Editorial: New insights into understanding and managing NAFLD

Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease with complications related to the metabolic syndrome and with a diverse histopathological spectrum ranging from simple steatosis, also termed fatty liver (NAFL) without significant inflammation to steatohepatitis (NASH) with varying stages of fibrosis and, ultimately, cirrhosis, and hepatocellular carcinoma. Since NAFLD is the most common chronic liver disease worldwide, causing a considerable health burden, there is an increasing number of research groups that are deeply interested in the identification of risk factors involved in the progression of the liver damage, the characterization of new biomarkers with utility for its non-invasive diagnosis and the recognition of novel molecular targets for its treatment.Fil: Escribano, Óscar. Universidad Complutense de Madrid; EspañaFil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Otero, Yolanda F.. Valbiotis; FranciaFil: Egea, Javier. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; EspañaFil: González Rodríguez, Águeda. Centro de Investigación Biomédica En Red de Diabetes y Enfermedades Metabólicas Asociadas; Argentina. Instituto de Salud Carlos III; Españ

Estudio de caracteres fenológicos, agronómicos, morfológicos y fisiológicos en relación con la tolerancia al estrés hidríco en cebada

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 21-12-2001La falta de agua al final del ciclo es el principal factor limitante del rendimiento de la cebada en la mayoría de las regiones españolas. Por tanto, el conocer los caracteres que contribuyen a mejorar el rendimiento en dichas condiciones presenta gran interés en la selección de genotipos tolerantes a la sequía. Para determinar la influencia de los caracteres fenológicos, agronómicos, morfológicos y fisiológicos en la tolerancia a la sequía y en el rendimiento en condiciones de estrés hídrico terminal, se estudió el comportamiento de diferentes genotipos de cebada en un refugio anti-lluvia. Todos los años se obtuvieron el rendimiento y sus componentes, siendo el peso de mil granos el componente del rendimiento que se vio más afectado por el estrés. La precocidad fue uno de los caracteres que más influyó en el rendimiento, especialmente en condiciones de estrés. Los genotipos más precoces tenían el periodo de llenado del grano más largo y los rendimientos en grano más altos en esas condiciones. Entre los caracteres fisiológicos, la mayor capacidad de ajuste osmótico y la actividad fotosintética alta durante el periodo de llenado del grano favorecían el rendimiento de los genotipos que los poseían al someterlos a estrés hídrico terminal. Las tasas de transpiración residual bajas se asociaron a mayores rendimientos en condiciones de estrés. En esas condiciones el contenido en ceras epicuticulares incrementó y mejoró el rendimiento en grano de los genotipos con mayor cantidad de ceras presentes en las hojas. Teniendo en cuenta la variabilidad encontrada para los caracteres estudiados, junto con las correlaciones que presentan con el rendimiento del grano podemos concluir que los caracteres fenológicos, agronómicos, morfológicos y fisiológicos son de gran interés en la mejora de cebada para tolerancia a la sequía, ya que contribuyen a que losrendimientos sean más altos y estables cuando la disponibilidad de agua por el cultivo es escasa, lo que ocurre, normalmente, al final del ciclo.Fac. de Ciencias BiológicasTRUEpu

Caracterización fotosintética de árboles de la laurisilva canaria (Laurus Azorica, Persea indica y Myrica faya)

Se establece una parcela experimental en el bosque de laurisilva de Agua García, realizando estudios estructurales para determinar el número, tamaño y distribución de las principales especies de árboles así como de las características morfológicas y fisiológicas de sus hojas a lo largo del perfil vertical del bosque, calculando su índice de área foliar. Se realizan ciclos diarios de intercambio gaseoso a lo largo de un año, en árboles adultos de Laurus azorica, Persea indica y Myrica faya, utilizando una torre de 20 m. para acceder tanto a las hojas de sol como de sombra, y facilitando la instalación de una estación meteorológica con registro contínuo de los principales factores. A partir de los datos obtenidos con estas medidas se calcula la fotosíntesis y transpiración máxima de cada especie y su variación a lo largo del año, así como su eficiencia en el uso del agua y la respuesta de la fotosíntesis a la luz, temperatura y conductancia estomática. También y en combinación con medidas de laboratorio se muestra la influencia de la fotorrespiración (con electrodo de oxígeno) y de la fotoinhibición realizando medidas combinadas de fluorescencia de la clorofila, con determinación de pigmentos y antioxidantes. También se realiza un estudio exhaustivo en el que se combinan técnicas de fluorescencia de la clorofila con conductividad eléctrica y observación de síntomas visibles para conocer los límites de supervivencia del aparato fotosintético de las tres especies a temperaturas extrema

PilotBystander-focusedProgram to Prevent Sexual and SexistHarassment. Teaching Innovation Proposal of the Faculty of Sciences

Fruto de una colaboración interdisciplinar, la Facultad de Ciencias desarrolló, durante el curso 2017-18, un programa piloto orientado a la formación de observadores entre el alumnado del centro. El objetivo general era preparar a estudiantes para intervenir de forma temprana frente a conductas inapropiadas. Además de informar y sensibilizar sobre el acoso y sus consecuencias, las actividades han estado dirigidas a desarrollar habilidades de comunicación eficaz, resolución de conflictos y empatía. Para evaluar la eficacia de la intervención, se utizó un diseño pre-post con dos grupos (intervención y control). Se diseñó un instrumento con cuatro sub-escalaspara medir: a) la adecuación dedistintas situaciones; b) la necesidad de intervenir en cada una de ellas; c) el conocimiento sobre cómo intervenir; y d) la disposición a intervenir.El instrumento fue depurado con alumnado de otros centros, demostrandobuenas propiedades psicométricas, evidencia de validez y capacidad discriminativa. Durante las Jornadas de Innovación Educativa presentamos únicamente los resultados preliminares del estudio exploratorio (N = 201), puesto que aún no contábamos con los resultados definitivos. Encontramos diferencias significtivas por género en varias medidas. Las mujeres valoraron peor las situaciones de acoso, mostraron más disposición e intención de intervenir, y mayor empatía haciaquienes sufren acoso que los varones.Los análisis de medidas repetidas mostraron mejoras significativas en el grupo de intervención en varias de las medidas (valoración del acoso sexual, conocimiento y disposición a intervenir, y empatía).As a result of an interdisciplinary collaboration, the Faculty of Sciences developed, during the academic year 2017-18, a pilot program aimed at the training of bystanders among the students of the center.The general objective was to prepare students to intervene early in the face of inappropriate behavior. In addition to informing and raising awareness about sexual harrasment and its consequences, the activities have been aimed at acquiring effective communication skills, conflict resolution and empathy. To evaluate the effectiveness of the intervention, a pre-post design with two groups (intervention and control) was used. An instrument with four sub-scales was designed to measure: a) the adequacy of different situations; b) the need to intervene in each of them; c) knowledge about how to intervene; and d) the willingness to intervene. The instrument was refined with students from other centers, demonstrating good psychometric properties, evidence of validity and discriminative capacity. During the Educational Innovation Conference we presented only the preliminary results of the exploratory study (N = 201), since we still did not have the final results. In addition to develop a new instrument, the results indicated significant differences by gender in several measures. Women rated harassment situations worse, showed more willingness and intention to intervene, and greater empathy towards those who suffer harassment than men do.The repeated measures analyses showed significant improvements in the intervention group in several measures (assessment of sexual harrassment, knowledge and willingness to intervene, and empathy)

Editorial: Role of Nrf2 in disease: Novel molecular mechanisms and therapeutic approaches

This is supported by FIS/FEDER CP14/00008, CP16/00014, CP16/00017, PI15/00448, PI16/00735, PI16/02057, PI17/00130, Spanish Ministry of Economy and Competitiveness (RYC-2017- 22369), Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT). Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)

Developmental switch from prolonged insulin action to increased insulin sensitivity in protein tyrosine phosphatase 1B-deficient hepatocytes

15 pages, 10 figures.Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. The purpose of this study was to evaluate the differences in insulin sensitivity between neonate and adult hepatocytes lacking PTP1B. Immortalized neonatal hepatocytes and primary neonatal and adult hepatocytes have been generated from PTP1B(-/-) and wild-type mice. PTP1B deficiency in immortalized neonatal hepatocytes prolonged insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and IR substrates (IRS) -1, -2 compared with wild-type control cells. Endogenous IR and IRS-2 were down-regulated, whereas IRS-1 was up-regulated in PTP1B(-/-) neonatal hepatocytes and livers of PTP1B(-/-) neonates. Insulin-induced activation of phosphatidylinositol 3-kinase/Akt pathway was prolonged in PTP1B(-/-) immortalized neonatal hepatocytes. However, insulin sensitivity was comparable to wild-type hepatocytes. Rescue of PTP1B in deficient cells suppressed the prolonged insulin signaling, whereas RNA interference in wild-type cells promoted prolonged signaling. In primary neonatal PTP1B(-/-) hepatocytes, insulin prolonged the inhibition of gluconeogenic mRNAs, but the sensitivity to this inhibition was similar to wild-type cells. By contrast, in adult PTP1B-deficient livers, p85alpha was down-regulated compared with the wild type. Moreover, primary hepatocytes from adult PTP1B(-/-) mice displayed enhanced Akt phosphorylation and a more pronounced inhibition of gluconeogenic mRNAs than wild-type cells. Hepatic insulin sensitivity due to PTP1B deficiency is acquired through postnatal development. Thus, changes in IR and IRS-2 expression and in the balance between regulatory and catalytic subunits of phosphatidylinositol 3-kinase are necessary to achieve insulin sensitization in adult PTP1B(-/-) hepatocytes.This work was supported by Grant BFU 2005-01615 (to A.M.V.) and Grant SAF 2004-5545 (to M.B.) from Ministerio de Educación y Ciencia (Spain), Grant CAM/GR/SAL/0384/2004 (to A.M.V.) from Comunidad de Madrid (Spain), and Red de Grupos de Diabetes Mellitus Grant G03/212, Instituto Carlos III (Spain). A.G.-R. was supported by Grant FPU (Ministerio de Educación, Spain). O.E. was supported by Juan de la Cierva programe (Ministerio de Educación, Spain).Peer reviewe

Sleep apnea-COPD overlap syndrome is associated with larger left carotid atherosclerotic plaques

BackgroundLittle is known about whether the overlap syndrome (OS) combining features of chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome increases the risk of stroke associated with COPD itself.MethodsWe prospectively studied 74 COPD patients and 32 subjects without lung disease. Spirometry and cardiorespiratory polygraphy were used to assess the pulmonary function of the study population and ultrasound measurements of intima media thickness (IMT) as well as the volume of plaques in both carotid arteries were also evaluated.ResultsPolygraphic criteria of OS were met in 51% of COPD patients. We found that 79% of patients with OS and 50% of COPD patients without OS had atherosclerotic plaques in the left carotid artery (p = 0.0509). Interestingly, the mean volume of atherosclerotic plaques was significantly higher in the left carotid artery of COPD patients with OS (0.07 ± 0.02 ml) than in those without OS (0.04 ± 0.02 ml, p = 0.0305). However, regardless of the presence of OS, no significant differences were observed in both presence and volume of atherosclerotic plaques in the right carotid artery of COPD patients. Adjusted-multivariate linear regression revealed age, current smoking and the apnea/hypopnea index (OR = 4.54, p = 0.012) as independent predictors of left carotid atherosclerotic plaques in COPD patients.ConclusionsThis study suggests that the presence of OS in COPD patients is associated with larger left carotid atherosclerotic plaques, indicating that OS might be screened in all COPD patients to identify those with higher risk of stroke

Improving the knowledge of sub-surface temperature, salinity and fluorescence variability patterns on the Southern Coast of Galicia

Since 2008, the Instituto Español de Oceanografía (IEO) keeps installed a thermosalinometer (TSG) on board of R/V J.M. Navaz that operates on Galician coastal waters. Weekly, it covers the area between Vigo and Muros in the framework of an harmful algal bloom monitoring. High resolution and quality coastal data are very important in order to develop accurate behavior models. The TSG continuously measures the sea subsurface salinity, temperature, and fluorescence along the ships tracks. The classical approach to distribution maps is performing objective analysis of the collected data and assumes errors associated to coastal features. Data-Interpolating Variational Analysis (DIVA) allows the spatial interpolation of data over an adaptable mesh grid, taking into account coastlines and inlets, but also advection constraints. Calculations are optimized and rely on a finite element resolution and the software allows optimizing the analysis parameters, checking for duplicates and performing quality controls. The results of performing and compare DIVA and objective analysis show slight differences that can be appreciated between the inner part of the inlets and the open sea areas. The relative length of the whole data set allows considering also monthly, seasonal and annual variability. These climatological results, that will be updated systematically, can be useful not only for scientific research but also for coastal management activities. All this products, together with quality check flags and metadata information, give added value to the original TSG measures and that will allow a future reuse of data

Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats

Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.This work was supported by MINECO (BFU2016-77931-R), CIBERdem (ISCIII, Spain) and MOIR-2 S2017-BMD-3684 (CAM

Hypoxia-inducible factor 2α drives hepatosteatosis through the fatty acid translocase CD36

Background & Aims: Molecular mechanisms by which hypoxia might contribute to hepatosteatosis, the earliest stage in non-alcoholic fatty liver disease (NAFLD) pathogenesis, remain still to be elucidated. We aimed to assess the impact of hypoxia-inducible factor 2α (HIF2α) on the fatty acid translocase CD36 expression and function in vivo and in vitro. Methods: CD36 expression and intracellular lipid content were determined in hypoxic hepatocytes, and in hypoxic CD36- or HIF2α -silenced human liver cells. Histological analysis, and HIF2α and CD36 expression were evaluated in livers from animals in which von Hippel-Lindau (Vhl) gene is inactivated (Vhl -deficient mice), or both Vhl and Hif2a are simultaneously inactivated (Vhl Hif2α -deficient mice), and from 33 biopsy-proven NAFLD patients and 18 subjects with histologically normal liver. Results: In hypoxic hepatocytes, CD36 expression and intracellular lipid content were augmented. Noteworthy, CD36 knockdown significantly reduced lipid accumulation, and HIF2A gene silencing markedly reverted both hypoxia-induced events in hypoxic liver cells. Moreover livers from Vhl -deficient mice showed histologic characteristics of non-alcoholic steatohepatitis (NASH) and increased CD36 mRNA and protein amounts, whereas both significantly decreased and NASH features markedly ameliorated in Vhl Hif2α -deficient mice. In addition, both HIF2α and CD36 were significantly overexpressed within the liver of NAFLD patients and, interestingly, a significant positive correlation between hepatic transcript levels of CD36 and erythropoietin (EPO), a HIF2α -dependent gene target, was observed in NAFLD patients. Conclusions: This study provides evidence that HIF2α drives lipid accumulation in human hepatocytes by upregulating CD36 expression and function, and could contribute to hepatosteatosis setup. f/f f/f /f f/f f/f f/fThis work was supported by PI13/01299, PI17/00535 and CIBEREHD from Instituto de Salud Carlos III (ISCIII/FEDER, Spain) to CGM; CP14/00181, PI16/00823 and PI19/00123 (ISCIII/FEDER, Spain), and Beca Eduardo Gallego 2016 (Fundación Francisco Cobos, Spain) to AGR; SAF2016-76815 (Ministerio de Economía y Competitividad/FEDER, Spain), 534/C/2016 (TV3 Marató, Spain) and CIBERCV (ISCIII/FEDER, Spain) to JA