Muerte celular dependiente de lisosoma : reguladores moleculares y consecuencias en la neurodegeneración

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, leída el 19-03-2018La muerte celular dependiente de lisosoma es un tipo de muerte en el que la estabilidad dela membrana se pierde, llevando a la liberación del contenido lisosomal al citosol. Parte delas proteínas del lumen lisosomal son activas en el citosol, lo que desencadena el corte de múltiples proteínas citoplasmaticas, llevando a muerte celular. Además, la autofagia,mecanismo necesario para la homeostasis celular, requiere de lisosomas en correcto estado para poder ser efectiva. En esta tesis, el papel de la autofagia y la estabilidad lisosomal fue estudiado en un modelo murino de degeneración retiniana llamado retinitis pigmentaria, demonstrando que en un modelo de ratón de esta enfermedad, la muerte celular dependiente de lisosoma está ocurriendo. Estos resultados nos llevaron a estudiar el mecanismo de esta muerte en modelos deficientes de autofagia, descubriendo que la proteína Atg7, necesaria para la inducción de la autofagia, podría tener un papel fundamental en la composición lipídica del lisosoma, afectando directamente a la estabilidad lisosomal...Lysosomal-dependent cell death is a kind of cell death which is characterized by the lost of the lysosomal stability, leading to the release of the lysosomal content to the cytosol. Someof the lyososomal protein are active in the cytosol, leading to the cleavage of several cytoplasmic proteins, promoting cell death. In addition, autophagy, which is a necessary mechanism for the cellular homeostasis, needs functional lysosomes to be effective. In this thesis, autophagy role and lysosomal stability was studied in a mouse model of a retinal degeneration disease called retinitis pigmentosa, demonstrating that in this model of the disease, lysosomal dependent-cell death is happening. These results leaded us to study this cell death mechanism in autophagy-deficient models, demonstrating that the protein Atg7,necessary for autophagy induction, could present a fundamental role in the lysosoma llipidic composition, afecting to the lysosomal stability...Fac. de Ciencias QuímicasTRUEunpu

Lysosome-dependent cell death: molecular players and implications for disease

La muerte celular dependiente de lisosoma es un tipo de muerte en el que la estabilidad dela membrana se pierde, llevando a la liberación del contenido lisosomal al citosol. Parte delas proteínas del lumen lisosomal son activas en el citosol, lo que desencadena el corte de múltiples proteínas citoplasmaticas, llevando a muerte celular. Además, la autofagia,mecanismo necesario para la homeostasis celular, requiere de lisosomas en correcto estado para poder ser efectiva. En esta tesis, el papel de la autofagia y la estabilidad lisosomal fue estudiado en un modelo murino de degeneración retiniana llamado retinitis pigmentaria, demonstrando que en un modelo de ratón de esta enfermedad, la muerte celular dependiente de lisosoma está ocurriendo. Estos resultados nos llevaron a estudiar el mecanismo de esta muerte en modelos deficientes de autofagia, descubriendo que la proteína Atg7, necesaria para la inducción de la autofagia, podría tener un papel fundamental en la composición lipídica del lisosoma, afectando directamente a la estabilidad lisosomal..

Fluorescent and Electroactive Monoalkyl BTD-Based Liquid Crystals with Tunable Self-Assembling and Electronic Properties

We report here on a series of redox active benzothiadiazole-based luminophores ffinctionalized on one edge with a phenyl-nonyl substituent, which confers these molecules a rodlike shape and a tendency to self-assemble into layered superstructures. On the other edge, the molecules are endowed with different p-substituted phenyl rings, which allows the modulation of their redox and optical properties on the basis of the electronic nature of the terminal substituents. We have found that just one lateral alkyl chain is sufficient to induce mesomorphism in these molecules, which present nematic or smectic mesophases upon therinal treatment. Single-crystal analysis allows us to get an insight into the nature of the forces responsible for different supramolecular assemblies in these derivatives, and point to a strong contribution of the terminal groups in the different arrangements observed. The interesting redox and optical properties together with their self-assembling tendencies render these new materials interesting candidates for optoelectromcs

New method to assess mitophagy flux by flow cytometry

PMID:25945953 WOS:000355323800009publishersversionpublishe

Electro-reforming of bioethanol produced by sugar fermentation on a Pt-Ni anodic catalyst supported on graphene nanoplatelets

A study of the electro-reforming of bioethanol produced through sugar fermentation using a Pt-Ni supported on graphene nanoplatelets (Pt-Ni/GNPs) anodic catalyst is presented here. The physicochemical characterization of the anodic catalyst showed a good dispersion and small sizes of the metallic crystallite. Then, the evolution of the electrochemical activity over time of three bioethanol batches with different initial sugar concentrations of 150, 200 and 250 g·L−1 was explored in a Proton Exchange Membrane (PEM) electrolysis cell. A general growth in the ethanol concentration over time was observed for all the bioethanol batches, along with an improvement in the electrochemical activity, principally associated to ethanol oxidation reaction (EOR). Additionally, the presence of non-fermented sugar and other molecules formed during fermentation exhibited a negative contribution in the electrochemical activity. The bioethanol batch with an initial sugar concentration of 200 g·L−1 presented the best compromise between bioethanol production, fermentation time and electrochemical activity, achieving competitive current densities (∼285 mA·cm−2 at 1.2 V) and energy consumption values (21.6 kWh·kgH2−1 at 100 mA·cm−2) to those from other publications using synthetic ethanol-water solutions. These results demonstrated the interest of the used Pt-Ni/GNPs anodic catalyst for the renewable hydrogen production via direct electro-reforming of liquid biofuels.Se presenta aquí un estudio del electro-reformado de bioetanol producido a través de la fermentación de azúcar usando un catalizador anódico de Pt-Ni soportado en nanoplaquetas de grafeno (Pt-Ni/GNPs). La caracterización fisicoquímica del catalizador anódico mostró una buena dispersión y pequeños tamaños de los cristalitos metálicos . Luego, se exploró la evolución de la actividad electroquímica en el tiempo de tres lotes de bioetanol con diferentes concentraciones iniciales de azúcar de 150, 200 y 250 g·L -1 en una celda de electrólisis de membrana de intercambio de protones (PEM). Se observó un crecimiento general en la concentración de etanol a lo largo del tiempo para todos los lotes de bioetanol, junto con una mejora en la actividad electroquímica, principalmente asociada a la reacción de oxidación del etanol.(EO). Adicionalmente, la presencia de azúcar no fermentado y otras moléculas formadas durante la fermentación exhibieron una contribución negativa en la actividad electroquímica. El lote de bioetanol con una concentración inicial de azúcar de 200 g·L −1 presentó el mejor compromiso entre producción de bioetanol, tiempo de fermentación y actividad electroquímica, alcanzando densidades de corriente (∼285 mA·cm −2 a 1,2 V) y valores de consumo de energía competitivos ( 21,6 kWh·kgH 2 −1 a 100 mA·cm −2 ) a los de otras publicaciones que utilizan soluciones sintéticas de etanol y agua. Estos resultados demostraron el interés del catalizador anódico Pt-Ni/GNPs utilizado para la producción de hidrógeno renovable.vía electro-reformado directo de biocombustibles líquidos

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Déu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience. Trial registration: NCT02561416. Registered 23 September 201

Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study)

Background: The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes. Methods: Effectiveness, cost-utility, and neurobiological analyses performed alongside a 12-month RCT. The participants will be 180 adult patients with FMS recruited at the Sant Joan de Deu hospital (St. Boi de Llobregat, Spain), randomly allocated to one of the three study arms: TAU + MBSR vs. TAU + FibroQol vs. TAU. A comprehensive assessment to collect functional, quality of life, distress, costs, and psychological variables will be conducted pre-, post-intervention, and at 12-month post-intervention. Fifty per cent of study participants will be evaluated at pre- and post-treatment using Voxel-Based Morphometry, Diffusion Tensor Imaging, pseudo-continuous Arterial Spin Labeling, and resting state fMRI. A cytokine multiplex kit of high-sensitivity will be applied (cytokines IL-6, IL-8, IL-10 + high-sensitivity CRP test). Discussion: The findings obtained from this RCT will indicate whether MBSR is potentially cost-effective for FMS and contribute to knowledge of any brain and inflammatory changes associated with MBSR in FMS patients. Specifically, we will determine whether there are morphometric and functional changes associated with participation in MBSR in brain regions related to meta-awareness, body awareness, memory consolidation-reconsolidation, emotion regulation and in networks postulated to underpin the sensory-discriminative, cognitive-evaluative and affective-motivational aspects of the pain experience

Graphene-like materials as an alternative to carbon Vulcan support for the electrochemical reforming of ethanol: Towards a complete optimization of the anodic catalyst

This study aims to investigate the viability of using commercial graphene-like materials as Pt based anodic catalyst supports as an alternative to the extended use of carbon Vulcan XC-72, for the ethanol oxidation reaction (EOR). Among the different investigated catalysts, Pt supported on graphene nanoplatelets (GNPs) resulted to be the most active, which was attributed to a combination of a higher BET surface area and a slightly higher amount of nitrogen in comparison with other supports. A higher BET surface area of the support could mean a larger pore volume available to settle the metal particles, whereas a greater amount of nitrogen may improve its electrical conductivity. A complete optimization of the Pt metal loading and Pt-Ni ratio on the final anodic bimetallic catalyst was also performed to prepare a membrane electrode assembly (MEA) for a proton exchange membrane ethanol electrolysis cell (PEMEC). Finally, the metal loading on MEA was optimized towards the production of hydrogen and value-added products resulting from the EOR. The MEA based on the optimized anodic Pt-Ni/GNPs catalyst allow to obtain current density values around 590 mA·cm−2 (at 1.4 V), higher than previous studies based on Pt-Ru and Pt-Sn catalysts supported on Carbon Vulcan.Este estudio tiene como objetivo investigar la viabilidad del uso de materiales comerciales similares al grafeno como soportes de catalizadores anódicos basados ​​en Pt como una alternativa al uso extendido de carbono Vulcan XC-72, para la reacción de oxidación de etanol (EOR). Entre los diferentes catalizadores investigados, el Pt soportado sobre nanoplaquetas de grafeno (GNP) resultó ser el más activo, lo que se atribuyó a una combinación de un área de superficie BET más alta y una cantidad de nitrógeno ligeramente superior en comparación con otros soportes. Una mayor superficie BET del soporte podría significar un mayor volumen de poros disponible para sedimentar las partículas metálicas, mientras que una mayor cantidad de nitrógeno podría mejorar su conductividad eléctrica. También se realizó una optimización completa de la carga de metal Pt y la relación Pt-Ni en el catalizador bimetálico anódico final para preparar un conjunto de electrodos de membrana (MEA) para una celda de electrólisis de etanol con membrana de intercambio de protones (PEMEC). Finalmente, la carga de metal en MEA se optimizó hacia la producción de hidrógeno y productos de valor agregado resultantes de la EOR. Los MEA basados ​​en el catalizador anódico optimizado Pt-Ni/GNPs permiten obtener valores de densidad de corriente en torno a 590 mA·cm−

The Bostrichidae of the Maltese Islands (Coleoptera)

The Bostrichidae of the Maltese Islands are reviewed. Ten species are recorded with certainty from this Archipelago, of which 6 namely, Trogoxylon impressum (Comolli, 1837), Amphicerus bimaculatus (A.G. Olivier, 1790), Heterobostrychus aequalis (Waterhouse, 1884), Sinoxylon unidentatum (Fabricius, 1801), Xyloperthella picea (A.G. Olivier, 1790) and Apate monachus Fabricius, 1775 are recorded for the first time. Two of the mentioned species (H. aequalis and S. unidentatum) are alien and recorded only on the basis of single captures and the possible establishment of these species is discussed. Earlier records of Scobicia pustulata (Fabricius, 1801) from Malta are incorrect and should be attributed to S. chevrieri (A. Villa & J.B. Villa, 1835). A zoogeographical analysis and an updated checklist of the 12 species of Bostrichidae recorded from the Maltese Islands and neighbouring Sicilian islands (Pantelleria, Linosa and Lampedusa) are also provided. Rhizopertha dominica (Fabricius, 1792) form granulipennis Lesne in Beeson & Bhatia, 1937 from Uttarakhand (northern India) was overlooked by almost all subsequent authors. Its history is summarized and the following new synonymy is established: Rhizopertha dominica (Fabricius, 1792) form granulipennis Lesne in Beeson & Bhatia, 1937 = Rhyzopertha dominica (Fabricius, 1792), syn. n. Finally, records of Amphicerus bimaculatus from Azerbaijan, of Bostrichus capucinus (Linnaeus, 1758) from Jordan and Syria, of Scobicia chevrieri from Jordan and Italy, of Xyloperthella picea from Italy, and of Apate monachus from Corsica (France) and Italy, are also provided.peer-reviewe

Assessing the skill of precipitation and temperature seasonal forecasts in Spain: windows of opportunity related to ENSO events

1. The skill of state-of-the-art operational seasonal forecast models in extratropical latitudes is assessed using a multimodel ensemble from the Development of a European Multimodel Ensemble System for Seasonalto- Interannual Prediction (DEMETER) project. In particular, probabilistic forecasts of surface precipitation and maximum temperature in Spain are analyzed using a high-resolution observation gridded dataset (Spain02). To this aim, a simple statistical test based on the observed and predicted tercile anomalies is used. First, the whole period 1960–2000 is considered and it is shown that the only significant skill is found for dry events in autumn. Then, the influence of ENSO events as a potential source of conditional predictability is studied and the validation to strong La Niña or El Niño periods is restricted. Skillful seasonal predictions are found in partial agreement with the observed teleconnections derived from the historical records. On the one hand, predictability is found in spring related to El Niño events for dry events over the south and the Mediterranean coast and for hot events in the southeast areas. In contrast, La Niña drives predictability in winter for dry events over the western part and for hot events in summer over the south and the Mediterranean coast. This study considers both the direct model outputs and the postprocessed predictions obtained using a statistical downscaling method based on analogs. In general, the use of the downscaling method outperforms the direct output for precipitation, whereas in the case of the temperature no improvement is obtained