Propuesta de protocolo para la identificación y evaluación de barreras arquitectònicas en situaciones de evacuación, en edificios de uso público

Para el desarrollo del trabajo hemos elaborado un protocolo con la finalidad de poder ser utilizado como checklist. Éste, está destinado para utilizarse en edificios de uso público, y ayudar a identificar las barreras arquitectónicas de manera rápida y cómoda, tanto en situación de uso normal como en situación de evacuación. Una parte ha sido elaborada con la legislación vigente y la otra con bibliografía especializada, junto con los técnicos especializados y agentes implicados. Las normativas aplicadas han sido por un lado, la correspondiente a nivel autonómico de Catalunya y por otro, las de nivel estatal. Las hemos examinado de manera cronológica analizando así su evolución en el tiempo. Con el fin de tener en cuenta el punto de vista de los agentes implicados, nos hemos reunido con el Departamento de Bomberos de Barcelona. Nos interesaba conocer su experiencia profesional para analizar la problemática con la que ellos se encuentran y saber su opinión con respecto a la normativa vigente. El hecho de entrevistarnos con los colectivos de minusválidos le da un valor añadido, porque aunque, en su mayoría no son técnicos, si que conocen las deficiencias que tienen los edificios de primera mano y, sobre todo, que opinan ellos que se debería mejorar, tanto a nivel legislativo como educativo. Con todos estos puntos de vista, hemos elaborado a través del checklist, una manera rápida y eficaz de identificar las barreras arquitectónicas de un edificio de uso público. Una vez elaborado el protocolo, hemos querido dar un paso más allá, poniéndolo en práctica en dos edificios y así comprobar la eficacia del mismo. Con los resultados obtenidos en la validación del protocolo, hemos concluido el trabajo con la incorporación de mejoras a las deficiencias. Lo que nos ha llevado a formarnos en el asesoramiento técnico sobre supresión de barreras arquitectónicas. Precisando de la investigación de industriales del sector (especializados y colaboradores de entes como el CEAPAT, ONCE, etc.), para conocer la innovación en sistemas existentes en el mercad

The Impact of the HydroxyMethylCytosine epigenetic signature on DNA structure and function.

Funder: Programa de Desarrollo de las Ciencias BasicasFunder: Institució Catalana de Recerca i Estudis AvancatsFunder: Sistema Nacional de Investigadores, Agencia Nacional de Investigación e Innovación, UruguayFunder: Government of SpainWe present a comprehensive, experimental and theoretical study of the impact of 5-hydroxymethylation of DNA cytosine. Using molecular dynamics, biophysical experiments and NMR spectroscopy, we found that Ten-Eleven translocation (TET) dioxygenases generate an epigenetic variant with structural and physical properties similar to those of 5-methylcytosine. Experiments and simulations demonstrate that 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) generally lead to stiffer DNA than normal cytosine, with poorer circularization efficiencies and lower ability to form nucleosomes. In particular, we can rule out the hypothesis that hydroxymethylation reverts to unmodified cytosine physical properties, as hmC is even more rigid than mC. Thus, we do not expect dramatic changes in the chromatin structure induced by differences in physical properties between d(mCpG) and d(hmCpG). Conversely, our simulations suggest that methylated-DNA binding domains (MBDs), associated with repression activities, are sensitive to the substitution d(mCpG) ➔ d(hmCpG), while MBD3 which has a dual activation/repression activity is not sensitive to the d(mCpG) d(hmCpG) change. Overall, while gene activity changes due to cytosine methylation are the result of the combination of stiffness-related chromatin reorganization and MBD binding, those associated to 5-hydroxylation of methylcytosine could be explained by a change in the balance of repression/activation pathways related to differential MBD binding

RPL30 regulation of splicing reveals distinct roles for Cbp80 in U1 and U2 snRNP cotranscriptional recruitment

This article is Open Access.Pre-mRNA splicing is catalyzed by the spliceosome, and its control is essential for correct gene expression. While splicing repressors typically interfere with transcript recognition by spliceosomal components, the yeast protein L30 blocks spliceosomal rearrangements required for the engagement of U2 snRNP (small ribonucleoprotein particle) to its own transcript RPL30. Using a mutation in the RPL30 binding site that disrupts this repression, we have taken a genetic approach to reveal that regulation of splicing is restored in this mutant by deletion of the cap-binding complex (CBC) component Cbp80. Indeed, our data indicate that Cbp80 plays distinct roles in the recognition of the intron by U1 and U2 snRNP. It promotes the initial 5′ splice site recognition by U1 and, independently, facilitates U2 recruitment, depending on sequences located in the vicinity of the 5′ splice site. These results reveal a novel function for CBC in splicing and imply that these molecular events can be the target of a splicing regulator.This research has been supported by the MEC (BFU grants), an EU-MC Contract (#510183), and Agaur, S.M. and j.V. has been supported by a Ramón y Cajal/IP3 contract (MEC).Peer Reviewe

Propuesta de protocolo para la identificación y evaluación de barreras arquitectònicas en situaciones de evacuación, en edificios de uso público

Para el desarrollo del trabajo hemos elaborado un protocolo con la finalidad de poder ser utilizado como checklist. Éste, está destinado para utilizarse en edificios de uso público, y ayudar a identificar las barreras arquitectónicas de manera rápida y cómoda, tanto en situación de uso normal como en situación de evacuación. Una parte ha sido elaborada con la legislación vigente y la otra con bibliografía especializada, junto con los técnicos especializados y agentes implicados. Las normativas aplicadas han sido por un lado, la correspondiente a nivel autonómico de Catalunya y por otro, las de nivel estatal. Las hemos examinado de manera cronológica analizando así su evolución en el tiempo. Con el fin de tener en cuenta el punto de vista de los agentes implicados, nos hemos reunido con el Departamento de Bomberos de Barcelona. Nos interesaba conocer su experiencia profesional para analizar la problemática con la que ellos se encuentran y saber su opinión con respecto a la normativa vigente. El hecho de entrevistarnos con los colectivos de minusválidos le da un valor añadido, porque aunque, en su mayoría no son técnicos, si que conocen las deficiencias que tienen los edificios de primera mano y, sobre todo, que opinan ellos que se debería mejorar, tanto a nivel legislativo como educativo. Con todos estos puntos de vista, hemos elaborado a través del checklist, una manera rápida y eficaz de identificar las barreras arquitectónicas de un edificio de uso público. Una vez elaborado el protocolo, hemos querido dar un paso más allá, poniéndolo en práctica en dos edificios y así comprobar la eficacia del mismo. Con los resultados obtenidos en la validación del protocolo, hemos concluido el trabajo con la incorporación de mejoras a las deficiencias. Lo que nos ha llevado a formarnos en el asesoramiento técnico sobre supresión de barreras arquitectónicas. Precisando de la investigación de industriales del sector (especializados y colaboradores de entes como el CEAPAT, ONCE, etc.), para conocer la innovación en sistemas existentes en el mercad

Impact of DNA methylation on 3D genome structure

Determining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. Despite lacking the machinery for positioning and reading methylation marks, induced DNA methylation follows a conserved pattern with low methylation levels at the 5' end of the gene increasing gradually toward the 3' end, with concentration of methylated DNA in linkers and nucleosome free regions, and with actively expressed genes showing low and high levels of methylation at transcription start and terminating sites respectively, mimicking the patterns seen in mammals. We also see that DNA methylation increases chromatin condensation in peri-centromeric regions, decreases overall DNA flexibility, and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.This work has been supported by the Spanish Ministry of Science (BIO2012-32868), the Catalan SGR, the Instituto Nacional de Bioinformática, the European Research Council (ERC_SimDNA) and the BioExcel and MuG VRE H2000 projects. M.O. is an ICREA Academia Fellow. This project also received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754510 [to J.P.A. and M.O.]. The work of S.H. was supported by the Spanish Ministry of Science (PGC2018-099640-B-I00). A.E.C. is funded by ISCIII /MINECO (PT17/0009/0019) and co-funded by FEDER

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols