GSK3 and tau: Two convergence points in Alzheimer's disease

Glycogen synthase kinase 3 (GSK3) is a ubiquitously expressed serine/threonine kinase that plays a key role in the pathogenesis of Alzheimer's disease (AD). GSK3 phosphorylates tau in most serine and threonine residues hyperphosphorylated in paired helical filaments, and GSK3 activity contributes both to amyloid-β production and amyloid-β-mediated neuronal death. Thus, mice generated in our laboratory with conditional overexpression of GSK3 in forebrain neurons (Tet/GSK3β mice) recapitulate aspects of AD neuropathology such as tau hyperphosphorylation, apoptotic neuronal death, and reactive astrocytosis, as well as spatial learning deficit. In this review, we describe recent contributions of our group showing that transgene shutdown in that animal model leads to normal GSK3 activity, normal phospho-tau levels, diminished neuronal death, and suppression of the cognitive deficit, thus further supporting the potential of GSK3 inhibitors for AD therapeutics. In addition, we have combined transgenic mice overexpressing the enzyme GSK3β with transgenic mice expressing tau with a triple FTDP-17 mutation that develop prefibrillar tau-aggregates. Our data suggest that progression of the tauopathy can be prevented by administration of lithium when the first signs of neuropathology appear. Further, it is possible to partially reverse tau pathology in advanced stages of the disease, although the presence of already assembled neurofibrillary tangle-like structures cannot be reversed. © 2013 The authors and IOS Press. All rights reserved.Peer Reviewe

Diseño de un software para relés de distancia para funcionamiento en sistemas de potencia radiales basado en máquinas de soporte vectorial

La calidad de la energía se ha convertido en un tema de estudio de gran interés tanto para los operadores de red como para los usuarios. Entre los aspectos más importantes de la calidad en el suministro de energía se tienen en cuenta la forma de onda y la continuidad del servicio. La importancia de estos aspectos está relacionada con el mercado re-estructurado que actualmente poseen varios países [SHOR.03]. Cambios económicos, políticos y técnicos en muchas de las empresas de distribución están presionando la manera en como éstas están siendo constituidas y operadas. La re-estructuración ha incrementado la presión sobre las empresas de distribución para recortar los costos de inversión operación y mantenimiento y ha concentrado su atención en incrementar la confiabilidad y la calidad del servicio en los sistemas. El gran temor que existe con la re-estructuración, está en que el servicio de energía sufrirá con el recorte de los costos de inversión en general, dificultando su monitoreo, operación y mantenimiento. Otro cambio que está causando preocupación es el de la introducción dentro de los sistemas de distribución de la generación distribuida, ya que los generadores a nivel de distribución pueden causar problemas en la coordinación de las protecciones debido a la circulación decorriente en diferentes sentidos en el sistema, y también con la regulación de tensión, ocasionada por la presencia de diferentes niveles de tensión en un mismo alimentador; también se pueden obtener grandes beneficios si son usados de manera adecuada. Los consumidores están presionando por tener costos bajos, mejor confiabilidad, y menor impacto visual por parte de la empresa de distribución

Análisis de los contenidos de historia en el ámbito educativo

En nuestro trabajo "Análisis de los contenidos de Historia en el ámbito educativo´´ hemos querido investigar la importancia de la asignatura dentro de la Educación Primaria y analizar los contenidos que la conforman. Dentro de la investigación hemos entrevistado a alumnos, docentes y futuros docentes para conocer su opinión sobre la misma, qué esperan de la asignatura y cuál creen que es la metodología correcta para impartirla y que sea motivante para ambos agentes educativos, también hemos analizado el papel que ha jugado la asignatura a lo largo de la historia de la educación en España y el papel que juega actualmente según los documentos oficiales, se podrá encontrar también análisis del material usado actualmente para impartir las clases, siendo estos libros de texto ya que es el material que usan los docentes que han sido entrevistados como base para sus sesiones, por ultimo podrán encontrar una propuesta didáctica que creemos motivante para los alumnos y con la que pueden aprender los contenidos que se exigen de una manera más interactiva y jugando ellos y ellas el papel protagonista en las clases.In our work "Analysis of the contents of History in the educational field '' we wanted to investigate the importance of the subject in Primary Education and analyze the contents that comprise it. Within the research we interviewed students, teachers and future teachers to know their opinion about it, what they expect from the subject and what they believe is the correct methodology to teach and that is motivating for both educational agents, we have also analyzed the role who has played the subject throughout the history of education in Spain and the role that currently plays according to official documents, you can also find analysis of the material currently used to teach the classes, these textbooks being that it is the material used by the teachers who have been interviewed as a basis for their sessions, finally they can find a didactic proposal that we believe motivating for the students and with which they can learn the contents that are required in a more interactive way and playing them and they protagonist role in the classes and playing, they will be the real protagonist in their classes.Universidad de Sevilla. Grado en Educación Primari

Notas corológicas del macrofitobentos de Andalucía (España). IX

La flora de macroalgas marinas de Andalucía se recoge en los catálogos de Flores-Moya et al. (1995a, 1995b) y Conde et al. (1996a), y en las adiciones posteriores de Conde et al. (1996b), Báez et al. (2001), Altamirano et al. (2006, 2008) e Invernón et al. (2009). En este trabajo, se aportan tres nuevas citas para Andalucía (señaladas con un asterisco), seis citas nuevas para la provincia de Cádiz y una confi rmación para esta provincia. El material recolectado fue identifi cado, y depositado (bien en formol al 4% o bien en pliegos) en el herbario MGC Phyc. Se ha utilizado ALGAEBASE (Guiry & Guiry, 2010) como referencia a la hora de nombrar los diferentes taxones

GSK-3 Mouse Models to Study Neuronal Apoptosis and Neurodegeneration

Increased GSK-3 activity is believed to contribute to the etiology of chronic disorders like Alzheimer’s disease (AD), schizophrenia, diabetes, and some types of cancer, thus supporting therapeutic potential of GSK-3 inhibitors. Numerous mouse models with modified GSK-3 have been generated in order to study the physiology of GSK-3, its implication in diverse pathologies and the potential effect of GSK-3 inhibitors. In this review we have focused on the relevance of these mouse models for the study of the role of GSK-3 in apoptosis. GSK-3 is involved in two apoptotic pathways, intrinsic and extrinsic pathways, and plays opposite roles depending on the apoptotic signaling process that is activated. It promotes cell death when acting through intrinsic pathway and plays an anti-apoptotic role if the extrinsic pathway is occurring. It is important to dissect this duality since, among the diseases in which GSK-3 is involved, excessive cell death is crucial in some illnesses like neurodegenerative diseases, while a deficient apoptosis is occurring in others such as cancer or autoimmune diseases. The clinical application of a classical GSK-3 inhibitor, lithium, is limited by its toxic consequences, including motor side effects. Recently, the mechanism leading to activation of apoptosis following chronic lithium administration has been described. Understanding this mechanism could help to minimize side effects and to improve application of GSK-3 inhibitors to the treatment of AD and to extend the application to other diseases.Peer reviewedPeer Reviewe

Aterrizaje del neutro para sistemas eléctricos

Este artículo presenta consideraciones básicas para la selección de parámetros de aterrizaje del neutro que permitan el control de sobretensión y la corriente de falla a tierra sobre todas las partes de un sistema eléctrico trifásico.This paper presents basic considerations for the selection of neutral grounding parameters that will provide for the control of overvoltage and ground-fault current on all parts of three-phase electrical utility systems

Culture of Gracilaria gracilis and Chondracanthus teedei from Vegetative Fragments in the Field and Carpospores in Laboratory

Gracilarioids and Gigartinales are of great economic importance due to the phycocolloids they contain in their cell wall and are used in different industries worldwide. Field and laboratory cultures of two species of red seaweeds (Gracilaria gracilis and Chondracanthus teedei), confirmed after DNA analysis, were carried out to foster the increasing use of this species in Spain as a food source. Vegetative cultures carried out in an open-lock gate within a traditional salina in the ay of Cadiz (Southern Spain) rendered maximum growth rates in April (3.64% day(-1)) for G. gracilis and in November (4.68% day(-1)) for C. teedei, the latter showing significant differences between the months of the year. For laboratory cultures, samples of the two species used for sporulation were obtained from tidal creeks in several nearby locations of the Bay. In order to grow fertile carposporophytes from spores, Provasoli enriched seawater medium (ES medium), Miquel A + B and f/2 were used as culture medium at a temperature of 18 degrees C and irradiance of 30 mu mol m(-2) s(-1) in 12:12 h photoperiod. Both species developed a basal disc after 12-15 days in ES medium and Miquel A + B, and new microscopic seedlings were observed at 20-25 days in ES medium. With f/2 medium, no growth was observed after sporulation. The life cycle of G. gracilis was completed in ES medium over a period of 11 months with a mean growth rate of 3.28% day(-1). The present study is an important step towards the development of seaweed cultivation in the Bay of Cadiz, especially in integrated multi-trophic cultivation in salinas as part of the more sustainable use of the marine resources in coastal communities

Decreased glycogen synthase kinase-3 levels and activity contribute to Huntington's disease

© The Author 2015. Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by brain atrophy particularly in striatum leading to personality changes, chorea and dementia. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase in the crossroad of many signaling pathways that is highly pleiotropic as it phosphorylates more than hundred substrates including structural, metabolic, and signaling proteins. Increased GSK-3 activity is believed to contribute to the pathogenesis of neurodegenerative diseases like Alzheimer's disease and GSK-3 inhibitors have been postulated as therapeutic agents for neurodegeneration. Regarding HD, GSK-3 inhibitors have shown beneficial effects in cell and invertebrate animal models but no evident efficacy in mouse models. Intriguingly, those studies were performed without interrogating GSK-3 level and activity in HD brain. Herewe aim to explore the level and also the enzymatic activity of GSK-3 in the striatum and other less affected brain regions of HD patients and of the R6/1 mouse model to then elucidate the possible contribution of its alteration to HD pathogenesis by genetic manipulation in mice.We report a dramatic decrease in GSK-3 levels and activity in striatum and cortex of HD patients with similar results in the mouse model. Correction of the GSK-3 deficit inHDmice, by combining with transgenic mice with conditional GSK-3 expression, resulted in amelioration of their brain atrophy and behavioral motor and learning deficits. Thus, our results demonstrate that decreased brain GSK-3 contributes to HD neurological phenotype and open new therapeutic opportunities based on increasing GSK-3 activity or attenuating the harmful consequences of its decrease.This work was supported by Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CiberNed-Instituto de salud Carlos III) and by grants from Ministerio de Ciencia (MEC, MICINN, MINECO), Comunidad Autónoma de Madrid and Fundación Ramón Areces. A.M.Peer Reviewe