an increasing frequency of childhood abuse from low subclinical psychosis to FEP patients. However, childhood abuse is equally common in FEP and at risk individuals

Retinal Pigment Epithelium-Secreted VEGF-A Induces Alpha-2-Macroglobulin Expression in Endothelial Cells.

Alpha-2-macroglobulin (A2M) is a protease inhibitor that regulates extracellular matrix (ECM) stability and turnover. Here, we show that A2M is expressed by endothelial cells (ECs) from human eye choroid. We demonstrate that retinal pigment epithelium (RPE)-conditioned medium induces A2M expression specifically in ECs. Experiments using chemical inhibitors, blocking antibodies, and recombinant proteins revealed a key role of VEGF-A in RPE-mediated A2M induction in ECs. Furthermore, incubation of ECs with RPE-conditioned medium reduces matrix metalloproteinase-2 gelatinase activity of culture supernatants, which is partially restored after A2M knockdown in ECs. We propose that dysfunctional RPE or choroidal blood vessels, as observed in retinal diseases such as age-related macular degeneration, may disrupt the crosstalk mechanism we describe here leading to alterations in the homeostasis of choroidal ECM, Bruch's membrane and visual function.This work was funded by grants EY08538 and GM34107 from NIH, award 2013-028 by the Tri-Institutional Stem Cell Initiative established by a grant from The Starr Foundation and by Departmental grants from Research to Prevent Blindness and Dyson Foundations (E.R.-B.). I.B. was supported by the Comunidad Autónoma de Madrid (grants 2017-T1/BMD-5247 and 2021-5A/BMD20944). The CNIC is supported by the Ministerio de Ciencia e Innovación (MCIN), the Instituto de Salud Carlos III, and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MCIN/AEI/10.13039/501100011033). R.F.M. and S.Z. were supported by grant EY024605 from NIH. J.M.-G. was supported by grant RTI2018-094727-B-100 funded by MCIN/AEI/10.13039/501100011033.S