Superbacteria: ¿el final del camino?

Durante los últimos años hemos visto como han ido apareciendo noticias sobre bacterias resistentes incluso frente a antibióticos considerados como último recurso, ejemplo de ello son las bacterias resistentes a meticilina, vancomicina, carbapenemas y más recientemente polymixina-E (colistina

Condensados Biomoleculares: Organizadores de la Vida

Life never fails to surprise us. Today, it does so with membrane-less organelles known as biomolecular condensates. These structures arise from a phenomenon of biomolecular self-organization capable of generating localized microenvironments with defined functions within the cell. In recent years, the significance of condensates in various aspects of cellular biology has been  unveiled, including the regulation  of gene expression, protein synthesis, cellular signaling control, cytoskeletal protein polymerization, and the formation of aggregates associated with neurodegenerative diseases, among many others yet to be discovered. These findings are revolutionizing our current understanding of cellular processes and providing new insights into cell process regulation. Condensates unveil previously unknown cellular mechanisms, more stochastic, that are shifting away from the dominance of genetic mechanisms in favor of cellular self-organization processes. The advancement in comprehending biomolecular condensates paves the way for exciting avenues of research in cellular and molecular biology, enabling the reinterpretation of processes that relate the genotype to the phenotype. Offering, in this way, the potential to better understand diseases and develop more effective therapeutic approaches in the future.La vida nunca deja de sorprendernos. Hoy lo hace con unos orgánulos libres de membrana conocidos como condensados biomoleculares. Éstos, son el resultado de un fenómeno de autoorganización de biomoléculas capaz de crear auténticos microentornos con funciones definidas en el interior de la célula. En los últimos años, se ha descubierto que los condensados desempeñan un papel relevante en diversos aspectos de la biología celular, como la regulación de la expresión génica, la síntesis de proteínas, el control de la señalización celular, la polimerización de proteínas del citoesqueleto o la formación de agregados asociados a enfermedades neurodegenerativas, entre muchas otras aún por descubrir. Estos hallazgos están desafiando nuestra comprensión actual de los procesos celulares y ofrecen nuevas maneras de entender el funcionamiento interno de las células. Los condensados muestran mecanismos celulares previamente desconocidos, mucho más estocásticos y que diluyen la preponderancia del mecanicismo genético en favor de los procesos de autoorganización celular. El avance en la comprensión de los condensados biomoleculares abre emocionantes vías de investigación en biología celular y molecular y permiten la reinterpretación de los procesos que relacionan el genotipo y el fenotipo, ofreciendo así la posibilidad de comprender mejor las enfermedades y desarrollar enfoques terapéuticos más efectivos en el futuro

Evaluation of metabolism and biosignaling in the angiogenic microenvironment as potential targets for therapeutic intervention

The "re-discovery" of Warburg effect at the turn of the present millennium has been a key determinant of the current renewed interest on cancer metabolism. In fact, metabolic reprogramming has been identified as one of the hallmarks of cancer. However, cancers grow in tight contact with non-tumoral accompanying cells and the surrounding extracellular matrix, as underlined by the concept of tumor microenvironment. Endothelial cells are key components of this tumor microenvironment, since they are requested for angiogenesis, another hallmark of cancer. In this complex system, rewiring of metabolism and signaling pathway in cancer, endothelial and other accompanying cell emerges as new potential targets for therapeutic intervention. In this communication, we will present the drug discovery and characterization approach of our group and our more recent results in this field, including new modeling with an evolutionary and ecological point of view.[Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)]. This communication has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech"

MICOBIOTA AISLADA DE SERPIENTES EN CUARENTENA DEL CENTRO PARA INVESTIGACIONES Y RESPUESTAS EN OFIDIOLOGÍA DE LA UNIVERSIDAD DE PANAMÁ (CEREO)

Snakes, like fungi, are organisms that over time have been stigmatized, thus not allowing to know and value their role in the biological processes in which they intervene.   This research was intended to determine the main groups of filamentous fungi that cohabit with quarantined snakes at the Center for Research and Responses in Odiology of the University of Panama (CEREO).   The same, was carried out having, as study subjects, 9 snakes belonging to various genera, which were quarantined, this sample was performed a mycological analysis, using classical microbiology techniques, based on the recognition of the genera found in morphological comparisons.   The analysis of the mycobiot of quarantined snakes in CEREO is intended as the main objective, to establish by comparing isolated morphotypes the main populations of filamentous fungi that are present in the sample; implementing microbiological techniques (isolation, selection and purification of samples).   The microscopic characterization and identification was performed using the microculture technique in PDA, V8 Agar and water Agar, using the taxonomic keys, based on observations of fungal and reproductive structures, which allowed identification only to gender. The main groups of isolated fungi are represented by the following genera, Penicillium, Curvularia, Aspergillus, Fusarium and Cladosporium; which are fungi typically found in soil, this pioneering study in our country lays the methodological and procedural basis for the analysis of filamentous fungi in ofidia and the possible relationships that might exist between these two groups of organisms.Las serpientes al igual que los hongos, son organismos que a lo largo del tiempo han sido estigmatizados, no permitiendo con ello conocer y valorar su rol en los procesos biológicos en los cuales intervienen.   Esta investigación tuvo como propósito, determinar los principales grupos de hongos filamentosos que cohabitan con las serpientes en cuarentena en el Centro para Investigaciones y Respuestas en Ofidiología de la Universidad de Panamá (CEREO).   La misma, fue realizada teniendo como sujetos de estudio, 9 serpientes pertenecientes a diversos géneros, que se encontraban en periodo de cuarentena, a dicha muestra se le realizó un análisis micológico, utilizando técnicas de microbiología clásica, basando el reconocimiento de los géneros encontrados en comparaciones morfológicas.   El análisis de la micobiota de las serpientes en cuarentena en el CEREO pretende como objetivo principal, establecer mediante la comparación de morfotipos aislados las principales poblaciones de hongos filamentosos que están presentes en la muestra; implementando técnicas microbiológicas (aislamiento, selección y purificación de muestras).   La caracterización e identificación microscópica se realizó mediante la técnica de microcultivo en PDA, agar V8 y agar Agua, empleando las claves taxonómicas, con base en las observaciones de estructuras fúngicas y reproductivas, que permitieron la identificación sólo hasta género. Los principales grupos de hongos aislados están representados por los siguientes géneros, Penicillium, Curvularia, Aspergillus, Fusarium y Cladosporium; que son hongos típicamente encontrados en el suelo, este estudio pionero en nuestro país, sienta las bases metodológicas y procedimentales para el análisis de hongos filamentosos en ofidios y las posibles relaciones que pudiesen existir entre estos dos grupos de organismos

Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson–Gilford Progeria

Inflammation is a hallmark of aging and accelerated aging syndromes such as Hutchinson–Gilford progeria syndrome (HGPS). In this study, we present evidence of increased expression of the components of the NLRP3 inflammasome pathway in HGPS skin fibroblasts, an outcome that was associated with morphological changes of the nuclei of the cells. Lymphoblasts from HGPS patients also showed increased basal levels of NLRP3 and caspase 1. Consistent with these results, the expression of caspase 1 and Nlrp3, but not of the other inflammasome receptors was higher in the heart and liver of Zmpste24−/− mice, which phenocopy the human disease. These data were further corroborated in LmnaG609G/G609G mice, another HGPS animal model. We also showed that pharmacological inhibition of the NLRP3 inflammasome by its selective inhibitor, MCC950, improved cellular phenotype, significantly extended the lifespan of progeroid animals, and reduced inflammasome-dependent inflammation. These findings suggest that inhibition of the NLRP3 inflammasome is a potential therapeutic approach for the treatment of HGPS.Junta de Andalucía PI-0036-201

Regulation of atrophin by both strands of the mir-8 precursor

In Drosophila melanogaster, miR-8-3p regulates mRNA levels of atrophin, a factor involved in neuromotor coordination, and we found that Blattella germanica with suppressed atrophin showed motor problems. Bionformatic predictions and luciferase-reporter tests indicated that B.germanica atrophin mRNA contains target sites for miR-8-3p and miR-8-5p. Suppression of miR-8-3p or miR-8-5p appeared to increase atrophin mRNA. The effects of suppression of Argonaute (AGO) 1 or AGO2 expression on miR-8-3p and miR-8-5p suggested that miR-8-3-p might predominantly bind to AGO1, whereas miR-8-5p might bind to a moderate extent to both AGO1 and AGO2 in the respective RNA-induced silencing complexes (RISCs). We propose that the interplay of miR-8-3p, miR-8-5p, AGO1 and AGO2, maintain the appropriate levels of atrophin mRNA. This would be the first example of two strands of the same miRNA precursor regulating a single transcript. © 2013 Elsevier Ltd.Support for this research was provided by the Spanish Spanish Ministry of Science and Innovation (grant CGL2008-03517/BOS to X.B.; BFU2010-21123 and CSD2007-00008 to M.M.), by FEDER funds, and by the CSIC (grant 2010TW0019, from the Formosa program, to X.B. and a predoctoral fellowship to M.R. from the JAE program). M.M. is an ICREA Research Professor.Peer Reviewe

Altered insulin secretion dynamics relate to oxidative stress and inflammasome activation in children with obesity and insulin resistance

Abstract Background Insulin resistance (IR) is considered the main driver of obesity related metabolic complications, and is related to oxidative stress and inflammation, which in turn promote each other. There is currently no specific definition of IR in children, rather, that for adult population is used by pediatric endocrinologists instead. Altered insulin secretion dynamics are associated with worse metabolic profiles and type 2 diabetes mellitus development, thus we aimed to test whether insulin response relates to oxidative stress and inflammation in children. Methods We conducted a case–control study, including 132 children classified as follows: 33 children without obesity (Lean); 42 with obesity but no IR according to the American Diabetes Association criteria for adults (OBIR-); 25 with obesity and IR and an early insulin response to an oral glucose tolerance test (OGTT) (EP-OBIR +); 32 with obesity, IR, and a late insulin peak (LP-OBIR +); and studied variables associated with lipid and carbohydrate metabolism, oxidative stress, inflammation and inflammasome activation. Results The measured parameters of children with obesity, IR, and an early insulin response were similar to those of children with obesity but without IR. It was late responders who presented an impaired antioxidant system and elevated oxidative damage in erythrocytes and plasma, and inflammasome activation at their white blood cells, despite lower classical inflammation markers. Increased uric acid levels seems to be one of the underlying mechanisms for inflammasome activation. Conclusions It is insulin response to an OGTT that identifies children with obesity suffering oxidative stress and inflammasome activation more specifically. Uric acid could be mediating this pathological inflammatory response by activating NLRP3 in peripheral blood mononuclear cells. Graphical Abstrac