Estudio de la degradación de complejos respiratorios en el proceso de mitofagia en respuesta a estrés

[ES] El control de calidad de las mitocondrias es una función esencial de las células eucariotas. En los seres humanos, la falta de eliminación de las mitocondrias dañadas o disfuncionales es una causa de neurodegeneración. Un importante mecanismo de control de calidad mitocondrial es la degradación regulada de las partes dañadas del orgánulo por vías autofágicas denominada mitofagia. En este trabajo se investiga en el modelo de levadura, si complejos específicos del transporte de electrones (ETC) se degradan diferencialmente en condiciones de estrés celular. Este trabajo pretende ampliar los estudios anteriores de nuestro grupo de investigación que mostraron evidencia de una degradación selectiva de los complejos mitocondriales y que la proteína Atg11 era necesaria para este reciclaje mitocondrial. En este trabajo se quiere ampliar estos estudios y (i) medir las tasas de degradación de subunidades específicas de CII, CIII y CV con diferentes grados de respiración y daños mitocondriales, (ii) visualizar mediante microscopía de fluorescencia el proceso de mitofagia en respuesta al daño mitocondrial, (iii) evaluar la importancia de diferentes proteínas Atg para el crecimiento eficiente a altas tasas de respiración y daño mitocondrial y (iv) comprobar cuáles de estas proteínas están involucradas en la generación de mayor estrés oxidativo al inducir un daño mitocondrial.[EN] The quality control of mitochondria is an essential function of eukaryotic cells. In humans, failure to remove damaged or dysfunctional mitochondria are the cause of neurodegeneration. One important mechanism of mitochondrial quality control is the regulated degradation of the damaged parts of the organelle by autophagic pathways termed mitophagy. In this work we investigate in the yeast model, whether specific respiratory or electron transport complexes (ETC) are differentially degraded upon cellular stress. Previous results from our group of investigation show evidence of selective ways of mitochondrial complex degradation and that Atg11 protein was required for this mitochondrial recycling. Here we want to extend these studies and (i) measure the degradation rates of specific subunits of CII, CIII and CV upon different respiratory activity and mitochondrial damage, (ii) visualize by fluorescence microscopy the process of mitophagy upon mitochondrial damage, (iii) evaluate the importance of different Atg proteins for efficient growth upon high respiration rates and mitochondrial damage and (iv) test which of these proteins are necessary for ROS balance upon mitochondrial damage.Sanfeliu Redondo, D. (2017). Estudio de la degradación de complejos respiratorios en el proceso de mitofagia en respuesta a estrés. http://hdl.handle.net/10251/86408TFG

Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature.

The poor prognosis of chronic liver disease (CLD) generates the need to investigate the evolving mechanisms of disease progression, thus disclosing therapeutic targets before development of clinical complications. Considering the central role of liver sinusoidal endothelial cells (LSECs) in pre-neoplastic advanced CLD, the present study aimed at investigating the progression of CLD from an endothelial holistic perspective. RNAseq defined the transcriptome of primary LSECs isolated from three pre-clinical models of advanced CLD, during the progression of the disease, and from fresh human cirrhotic tissue. At each stage of the disease, the effects of LSECs secretome on neighboring cells and proteomic analysis of LSECs-derived extracellular vesicles (EVs) were also determined. CLD was associated with deep common modifications in the transcriptome of LSECs in the pre-clinical models. Pathway enrichment analysis showed predominance of genes related with pro-oncogenic, cellular communication processes, and EVs biogenesis during CLD progression. Crosstalk experiments revealed endothelial EVs as potent angiocrine effectors. The proteome of LSECs EVs showed stage-specific signatures, including over-expression of tropomyosin-1. Proof-of-principle experiments treating cirrhotic HSCs with recombinant tropomyosin-1 suggested de-activating effects. Our data provide the basis for discovering novel biomarkers and therapeutic targets for new disease-modifying treatments for patients with advanced CLD

Lisbon Symbol Database - LSD : Subjective norms for 600 symbols

This article presents subjective rating norms for a new set of 600 symbols, depicting various contents (e.g., transportation, technology, and leisure activities) that can be used by researchers in different fields. Symbols were evaluated for aesthetic appeal, familiarity, visual complexity, concreteness, valence, arousal, and meaningfulness. The normative data were obtained from 388 participants, and no gender differences were found. Descriptive results (means, standard deviations, and confidence intervals) for each symbol in each dimension are presented. Overall, the dimensions were highly correlated. Additionally, participants were asked to briefly describe the meaning of each symbol. The results indicate that the present symbol set is varied, allowing for the selection of exemplars with different levels on the seven examined dimensions. This set of symbols constitutes a tool with potential for research in different areas. The database with all of the symbols is available as supplemental materials.Fundação para a Ciência e a Tecnologia (FCT

Delaying surgery for patients with a previous SARS-CoV-2 infection

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