Histone Mutants Separate R Loop Formation from Genome Instability Induction

R loops have positive physiological roles, but they can also be deleterious by causing genome instability, and the mechanisms for this are unknown. Here we identified yeast histone H3 and H4 mutations that facilitate R loops but do not cause instability. R loops containing single-stranded DNA (ssDNA), versus RNA-DNA hybrids alone, were demonstrated using ssDNA-specific human AID and bisulfite. Notably, they are similar size regardless of whether or not they induce genome instability. Contrary to mutants causing R loop-mediated instability, these histone mutants do not accumulate H3 serine-10 phosphate (H3S10-P). We propose a two-step mechanism in which, first, an altered chromatin facilitates R loops, and second, chromatin is modified, including H3S10-P, as a requisite for compromising genome integrity. Consistently, these histone mutations suppress the high H3S10 phosphorylation and genomic instability of hpr1 and sen1 mutants. Therefore, contrary to what was previously believed, R loops do not cause genome instability by themselves.European Research Council ERC2014 AdG669898Ministerio de Economía y Competitividad BFU2013-42918-P, BFU2016-75058-

A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses

The extreme genetic diversity of the protozoan Trypanosoma cruzi has been proposed to be associated with the clinical outcomes of the disease it provokes: Chagas disease (CD). To address this question, we analysed the similarities and differences in the CD pathophysiogenesis caused by different parasite strains. Using syngeneic mice infected acutely or chronically with 6 distant parasite strains, we integrated simultaneously 66 parameters: parasite tropism (7 parameters), organ and immune responses (local and systemic; 57 parameters), and clinical presentations of CD (2 parameters). While the parasite genetic background consistently impacts most of these parameters, they remain highly variable, as observed in patients, impeding reliable one-dimensional association with phases, strains, and damage. However, multi-dimensional statistics overcame this extreme intra-group variability for each individual parameter and revealed some pathophysiological patterns that accurately allow defining (i) the infection phase, (ii) the infecting parasite strains, and (iii) organ damage type and intensity. Our results demonstrated a greater variability of clinical outcomes and host responses to T. cruzi infection than previously thought, while our multi-parametric analysis defined common pathophysiological patterns linked to clinical outcome of CD, conserved among the genetically diverse infecting strains

The DNA damage response acts as a safeguardagainst harmful DNA–RNA hybrids ofdifferent origins

Despite playing physiological roles in specific situations, DNA–RNA hybrids threat genome integrity. To investigate how cells do counteract spontaneous DNA–RNA hybrids, here we screen an siRNA library covering 240 human DNA damage response (DDR) genes and select siRNAs causing DNA–RNA hybrid accumulation and a significant increase in hybrid‐dependent DNA breakage. We identify post‐replicative repair and DNA damage checkpoint factors, including those of the ATM/CHK2 and ATR/CHK1 pathways. Thus, spontaneous DNA–RNA hybrids are likely a major source of replication stress, but they can also accumulate and menace genome integrity as a consequence of unrepaired DSBs and post‐replicative ssDNA gaps in normal cells. We show that DNA–RNA hybrid accumulation correlates with increased DNA damage and chromatin compaction marks. Our results suggest that different mechanisms can lead to DNA–RNA hybrids with distinct consequences for replication and DNA dynamics at each cell cycle stage and support the conclusion that DNA–RNA hybrids are a common source of spontaneous DNA damage that remains unsolved under a deficient DDR.European Research Council (ERC2014AdG669898TARLOOP)Worldwide Cancer Research (WCR15-00098

Molecular evidence that the eukaryotic THO/TREX complex is required for efficient transcription elongation

THO/TREX is a conserved eukaryotic complex formed by the core THO complex plus proteins involved in mRNA metabolism and export such as Sub2 and Yra1. Mutations in any of the THO/TREX structural genes cause pleiotropic phenotypes such as transcription impairment, increased transcription-associated recombination, and mRNA export defects. To assay the relevance of THO/TREX complex in transcription, we performed in vitro transcription elongation assays in mutant cell extracts using supercoiled DNA templates containing two G-less cassettes. With these assays, we demonstrate that hpr1Δ, tho2Δ, and mft1Δ mutants of the THO complex and sub2 mutants show significant reductions in the efficiency of transcription elongation. The mRNA expression defect of hpr1Δ mutants was not due to an increase in mRNA decay, as determined by mRNA half-life measurements and mRNA time course accumulation experiments in the absence of Rrp6p exoribonuclease. This work demonstrates that THO and Sub2 are required for efficient transcription elongation, providing further evidence for the coupling between transcription and mRNA metabolism and export.Ministerio de Ciencia y Tecnología BMC2000-0439Human Frontier Science Program RG1999/007

Stress compensation by gap monolayers for stacked InAs/GaAs quantum dots solar cells

In this work we report the stacking of 10 and 50 InAs quantum dots layers using 2 monolayers of GaP for stress compensation and a stack period of 18 nm on GaAs (001) substrates. Very good structural and optical quality is found in both samples. Vertical alignment of the dots is observed by transmission electron microscopy suggesting the existence of residual stress around them. Photocurrent measurements show light absorption up to 1.2 μm in the nanostructures together with a reduction in the blue response of the device. As a result of the phosphorus incorporation in the barriers, a very high thermal activation energy (431 meV) has also been obtained for the quantum dot emission

Internal dynamics within primary care teams in two Spanish regions during the COVID-19 pandemic: a qualitative study

Background: Pandemics and epidemics have represented public health emergencies with severe consequences at a global level. Primary care teams have played a crucial role in disease surveillance and monitoring during the COVID-19 pandemic through early detection, contact tracing, and isolation of positive cases. The objective of this study was to explore the impact of the COVID-19 pandemic on primary care teams regarding their internal dynamics and their professional performance. Methods: Qualitative study carried out between July and December 2020 in two large central and southern Spanish regions (Castilla la Mancha and Madrid). Semi-structured interviews and focus groups were conducted with primary care workers. Data was analysed using thematic content analysis. Participants were accessed using purposive sampling. Results: A total of 53 primary care workers participated in the study, of which 38 were individually interviewed, and 15 participated in three focus groups.The analysis of their experiences revealed two main themes regarding the impact of the COVID-19 pandemic on primary care teams: 1) The need to reorganise traditional roles: Primary care settings closed their doors to the public and their workers restructured their roles to ensure the delivery of essential services; 2) The need to implement a new primary care delivery model: Each primary care team had to self-organise, making sure their reference population was cared for and developing resource optimisation strategies. Conclusions: Primary care teams have quickly adapted their roles and internal dynamics to respond to the demands generated by COVID-19. In the new delivery model, some positive aspects could be highlighted – such as increased communication between professionals and the use of telemedicine for some cases. However, it is important to address the negative impact that the COVID-19 crisis has had on of the main functions of primary care. These measures are necessary to promote well-being in primary care teams, and to provide quality care that addresses the complex and individual needs of each person and reduces inequalities in healthcare deliveryThis work was supported by the FONDO SUPERA COVID-19, organised by Santander Bank, the Spanish National Research Council (CSIC), and the Conference of Rectors of Spanish Universities (CRUE). It aims to fund programs, collaborative projects, and support activities to minimise the impact of the COVID-19 crisis in the health, education, and social sector

Aspergilosis pulmonar invasiva en paciente con EPOC

Severe COPD patient admitted to hospital with sustained fever, dyspnea, productive cough and constitutional syndrome, following several hospitalizations in the previous months due to superinfection with Pseudomonas aeruginosa. After investigation, the chronic form of Invasive Pulmonary Aspergillosis was diagnosed. The patient was treated with antifungals for 8 weeks, achieving clinical and radiological improvement, and sputum negativization. A high index of suspicion of this entity is very important for early diagnosis and early treatment in bronchopaths, since mortality has been estimated to reach 80-95% in untreated patients.Paciente con EPOC grave que ingresó con febrícula mantenida, disnea, tos productiva y síndrome constitucional, tras hospitalizaciones en los últimos meses por sobreinfecciones por Pseudomonas aeruginosa. Se confirmó aspergilosis pulmonar invasiva, variante crónica, tras estudio completo. Fue tratada con antifúngicos durante 8 semanas, con mejoría clínica, radiológica y negativización de esputos. Es vital tener un alto índice de sospecha de esta entidad en broncópatas con esteroides previos y tratar de forma precoz, pues alcanza una mortalidad del 80-95% sin tratamiento.      

Cambios que se producen en las narrativas de familias con hijos que atraviesan por la etapa de la adolescencia con problemas de comportamiento con diagnostico, durante un proceso de terapia asistida con animales

Psicólogo (a)Pregrad

Mejora en la evaluación de las prácticas externas realizada por los tutores académicos del Grado de Pedagogía

Memoria ID-0211. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2017-2018

Supercritical fluid extraction of corn germ oil: Study of the influence of process parameters on the extraction yield and oil quality

The supercritical fluid extraction of corn germ oil has been studied in this work. Extractions were carried out at different pressure, temperature and flow rate to analyze the influence of these variables on the extraction kinetics and the oil quality obtained. Extraction curves are initially linear with a slope close to the oil solubility value in supercritical CO2. Based on these results a mathematical model was successfully applied to describe the extraction curves. Characterization of supercritical crude corn oil was performed by determining some physical parameters such as refraction index, density and color. Additionally, the fatty acid composition, neutral lipids, the content of tocopherols, acid index, peroxide value, antioxidant capacity and the oxidative stability were determined in the corn oil extracted. Fatty acid composition was compared with that for crude germ oil and no significant differences between the oils extracted by both methods were found. Oxidative stability test using the Rancimat showed that supercritical CO2 extracted corn oil is less protected against oxidation than n-hexane extracted oils