3,694 research outputs found

    Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells

    Get PDF
    AbstractBH3-only proteins are required for execution of apoptotic cell death. We have found that one of these proteins, Bik, is strongly induced in cancer cells treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy-induced expression of bik is independent of p53. Consistent with its pro-apoptotic activity, blockade of bik expression reduces the adriamycin-mediated apoptotic cell death. We also found that the bik gene is transcriptionally activated by E2F proteins. Consistently, adriamycin induces the E2F-bik pathway. In addition, E2Fs transactivate bik by a p53-independent mechanism. Thus, our data indicate that transcriptional regulation of bik contributes to the efficient apoptotic response to chemotherapeutic agents

    Recomendaciones para la informatización de los servicios de neonatología

    Get PDF
    El objetivo es proporcionar el marco para la recopilación de datos en el área de la salud de los recién nacidos que permitan la armonización de la asistencia sea cual sea su lugar de nacimiento. Para ello es necesario conocer la población atendida y la mayor dificultad es la ausencia de un sistema de recopilación de datos y de unos estándares asistenciales para todas las condiciones del recién nacido. Es imprescindible disponer de un registro único en el que se recojan los principales datos perinatales y neonatales de todos los recién nacidos. La Sociedad Española de Neonatología (SEN) debe ser el depositario y responsable de la base de datos, que debe cumplir todas las exigencias legales de privacidad y confidencialidad. A nivel de cada centro es posible conocer el peso relativo de la afección atendida por grupos de diagnósticos relacionados (DRG) y los resultados desde el aspecto de calidad asistencial. Mediante análisis comparativos (estudios de benchmarking,. . .) es posible establecer las pautas de diagnóstico y tratamiento. Es necesario conocer la población de recién nacidos atendida y definir criterios de diagnóstico y tratamiento para mejorar la calidad asistencial. La SEN desea dirigirse a los responsables asistenciales de los centros hospitalarios para pedirles su apoyo y colaboración en la puesta en marcha de estas recomendaciones

    Formation of a disk-structure and jets in the symbiotic prototype Z And during its 2006-2010 active phase

    Full text link
    We present an analysis of spectrophotometric observations of the latest cycle of activity of the symbiotic binary Z And from 2006 to 2010. We estimate the temperature of the hot component of Z And to be \approx 150000 - 170000 K at minimum brightness, decreasing to \approx 90000 K at the brightness maximum. Our estimate of the electron density in the gaseous nebula is N_{e}=10^{10}-10^{12} cm^{-3} in the region of formation of lines of neutral helium and 10^6-10^7 cm^{-3} in the region of formation of the [OIII] and [NeIII] nebular lines. A trend for the gas density derived from helium lines to increase and the gas density derived from [OIII] and [NeIII] lines to simultaneously decrease with increasing brightness of the system was observed. Our estimates show that the ratios of the theoretical and observed fluxes in the [OIII] and [NeIII] lines agree best when the O/Ne ratio is similar to its value for planetary nebulae. The model spectral energy distribution showed that, in addition to a cool component and gaseous nebula, a relatively cool pseudophotosphere (5250-11 500 K) is present in the system. The simultaneous presence of a relatively cool pseudophotosphere and high-ionization spectral lines is probably related to a disk-like structure of the pseudophotosphere. The pseudophotosphere formed very rapidly, over several weeks, during a period of increasing brightness of Z And. We infer that in 2009, as in 2006, the activity of the system was accompanied by a collimated bipolar ejection of matter. In contrast to the situation in 2006, the jets were detected even before the system reached its maximum brightness. Moreover, components with velocities close to 1200 km/s disappeared at the maximum, while those with velocities close to 1800 km/s appeared.Comment: 18 pages, 19 figures, Accepted for publication in Astronomy Report

    Wilms tumour

    Get PDF
    Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research

    Mutation study of Spanish patients with Hereditary Hemorrhagic Telangiectasia

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes.</p> <p>Methods</p> <p>Here, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT.</p> <p>Results</p> <p>We identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM) in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model.</p> <p>Conclusion</p> <p>Overall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1) in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy), but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.</p

    Detección y seguimiento de objetos en vídeos de actividades de vida diaria para rehabilitación de pacientes con daño cerebral adquirido

    Get PDF
    Las técnicas de rehabilitación permiten la recuperación y mejora de las funciones dañadas o deterioradas y ayuda al paciente con DCA a adaptarse a su nueva situación. El avance tecnológico que se ha producido en las últimas décadas, ha impulsado la investigación en el diseño y desarrollo de nuevos modelos de rehabilitación. La tecnología de vídeo interactivo se convierte en un elemento de apoyo en estos nuevos modelos rehabilitadores. Se hace necesario desarrollar nuevos algoritmos de segmentación y seguimiento que permitan dotar de información adicional a los vídeos. En este trabajo se han implementado y evaluado dos métodos que permiten realizar la detección y el seguimiento de objetos de interés

    Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis

    Get PDF
    Purpose and Experimental Design: The stem cell factor/ KIT receptor loop may represent a novel target for molecular- based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. Results: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. KIT expression was stronger in Ewing tumors showing EWSFLI1 nontype 1 fusions. Despite absence of c-kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. Treatment with KIT tyrosine kinase inhibitor imatinib (0.5–20 M) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC50, 12–15 M). However, imatinib administered alone at doses close to IC50 for growth inhibition (10 M) did not induce a significant increase in apoptosis. We then analyzed if blockade of KIT loop through imatinib (10 M) was able to increase the antitumor in vitro effect of doxorubicin (DXR)and vincristine (VCR), drugs usually used in Ewing tumor treatment. Addition of imatinib decreased in 15–20 and 15–36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. Conclusions: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Inhibition of KIT increases sensitivity of these cells to DXR and VCR. This study supports a potential role for imatinib in the treatment of Ewing tumor

    Reduction in the levels of CoQ biosynthetic proteins is related to an increase in lifespan without evidence of hepatic mitohormesis

    Get PDF
    Mitohormesis is an adaptive response induced by a mild mitochondrial stress that promotes longevity and metabolic health in different organisms. This mechanism has been proposed as the cause of the increase in the survival in Coq7+/− (Mclk1+/−) mice, which show hepatic reduction of COQ7, early mitochondrial dysfunction and increased oxidative stress. Our study shows that the lack of COQ9 in Coq9Q95X mice triggers the reduction of COQ7, COQ6 and COQ5, which results in an increase in life expectancy. However, our results reveal that the hepatic CoQ levels are not decreased and, therefore, neither mitochondrial dysfunction or increased oxidative stress are observed in liver of Coq9Q95X mice. These data point out the tissue specific differences in CoQ biosynthesis. Moreover, our results suggest that the effect of reduced levels of COQ7 on the increased survival in Coq9Q95X mice may be due to mitochondrial mechanisms in non-liver tissues or to other unknown mechanisms.This work was supported by grants from Ministerio de Economía Competitividad, Spain, and the ERDF (Grant Number SAF2015-65786-R), from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (grant number P10-CTS-6133) and from the University of Granada (grant reference “UNETE”, UCE-PP2017-06). AHG is a “FPU fellow” from the Ministerio de Educación Cultura y Deporte, Spain. MLS was a predoctoral fellow from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía. LCL was supported by the “Ramón y Cajal” National Programme, Ministerio de Economía y Competitividad, Spain (RYC-2011-07643)
    corecore