Aggregation of 25-hydroxycholesterol in a complex biomembrane. Differences with cholesterol

25-Hydroxycholesterol (25HC), one of the most important oxysterol molecules, can be used by cells to fight bacterial and viral infections but the mechanism that defines its biological effects are unknown. Using molecular dynamics, we have aimed to describe the orientation and location of 25HC in the membrane as well as the interactions it might have with lipids. We have studied two complex model membrane systems, one similar to the late endosome membrane and the other one to the plasma membrane. Our results reinforce that 25HC is inserted in the membrane in a relative stable location similar to but not identical to cholesterol. 25HC fluctuates in the membrane to a much greater degree than cholesterol, but the effect of 25HC on the phospholipid order parameters is not significantly different. One of the most notable facts about 25HC is that, unlike cholesterol, this molecule tends to aggregate, forming dimers, trimers and higher-order aggregates. These aggregates are formed spontaneously through the formation of hydrogen bonds between the two 25HC atoms, the formation of hydrogen bonds being independent of the studied system. Remarkably, no contacts or hydrogen bonds are observed between 25HC and cholesterol molecules, as well as between cholesterol molecules themselves at any time. It would be conceivable that 25HC, by forming high order aggregates without significantly altering the membrane properties, would modify the way proteins interact with the membrane and henceforth form a true innate antiviral molecule

Location, Orientation and Aggregation of Bardoxolone-ME, CDDO-ME, in a Complex Phospholipid Bilayer Membrane

Bardoxolone methyl (CDDO-Me), a synthetic derivative of the naturally occurring triterpenoid oleanolic acid, displays strong antioxidant, anticancer and anti-infammatory activities, according to diferent bibliographical sources. However, the understanding of its molecular mechanism is missing. Furthermore, CDDO-Me has displayed a signifcant cytotoxicity against various types of cancer cells. CDDO-Me has a noticeable hydrophobic character and several of its efects could be attributed to its ability to be incorporated inside the biological membrane and therefore modify its structure and specifcally interact with its components. In this study, we have used full-atom molecular dynamics to determine the location, orientation and interactions of CDDO-Me in phospholipid model membranes. Our results support the location of CDDO-Me in the middle of the membrane, it specifcally orients so that the cyano group lean towards the phospholipid interface and it specifcally interacts with particular phospholipids. Signifcantly, in the membrane the CDDO-Me molecules specifcally interact with POPE and POPS. Moreover, CDDO-Me does not aggregates in the membrane but it forms a complex conglomerate in solution. The formation of a complex aggregate in solution might hamper its biological activity and therefore it should be taken into account when intended to be used in clinical assays. This work should aid in the development of these molecules opening new avenues for future therapeutic developments

Estudio fisiopatológico y experimental del seston en las muertes por sumersión

Tesis Univ. Complutense.Fac. de MedicinaTRUEProQuestpu

Evidence of remagnetized red-beds in the Middle Atlas (Morocco)

Se ha realizado un estudio paleomagnético en el límite entre el Atlas Medio Plegado y el Atlas Medio Tabular, en el entorno de los sinclinales de Skoura y Tighboula y el anticlinal de Boulemane. La finalidad de este trabajo es tratar de reconocer una remagnetización que afecte a los materiales sedimentarios de dicha área. Para ello se han realizado diferentes test de estabilidad: (i) dos test del pliegue, uno en el anticlinal de Boulemane muestreando cinco estaciones paleomagnéticas en calizas jurásicas, y otro en el sinclinal de Tighboula, con tres estaciones en capas rojas del Cretácico Inferior; (ii) un test del conglomerado en un nivel basal del Cretácico. Los resultados de dichos test indican que en capas rojas la componente característica es una remagnetización sinpliegue, mientras que la señal magnética en las calizas es débil y no permite aislar ninguna componente paleomagnética. La similitud en el comportamiento paleomagnético de las capas rojas (propiedades de la magnetización remanente natural, probable dirección NNW de la remagnetización, polaridad normal sistemática) con la observada en cuencas de similares características del Alto Atlas podrían indicar que ambas remagnetizaciones están relacionadas.A paleomagnetic study has been carried out in the boundary between the Folded Middle Atlas and the Tabular Middle Atlas, around Skoura and Tighboula synclines and Boulemane anticline. The goal of this work is to test the existence of a remagnetization affecting the sedimentary rocks in this area. For this purpose different stability tests were done: (i) two fold tests, one in the Boulemane anticline by studying five paleomagnetic sites located in Jurassic limestones, and the other in the Tighboula syncline in three sites from Cretaceous red-beds; (ii) a conglomerate test was done sampling a Cretaceous basal level and the overlying red-beds. The results of these tests show a synfolding remagnetization in the redbeds, whereas the magnetic signal of the limestones is too weak and it is not possible to isolate a magnetic component. Red-beds shows similar paleomagnetic properties than in other basins of the High Atlas (properties of the natural remanent magnetization, a probably NNW trend of the remagnetization and a systematic normal polarity), which could indicate a relationship between both.Proyecto CGL2012-38481 de la DGICyT, MINECO y por fondos FEDER de la Unión Europea

Capsaicin affects the structure and phase organization of phospholipid membranes

AbstractCapsaicin is a natural compound with pharmacological and toxicological effects, which given its hydrophobicity, can influence the structure of membranes. The interaction of capsaicin with model membranes of dipalmitoylphosphatidylcholine and dielaidoylphosphatidylethanolamine has been studied by using differential scanning calorimetry, fluorescent probe spectroscopy and 31P-nuclear magnetic resonance. Capsaicin remarkably affects the phase transition of dipalmitoylphosphatidylcholine, shifting the transition temperature to lower values, and giving rise, at relatively high capsaicin concentrations, to the appearance of two peaks in the thermogram. These peaks may correspond to separated phases as indicated by the partial phase diagram. Whereas capsaicin did not affect the fluorescence polarization of the probes diphenylhexatriene and trimethylammonium-diphenylhexatriene, it clearly affected that of the probe 2-anthroyloxystearic acid, indicating that the perturbation produced by capsaicin on the membrane would be mainly at the position where this fluorophore is located. On the other hand, capsaicin, at relatively low concentrations, gives rise to immiscible phases in the presence of dielaidoylphoshatidylethanolamine and decrease the temperature of the lamellar to hexagonal HII phase transition. At concentrations of capsaicin higher than 0.3 mol fraction, isotropic phases were detected. The possible implications of the effects of capsaicin on biological membranes are discussed

Entrevista a Manuel de Puelles Benítez

Interview with Manuel de Puelles Benítez, Professor of Educational Policy at the Universidad Nacional de Educación a Distancia (UNED) in Madrid since 1986. The interview addresses especially his academic activity in relation to the political history of education in Spain, but also his work in the Ministry of Education during the last years of the Franco dictatorship and the transition to democracy is discussed. Among other topics, Puelles has studied the birth of the Spanish education system in relation to the formation and consolidation of the modern nation-state, also debating political modernity and education throughout the twentieth centuryEntrevista a Manuel de Puelles Benítez, Profesor de Política Educativa en la Universidad Nacional de Educación a Distancia (UNED) de Madrid desde 1986. En la entrevista se aborda sobre todo su actividad académica en relación a la historia política de la educación en España, aunque también se analiza su labor en el Ministerio de Educación durante los últimos años del Franquismo y la Transición Democrática. Entre otros temas, Puelles ha estudiado el nacimiento del sistema educativo español en relación con la formación y consolidación del moderno Estado nacional, debatiendo también acerca de la modernidad política y la educación a lo largo del siglo x