Factores genéticos y ambientales modificadores de la toxicidad por amiloide en un modelo murino de enfermedad de Alzheimer

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Anatomía, Histología y Neurociencia. Fecha de lectura: 12 de Mayo de 201

Frameshift mutations in Fas, Apaf-1, and Bcl-10 in gastro-intestinal cancer of the microsatellite mutator phenotype

Dear Editor, in a letter to the editor in a recent issue of Cell Death and Differentiation, Abdel-Rahman et al1. reported the absence of mutations in the death pathways gene Fas (Apo-1/CD95) in colorectal carcinomas. From the absence of mutations in 24 colon cancers, 12 of which were classified as replication error positive (RER+), Abdel-Rahman et al1. concluded that such mutations confer no substantial growth advantage in colorectal carcinogenesis. In agreement with this report, we identified Fas mutations in only 10% of colon and gastric cancers of the microsatellite mutator phenotype (MMP), also denominated as RER or microsatellite instability (MSI). Mutations were also found in Apaf-1 and Bcl-10, two other genes involved in the cell death pathways. The mutations were detected in mononucleotide tracts within these three genes (Figure 1). The frequency of these frameshift mutations was low (Table 1) and they appeared to be heterozygous (Figure 2). However, considering the peculiar features of these tumors, we suggest that these frameshift mutations contribute to cancer progression by providing survival advantage

Cuadrilátero

Máster en Dirección de la Empresa Audiovisual. Curso 2010/201

Coupling AnMBR, Primary Settling and Anaerobic Digestion to Improve Carbon Fate when Treating Sulfate-Rich Wastewater

[EN] The present work involved an assessment of the technical feasibility of coupling AnMBR, primary settling and anaerobic digestion to treat sulfate-rich wastewater at ambient temperature. The innovative approach used focused on reducing the carbon footprint of wastewater treatment while maximizing the energy recovered from influent organic matter. In this process, primary settling reduces the COD/SO4-S ratio in the influent of the AnMBR system and completely removes organic matter by sulfate-reducing bacteria (SRB), while increasing the COD/SO4-S ratio in the sidestream anaerobic digester (AD), enhancing energy recovery and biogas quality. This approach has the significant advantage of only producing methane in the AD, so that the AnMBR produces a high-quality, methane-free effluent with no environmental impact from fugitive methane emissions. The performance of this treatment scheme was assessed by operating a demonstration-scale AnMBR plant fed by primary settled municipal wastewater at the hydraulic retention times of 25, 12 and 8.5 h. The results showed that the COD and BOD removed by SRB enabled setting the discharge limits at 25 and 12 h and lowered the carbon footprint to levels below those of an AnMBR plant fed by raw municipal wastewater, mainly by eliminating fugitive methane emissions.The authors would like to acknowledge the Ministry of Science and Innovation for supporting the project "RECREATE" (PID2020-114315RB-C22) and "BIONUTEN" (CTM2014-54980-C2-R)where this research is framed and the Ministry of Universities for the financial research fellowship of the first author (BES-2015-073403).Mateo, O.; Sanchis-Perucho, P.; Giménez, JB.; Robles, Á.; Martí, N.; Serralta Sevilla, J.; Seco, A. (2023). Coupling AnMBR, Primary Settling and Anaerobic Digestion to Improve Carbon Fate when Treating Sulfate-Rich Wastewater. Water. 15(20):1-18. https://doi.org/10.3390/w15203574118152

Analysis of genetic variability and mapping of point mutations in influenza virus by the RNase A mismatch cleavage method

We have applied the RNase A mismatch cleavage method to analyze genetic variability in RNA viruses by using influenza virus as a model system. Uniformly labeled RNA probes synthesized from a cloned hemagglutinin gene of a given viral strain were hybridized to RNA isolated from other strains of characterized or uncharacterized genetic composition. The RNA.RNA heteroduplexes containing a variable number of base mismatches were digested with RNase A, and the resistant products were analyzed by denaturing polyacrylamide gel electrophoresis. We show that many of these single base mismatches are cleaved by RNase A, generating unique and characteristic patterns of resistant RNA fragments specific for each of the different viral strains. Comparative analysis of the cleavage patterns allows a qualitative estimation of the genetic relatedness and evolution of field strains. We also show that cleavage by RNase A at single base mismatches can readily detect and localize point mutations present in monoclonal antibody-resistant variants. This method should have wide applications in the study of RNA viruses, not only for epidemiological analysis but also in some diagnostic problems, such as characterization of phenotypic mutants.This work was supported by National Institutes of Health Grant CA33021 awarded by the Nationa l Cancer Institute to M.P. and by grants from the Comision Asesora de Investigacion Cientificay Tecnica (Grant 608/438) and Fondo de Investigaciones Sanitarias to J.O. and J.A.M.C.L.-G. was a recipient of a NATO short-term post doctoral fellow-ship while on leave from the Centro Nacional de Microbiologia, Majadahonda, Madri

Genetic profile in genes associated with muscle injuries and injury etiology in professional soccer players.

post-print1255 K

Genetic profiles to identify talents in elite endurance athletes and professional football players.

The genetic profile that is needed to identify talents has been studied extensively in recent years. The main objective of this investigation was to approach, for the first time, the study of genetic variants in several polygenic profiles and their role in elite endurance and professional football performance by comparing the allelic and genotypic frequencies to the non-athlete population. In this study, genotypic and allelic frequencies were determined in 452 subjects: 292 professional athletes (160 elite endurance athletes and 132 professional football players) and 160 non-athlete subjects. Genotyping of polymorphisms in liver metabolisers (CYP2D6, GSTM1, GSTP and GSTT), iron metabolism and energy efficiency (HFE, AMPD1 and PGC1a), cardiorespiratory fitness (ACE, NOS3, ADRA2A, ADRB2 and BDKRB2) and muscle injuries (ACE, ACTN3, AMPD1, CKM and MLCK) was performed by Polymerase Chain Reaction-Single Nucleotide Primer Extension (PCR-SNPE). The combination of the polymorphisms for the “optimal” polygenic profile was quantified using the genotype score (GS) and total genotype score (TGS). Statistical differences were found in the genetic distributions between professional athletes and the non-athlete population in liver metabolism, iron metabolism and energy efficiency, and muscle injuries (p<0.001). The binary logistic regression model showed a favourable OR (odds ratio) of being a professional athlete against a non-athlete in liver metabolism (OR: 1.96; 95% CI: 1.28–3.01; p = 0.002), iron metabolism and energy efficiency (OR: 2.21; 95% CI: 1.42–3.43; p < 0.001), and muscle injuries (OR: 2.70; 95% CI: 1.75–4.16; p < 0.001) in the polymorphisms studied. Genetic distribution in professional athletes as regards endurance (professional cyclists and elite runners) and professional football players shows genetic selection in these sports disciplines.post-print1592 K

Resonant Kelvin-Helmholtz modes in sheared relativistic flows

Qualitatively new aspects of the (linear and non-linear) stability of sheared relativistic (slab) jets are analyzed. The linear problem has been solved for a wide range of jet models well inside the ultrarelativistic domain (flow Lorentz factors up to 20; specific internal energies $\approx 60c^2$). As a distinct feature of our work, we have combined the analytical linear approach with high-resolution relativistic hydrodynamical simulations, which has allowed us i) to identify, in the linear regime, resonant modes specific to the relativistic shear layer ii) to confirm the result of the linear analysis with numerical simulations and, iii) more interestingly, to follow the instability development through the non-linear regime. We find that very high-order reflection modes with dominant growth rates can modify the global, long-term stability of the relativistic flow. We discuss the dependence of these resonant modes on the jet flow Lorentz factor and specific internal energy, and on the shear layer thickness. The results could have potential applications in the field of extragalactic relativistic jets.Comment: Accepted for publication in Physical Review E. For better quality images, please check http://www.mpifr-bonn.mpg.de/staff/mperucho/Research.htm

Methylation of MGMT and ADAMTS14 in normal colon mucosa : biomarkers of a field defect for cancerization preferentially targeting elder African-Americans

Altres ajuts: National Institutes of Health Grant R37CA63585, RO1CA83017 i RO1CA157328Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0.5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0.001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0.001) patients, and particularly in African Americans (p = 1 × 10-5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North Americ

Alterations in tissue oxygen saturation measured by near-infrared spectroscopy in trauma patients after initial resuscitation are associated with occult shock

Acord transformatiu CRUE-CSICPurpose: Persistent occult hypoperfusion after initial resuscitation is strongly associated with increased morbidity and mor- tality after severe trauma. The objective of this study was to analyze regional tissue oxygenation, along with other global markers, as potential detectors of occult shock in otherwise hemodynamically stable trauma patients. Methods: Trauma patients undergoing active resuscitation were evaluated 8 h after hospital admission with the measure- ment of several global and local hemodynamic/metabolic parameters. Apparently hemodynamically stable (AHD) patients, defined as having SBP ≥ 90 mmHg, HR < 100 bpm and no vasopressor support, were followed for 48 h, and finally classified according to the need for further treatment for persistent bleeding (defined as requiring additional red blood cell transfusion), initiation of vasopressors and/or bleeding control with surgery and/or angioembolization. Patients were labeled as "Occult shock" (OS) if they required any intervention or "Truly hemodynamically stable" (THD) if they did not. Regional tissue oxygenation (rSO2) was measured non-invasively by near-infrared spectroscopy (NIRS) on the forearm. A vascular occlu- sion test was performed, allowing a 3-min deoxygenation period and a reoxygenation period following occlusion release. Minimal rSO2 (rSO2min), Delta-down (rSO2-rSO2min), maximal rSO2 following cuff-release (rSO2max), and Delta-up (rSO2max-rSO2min) were computed. The NIRS response to the occlusion test was also measured in a control group of healthy volunteers. Results: Sixty-six consecutive trauma patients were included. After 8 h, 17 patients were classified as AHD, of whom five were finally considered to have OS and 12 THD. No hemodynamic, metabolic or coagulopathic differences were observed between the two groups, while NIRS-derived parameters showed statistically significant differences in Delta-down, rSO2min, and Delta-up. Conclusions: After 8 h of care, NIRS evaluation with an occlusion test is helpful for identifying occult shock in apparently hemodynamically stable patients