Papel del receptor S1P sobre el estrés oxidativo mitocondrial en cultivo neuronal

Introducción: Fingolimod, fármaco inmunomodulador, presenta propiedades neuroprotectoras que podrían promover la recuperación de la función cognitiva en enfermedades neurodegenerativas. El estrés oxidativo parece tener un papel fundamental en la patogénesis de dichas enfermedades, siendo la mitocondria una de las fuentes más importantes de especies reactivas de oxigeno (ROS). Objetivo: Determinar la implicación del receptor S1P en los efectos neuroprotectores mostrados por fingolimod fosfato (FP), forma activa de fingolimod, en un modelo celular de estrés oxidativo mitocondrial inducido por menadiona (Vitk3). Material y métodos: La línea celular SN4741 (70-80 % confluencia), se utilizó como control o se trató con Vitk3 15 µM en presencia o ausencia de FP 50 nM o FP 50 nM + W123 10 µM (antagonista S1P) durante 4 horas para estudiar: niveles de ROS mitocondrial según el marcaje de la producción de anión superóxido (O2−.); activación de caspasa-3; niveles de tioles totales (TTLs); marcadores mitocondriales (potencial de membrana mitocondrial-PMM-, actividad citocromo c oxidasa-COX- y consumo de oxígeno-OCR-). Las diferencias estadísticas se determinaron usando ANOVA de un factor. Resultados: W123 revierte parcialmente el efecto protector de FP sobe muerte celular programada, desencadenada por aumento de ROS (p<0,05) y consumo de reserva de antioxidante (p<0,05). El efecto de FP sobre los marcadores mitocondriales PMM, actividad COX y OCR es abolido con W123 (p<0,05). Conclusión: El receptor S1P está implicado en gran parte de los efectos protectores de FP, indicando un papel fundamental de S1P en el mantenimiento de la homeostasis mitocondrial. Proyecto financiado por Novartis Farmacéutica SA (PS13/14).Campus de Excelencia Internacional Andalucía Tech. Proyecto financiado por Novartis Farmacéutica SA (PS13/14). Programa operativo de empleo juvenil; Junta de Andalucía and Fondo Social Europeo (EU). CTS507 and CTS156 from Consejería de Economía Innovación Ciencia y Empresa, Junta de Andalucía and Plan Propio de la Universidad de Málaga 2016

Dietary antioxidant intake is inversely associated with 2,3-dinor oxylipin metabolites, the major excreted oxylipins in overweight and obese subjects

Cardiometabolic disease risk factors, including obesity, insulin resistance, high blood pressure, and dyslipidemia, are associated with elevated oxidative stress biomarkers like oxylipins. Increased adiposity by itself induces various isomers of this oxidized lipid family, while dietary polyphenols show benefits in its regulation. Previously, we showed that specific co-abundant microorganisms characterized the gut microbiota of Colombians and associated differentially with diet, lifestyle, obesity, and cardiometabolic health status, which led us to hypothesize that urinary oxylipins would reflect the intensity of oxidative metabolism linked to gut microbiota dysbiosis. Thus, we selected a convenience sample of 105 participants (age: 40.2 ± 11.9 years, 47.6% women), grouped according to microbiota, cardiometabolic health status, and body mass index (BMI); and evaluated 33 urinary oxylipins by HPLC-QqQ-MS/MS (e.g., isoprostanes, prostaglandins, and metabolites), paired with anthropometry and blood chemistry information and dietary antioxidants estimated from a 24-h food recall. In general, oxylipins did not show differences among individuals who differed in gut microbiota. While the unmetabolized oxylipin levels were not associated with BMI, the total content of oxylipin metabolites was highest in obese and cardiometabolically abnormal subjects (e.g., insulin resistant), mainly by prostaglandin-D (2,3-dinor-11β-PGF) and 15-F-IsoPs (2,3-dinor-15-F-IsoP and 2,3-dinor-15-epi-15-F-IsoP) metabolites. The total polyphenol intake in this cohort was 1070 ± 627 mg/day. After adjusting for body weight, the polyphenol intake was significantly higher in lean than overweight and showed an inverse association with dinor-oxylipin levels in principal component analysis. These results suggest that the 2,3-dinor-oxylipins could be more specific biomarkers associated with BMI than their parent oxylipins and that are sensitive to be regulated by dietary antioxidants.The authors thank the volunteers who agreed to participate in this study, the Colombian Ministry of science, technology, and innovation (Minciencias; grant number 832-2018), and Grupo Empresarial Nutresa. They also thank the Ibero-American Programme for Science, Technology and Development (CYTED) – Action 112RT0460 CORNUCOPIA networ

Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage

Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from oxidative damage, and the preservation of different sources of energy production is essential to preserve neuronal function. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of multiple sclerosis. This work was performed in a model of oxidative damage on neuronal cell cultures exposed to menadione in the presence or absence of fingolimod phosphate. We studied the mitochondrial function, antioxidant enzymes, protein nitrosylation, and several pathways related with glucose metabolism and glycolytic and pentose phosphate in neuronal cells cultures. Our results showed that menadione produces a decrease in mitochondrial function, an imbalance in antioxidant enzymes, and an increase in nitrosylated proteins with a decrease in glycolysis and glucose-6-phosphate dehydrogenase. All these effects were counteracted when fingolimod phosphate was present in the incubation media. These effects were mediated, at least in part, by the interaction of this drug with its specific S1P receptors. These actions would make this drug a potential tool in the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms.This research was supported by the following projects: PS13/14: Study of the non immunological mechanisms of action of Gilenya (Fingolimod) as therapeutic tool in Multiple Sclerosis and/or other neurodegenerative diseases, Novartis Farmacéutica S.A.; CTS507 and CTS156 from Consejería de Economía Innovación Ciencia y Empresa, Junta de Andalucía. N. Valverde was supported by Proyectos I+D+I-Programa Operativo FEDER Andalucía 2014-2020 (UMA18-FEDERJA 004) Junta de Andalucía and Fondo Social Europeo (EU).Ye

Marejadas rurales y luchas por la vida, vol. iv: permanencias, resistencias y luchas por la vida

Volumen 4. Permanencias, resistencias y luchas por la vida, coordinado por: Elisabeth A. Mager Hois, Miguel Ángel Paz Frayre y Carla Zamora Lomelí, integra 15 capítulos y está dividido en tres secciones, la primera denominada Permanencia, contiene 5 capítulos que intentan establecer como eje común la lucha continua en las comunidades campesinas para continuar con la vida rural. La segunda, Identidad y resistencia, está compuesta por 4 capítulos que reflexionan sobre varios procesos de resistencia de la vida rural ante los cambios globales e internos en su propio proceso de vida, otros trabajos intentan encontrar aquellos elementos que generan y mantienen alguna forma de identidad, y la tercera sección, Lucha por la vida, contiene 6 trabajos que demuestran todas aquellas posibilidades que existen en el medio rural para sostenerse y mantenerse, generando diferentes formas y estrategias que los une en la continua lucha por vivir con pocas pretensiones y con difíciles perspectivas pero siempre encontrando alternativas.ASOCIACIÓN MEXICANA DE ESTUDIOS RURALES, INSTITUTO DE CIENCIAS AGROPECUARIAS Y RURALES (ICAR), UNIVERSIDAD DE GUADALAJARA, FACULTAD DE ESTUDIOS SUPERIORES ACATLÁN-UNAM, ECOSUR, CUCOSTA SUR GRANA, EL COLEGIO DE MICHOACÁN A.C., UNIVERSIDAD MICHOACANA DE SAN NICOLAS HIDALG

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI