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

Monitoring of the Canales Dam and Its Control During Construction Period

This paper presents a study of the stress-deformation behaviour of the Canales Dam (Granada) during construction. The basis for this study has been the three dimensional (3D) finite elements method with hyperbolic material response. The analytical procedure used is presented and the study concludes with a comparative study of the results obtained from the calculation programme used and monitoring system\u27s measurements

A controlled antibiotic release system to prevent orthopedic-implant associated infections: An in vitro study

A new device for local delivery of antibiotics is presented, with potential use as a drug-eluting fixation pin for orthopedic applications. The implant consists of a stainless steel hollow tubular reservoir packed with the desired antibiotic. Release takes place through several orifices previously drilled in the reservoir wall, a process that does not compromise the mechanical properties required for the implant. Depending on the antibiotic chosen and the number of orifices, the release profile can be tailored from a rapid release of the load (ca. 20 h) to a combination of rapid initial release and slower, sustained release for a longer period of time (ca. 200 h). An excellent bactericidal action is obtained, with 4-log reductions achieved in as little as 2 h, and total bacterial eradication in 8 h using 6-pinholed implants filled with cefazolin

Performance of Starch Gels on In Vitro Enzymatic Hydrolysis Assessed by Rheological Methodologies

Starch hydrolysis is attracting much attention due to its relationship to digestion and glucose release. The objective is to propose rapid and continuous analytical methods that allow measuring gels hydrolysis following apparent viscosity (μ). Three different starches (corn, wheat, and rice) are tested recording starch gelatinization followed by gels digestions (digestograms) using a rapid-visco analyzer (RVA) or a rheometer. Results are compared with those obtained by measuring glucose release along hydrolysis. A modified first-order kinetic model in the RVA (R2 > 0.99) and rheometer (R2 > 0.99) describes the gels digestograms. Wheat gel shows a higher hydrolysis rate (k), which indicates faster digestion followed by rice and corn gels. The proposed models allow rapid analysis of starch digestograms, allowing to discriminate among hydrolysis rate of different starches. These less time-consuming methods can be an option to continuously analyze starch gelatinization followed by enzymatic digestion.Generalitat Valenciana (Prometeo 2017/189) and Xunta de Galicia (Consolidation Project ED431B 2019/01).S

Relación de la estructura con las propiedades eléctricas en solución sólida La2/3-xLi3xTiO3 (0.03 x 0.167)

En este trabajo se investigó la solución sólida La2/3-xLi3xTiO3 (0.03<x<0.167) por las técnicas de difracción de rayos-X en polvos (DRX), espectroscopía de impedancias (EI) y resonancia magnética nuclear (RMN) de 7Li. En estas muestras se observó un cambio en la simetría de tetragonal a ortorrómbica cuando disminuye el contenido de litio por debajo de x=0.06. Hallamos que las modificaciones estructurales producidas se deben principalmente al ordenamiento de las vacancias a lo largo del eje c. Estas modificaciones disminuyen gradualmente al incrementarse el contenido de litio en la solución sólida. Se detectaron dos señales de litio con diferente constante cuadrupolar para el espectro de RMN del 7Li en las perovskitas ortorrómbicas/tetragonales, las cuales asociamos con dos sitios cristalográficos para el litio dentro de la estructura. Para la perovskita de composición La0.5Li0.5TiO3, se realizó un experimento enfriándola rápidamente desde 1300° C en nitrógeno líquido. En ésta se detectó una elevada movili- dad del litio en el espectro de RMN del 7Li. Para las perovskitas analizadas, la dependencia de la conductividad eléctrica con el contenido de litio no sigue el comportamiento esperado, basado en la teoría de una distribución aleatoria de los átomos de La y Li sobre los sitios A. La conductividad DC aumenta rápidamente con el contenido de litio en las muestras ortorrómbicas, aunque el cambio es mucho más gradual en las tetragonales, donde la distribución de las vacancias se desordena progresivamente. En todas las perovskitas analizadas, la dependencia de la conductividad dc con la temperatura muestra un comportamiento no-Arrhenius con energías de activación de 0.39±0.02 eV y 0.29±0.02 eV en los rangos de temperatura de 160 – 250 y 250 – 360 K, respectivamente

Macrofauna de invertebrados del Cretácico superior de la Depresión Central Asturiana

Se reporta y comenta la fauna de inocerámidos, rudistas, ammonites, braquiópodos y equmnidos recogida y localizada en yacimientos o series estratigráficas de detalle, durante los trabajos de campo de la tesis doctoral del primero de los autores (E.B.) sobre los seláceos del Cretácico de Asturias. La distribución, principalmente de inocerámidos y ammonites, permite identificar el Cenomaniense superior y el Turoniense inferior y medio. Se han reconocido rudistas del Turoniense superior y del Coniaciense, braquiópodos del Cenomaniense y del Santoniense inferior y un registro relativamente rico y variado de equínidos desde el Cenomaniense hasta el Coniaciense.The fauna collected and located on fossil localities or stratigraphical profiles, during the field work of the first author's doctoral thesis on the Cretaceous selachians from Asturias, is reported and commented. It includes inoceramids, rudists, ammonoids, brachiopods and echinoids. Distribution of, mainly inoceramids and ammonoids, allowed to identify the Upper Cenomanian and the Lower and Middle Turonian. LateTuronian and Coniacian rudists have been recognized, as well as Cenomanian and lower Santonian brachiopods and a quite rich and diversified record of echinoids ranging from Cenomanian to Coniacian

Factores psicosociales, asociados al embarazo en adolescentes, en un grupo de 100 adolescentes embarazadas atendidas en el Centro de Salud de Nuevo Veranillo.

Objetivo general: Determinar los factores psicosociales asociados al embarazo en la adolescente, en un grupo de adolescentes atendidas en el Centro de Salud de Nuevo Veranillo. Objetivos específicos: Delimitar el concepto de adolescencia. Identificar las características psicosociales de la adolescente embarazada. Identificar los factores psicosociales asociados al embarazo en adolescentes. Clasificar los factores psicosociales encontrados en la adolescente embarazada. Determinar el grado de asociación entre los factores psicosociales y el embarazo en la adolescencia

Synergistic assembly of gold and copper-iron oxide nanocatalysts to promote the simultaneous depletion of glucose and glutathione

Glucose and glutathione (GSH) are key biomolecules for the regulation and growth of tumor cells. The use of inorganic nanocatalysts in biomedicine to target and deplete such specific molecules represents a novel and promising strategy against cancer. In this work, we present a ternary assembled nanohybrid based on Au and CuFe2O4 with the capability to simultaneously deplete glucose and GSH and generate reactive oxidative species (ROS) in a cascade process. We describe an example of a synergistic heterogeneous nanoarchitecture able to maintain the glucose oxidase-like activity of Au while preventing its deactivation in the presence of GSH. Au sites remain active due to the rapid response of the Cu–Fe co-catalyst to deplete GSH levels. This example of hybrid heterostructure represents an appealing alternative with dual-activity within the tumor microenvironment (TME) for potential anticancer therapy