Inhibition of PTEN by peroxynitrite activates the phosphoinositide-3-kinase/Akt neuroprotective signaling pathway

El derivado del óxido nítrico, peroxinitrito, activa una cascada de señalización de supervivencia en neuronas. El mecanismo implica la oxidación de la fosfatasa PTEN, que permite incrementar la forma fosforilada (neuroprotectora) de akt.Peroxynitrite is usually considered as a neurotoxic nitric oxidederivative. However, an increasing body of evidence suggests that, at low concentrations, peroxynitrite affords transient cytoprotection, both in vitro and in vivo. Here, we addressed the signaling mechanism responsible for this effect, and found that rat cortical neurons in primary culture acutely exposed to peroxynitrite (0.1 mmol/L) rapidly elicited Akt-Ser473 phosphorylation. Inhibition of phosphoinositide-3-kinase (PI3K)/Akt pathway with wortmannin or Akt small hairpin RNA (shRNA) abolished the ability of peroxynitrite to prevent etoposide-induced apoptotic death. Endogenous peroxynitrite formation by short-term incubation of neurons with glutamate stimulated Akt-Ser473 phosphorylation, whereas Akt shRNA enhanced the vulnerability of neurons against glutamate. We further show that Akt-Ser473 phosphorylation was consequence of the oxidizing, but not the nitrating properties of peroxynitrite. Peroxynitrite failed to nitrate or phosphorylate neurotrophin tyrosine kinase receptors (Trks), and it did not modify the ability of brain-derived neurotrophic factor (BDNF), to phosphorylate its cognate receptor, TrkB; however, peroxynitrite enhanced BDNF-mediated Akt-Ser473 phosphorylation. Finally, we found that peroxynitrite-stimulated Akt-Ser473 phosphorylation was associated with an increased proportion of oxidized phosphoinositide phosphatase, PTEN, in neurons. Moreover, peroxynitrite prevented the increase of apoptotic neuronal death caused by over-expression of PTEN. Thus, peroxynitrite exerts neuroprotection by inhibiting PTEN, hence activating the anti-apoptotic PI3K/Akt pathway in primary neurons

Recursos tecnológicos didácticos y de investigación. Cuaderno de prácticas

Este manual pretende ofrecer al estudiante una aproximación a los fundamentos teóricos y prácticos de la asignatura «Recursos Tecnológicos Didácticos y de Investigación», en el Grado de Educación Primaria. Tiene un carácter básico, aplicado y transversal centrado en las siguientes temáticas: • Tecnología educativa y alfabetización digital. Características e impacto social y educativo de la cultura audiovisual y digital. Conceptualización de términos productos de la Sociedad del Conocimiento y la Información. • Los medios y recursos tecnológicos para la educación. Materiales educativos multimedia. Diseño, desarrollo y evaluación de procesos de enseñanza aprendizaje con TIC y utilización de distintas aplicaciones didácticas, organizativas y administrativas. Entornos virtuales de aprendizaje. Trabajo colaborativo en espacios virtuales. Aspectos relacionados con los programas específicos de la Junta de Extremadura en TIC. El diseño y elaboración de materiales didácticos para la práctica del maestro de Educación Primaria. • La investigación en Educación. Fundamentación epistemológica de los métodos científicos en contextos educativos. Desarrollo de una investigación científica: proceso y conceptos fundamentales.This manual is intended to provide the student with an approximation to the theoretical and practical foundations of the subject "Teaching and Research Technology Resources", in the grade of Primary Education. It has a basic, applied and transversal character focused on the following topics: • Educational technology and digital literacy. Characteristics and impact social and educational advancement of the audiovisual and digital culture. Conceptualization of terms products of the Knowledge and Information Society. • Means and technology resources for education. Multimedia Educational Materials. Design, development and evaluation of processes of teaching and learning with ICT and use of different didactic applications, organizational and administrative matters. Virtual learning environments. Collaborative work in virtual spaces. Aspects related to the specific programs of the Junta de Extremadura in ICT. The design and development of training materials for the practice of the teacher of Primary Education. • Research in Education. The epistemological foundations of scientific methods in educational contexts. Development of a scientific research: process and fundamental concepts

Trade Networks in the Neighbouring Roman Provinces of Aquitania-Tarraconensis on the Bay of Biscay: Evidence from Petrographic and Chemical Analyses of Common Coarse Ware Pottery

Common non-wheel-thrown Roman pottery from the southern Aquitania and north-eastern of Tarraconensis provinces (CNT-AQTA) of the Early and Later Roman Empire (1st to 5th centuries AD) has been studied. Petrological, mineralogical, and chemical analyses were conducted to contrast with the archaeological study of the pottery. The chemical composition of many pottery samples displays different patterns of burial chemical modification, limiting their use for provenance and diffusion studies. Particular emphasis has been paid to the petrographic features of the fabrics, as they do not change during burial, reflecting the nature of the raw material and making it possible to identify the provenance areas of the raw materials. Around the Bay of Biscay, the same pottery tradition continued in the neighbouring provinces during Roman times. Petrographic studies make it possible to determine the distribution of pottery and the changes in trade networks during the Roman period across the area of the Bay of Biscay being studied.This research was funded by Fundación José Miguel de Barandiaran Fundazioa, grant number 2004, and the Basque Country government, grant number IT1442-22. The APC was funded by the Basque Country government, grant number IT1442-22

The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia

Article number: 1610 (2018)[EN]Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemia-induced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance

Analysis of two SMC HII Regions Considering Thermal Inhomogeneities: Implications for the Determinations of Extragalactic Chemical Abundances

We present long slit spectrophotometry considering the presence of thermal inhomogeneities (t^2) of two HII regions in the Small Magellanic Cloud (SMC): NGC 456 and NGC 460. Physical conditions and chemical abundances were determined for three positions in NGC 456 and one position in NGC 460, first under the assumption of uniform temperature and then allowing for the possibility of thermal inhomogeneities. We determined t^2 values based on three different methods: i) by comparing the temperature derived using oxygen forbidden lines with the temperature derived using helium recombination lines, ii) by comparing the abundances derived from oxygen forbidden lines with those derived from oxygen recombination lines, and iii) by comparing the abundances derived from ultraviolet carbon forbidden lines with those derived from optical carbon recombination lines. The first two methods averaged t^2=0.067+-0.013 for NGC 456 and t^2=0.036+-0.027 for NGC 460. These values of t^2 imply that when gaseous abundances are determined with collisionally excited lines they are underestimated by a factor of nearly 2. From these objects and others in the literature, we find that in order to account for thermal inhomogeneities and dust depletion, the O/H ratio in low metallicity HII regions should be corrected by 0.25-0.45 dex depending on the thermal structure of the nebula, or by 0.35 dex if such information is not available.Comment: Accepted for publication in The Astrophysical Journal. 41 pages in pre-print format. 3 figure

Generación de un modelo de precipitación-escorrentía en la cuenca del Río Samborombón

La cuenca del Río Samborombón, situada en la provincia de Buenos Aires, se caracteriza por la escasa pendiente, suelos limo-arcillosos y estructuras viales que la interceptan. Actualmente en la cuenca no existen estaciones limnigráficas ni estaciones meteorológicas oficiales activas. El objetivo del trabajo fue generar un modelo de precipitación-escorrentía en la cuenca del Río Samborombón mediante el software HECHMS 4.1, con el fin de contribuir al conocimiento de su funcionamiento hidrológico. El modelo se ajustó en base al máximo caudal registrado. La cuenca fue dividida en subcuencas, asignándole valores de área, precipitación, evapotranspiración y pendiente; para el cálculo de las pérdidas por infiltración se utilizó el Número de Curva, y como método de transformación el Hidrograma Unitario de Clark. El caudal máximo simulado ocurrió un día posterior al de la máxima precipitación, comparable con los caudales registrados. Por su parte, la incorporación de las estructuras viales transversales, corroboró que las mismas funcionan parcialmente como diques durante eventos de gran precipitación, elevando el nivel aguas arriba. La modelización permitió obtener buenos resultados a partir de escasos datos base, y contribuyó a un mayor entendimiento de los procesos hidrológicos en cuencas de llanura y su posible relación con las obras viales.Facultad de Ciencias Naturales y MuseoFacultad de Ingenierí

On the Optimal Identification of Tag Sets in Time-Constrained RFID Configurations

In Radio Frequency Identification facilities the identification delay of a set of tags is mainly caused by the random access nature of the reading protocol, yielding a random identification time of the set of tags. In this paper, the cumulative distribution function of the identification time is evaluated using a discrete time Markov chain for single-set time-constrained passive RFID systems, namely those ones where a single group of tags is assumed to be in the reading area and only for a bounded time (sojourn time) before leaving. In these scenarios some tags in a set may leave the reader coverage area unidentified. The probability of this event is obtained from the cumulative distribution function of the identification time as a function of the sojourn time. This result provides a suitable criterion to minimize the probability of losing tags. Besides, an identification strategy based on splitting the set of tags in smaller subsets is also considered. Results demonstrate that there are optimal splitting configurations that reduce the overall identification time while keeping the same probability of losing tags

Landslide Susceptibility Analysis on the Vicinity of Bogotá-Villavicencio Road (Eastern Cordillera of the Colombian Andes)

Landslide occurrence in Colombia is very frequent due to its geographical location in the Andean mountain range, with a very pronounced orography, a significant geological complexity and an outstanding climatic variability. More specifically, the study area around the Bogotá-Villavicencio road in the central sector of the Eastern Cordillera is one of the regions with the highest concentration of phenomena, which makes its study a priority. An inventory and detailed analysis of 2506 landslides has been carried out, in which five basic typologies have been differentiated: avalanches, debris flows, slides, earth flows and creeping areas. Debris avalanches and debris flows occur mainly in metamorphic materials (phyllites, schists and quartz-sandstones), areas with sparse vegetation, steep slopes and lower sections of hillslopes; meanwhile, slides, earth flows and creep occur in Cretaceous lutites, crop/grass lands, medium and low slopes and lower-middle sections of the hillslopes. Based on this analysis, landslide susceptibility models have been made for the different typologies and with different methods (matrix, discriminant analysis, random forest and neural networks) and input factors. The results are generally quite good, with average AUC-ROC values above 0.7–0.8, and the machine learning methods are the most appropriate, especially random forest, with a selected number of factors (between 6 and 8). The degree of fit (DF) usually shows relative errors lower than 5% and success higher than 90%. Finally, an integrated landslide susceptibility map (LSM) has been made for shallower and deeper types of movements. All the LSM show a clear zonation as a consequence of the geological control of the susceptibility

Bisphenol A Induces Accelerated Cell Aging in Murine Endothelium.

Bisphenol A (BPA) is a widespread endocrine disruptor affecting many organs and systems. Previous work in our laboratory demonstrated that BPA could induce death due to necroptosis in murine aortic endothelial cells (MAECs). This work aims to evaluate the possible involvement of BPA-induced senescence mechanisms in endothelial cells. The β-Gal assays showed interesting differences in cell senescence at relatively low doses (100 nM and 5 µM). Western blots confirmed that proteins involved in senescence mechanisms, p16 and p21, were overexpressed in the presence of BPA. In addition, the UPR (unfolding protein response) system, which is part of the senescent phenotype, was also explored by Western blot and qPCR, confirming the involvement of the PERK-ATF4-CHOP pathway (related to pathological processes). The endothelium of mice treated with BPA showed an evident increase in the expression of the proteins p16, p21, and CHOP, confirming the results observed in cells. Our results demonstrate that oxidative stress induced by BPA leads to UPR activation and senescence since pretreatment with N-acetylcysteine (NAC) in BPA-treated cells reduced the percentage of senescent cells prevented the overexpression of proteins related to BPA-induced senescence and reduced the activation of the UPR system. The results suggest that BPA participates actively in accelerated cell aging mechanisms, affecting the vascular endothelium and promoting cardiovascular diseases.post-print3206 K