Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Influencia de componentes de la matriz extracelular en el comportamiento de las células BCS-TC2 de adenocarcinoma de colon humano: estudios "in vitro" e "in vivo".

Las células tumorales malignas se caracterizan por su crecimiento anormal y su tendencia a atravesar las barreras tisulares, a invadir los tejidos adyacentes, y a diseminarse a sitios distantes del foco primario, originando focos metastáticos. En condiciones fisiológicas, y de forma controlada, ciertostipos celulares normalesmanifiestan también un comportamiento invasivo. Por ejemplo, para la formación de nuevos vasos sanguíneos, las células endoteliales deben invadir los basamentos membranosos y la matriz intersticial. La gran similitud entre ciertos procesos fisiológicos y la metástasis tumoral, cuando se observan a nivel molecular, sugiere que la capacidad de las células malignas para atravesar múltiples barreras tisulares resulta de la pérdida del control que las células normales tienen sobre la expresión del fenotipo invasívo. Ya que este fenotipo invasivo es esencial para que tengan lugar las diferentes etapas de la cascada metastática, el conocimiento de las bases moleculares asociadas al mismo pueden contribuir al desarrollo de nuevas estrategias terapéuticas contra el cáncer

Flipped learning strategies for genetic engineering

La asignatura de Fundamentos de Ingeniería genética del grado de Biología resulta muy árida en su actual formulación. Este proyecto pretende darle la vuelta para que sea el alumno quien construya el conocimiento y participe en el aprendizaje.The subject "Fundamentals of Genetic Engineering" of the degree of Biology is very arid in its current formulation. This project aims to turn it around so that are the students who build knowledge and participate in the learning.Depto. de Bioquímica y Biología MolecularFac. de Ciencias QuímicasFALSEsubmitte

Kinetically controlled acylation of 6-APA catalyzed by penicillin acylase from Streptomyces lavendulae: effect of reaction conditions in the enzymatic synthesis of penicillin V

Enzymatic synthesis of penicillin V (penV) by acylation of 6-aminopenicillanic acid (6-APA) was carried out using methyl phenoxyacetate (MPOA) as activated acyl donor and soluble penicillin acylase from Streptomyces lavendulae (SlPVA) as biocatalyst. The effect of different reaction conditions on penV synthesis was investigated, such as enzyme concentration, pH, molar ratio of 6-APA to MPOA, as well as presence of DMSO as water-miscible co-solvent at different concentrations. Time-course profiles of all reactions followed the typical pattern of kinetically controlled synthesis (KCS) of β-lactam antibiotics: penV concentration reached a maximum (highest yield or Ymax) and then decreased gradually. Such maximum was higher at pH 7.0, observing that final penV concentration was abruptly reduced when basic pH values were employed in the reaction. Under the selected conditions (100 mM Tris/HCl buffer pH 7.0, 30 °C, 2.7% (v/v) DMSO, 20 mM MPOA, 0.3 UI/ml of SlPVA), Ymax was enhanced by increasing the substrate molar ratio (6-APA to MPOA) up to 5, reaching a maximum of 94.5% and a S/H value of 16.4 (ratio of synthetic activity to hydrolytic activity). As a consequence, the use of an excess of 6-APA as nucleophile has allowed us to obtain some of the highest Ymax and S/H values among those reported in literature for KCS of β-lactam antibiotics. Although many penicillin G acylases (PGAs) have been described in kinetically controlled acylations, SlPVA should be considered as a different enzyme in the biocatalytic tool-box for novel potential synthetic processes, mainly due to its different substrate specificity compared to PGAs

PANDEMIC: how to save the World through Genetic Engineering

Este proyecto se ha presentado a la XII Edición del ICERI el 11-13 de noviembre de 2019 celebrado en Sevilla siendo aceptado y publicado en el Conference Proceedings ISBN: 978-84-09-14755-7, DP. LEGAL: V-2804-2019Proyecto de Innovación llevado a cabo en la UCM, grado de Biología para el aprendizaje de técnicas de ingeniería genética. Se ha dividido a los alumnos en equipos y se realizado una gamificación de la asignatura basado en el juego de mesa de Pandemic. Brevemente, cada equipo se enfrenta a una enfermedad desconocida y en cada tema adquiere las competencias necesarias para caracterizar al patógeno, conocer su genoma y acabar obteniendo una vacuna contra el agente.This is an Innovation project based on Pandemic game for students of 2nd Grade of Biology Sciences. They learn the Genetic engineering techniques by joining a game in which they get points in each topic and they learn how to recognize the pathogen, how to isolate the DNA and how to get a vaccine.Depto. de Dibujo y GrabadoFac. de Bellas ArtesFALSEUCMsubmitte

Connecting the biochemistry laboratory to the Web 2.0.

Proyecto de innovación realizado en el curso 16-17 en la asignatura del laboratorio integrado BBM1 del segundo curso del grado de Bioquimica de la UCM.Sección Deptal. de Bioquímica y Biología Molecular (Biológicas)Fac. de Ciencias BiológicasFALSEUCMsubmitte