Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function

Non-alcoholic fatty liver disease (NAFLD) is a major health threat in both developed and developing countries and is a precursor of the more advanced liver diseases, including non-alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Currently, understanding the multiple and complex molecular pathways implicated in NAFLD onset and progression is a major priority. The transcription factor p63, which belongs to a family comprising p53, p63, and p73,1 is one of many factors that contributes to the development of liver steatosis. The role of p63 as a tumor suppressor and in cell maintenance and renewal is well studied, but we have recently reported that it is also relevant in the control of lipid metabolism.2 p63 encodes multiple isoforms that can be grouped into 2 categories; isoforms with an acidic transactivation domain (TA) and those without this domain (domain negative). The TAp63α isoform is elevated in the liver of animal models of NAFLD as well as in liver biopsies from obese patients with NAFLD. Furthermore, downregulation of p63α in the liver attenuates liver steatosis in diet-induced obese (DIO) mice, while the activation of TAp63α increases hepatic fat content, mediated by the activation of IKKβ and endoplasmic reticulum stress.2 A specialized form of autophagy that degrades lipid droplets, termed “lipophagy”, is a major pathway of lipid mobilization in hepatocytes. Lipophagy is elevated in hepatoma cells upon exposure to free fatty acids,3 and reduces the fatty acid load in mouse hepatocytes.4 Its impairment has been associated with the development of fatty liver and insulin resistance3,5; in contrast, the autophagic flux is increased during the activation of hepatic stellate cells.6 In the present study, we used an unbiased proteomics approach to gain insight into novel proteins modulating lipid metabolism in the liver of mice with genetic knockdown or overexpression of TAp63α. We found that autophagy-related gene 3 (ATG3) was upregulated by TAp63α activation and downregulated after p63α inhibition. ATG3 is elevated in several animal models of NAFLD and in the liver of patients with NAFLD. Genetic overexpression of ATG3 increased the lipid load in hepatocytes, while its repression alleviated TAp63α- and diet-induced steatosis. ATG3 exerted its role in lipid metabolism by regulating SIRT1 and mitochondrial function. Collectively, these findings identify ATG3 as a novel factor implicated in the development of steatosisThis work has been supported by grants from FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación (PA: RTI2018-095134-B-100; DS and LH: SAF2017-83813-C3-1-R; MLMC: RTC2019-007125-1; CD: BFU2017-87721; ML: RTI2018–101840-B-I00; GS; PID2019-104399RB-I00; RN: RTI2018-099413-B-I00 and RED2018-102379-T; MLMC: SAF2017-87301-R; TCD: RTI2018-096759-A-100), FEDER/Instituto de Salud Carlos III (AGR: PI19/00123), Xunta de Galicia (ML: 2016-PG068; RN: 2015-CP080 and 2016-PG057), Fundación BBVA (RN, GS and MLM), Proyectos Investigación en Salud (MLMC: DTS20/00138), Sistema Universitario Vasco (PA: IT971-16); Fundación Atresmedia (ML and RN), Fundación La Caixa (M.L., R.N. and M.C.), Gilead Sciences International Research Scholars Program in Liver Disease (MVR), Marató TV3 Foundation (DS: 201627), Government of Catalonia (DS: 2017SGR278) and European Foundation for the Study of Diabetes (RN and GS). This research also received funding from the European Community’s H2020 Framework Programme (ERC Synergy Grant-2019-WATCH- 810331, to RN, VP and MS). Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Hepáticas y Digestivas (CIBERehd) and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem). CIBERobn, CIBERehd and CIBERdem are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)S

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Estrategia de content curation, septiembre 2016

Recurs d'aprenentatge de la Universitat Oberta de Catalunya. Material publicat amb llicència Creative Commons passats 6 semestres des de la data de publicació.Recurso de aprendizaje de la Universitat Oberta de Catalunya. Material publicado con licencia Creative Commons pasados 6 semestres desde la fecha de publicación.Learning material of the Universitat Oberta de Catalunya. Material published under a Creative Commons license after 6 semesters from the date of publication

Documentación informativa en Internet, febrero 2012

Material docent de la Universitat Oberta de Catalunya.Material docente de la "Universitat Oberta de Catalunya".Learning material of the "Universitat Oberta de Catalunya"

Documentación informativa en Internet, febrero 2012

Material docent de la Universitat Oberta de Catalunya.Material docente de la "Universitat Oberta de Catalunya".Learning material of the "Universitat Oberta de Catalunya"

Funcions del documentalista en un mitjà de comunicació audiovisual digital. Estudi de cas: RelTV

Es mostra un estudi de cas sobre la intervenció d'un documentalista en un nou mitjà de comunicació audiovisual a Internet, RelTV. Es presenten tres projectes diferents duts a terme pel documentalista en aquest context: una base de dades relacional, un pla de preservació digital i un exemple de producte periodístic-documental: un mapa interactiu de vídeos. Es presenta el disseny i desenvolupament dels tres productes, se n'analitza la repercussió i viabilitat, i es reflexiona sobre l'aportació del professional de la documentació en aquest àmbit.Se muestra un estudio de caso sobre la intervención de un documentalista en un nuevo medio de comunicación audiovisual en Internet, RelTV. Se presentan tres proyectos diferentes llevados a cabo por el documentalista en este contexto: una base de datos relacional, un plan de preservación digital y un ejemplo de producto periodístico-documental: un mapa interactivo de vídeos. Se presenta el diseño y desarrollo de los tres productos, se analiza su repercusión y viabilidad, y se reflexiona sobre la aportación del profesional de la documentación en este ámbito.This paper reports on three projects completed by a documentalist for the new audiovisual platform RelTV: a relational database, a digital preservation plan and an example of a journalistic-documental product in the form of an interactive map of videos. The paper reports on how the three projects were designed and developed and then analyzes the implications and viability of such initiatives, reflecting on the professional contribution that documentalists can make in this field

La calidad de las revistas científicas en ciencias sociales

En este taller se mostrará una panorámica de los sistemas para medir y evaluar la publicación científica en ciencias sociales: los principales indicadores nacionales e internacionales y cómo afectan a las publicaciones y a los investigadores.En aquest taller es mostrarà una panoràmica dels sistemes per a mesurar i avaluar la publicació científica en ciències socials: els principals indicadors nacionals e internacionals i com afecten a les publicacions i als investigadors.This workshop will show an overview of the systems to measure and evaluate scientific publishing in social science major national and international indicators and how they affect the public and researchers