Desarrollo de un método de cribado de fármacos para identificar nuevas drogas capaces de revertir el fenotipo resistente de las células cancerosas a la destrucción por células CAR-T.

En los últimos años, la terapia de células T con receptor de antígeno quimérico (CAR) se ha convertido en un tratamiento prometedor para el tratamiento del cáncer. A pesar de este progreso, una proporción significativa de pacientes experimenta resistencia a la terapia CAR-T. Las células cancerosas pueden ser insensibles a la destrucción por las células CAR-T, lo que se conoce como resistencia intrínseca. Esta resistencia intrínseca es responsable de una parte muy significativa del fracaso de este tipo de terapias que afecta a todo tipo de tumores, siendo una dificultad adicional para la eficacia de las células CAR-T en el tratamiento de tumores sólidos. Mucho de los mecanismos de resistencia intrínseca están regulados a nivel epigenético. Recientemente, se han desarrollado y probado varios inhibidores epigenéticos en cáncer. El enfoque principal de la mayoría de los estudios hasta ahora ha sido el efecto citotóxico directo de estos compuestos, y pocos estudios han investigado la capacidad de revertir el fenotipo resistente de las células cancerosas a la terapia CAR-T. Existe la necesidad de una metodología sistemática para identificar nuevas drogas que sensibilicen a la célula tumoral a la destrucción por las células CAR-T. Mediante la expresión de flaying luciferase (fLuc) en líneas murinas de tumores sólidos que expresan el antígeno EGFRvIII, hemos establecido un protocolo simple, preciso, sensible y robusto para detectar sensibilizadores epigenéticos. Demostramos la eficacia de nuestro protocolo e identificamos varios inhibidores epigenéticos capaces de sensibilizar a las células tumorales a la destrucción por un CAR anti-EGFRvIII

Working memory of emotional stimuli: electrophysiological characterization

Memorizing emotional stimuli in a preferential way seems to be one of the adaptive strategies brought on by evolution for supporting survival. However, there is a lack of electrophysiological evidence on this bias in working memory. The present study analyzed the influence of emotion on the updating component of working memory. Behavioral and electrophysiological indices were measured from a 3-back task using negative, neutral, and positive faces. Electrophysiological data evidenced an emotional influence on the working memory sensitive P3 component, which presented larger amplitudes for negative matching faces compared to neutral ones. This effect originated in the superior parietal cortex, previously reported to be involved in N-back tasks. Additionally, P3 results showed a correlation with reaction times, where higher amplitudes were associated with faster responses for negative matching faces. These findings indicate that electrophysiological measures seem to be very suitable indices of the emotional influence on working memory

La pesca y la acuicultura en la protección de los ecosistemas marinos

Versión del editor

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

Mejora de las habilidades comunicativas y el pensamiento crítico en estudiantes de Ciencias de la Salud mediante la combinación de flipped classroom (clase invertida) y debate formal

Se propone la clase invertida (flipped classroom) y el debate formal como metodologías innovadoras para mejorar las habilidades comunicativas y el pensamiento crítico en respuesta a la demanda de tener futuros profesionales biomédicos mejor formados en estos ámbitos

Export and turnover of transparent exopolymer particles into the deep ocean

2nd Meeting of the Iberian Ecological Society (SIBECOL), XXI conference of the Iberian Association of Limnology (AIL) and 21st National Congress of the Portuguese Ecological Society (SPECO), 3-8 July 2022, AveiroAcidic polysaccharides released by phytoplankton and prokaryotic heterotrophs promote the formation of gel-like transparent exopolymer particles (TEPs). TEPs play a key role in the biological carbon pump due to their carbon-rich composition and their ability to coagulate and sink towards the deep ocean. Yet, very little is known about TEP distribution, export, and turnover at a global scale, particularly at deep ocean depths. We provide the first inventory of TEP from the surface up to 4000 m depth in the Atlantic, Indian, and Pacific Oceans and have assessed their contribution to carbon export into the deep ocean. Primary production determines TEP concentration above the deep chlorophyll maximum, and prokaryotic biomass also contributes in deeper waters. In the deep ocean waters, TEP concentrations are lower and mirror the concentrations in the surface, evidencing the importance of TEP sinking both at the export depth (200 m) with a global value of 2.9 Pg C year-1 and at the sequestration depth (1000 m) of 0.9 Pg C year-1 of particulate carbon. However, incubation experiments across ocean basins depicted rapid TEP turnover rates of 71 and 333 days (on average) within the export and sequestration depths, respectively. These findings reveal that the export of carbon by TEP sinking towards deep oceans escapes from long-term paths of the global carbon cycleN

Vocabulario de la sociedad civil, la ruralidad y los movimientos sociales en América Latina

El Vocabulario de la Sociedad Civil, la Ruralidad y los Movimientos Sociales en América Latina tiene como objetivo desarrollar vocablos relacionados con temas de gran trascendencia para la vida colectiva de la población Latinoamericana; pretende introducir a estudiantes, personas del ámbito académico y activistas en la comprensión de estas categorías de análisis. A través de la mirada de 70 especialistas que participaron en este vocabulario, es posible comprender muchos de los términos que se utilizan dentro de la investigación social y áreas relacionadas con las ciencias políticas, ambientales y rurales, a partir de una mayor explicación y detalle. Es por ello que se inserta este trabajo desde una mirada colectiva y amplia de los conceptos que se exponen. En este libro podrá encontrar las ideas de varios autores y autoras de distintas universidades, con una visión multi, inter y transdisciplinaria. El esfuerzo que se realizó para conjuntar varios términos y analizar su compleja red de interpretaciones, permitirá que este manuscrito pueda ser consultado por estudiantes, personas del ámbito científico-académico, y ciudadanía; porque contiene el estado del arte, la historia del paulatino avance de múltiples conceptos y su vigencia en el contexto actual

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

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