400 research outputs found
Iruñearen irudia Aingeru Epaltzaren Rock'n'roll-en
No full textIRATI ARRATIBEL eta AMAIA MUNARRIZ. Iruñearen irudiaAingeru Epaltzaren Rock'n'roll-e
Estudio integral del riesgo de desastres por deslizamiento en las microcuencas Alto Peú y San Martín - Cerro La Picota - Ayacucho
No full textEl Perú posee una riqueza invaluable en recursos naturales gracias a que presenta una geografía por demás diversa. Estos mismos atributos también configuran espacios geográficos propensos a desastres naturales, como es el caso de la microcuenca Alto Perú y San Martín ubicados en el distrito de Ayacucho. El estudio realizado tuvo como objetivo general, determinar los niveles de riesgo de desastre por deslizamiento en las microcuencas de Alto Perú y San Martín, que permita a las autoridades y responsables del Gobierno Regional y Municipal, implementar estrategias orientadas a reducir el impacto y la vulnerabilidad por desastre de esta parte de la ciudad. La metodología de investigación asumida para la realización de este estudio se ciñe a los lineamientos metodológicos de la investigación cuantitativa, en la medida que se utilizó el diseño descriptivo correlaciona! para comprobar las hipótesis investigativas formuladas. La muestra de estudio estuvo conformada por 320 lotes ubicados en la micro cuenca de Alto Perú y San Martín, registrados en una base de datos, bajo los criterios de riesgo muy alta, alta, media, baja y muy baja. Las técnicas e instrumentos para el recojo de información consideró herramientas tecnológicas como es el caso de las técnicas de teledetección y los sistemas de información geográfica (SIG), así como información documental registrada en instituciones responsables de velar por la seguridad de la población. Los resultados obtenidos en el estudio demuestran que existe correlaCión directa y significativa entre niveles de riesgo y las dimensiones de peligro y vulnerabilidad, en la medida que el coeficiente de correlación es 0.895, con un nivel de significancia del 1% y un intervalo de confianza del 95%. Palabras clave: Riesgo de desastre, deslizamiento, peligro, vulnerabilidad xiii ABSTRACT Peru has an invaluable wealth of natural resources by presenting a diverse geography others. These same attributes also shape prone to natural disasters geographical areas, such as the micro watershed Alto Peru and San Martín located in the district of Ayacucho. The study had overall objective is to determine levels of disaster risk sliding into the micro basins of Alto Peru and San Martín, which allows authorities and officials of Regional and Municipal Government, implement targeted strategies to reduce the impact and disaster vulnerability of this area of the city. The research methodology assumed for this study is limited to the methodologicat guidelines of quantitative research, to the extent that the descriptiva correlational design was used to test the investigative assumptions made. The study sample consisted of 320 lots located in the micro watershed Alto Peru and San Martín, recorded in a database under the standards very high, high, medium, low and very low risk. The techniques and tools for information gathering considerad technological tools such as remote sensing techniques and geographic information systems (CIS) and documentary information recorded in charge of ensuring the safety of public institutions. The results obtained in the study demonstrate significant and direct correlation between risk of sliding and disaster warning size and vulnerability, as the correlation coefficient is 0.895, with a significance level of 1% and a range of 95% confidence. Keywords: Risk of disaster slip hazard vulnerabilityTesi
DNA damage induces the rapid and selective degradation of the ΔNp73 isoform, allowing apoptosis to occur
No full textAlteraciones en la transducción de señales inducida por la activación constitutiva del adaptador molecular Shc en fibroblastos que expresan el antígeno T Grande del virus Polioma
No full textHa sido claramente demostrado que los factores de crecimiento poseen una función clave en la regulación de la proliferación celular. Numerosas evidencias experimentales avalan la hipótesis de que en ausencia de factores de crecimiento, los oncogenes activan a los receptores para dichos factores o sus respectivos sustratos o, alternativamente, inducen la secreción de factores de crecimiento. Las células que expresan el antígeno T Grande del Polioma reducen sus requerimientos de factores de crecimiento. Sin embargo, los mecanismos moleculares por los cuales se produce este fenómeno no habían sido estudiados. En este trabajo experimental se estudió si la disminución en la necesidad de factores de crecimiento en las células que expresan el antígeno T Grande del Polioma se correlacionaba con la activación del adaptador molecular Shc, que es un sustrato universal de los receptores para factores de crecimiento tirosínquinásicos. Se demostró que el nivel de fosforilación del adaptador molecular Shc en células que expresan el antígeno T Grande del Polioma no disminuye en ausencia de factores de crecimiento en el medio de cultivo. También se provó que este efecto es independiente de la unión del antígeno T Grande a la proteína de Retinoblastoma. La fosforilación constitutiva del adaptador molecular Shc se correlaciona con la formación del complejo Shc/Grb-Z que provoca alteraciones en la vía de transducción de señales induciendo la activación de las MAPK . En este trabajo también se demostró que el adaptador molecular Shc y el antígeno T Grande del Polioma interactuan formando un complejo, el cual podría ser la causa de la fosforilación constitutiva de Shc. Estos resultados indican que la inducción del ciclo celular provocada por el antígeno T Grande del Polioma es una consecuencia no sólo de la unión e inactivación de anti-oncogenes nucleares, sino también de alteraciones citoplasmátícas en las vías de transducción de señales de los factores de crecimiento.Fil: Munarriz, Eliana Rosa. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Polyomavirus large T antigen induces alterations in cytoplasmic signalling pathways involving Shc activation
No full textIt has been extensively demonstrated that growth factors play a key role in the regulation of proliferation. Several lines of evidence support the hypothesis that for the induction of cell cycle progression in the absence of exogenous growth factors, oncogenes must either induce autocrine growth factor secretion or, alternatively, activate their receptors or their receptor substrates. Cells expressing polyomavirus large T antigen (PyLT) display reduced growth factor requirements, but the mechanisms underlying this phenomenon have yet to be explored. We conducted tests to see whether the reduction in growth factor requirements induced by PyLT was related to alterations of growth factor-dependent signals. To this end, we analyzed the phosphorylation status of a universal tyrosine kinase substrate, the transforming Shc adapter protein, in fibroblasts expressing the viral oncogene. We report that the level of Shc phosphorylation does not decrease in PyLT-expressing fibroblasts after growth factor withdrawal and that this PyLT-mediated effect does not require interaction with protein encoded by the retinoblastoma susceptibility gene. We also found that the chronic activation of the adapter protein is correlated with the binding of Shc to Grb-2 and with defects in the downregulation of mitogen-activated protein kinases. In fibroblasts expressing the nuclear oncoprotein, we also observed the formation of a PyLT-Shc complex that might be involved in constitutive phosphorylation of the adapter protein. Viewed comprehensively, these results suggest that the cell cycle progression induced by PyLT may depend not only on the direct inactivation of nuclear antioncogene products but also on the indirect induction, through the alteration of cytoplasmic pathways, of growth factor-dependent nuclear signals
Ryanodine receptor-2 upregulation and nicotine-mediated plasticity
No full textNicotine, the major psychoactive component of cigarette smoke, modulates neuronal activity to produce Ca 2+-dependent changes in gene transcription. However, the downstream targets that underlie the long-term effects of nicotine on neuronal function, and hence behaviour, remain to be elucidated. Here, we demonstrate that nicotine administration to mice upregulates levels of the type 2 ryanodine receptor (RyR2), a Ca 2+-release channel present on the endoplasmic reticulum, in a number of brain areas associated with cognition and addiction, notably the cortex and ventral midbrain. Nicotine-mediated RyR2 upregulation was driven by CREB, and caused a long-lasting reinforcement of Ca 2+ signalling via the process of Ca 2+-induced Ca 2+ release. RyR2 upregulation was itself required for long-term phosphorylation of CREB in a positive-feedback signalling loop. We further demonstrate that inhibition of RyR-activation in vivo abolishes sensitization to nicotine-induced habituated locomotion, a well-characterised model for onset of drug dependence. Our findings, therefore, indicate that gene-dependent reprogramming of Ca 2+ signalling is involved in nicotine-induced behavioural changes
Polyomavirus large T antigen induces alterations in cytoplasmic signalling pathways involving Shc activation
No full textThe Plasma Membrane Na+/Ca2+ Exchanger Is Cleaved by Distinct Protease Families in Neuronal Cell Death
No full textNeurodegenerative conditions commonly involve loss of neuronal connectivity, synaptic dysfunction with excessive pruning, and ionic imbalances. These often serve as a prelude to cell death either through the activation of apoptotic or necrotic death routines or excess autophagy. In many instances, a local or generalized Ca2+ deregulation is involved in signaling or executing cell death. We have recently shown that in brain ischemia, and during excitotoxicity triggered by excess glutamate, the irreversible Ca2+ deregulation leading to necrosis is due to calpain-mediated modulation of the plasma membrane Na+/Ca2+ exchanger (NCX). Here we show that the NCX can also be cleaved by caspases in neurons undergoing apoptosis, which suggests that cleavage of the main Ca2+ extrusion pathway is a lethal event in multiple forms of cell death
Apaf1-dependent programmed cell death is required for inner ear morphogenesis and growth
No full textDuring inner ear development programmed cell death occurs in specific areas of the otic epithelium but the significance of it and the molecules involved have remained unclear. We undertook an analysis of mouse mutants in which genes encoding apoptosis-associated molecules have been inactivated. Disruption of the Apaf1 gene led to a dramatic decrease in apoptosis in the inner ear epithelium, severe morphogenetic defects and a significant size reduction of the membranous labyrinth, demonstrating that an Apaf1-dependent apoptotic pathway is necessary for normal inner ear development. This pathway most probably operates through the apoptosome complex because caspase 9 mutant mice suffered similar defects. Inactivation of the Bcl2-like (Bcl2l) gene led to an overall increase in the number of cells undergoing apoptosis but did not cause any major morphogenetic defects. In contrast, decreased apoptosis was observed in specific locations that suffered from developmental deficits, indicating that proapoptotic isoform(s) produced from Bcl2l might have roles in inner ear development. In Apaf1-/-/Bcl2l-/- double mutant embryos, no cell death could be detected in the otic epithelium, demonstrating that the cell death regulated by the anti-apoptotic Bcl2l isoform, Bcl-XL in the otic epithelium is Apaf1-dependent. Furthermore, the otic vesicle failed to close completely in all double mutant embryos analyzed. These results indicate important roles for both Apaf1 and Bcl2l in inner ear development
The Ubiquitin-Protein Ligase Itch regulates p73 stability
No full textp73, a member of the p53 family of transcription factors, is upregulated in response to DNA damage, inducing cell cycle arrest and apoptosis. Besides indications that this p73 response is post- transcriptional, little is known about the underlying molecular mechanisms of p73 protein degradation. Ubiquitination and proteasomal- dependent degradation of p53 are regulated by its transcriptional target MDM2. However, unlike p53, p73 binds to, but is not degraded by, MDM2. Here we describe the binding of p73 to Itch, a Hect ubiquitin - protein ligase. Itch selectively binds and ubiquitinates p73 but not p53; this results in the rapid proteasome- dependent degradation of p73. Upon DNA damage Itch itself is downregulated, allowing p73 protein levels to rise and thus interfere with p73 function. In conclusion, we have identified a key mechanism in the control of p73 protein levels both in normal as well as in stress conditions
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