The mutational landscape of a prion-like domain

Insoluble protein aggregates are the hallmarks of many neurodegenerative diseases. For example, aggregates of TDP-43 occur in nearly all cases of amyotrophic lateral sclerosis (ALS). However, whether aggregates cause cellular toxicity is still not clear, even in simpler cellular systems. We reasoned that deep mutagenesis might be a powerful approach to disentangle the relationship between aggregation and toxicity. We generated >50,000 mutations in the prion-like domain (PRD) of TDP-43 and quantified their toxicity in yeast cells. Surprisingly, mutations that increase hydrophobicity and aggregation strongly decrease toxicity. In contrast, toxic variants promote the formation of dynamic liquid-like condensates. Mutations have their strongest effects in a hotspot that genetic interactions reveal to be structured in vivo, illustrating how mutagenesis can probe the in vivo structures of unstructured proteins. Our results show that aggregation of TDP-43 is not harmful but protects cells, most likely by titrating the protein away from a toxic liquid-like phase

Lactobacillus paracasei supplementation throughout the rat suckling and early post-weaning periods as strain-specific modulators of body growth and antibody response

Podeu consultar el III Workshop anual INSA-UB complet a: http://hdl.handle.net/2445/118993Sessió 1. Pòster núm.

Tarteso. Nuevas Fronteras (I)

El presente volumen recoge las contribuciones presentadas al II Congreso Internacional sobre Tarteso, Nuevas Fronteras, que tuvo lugar en Mérida entre los días 17 y 19 de noviembre de 2021. Su lectura permite un viaje desde el extremo oriental del Mediterráneo hasta el suroeste de la península ibérica, mostrando las diversas realidades históricas acontecidas en este territorio durante la I Edad del Hierro. El objetivo de esta publicación es mostrar la situación que atravesaba el Mediterráneo durante los años de surgimiento y desarrollo de la cultura tartésica para así comprender mejor la formación y evolución de dicha cultura. El conocimiento de Tarteso ha evolucionado sensiblemente en la última década, desde la celebración y publicación de las actas del I Congreso Internacional, Tarteso. El emporio del metal (Almuzara, 2013). La incorporación de nuevas voces y visiones enfocadas al conocimiento de la protohistoria peninsular, así como de algunos temas nunca antes abordados en el conocimiento de Tarteso, permiten presentar en este volumen una visión renovada, donde destaca la incorporación de unos nuevos límites territoriales para esta cultura.Esta publicación se ha beneficiado de las siguientes ayudas para su financiación: Proyecto de Investigación del Plan Nacional I+D+i: “Construyendo Tarteso 2.0: análisis constructivo, espacial y territorial de un modelo arquitectónico en el valle medio del Guadiana” (PID2019-108180GB- I00), financiado por MCIN AEI/10.13039/501100011033). Subvención global de la Secretaría General de Ciencia, Tecnología, Innovación y Universidad de la Junta de Extremadura al Instituto de Arqueología.Peer reviewe

Importance of Certification for Embedded Real-Time Systems

International audienceBrief biography: Jean-Pierre Seuma Vidal is Ph. D. student in the team Systems Dependability of the LESIA laboratory. His thesis deals with the use of UML to develop systems which must be certified: assessment of the modelling language features and guidelines to use them. The increasing of the number of such systems is correlated with the increasing of the number of the services they offer. This is mainly due to the software technology which, at first, allowed the improvement of the former functionalities replacing other technologies for implementation. Software is now used to offer functionalities to compensate for inadequacies of the capacities of users or other products, taking charge of new responsibilities. Finally, embedded real-time systems are now completely integrated in global systems and cannot be considered as independent elements. In the following subsections , these new characteristics and roles of software technology included in real-time embedded systems are analysed to highlight their consequences

The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer's disease mutations

Plaques of the amyloid beta (Aß) peptide are a pathological hallmark of Alzheimer's disease (AD), the most common form of dementia. Mutations in Aß also cause familial forms of AD (fAD). Here, we use deep mutational scanning to quantify the effects of >14,000 mutations on the aggregation of Aß. The resulting genetic landscape reveals mechanistic insights into fibril nucleation, including the importance of charge and gatekeeper residues in the disordered region outside of the amyloid core in preventing nucleation. Strikingly, unlike computational predictors and previous measurements, the empirical nucleation scores accurately identify all known dominant fAD mutations in Aß, genetically validating that the mechanism of nucleation in a cell-based assay is likely to be very similar to the mechanism that causes the human disease. These results provide the first comprehensive atlas of how mutations alter the formation of any amyloid fibril and a resource for the interpretation of genetic variation in Aß.Work in the lab of BB is supported by the Spanish Ministry of Science, Innovation and Universities through the project RTI2018-101491-A-I00 (MICIU/FEDER), by the CERCA Program/Generalitat de Catalunya and by funding from the Agencia de Gestio d’Ajuts Universitaris i de Recerca (2019FI_B 01311) to MS Work in the lab of BL is supported by a European Research Council (ERC) Consolidator grant (616434), the Spanish Ministry of Science, Innovation and Universities (BFU2017-89488-P and SEV-2012–0208), the Bettencourt Schueller Foundation, Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 1322.), and the CERCA Program/Generalitat de Cataluny

First European interlaboratory study of the analysis of benzoxazinone derivatives in plants by liquid chromatography

8 pages, 4 figures, 6 tables.-- PMID: 15481461 [PubMed].-- Printed version published Aug 20, 2004.-- Presented at the 3rd Meeting of the Spanish Association of Chromatography and Related Techniques and the European Workshop: 3rd Waste Water Cluster, Aguadulce (Almeria), Spain, Nov 19–21, 2003.Six laboratories from four different countries participated in the first European interlaboratory comparison exercise within the framework of the “Fate and toxicity of allelochemicals (natural plant toxins) in relation to environment and consumer” (FATEALLCHEM) European Union Project. The study, organized between November 2002 and March 2003, involved the analyses of seven benzoxazinone derivatives in two standard solutions and one purified extract of root material. Results are reported from the first phase of the study that examined the variability associated with different detection methods and different laboratories. The analytical strategies were based on liquid chromatography (LC) with diode array detection, LC coupled to mass spectrometry (MS) and LC coupled to tandem MS. When data from all laboratories were pooled, the relative standard deviation values ranged from 2 to 14% for the determination of target compounds in standard solutions, and between 19 and 47% for the analysis in root material. Comparison of the three detection techniques leads to the conclusion that MS approaches are the most accurate and precise techniques for the determination of benzoxazinone derivatives at ng/μL level in plant material.This work was financially supported by the programme “Quality of life and management of living resources (1998 to 2002)” of the European Union, FATEALLCHEM Contract No. QLRT-2000-01967, and by the Spanish Ministerio de Ciencia y Tecnología (AGL2001-4952-E).Peer reviewe

First European interlaboratory study of the analysis of benzoxazinone.

First European interlaboratory study of the analysis of benzoxazinone derivatives in plants by liquid chromatography (Eljarrat, E.; Guillamón, M.; Seuma, J.; Mogensen, B. B.; Fomsgaard, I. S.; Oliveros Bastidas, Alberto; Macías, F. A.; Stochmal, A.; Oleszek, W.; Shakaliene, O.; Barceló, D.) Abstract Six laboratories from four different countries participated in the first European interlaboratory comparison exercise within the framework of the "Fate and toxicity of allelochemicals (natural plant toxins) in relation to environment and consumer" (FATEALLCHEM) European Union Project. The study, organized between November 2002 and March 2003, involved the analyses of seven benzoxazinone derivatives in two standard solutions and one purified extract of root material. Results are reported from the first phase of the study that examined the variability associated with different detection methods and different laboratories. The analytical strategies were based on liquid chromatography (LC) with diode array detection, LC coupled to mass spectrometry (MS) and LC coupled to tandem MS. When data from all laboratories were pooled, the relative standard deviation values ranged from 2 to 14% for the determination of target compounds in standard solutions, and between 19 and 47% for the analysis in root material. Comparison of the three detection techniques leads to the conclusion that MS approaches are the most accurate and precise techniques for the determination of benzoxazinone derivatives at ng/µL level in plant material. © 2004 Elsevier B.V. All rights reserved. This article was presented at the 3rd Meeting of the Spanish Association of Chromatography and Related Techniques and the EuropeanWorkshop: 3rdWasteWater Cluster, Aguadulce (Almeria), 19-21 November, [email protected]@[email protected] monográfic

Evaluación de las prácticas clínicas de Dermatología en el grado de Medicina

La adquisición de competencias (conjunto de conocimientos, habilidades y actitudesque conforman la actuación profesional) se considera un requisito necesario para la acreditacióndel grado de Medicina. Las competencias en Dermatología deberían ser, además de la realizaciónde la entrevista clínica y la descripción precisa de las lesiones cutáneas, el correcto manejo(diagnosticar, diferenciar y tratar) de las dermatosis y tumores comunes. Estas habilidadessolo pueden adquirirse durante una rotación especializada. Proponemos que para certificarlasdebemos evaluar los conocimientos adquiridos con exámenes clínicos o mediante la discusiónde incidentes críticos; mientras que, para la evaluación de las habilidades de comunicación yalgunas habilidades instrumentales, podríamos poner en práctica la observación estructurada dela práctica clínica, tras elaborar indicadores para cada una de ellas; y para las actitudes, adoptarun consenso entre los miembros del servicio que han estado en contacto con el estudiante

Modeling the impact on wheel sensor readouts by Eddy Current Brakes installed in high-speed trains

This paper presents a model to anticipate the impact of Eddy Current Brakes (ECBs) installed in high-speed trains on the readouts of rail-side wheel sensors. The purpose is to anticipate false positive readouts of train wheels when traversing, one of the main obstacles for full ECB deployment. The ECB type EWB 154 from Knorr-Bremse and Wheel Sensor types RSR180 and RSR123 from Frauscher Sensor Technology are represented in a comprehensive model, integrating LTSpice and CST Microwave Studio. The wheel sensor predicted readout error is 4% compared to measurements when DC current is not applied to the ECB (passive case). It is demonstrated that the RSR180 is not compatible with ECBs, whereas the RSR123 is. The impact of active (DC current fed) brakes is analyzed when performing running tests with a high-speed ICE 3 train equipped with ECBs. The model is adjusted to study the saturation of the rail and ECB pole cores. The extra damping of the wheel sensor fingerprint is modeled by an extra 6% drop that may well be applicable to passive tests in a laboratory setting to shift to active tests without actually performing them. In this way, cost and time would be saved. Based on the model outcomes, a test bench is recommended for laboratory tests to emulate active behavior