Estimación del retraso crítico en la señalización celular

Las oscilaciones en los tejidos biológicos son muy habituales y se pueden manifestar de forma mecánica o química. En este informe mostraremos el modelo de alargamiento activo introducido por J.Muñoz y S. Albo en 2013 [Ref.5], al cual añadiremos una demora para simular oscilaciones en un sistema unidimensional con una, dos y tres células. En dicho sistema la masa es despreciable y esta basado en leyes simples de la reología. Podremos observar como con diferentes valores de retraso de tiempo obtenemos diferentes respuestas en la longitud de reposo de la célula (sin oscilaciones, con oscilaciones estables y oscilaciones inestables). Esto se demostrará analítica y numéricamente

La preparación de la familia del niño con Trastorno del Espectro Autista

La atención educativa integral a los niños con autismo ha sido un tema pocoincursionado por la Pedagogía Especial. Estos niños tienen un grupo de habilidadesgenerales afectadas debido a sus características clínicas, por tanto lograr que estas seadquieran y desarrollen, es un reto para todas las personas que interactúan con ellos. Eléxito depende en gran medida de la preparación de la familia. Se reflexiona en esteartículo la importancia de la preparación familiar para cumplir su gestión educativa y seexponen diferentes actividades didácticas para desarrollar la misma, con la intervenciónde los profesionales de la Educación Especial

Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress

This study was partially funded by Project P20-01029 (I+D+i-Junta de Andalucia, Spain) and by Project B-FQM-308-UGR20 (Universidad de Granada, Proyectos I+D+i del Programa Operativo FEDER Andalucia 2020) which means that it was also partially supported by European Regional Development Funds.Nivolumab, formulated in the medicine Opdivo (R) (10 mg/mL), is a therapeutic monoclonal antibody (mAb) used in the treatment of different types of cancer. Currently, there is insufficient knowledge about the behaviour of this protein with regards to the risk associated with its routine handling or unintentional mishandling, or when subjected to stress conditions in hospitals. These conditions can be simulated in forced degradation studies, which provide an in-depth understanding of the biophysical and biochemical properties of mAbs. In this study, we carried out a physicochemical and functional characterisation of nivolumab, which was subjected to various stress conditions: heat, freeze/thaw cycles, agitation, light exposure and high hypertonic solution. We used a wide range of analytical techniques: Far-UV CD, IT-FS, DLS, SE/UHPLC(UV)-[Native]MS, and ELISA. The results show that exposure to light was the stress test with the greatest impact on the samples, revelling the formation of non-natural dimers and a different isoform profile. In addition, nivolumab (Opdivo (R)) demonstrated stability up to 60 degrees C (1 h). As regards functionality all the nivolumab (Opdivo (R)) stressed samples were found to be stable except for those subjected to light and agitation, and to a lesser extent, those subjected to FTC 5 and NaCl stresses.I+D+i-Junta de Andalucia, Spain P20-01029European Commission B-FQM-308-UGR2

Exploring microbial life in the multi-extreme environment of Dallol, Ethiopia

Early Earth and ExoEarths: origin and evolution of life (2017. Varsovia)The Danakil depression at the Afar region in Ethiopia is one of the most unique and extreme environments on Earth. At the confluence of three tectonic plates in the East African rift (Triple Afar Junction), the Afar Depression is the only place on Earth where the transition from continental to oceanic crust (rift-to drift process) can be observed on land. Several types of extreme environments co-exist in this area, including highly acidic hydrothermal springs linked to the local volcanic activity at the Dallol dome, as well as desert evaporites and hypersaline lakes that resulted from the intense evaporation of an ancient enclosed sea. Although there have been more than 50 years since the area was first explored, information about its chemistry and geology is limited, and its biology remains completely unknown. In January 2016 and in January 2017, after several years of preparation, we organized two interdisciplinary expeditions to the Dallol area in order to explore the presence of life and mineral-microbe interactions under these geochemical extremes. To do so, and in combination with geochemical and mineralogical studies, we are applying molecular analyses based on 16S rRNA gene sequences, metagenomic and cultural approaches. Here, we will present preliminary results on the presence of life and microbial diversity identified in several sites of this multi-extreme environment.Centre National de la Recherche Scientifique, Université Paris-Sud, FranciaLaboratoire de microbiologie des environnements extrêmes, Centre National de la Recherche Scientifique, Université de Bretagne Occidentale, FranciaDepartamento de Ecología, Universidad Autónoma de Madrid, EspañaUnidad de Baleares, Instituto Geológico y Minero de España, EspañaInstituto Andaluz de Ciencias de la Tierra, Consejo Superior de Investigaciones Científicas, EspañaInstituto Andaluz de Ciencias de la Tierra, Universidad de Granada, EspañaLaboratoire de Minéralogie, Physique des Matériaux et Cosmochimie , Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, FranciaPeer reviewe

Solid particles formation from solutions, an intellectual and industrial meeting point and challenge

En aquest article presentem un recull d'experiències i idees sobre el problema de la formació de partícules sòlides nanomètriques i micromètriques a partir d'una solució. Presentem l'estat de la qüestió, alguns avanços en tècniques de precipitació, una descripció dels mecanismes de formació de partícules a partir d'una solució, amb una anàlisi de la influència de l'energia superficial formada en el curs de la nucleació sobre el procés d'agregació de nuclis. Es presenta un model d'agregació de partícules basat en la influència de les impureses.In this paper we will attempt to summarize a number of experiences and ideas concerning the problem of the formation of nanometric and micrometric solid particles from solutions. We will present the scope of the problem, some new advanced in techniques to produce and control the formation of solid particles, a description of a number of formation mechanisms of particles from solution, together with an analysis of the influence of the surface energy created in the nucleation process on the aggregation behavior of the nuclei formed. A new heuristic model on the aggregation mechanisms of particles, based on the action of impurities is proposed

The Relevance of Monoclonal Antibodies in the Treatment of COVID-19

This study was partially funded by Project FIS: PI-17/00547 (Institute of Health 'Carlos III', Ministry of Economy and Competitiveness, Spain), which means that it was also partially supported by European Regional Development Funds (ERDF).Major efforts have been made in the search for effective treatments since the outbreak of the COVID-19 infection in December 2019. Extensive research has been conducted on drugs that are already available and new treatments are also under development. Within this context, therapeutic monoclonal antibodies (mAbs) have been the subject of widespread investigation focusing on two target-based groups, i.e., non-SARS-CoV-2 specific mAbs, that target immune system responses, and SARS-CoV-2 specific mAbs, designed to neutralize the virus protein structure. Here we review the latest literature about the use of mAbs in order to describe the state of the art of the clinical trials and the benefits of using these biotherapeutics in the treatment of COVID-19. The clinical trials considered in the present review include both observational and randomized studies. We begin by presenting the studies conducted using non-SARS-CoV-2 specific mAbs for treating different immune disorders that were already on the market. Within this group of mAbs, we focus particularly on anti-IL-6/IL-6R. This is followed by a discussion of the studies on SARS-CoV-2 specific mAbs. Our findings indicate that SARS-CoV-2 specific mAbs are significantly more effective than non-specific ones.Institute of Health 'Carlos III', Ministry of Economy and Competitiveness, Spain - European Regional Development Funds (ERDF) FIS: PI-17/0054

Combined use of UV and MS data for ICH Stability-Indication Method: Quantification and isoforms identification of intact nivolumab

Nivolumab (Opdivo®) is a fully human immunoglobulin G4 isotype approved for the treatment of many cancers. It acts as an immune checkpoint inhibitor by blocking the interaction between PD-1 (Programmed Cell Death Protein 1) – an inhibitory receptor expressed on activated T cells- and its ligands, PD-L1 and PD-L2. The quantification of therapeutic proteins in their medicines and pharmaceutical preparations remains challenging because the protein content, a critical quality attribute, must be rigorously calculated using a validated stabilityindicating method, such as that indicated by the International Conference on Harmonization (ICH) quality guidelines, and this requires the analysis of the drug in the presence of its degraded products. In this work, we present an strategy based on the combined use of the UV and MS data to full file the requirement of the ICH-Q2 (R1) to develop and validated as stability indicated a (RP)UHPLC/UV-(HESI/Orbitrap™)MS method for the quantification of nivolumab in medicinal products. A comparative study of all figures of merit of the method using UV or MS data are shown and discussed. The results show that linearity was similar for the two detectors and was established over a range of 4–45 μg/mL and 1–45 μg/mL for the UV and (HESI/Orbitrap™)MS signals, respectively. The sensitivity of the method was higher when using the (HESI/Orbitrap™)MS signal (0.2 μg/mL) than with the UV(2.0 μg/mL). However, the UV signal provided better accuracy and precision than the (HESI/ Orbitrap™)MS signal, which did not meet the criteria for method robustness and system suitability. In spite of this, the MS signal plays a crucial role in this methodology by obtaining the molecular weight profile of the nivolumab isoforms, so enabling us to propose the glycans profile and detect structural modification due to degradation. The specificity of the method was evaluated by conducting forced degradation tests on samples of nivolumab in medicine form. The aim was to find out whether nivolumab suffers structural modifications when subject to stress. Structural modifications were detected by analysing the MS isoform profile, as changes of this kind promote new isoforms that are not chromatographically separated or detected by the UV signal. In this way, we demonstrated that the (RP)UHPLC/UV-(HESI/Orbitrap™)MS method was capable of detecting nivolumab degradation, and was suitable for use in nivolumab stability studies. Thus, the protein content in the daily surplus of the Opdivo® medicine, stored either at room temperature (20 ◦C) or refrigerated at 4 ◦C, could be tracked for 15 days.FPU18/03131 Ministry of Universities, Spain(P20_01029) Junta de Andalucía (Spain) and European Regional Development Fundspostdoctoral position from the Junta de Andalucía, SpainProject P20-01029 (I + D + i - Junta de Andalucía, Spain) Project B-FQM-308-UGR20 (Universidad de Granada, Proyectos I + D + i del Programa Operativo FEDER Andalucía 2020)CBUA/ Universidad de Granad

Competências transversais no mercado de tradução

Publicado originalmente em língua espanhola, o artigo apresenta uma breve descrição do conceito e de classificações de competências transversais, assim como a sua localização no mercado de tradução. Com a finalidade de identificar quais competências transversais são mais importantes no processo de seleção de tradutores profissionais, o estudo levantou dados quantitativos de 31 empresas que contratam serviços de tradução regularmente. As competências mais destacadas foram: motivação, criatividade, iniciativa, comunicação, planejamento e trabalho em equipe. Por fim, a pesquisa apresenta a necessidade da utilização de metodologias de ensino ativas para a formação de tradutores, bem como o uso de documentos autênticos em atividades práticas integrais e destaca o papel das empresas juniores neste processo

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

<p>Abstract</p> <p>Background</p> <p>Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH.</p> <p>Results</p> <p>This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97).</p> <p>Conclusions</p> <p>Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.</p