9 research outputs found
JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
Background and aim: The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements. Methods: Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP‑ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss. Results: Our studies demonstrated that HFD in Jnk3-/- lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed. Conclusions: Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.This work was supported by funds from the Spanish Ministerio de Economía y Competitividad (SAF2017-84283-R to AC), the Generalitat de Catalunya (2014SGR-525 to CA) and CIBERNED (Grant CB06/05/2004 to AC).S
Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications
Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions
About zeroing: methodology of anti-dumping calculation and source of international conflicts at the WTO
El documento presenta la metodología de cálculo antidumping, "Zeroing", mediante la exposición de sus antecedentes en el marco del Comercio Internacional, prestando especial atención a los conflictos que ha suscitado en el seno de la Organización Mundial del Comercio y en las relaciones de Estados Unidos con economías globales de primer nivel. Con motivo de la dispersión teórica del "Zeroing" y de la dificultad de comprensión que le es connatural, el "paper" adhiere un planteamiento conceptual de la conducta, estructurado en torno a las “variables” que suscita su empleo o no aplicación a un supuesto de hecho particular. Evidenciando igualmente, la actualidad del "Zeroing" en el contexto del comercio internacional, en determinación de la atención que han prestado sus exponentes a las recomendaciones de la OMC, de abolición de la conducta en sus investigaciones antidumping.The paper presents the anti-dumping methodology named Zeroing, by the exposure of its precedents in the framework of international trade, with particular attention to the conflicts that has caused within the World Trade Organization and on the relations of the United States with other top-tier global economies. By virtue of the theoretical dispersion of the zeroing and its innate difficulty of understanding, the paper adheres to a conceptual approach of the conduct, structured around the “variables” that raises their use or inapplicability to a specific case. The document also shows the topicality of the Zeroing in the foreign trade context, trying to understand the regard given by it’s principal actors to the recommendations of the WTO, about the cessation of the methodology in anti-dumping investigations.Sin financiaciónNo data (2017)UE
Incidencia de la patología tumoral en pacientes con fibrosis quística en la Comunidad de Madrid
Neurological Disorders in Central Spain, Second Survey: Feasibility Pilot Observational Study
Background
The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank.
Objective
The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and questionnaires, as well as interexpert rating of the neurological diagnoses) in each one of the planned areas (all of them in central Spain) and to test the possibility of obtaining biological samples from each participant.
Methods
A selection of patients and participants of the planned NEDICES-2 underwent face-to-face interviews including a comprehensive questionnaire on demographics, current medications, medical conditions, and lifestyle habits. Biological samples (blood, saliva, urine, and hair) were also obtained. Furthermore, every participant was examined by a neurologist.
Results
In this pilot study, 567 study participants were enrolled (196 from hospitals and 371 from primary care physician lists). Of these 567, 310 completed all study procedures (questionnaires and the neurological evaluation). The study was time-consuming for several primary care physicians. Hence, a few primary care physicians from some areas refused to participate, which led to a reconfiguration of study areas. In addition, the central biobank needed to be supplemented by the biobanks of local Spanish National Health System hospitals.
Conclusions
Population-based epidemiological surveys, such as the NEDICES-2, require a pilot study to evaluate the feasibility of all aspects of a future field study (population selection, methods and instruments to be used, neurological diagnosis agreement, and data collection).Our thanks to all collaborators in this feasibility pilot study, the Instituto de Salud Carlos III and the Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), and the two hospital computer experts (Victoria Garcia Baquero and Teresa Garcia Morales), who created the website (http://nedices2.ciberned.com/estudio-de-salud-nedices-2/). We would also like to thank Miss Jennifer Gates for the editing and proofreading of the manuscript.Peer reviewe
Genetic association and sequencing of the insulin-like growth factor 1 gene in bipolar affective disorder
Role of copy number variants in sudden cardiac death and related diseases: genetic analysis and translation into clinical practice.
Several studies have identified copy number variants (CNVs) as responsible for cardiac diseases associated with sudden cardiac death (SCD), but very few exhaustive analyses in large cohorts of patients have been performed, and they have been generally focused on a specific SCD-related disease. The aim of the present study was to screen for CNVs the most prevalent genes associated with SCD in a large cohort of patients who suffered sudden unexplained death or had an inherited cardiac disease (cardiomyopathy or channelopathy). A total of 1765 European patients were analyzed with a homemade algorithm for the assessment of CNVs using high-throughput sequencing data. Thirty-six CNVs were identified (2%), and most of them appeared to have a pathogenic role. The frequency of CNVs among cases of sudden unexplained death, patients with a cardiomyopathy or a channelopathy was 1.4% (8/587), 2.3% (20/874), and 2.6% (8/304), respectively. Detection rates were particularly high for arrhythmogenic cardiomyopathy (5.1%), long QT syndrome (4.7%), and dilated cardiomyopathy (4.4%). As such large genomic rearrangements underlie a non-neglectable portion of cases, we consider that their analysis should be performed as part of the routine genetic testing of sudden unexpected death cases and patients with SCD-related diseases
Bustarviejo. Propuestas bioclimáticas en el espacio público.
Bustarviejo. Propuestas bioclimáticas en el espacio público. Publicación digital de los trabajos elaborados por los estudiantes del curso 2017/18 de la asignatura La Ciudad y el Medio de la Escuela Técnica Superior de Arquitectura de Madrid de la Universidad Politécnica de Madrid. Muestra una serie de propuestas elaboradas en la asignatura para mejorar bioclimáticamente diferentes espacios públicos municipales en el marco del acuerdo realizado entre el Departamento de Urbanística y Ordenación del Territorio y el Excmo. Ayuntamiento de Bustarviejo (Madrid)
Tiempo e historia en el teatro del Siglo de Oro
Aprovechar las enseñanzas de la Historia, recurrir al pasado remoto o reciente para mostrar en sus héroes, recreados por el teatro, su dimensión arquetípica y modélica, tales son los propósitos de la dramatización de la materia histórica durante el Siglo de Oro español. La Historia no sólo sirvió de mero marco temporal para ubicar la acción dramática de las piezas en un contexto preciso. Las variaciones, anacronismos evidentes o sincronismos implícitos, a partir dde las fuentes manejadas deben leerse como verdaderas estrategias del dramaturgo. El anclaje histórico de los argumentos, mediante juegos de simetrías y contrastes entre realidad y ficción, enfoca la recepción ideológica de las obras. La poética del tiempo histórico en el teatro se pone al servicio de la emergencia de una conciencia nacional: representar el pasado supone mejor decir y cuestionar el presente. Este libro examina también la estética de la temporalidad que nace de las variaciones cronológicas en las obras contempladas. Las diferentes contribuciones de los autores revelan la distancia tomada por los dramaturgos del Siglo de Oro respecto a la preceptiva clásica. Semejante actitud no exenta de críticas en su época, demuestra la libertad con la que aquellos creadores supieron superar los apremios teóricos de la unidad de tiempo a favor de un dinamismo celebrado en su tiempo por el público heterogéneo y exigente de los corrales