Efficient execution of cell death in non-glycolytic cells requires the generation of ROS controlled by the activity of mitochondrial H+-ATP synthase

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version Carcinogenesis 2006 27(5):925-935 is available at: http://dx.doi.org/10.1093/carcin/bgi315There is a large body of clinical data documenting that most human carcinomas contain reduced levels of the catalytic subunit of the mitochondrial H+-ATP synthase. In colon and lung cancer this alteration correlates with a poor patient prognosis. Furthermore, recent findings in colon cancer cells indicate that downregulation of the H+-ATP synthase is linked to the resistance of the cells to chemotherapy. However, the mechanism by which the H+-ATP synthase participates in cancer progression is unknown. In this work, we show that inhibitors of the H+-ATP synthase delay staurosporine (STS)-induced cell death in liver cells that are dependent on oxidative phosphorylation for energy provision whereas it has no effect on glycolytic cells. Efficient execution of cell death requires the generation of reactive oxygen species (ROS) controlled by the activity of the H+-ATP synthase in a process that is concurrent with the rapid disorganization of the cellular mitochondrial network. The generation of ROS after STS treatment is highly dependent on the mitochondrial membrane potential and most likely caused by reverse electron flow to Complex I. The generated ROS promote the carbonylation and covalent modification of cellular and mitochondrial proteins. Inhibition of the activity of the H+-ATP synthase blunted ROS production prevented the oxidation of cellular proteins and the modification of mitochondrial proteins delaying the release of cytochrome c and the execution of cell death. The results in this work establish the downregulation of the H+-ATP synthase, and thus of oxidative phosphorylation, as part of the molecular strategy adapted by cancer cells to avoid ROS-mediated cell death. Furthermore, the results provide a mechanistic explanation to understand chemotherapeutic resistance of cancer cells that rely on glycolysis as the main energy provision pathway.G.S. and M.M-D. were supported by pre-doctoral fellowships from the Ministerio de Ciencia y Tecnología. This work was supported by grants from the Ministerio de Sanidad y Consumo (PI041255), Comunidad de Madrid (SAL/0026/2004) and Ministerio de Ciencia y Tecnología (BMC2001-0710). The CBMSO receives an institutional grant from Fundación Ramón Areces.Peer reviewe

Sumar nueve… Y analizar el resultado en el mercado televisual español.

The abolition of the legal prohibition of combining significant participations in the shared capital of different operators of television at the beginning of 2009 in Spain, immediately caused strategic moves aimed at the concentration of private television channels. On the one hand, Telecinco and Cuatro; on the other hand, Antena 3 and La Sexta. In short: to add nine in order to establish the two main Spanish media holdings. This paper analyses these market movements through three major drivers of change.La supresión a comienzos de 2009 en España de la prohibición legal de simultanear participaciones significativas en el capital social de distintos operadores de televisión, provocó de manera inmediata el inicio de movimientos estratégicos orientados a la concentración de las cadenas de televisión privadas. Por un lado, Telecinco y Cuatro; por otro, Antena 3 y La Sexta. En definitiva: sumar nueve, para constituir los dos principales holdings mediáticos españoles. En el artículo se analizan estos movimientos del mercado, a través de tres importantes motores de cambio

Determinants of Support for Extralegal Violence in Latin America and the Caribbean

What are the factors behind citizen support for the use of extralegal violence in Latin America? The prevailing argument is that, in countries overwhelmed by skyrocketing levels of criminal violence, people endorse the use of extralegal violence as a way to cope with insecurity. Other scholars believe that support for extralegal violence is the result of state withdrawal and failure. Few empirical studies, however, have tested any of these arguments. In this article, using regional data from the 2012 AmericasBarometer, we examine different explanations regarding citizen support for the utilization of extralegal violence in Latin America and the Caribbean. We developed a multi-item scale that gauges support for different forms of extralegal violence across the Americas, and we hypothesize that support for extralegal violence is higher not only in countries with extreme levels of violence but especially in countries in which people distrust the political system. Results indicate that support for extralegal violence is significantly higher in societies characterized by little support for the existing political system.   Resumen ¿Cuáles son los factores que determinan el apoyo ciudadano al uso de la violencia extralegal en América Latina? El argumento predominante es que en países con niveles altos de violencia criminal, las personas apoyan el uso de la violencia extralegal como un mecanismo para hacer frente a la inseguridad. Otros trabajos consideran que el apoyo a la violencia extralegal es el resultado del fracaso o ausencia del Estado. Pocos estudios empíricos, sin embargo, han tratado de probar dichos argumentos. En este artículo, utilizando datos regionales de la encuesta de 2012 del Barómetro de las Américas, analizamos las diferentes explicaciones detrás del apoyo ciudadano al uso de la violencia extralegal en América Latina y el Caribe. Desarrollamos una escala que contiene múltiples ítems, la cual estima el apoyo a distintas formas de violencia ilegal en las Américas y planteamos la hipótesis de que el apoyo a la violencia extralegal no es solo alto en países con niveles de violencia extrema, sino que lo es especialmente en aquellos en los cuales las personas no creen en el sistema político. Los resultados obtenidos indican que el apoyo a la violencia extralegal es significativamente más alto en sociedades caracterizadas por bajos niveles de apoyo al sistema político existente

Mediapro: the conversion of a carrier into a global communication group

Se estudia la transformación que ha experimentado la empresa española Mediapro desde sus inicios como carrier (transportador de señal) hasta convertirse en un grupo global de comunicación -el primero de España por ingresos netos y ebitda-, además de una de las mayores productoras europeas y uno de los mayores difusores de derechos de retransmisiones deportivas mundiales, y que opera en numerosos países. Partiendo de un análisis de las fortalezas y debilidades de Mediapro y de un estudio profundo de sus políticas de diversificación industrial y de sus resultados empresariales, así como de su reputación corporativa, íntimamente unida al comportamiento corporativo, el texto indaga también en algunas de las claves de su futuro como gran conglomerado mediático, sujeto a un sector extraordinaria-mente competitivo y en plena transformación digital. La conclusión es que en un contexto de negocio en el que debe competir con las mayores productoras de contenidos mundiales, así como con los grandes poseedores de los derechos de retransmisiones deportivas, este futuro debe pasar necesariamente por una menor dependencia de los derechos deportivos "sujetos a una férrea negociación con grandes conglomerados mundiales" y, al mismo tiempo, por un claro reforzamiento de su reputación corporativaThe transformation that the Spanish company Mediapro has undergone from its beginning as carrier to become a global communication group -the first in Spain by net income- is studied. Mediapro is one of the largest European producers and one of the largest broadcasters of world sports broadcasting rights. Starting from an analysis of its strengths and weaknesses and an in-depth study of its industrial diversification policies and its business results, as well as its corporate reputation, closely linked to corporate behavior, the text also investigates some of the keys to its future as a large media conglomerate, subject to an extraordinarily competitive sector and in full digital transformation. The conclusion is that in a business context in which it must compete with the world's largest content producers, as well as with the large holders of sports broadcasting rights, this future must necessarily go through less dependence on sports rights -subject to a fierce negotiation with large global conglomerates- and, at the same time, for a clear reinforcement of its corporate reputation

Measurement Of Students Attitude Towards Statistics: A Mokken Scales Analysis Of Its Dimensions

 Nowadays, almost all curricula in the social sciences contain at least one course in statistics, given the importance of this discipline as a basic knowledge to understand the modern world. It’s necessary reflects on the student’s attitude to statistics, because it’s could be an obstacle or an advantage in their learning process. To measure the student’s attitude and incentives about statistics, we use a test (Bayot et al., 2005), related to other ones which exists in the specialized literature, that identifies the latent factors relating to students’ motivation and attitude towards statistics. This paper describes the formal and metric characteristics of the non-parametric model of item response theory for the latent factors using an extension of Mokken scales analysis

Sumar nueve… Y analizar el resultado en el mercado televisual español.

La supresión a comienzos de 2009 en España de la prohibición legal de simultanear participaciones significativas en el capital social de distintos operadores de televisión, provocó de manera inmediata el inicio de movimientos estratégicos orientados a la concentración de las cadenas de televisión privadas. Por un lado, Telecinco y Cuatro; por otro, Antena 3 y La Sexta. En definitiva: sumar nueve, para constituir los dos principales holdings mediáticos españoles. En el artículo se analizan estos movimientos del mercado, a través de tres importantes motores de cambio

Prisa en el sistema mediático español: del liderazgo a la pérdida de centralidad

Prisa lideró desde el comienzo de los años noventa hasta 2009 el sistema mediático español, llegando a facturar 4.000 millones de euros anuales en 2008. Y, hasta desprenderse de su participación en Canal+, fue el mayor grupo multimedia de nuestro país, tanto en ingresos netos como en audiencia acumulada (15,65%) de prensa, radio, televisión e Internet. Las razones por las que un grupo, destinado a ser uno de los grandes campeones europeos, perdió su centralidad y buena parte de su tamaño, medido en ingresos netos, son el objeto de este artículo. Desde la perspectiva teórica, esta investigación se basa en la Economía Política de la Comunicación, aunque también se detiene en el análisis de la “financiarización” y de la consiguiente deuda que lastró el desarrollo del grupo y que explica, junto con otras erróneas decisiones estratégicas, el desmantelamiento de un conglomerado que había tardado más de treinta años en construirse

Effect of hip muscle strengthening exercises on pain and disability in patients with non-specific low back pain—a systematic review

Low back pain (LBP) is a health problem that affects 70–80% of the population in Western countries. Because of the biomechanical relationship between the lumbar region and the hip, it is thought that strengthening the muscles of this joint could improve the symptoms of people with LBP. The objective of this study is to evaluate the current evidence on the efficacy of hip strengthening exercises to reduce pain and disability in people with LBP. Clinical trials were collected from the PubMed, PEDro, and Scopus databases published up to September 2022. Based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and using CASP and PEDro tools for methodological quality assessment, we selected studies that included hip strengthening exercises as part of LBP treatment and measured pain and/or disability parameters. Among the 966 records identified in the search, a total of 7 studies met the established selection criteria. Overall, participants who performed hip strengthening exercises had significantly improved in pain and disability. The methodological quality of the included studies was assessed as “good”. In conclusion, the addition of hip muscle strengthening exercises iterating interacted with LBP, effectively improving pain and disability