HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis

Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 as a central oncogenic driver for malignant peripheral nerve sheath tumors (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacological inhibition of HuR had potent cytostatic and cytotoxic effects on tumor growth, and strongly suppressed metastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to its ability to simultaneously regulate multiple essential oncogenic pathways in MPNST cells, including the Wnt/β-catenin, YAP/TAZ, RB/E2F, and BET pathways, which converge on key transcriptional networks. Given the exceptional dependency of MPNST cells on HuR for survival, proliferation, and dissemination, we propose that HuR represents a promising therapeutic target for MPNST treatment

Redución de la ansiedad a través del entrenamiento en habilidades sociales

El presente trabajo consiste en un programa de entrenamiento en habilidades sociales de carácter grupal, a partir del cual se analiza y estudia la relación entre el incremento de las habilidades sociales y la disminución de los niveles de ansiedad, evaluada en sus tres sistemas de respuesta. Diversos estudios apuntan la existencia de una relación inversamente proporcional entre la ansiedad y el comportamiento socialmente hábil. Tal es así, que en las intervenciones realizadas mediante programas de entrenamiento en habilidades sociales no sólo se obtiene de forma directa una mejoría de esta, sino que, de forma indirecta, parece facilitarse importantes reducciones de la ansiedad en aquellas áreas relacionadas con aspectos interpersonales y sociales, incluso en sus manifestaciones clínicas. Los mecanismos que explican esta relación no están aún claramente definidos. Se ha señalado la influencia de diversas variables en función de distintos modelos explicativos de la adquisición y el mantenimiento de la ansiedad (exposición a situaciones ansiógenas durante el entrenamiento, modificación de variables cognitivas como las expectativas de autoeficacia, aumento de la capacidad de controlar el contexto con la consiguiente reducción de su potencialidard ansiógena,etc). Probablemente sean todas ellas las que, de forma conjunta, pueden dar cuenta de estas reducciones de ansiedad. Como instrumentos de evaluación se han empleado el Inventario de Situaciones y Respuestas de Ansiedad -ISRA- (Miguel Tobal y Cano Vindel, 1986,1988,1994); La Escala Multidimensional de Expresión Social, Parte Cognitiva -EMES-C- (Caballo, 1987) y la Escala Multidimensional de Expresión Social, Parte Motora -EMES-M- ( Caballo,1987). Se presentan finalmente los resultados de la evaluación pre y postratamiento en las diversas variables contempladas, así como las relaciones que aparecen entre esta

Lipidomics and biodistribution of extracellular vesicles‐secreted by hepatocytes from Zucker lean and fatty rats

Abstract Extracellular vesicles (EVs) have been involved in metabolic syndrome, although their specific role in the development of the pathology is still unknown. To further study the role of EVs, we have analysed by Raman tweezers microspectroscopy and mass spectrometry‐based lipidomics the small EVs population secreted by fatty (ZF) and lean (ZL) hepatocytes obtained from Zucker rats. We have also explored in vivo and ex vivo biodistribution of these EVs through fluorine‐18‐radiolabelling using a positron emission tomography imaging. Based on the proportion of proteins to lipids and the types of lipids, our results indicate that within the range of small EVs, primary hepatocytes secrete different subpopulations of particles. These differences were observed in the enrichment of triglyceride species in EVs secreted by ZF hepatocytes. Biodistribution experiments showed accumulation in the brain, heart, lungs, kidney and specially in bladder after intravenous administration. In summary, we show that EVs released by a fatty hepatocytes carry a different lipid signature compared to their lean counterpart. Biodistribution experiment has shown no difference in the distribution of EVs secreted by ZF and ZL hepatocytes but has given us a first view of possible target organs for these particles. Our results might open a door to both pathology studies and therapeutic interventions

Efeitos a curto e longo prazo de um grupo de desenvolvimento de habilidades sociais para universitários

Apesar da introdução na atuação comunitária de práticas baseadas em evidências, sabemos pouco sobre a eficácia das intervenções fora de contextos de pesquisa. A área dos treinamentos de habilidades sociais carece de estudos em settings de mundo real, com números suficientes de participantes e follow-up. Investigou-se, em 34 universitários, o efeito a curto e longo prazo de um grupo de treinamento de habilidades sociais, num contexto de mundo real. Escores de habilidades sociais (IHS) e ansiedade (IDATE) foram verificados antes, depois da intervenção e após um intervalo de follow up. Os escores em ambos os testes melhoraram do pré-teste para o pós-teste, e se mantiveram estáveis do pós-teste para o follow-up no intervalo de três meses a cinco anos