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

Magnetic extractions and electronic microscopy observations in Jurassic remagnetized carbonates

IX Congreso Geológico de España, Huelva, 12-14 de septiembre, 2016El estudio de la remagnetización en rocas carbonatadas viene realizándose durante los últimos 40 años, tanto por medio del análisis de sus propiedades magnéticas como tratando de realizar observaciones por medio de microscopía electrónica (SEM/TEM). Los resultados obtenidos con el primer análisis han proporcionado numerosos datos y hoy en día sabemos que generalmente la remagnetización es portada por magnetita. Ésta es de tamaño nanométrico generada durante la diagénesis, correspondiéndose con una remagnetización química. Sin embargo, los numerosos intentos de observación de dichos cristales por medio de SEM/TEM siempre han sido infructuosos y los cristales observados siempre presentan tamaños dentro del rango multidominio. En un nuevo intento de observación directa de dichos cristales mediante microscopía electrónica, hemos realizado nuevos ensayos sobre extractos magnéticos en calizas jurásicas remagnetizadas de las cuencas del Alto Atlas (Marruecos), Cameros y Vasco-Cantábrica (España) según las últimas técnicas propuestas en la literatura. Las propiedades magnéticas de los diferentes subproductos provenientes del proceso de extracción indican una pérdida de material magnético durante el mismo, principalmente las partículas de grano más fino (granos de tamaño monodominio y superparamagnético). Igualmente, mediante SEM/TEM únicamente han podido observarse cristales de magnetita multidominio.Since the last 40 years the analysis of remagnetized carbonates is under debate, by studying their magnetic properties and by using electronic microscopy (SEM/TEM). Results obtained from the first analyses allowed to infer that remagnetization is carried generally by nanometric magnetite and generated during the diagenesis, therefore it corresponds to a chemical remagnetization. However, several attempts to observe these magnetites by SEM/TEM were unsuccessful and in all cases the observed magnetite was in the range of multidomain size. In a new attempt to observe these crystals by electronic microscopy we did new magnetic extracts (according the last techniques proposed in the literature) in Jurassic remagnetized limestones of the High Atlas (Morocco), Cameros and Basque-Cantabrian (Spain) basins. Magnetic properties of the different sub-products of the extracts show a lost of magnetic material during the procedure, mostly of the smallest size (superparamagnetic and single-domain size). Likewise, only multi-domain magnetite grains were observed by SEM/TEM.proyecto CGL2012-38481 de la DGICyT, MINECO y fondos FEDER de la Unión Europea, así cómo por el programa de financiación de la NSF (EEUU) al Institute for Rock Magnetis

The carriers of AMS in remagnetized carbonates. Insights for remagnetization mechanism and basin evolution

Magnetic fabrics are usually studied to unravel the evolution of sedimentary basins, mainly focusing the attention in paramagnetic minerals. However, since basins are sometimes affected by burial-related chemical remagnetizations, magnetic fabrics can also be carried by authigenic ferromagnetic minerals related to remagnetization processes. Consequently, the study of the different types of fabrics can give complementary and valuable information about the evolution of sedimentary basins. Here, we explore, in the Jurassic carbonates of the Central High Atlas (Morocco), the role in magnetic fabrics of authigenic magnetite that grew during the Cretaceous (ca. 100 Ma) widespread remagnetization event. Magnetic fabrics are studied in 53 sites using the anisotropy of the magnetic susceptibility measured at room temperature (RT-AMS) and comparing results with sub-fabrics that alternatively enhance the paramagnetic and the ferromagnetic signal. Furthermore, an innovative analysis is proposed, comparing the magnetic fabrics before and after bedding correction (the common procedure) with fabric orientation after partial bedding correction. We use the paleomagnetic information to reconstruct the attitude of bedding at the remagnetization time and to restore the magnetic fabrics at this time. The performed analysis allows interpreting RT-AMS in terms of the contribution of different subfabrics, and the relationship between these, tectonic processes and the magnetic mineralogy. Four RT-AMS types are defined: T1 is carried by superparamagnetic magnetite that grew during the remagnetization stage and shows a horizontal lineation parallel to the extension direction at this time; T3 and T4 are carried by paramagnetic minerals and show compressive fabrics with the magnetic lineation parallel to intersection (bedding-cleavage) lineation; finally, T2 shows a mix between ferrimagnetic and paramagnetic fabrics.MINECO (Spanish Ministry of Economy and Competitiveness) cofinanced by the ERDF (European Union) (research projects CGL2012-38481 and CGL2016-77560)