A new microbial gluten-degrading prolyl endopeptidase: Potential application in celiac disease to reduce gluten immunogenic peptides

Gluten is a complex of proteins present in barley, wheat, rye and several varieties of oats that triggers celiac disease in genetically predisposed subjects. Gluten is notoriously difficult to digest by mammalian proteolytic enzymes and therefore, proline-rich digestion-resistant peptides contain multiple immunogenic epitopes. Prolyl endopeptidases (PEP) hydrolyse internal proline residues on the carboxyl side of peptides and have been proposed for food gluten detoxification and as oral enzyme supplementation for celiacs. The aim of this study was to identify new gluten-degrading microbial enzymes with the potential to reduce gluten immunogenicity by neutralizing its antigenic epitopes. Using a gluten-degrading colony screening approach, a bacterial isolate (2RA3) displaying the highest glutenase activity was selected, characterized and its genome completely sequenced. The identification through 16S rDNA gene sequencing showed a 99,1% similarity to Chryseobacterium taeanense. Hydrolysis of gluten immunogenic peptides (GIP) was further monitored, over a 48-hour period, by colony encapsulation in gliadin-containing microspheres, followed by detection with the G12 anti-GIP monoclonal antibody. Glutenase activity was detected in the extracellular medium of 2RA3 cultures, where gel electrophoresis and gliadin zymography revealed the presence of a ~50 kDa gluten-degrading enzyme. Nano-ESI-Q-TOF of the excised active band identified 7 peptides contained in the protein product predicted for an open reading frame (ORF) in the 2RA3 genome. Based on sequence similarity to the PEP family, the new enzyme was named PEP 2RA3. The PEP 2RA3 coding sequence was PCR-amplified from C. taeanense 2RA3, cloned and expressed in Escherichia coli as a C-terminally His-tagged recombinant protein and purified by Ni-NTA affinity chromatography. The recombinant protein, with predicted molecular mass and isoelectric point of 78.95 kDa and 6.8, respectively, shows PEP activity with standard chromogenic substrates, works optimally at pH 8.0 and 30°C and remains stable at pH 6.0 and 50°C, indicating a potential use in gluten-containing food process applications. The ability of the recombinant enzyme to degrade GIP in beer into smaller peptides was confirmed.Ministry of Science and Innovation AGL2009-0906

La evolución del inglés como lengua franca, su enseñanza y aplicación en los negocios

El inglés se ha convertido en la lengua universal (franca) en el ámbito de los negocios, científico y profesional. Mediante un breve análisis histórico-lingüístico, el artículo tiene como objetivo explorar la evolución del inglés como lengua franca y su función en los negocios internacionales. Para ello, se exploran las relaciones del inglés y sus diferentes aplicaciones. Por otra parte, se realiza un breve examen de la capacitación en inglés en el Ecuador bajo la perspectiva del Régimen de Reglamento Académico del Consejo de Educación Superior de la República del Ecuador, los Estándares de Aprendizaje del Ministerio de Educación y el Marco Común Europeo de Referencia para las Lenguas. Se incluye una  mirada histórica hacia los diferentes métodos de enseñanza del inglés y la evolución de este idioma en un mundo globalizado. Los autores concluyen que, para poder participar de manera exitosa en el mundo internacional de los negocios, se requiere de un inglés profesional que vaya más allá de las destrezas de comunicación interpersonal básica para poder integrar contextos auténticos, normas culturales, y pensamiento crítico

Formación académica e iniciativa emprendedora de los estudiantes de educación superior tecnológica

Entrepreneurship is a key element for job creation, and for Higher Education Institutions. It plays a fundamental role in academic training and it furthers business development. This article purports to evaluate higher technological education students’ entrepreneurial initiative in Mexico. Planning Behavior Theory is used to identify significant differences in academic training. The GUESSS (Global University Entrepreneurial Spirit Student's Survey) questionnaire was applied to 919 students. The research was an empirical, quantitative, cross-sectional study with a descriptive and explanatory scope. The ANOVA analysis method of factorial variance was use. The hypothesis that concerns the existence of statistically significant differences regarding academic training was proved; it concerned medium personal attitude scores towards entrepreneurship, subjective rules, and entrepreneurial initiative global index.  El emprendimiento es un elemento clave para la generación de empleo, y las Instituciones de Educación Superior (IES) juegan un papel fundamental en la formación académica y fomento al desarrollo empresarial. El objetivo de este artículo es evaluar la iniciativa emprendedora de los estudiantes de educación superior tecnológica en México, mediante la Teoría del Comportamiento Planificado, con la finalidad de identificar diferencias significativas respecto a la formación académica. Se aplicó el cuestionario GUESSS (Global University Entrepreurial Spirit Student's Survey) a 919 estudiantes. Es un estudio empírico, cuantitativo, de corte transversal, con alcance descriptivo y explicativo. Se aplicó el método de análisis de varianza factorial ANOVA. Se comprueba la hipótesis que plantea la existencia de diferencias estadísticamente significativas respecto a la formación académica en las puntuaciones medias de actitud personal hacia el emprendimiento, normas subjetivas y el índice global de iniciativa emprendedora

Desempeño económico, implementación de las TIC e innovación en empresas, comparativo entre México y Colombia

In a changing economy and a more educated consumer, innovation is one of the fundamental axes in the growth of MSMEs that leads them to be competitive in the market. The purpose of this research is to analyze the economic performance of companies in Mexico and Colombia in the use of innovation and ICT as tools for their permanence in the market since they are fundamental pillars in the development of the Colombian and Mexican economy.  The type of research is quantitative with a cross-sectional and descriptive section, the data collection was carried out through a Google Form questionnaire built from a review of the literature designed from 4 constructs that are organizational performance, economic factor, innovation and use of ICT with a sample for convenience to a total of 30 MSMEs between both countries where it is observed that these companies are aware of the benefits of the implementation of ICT, therefore they are included in most business actions. Identifying that with respect to the comparison of means, the performance is the one with the highest level and the lowest innovation in both countries, in the same way the country has a significant influence on the Use of ICT with significance of 0.012 and does not do so in the elements. of innovation with significance of .335, performance with significance of 0.069 and economic factor the least influential with 0.421.En una economía cambiante y un consumidor más educado, la innovación es uno de los ejes fundamentales en el crecimiento de las MiPymes que las lleva a ser competitivas en el mercado. El objeto de esta investigación es analizar el desempeño económico de las empresas de México y Colombia en el uso de la innovación y de las TIC como herramientas para su permanencia en el mercado, dado que son pilares fundamentales en el desarrollo de la economía colombiana y mexicana. El tipo de investigación es cuantitativa con corte transversal y descriptivo, la recolección de datos se realizó por medio de un cuestionario en Formulario de Google construido a partir de una revisión de la literatura diseñado a partir de 4 constructos que son desempeño organizacional, factor económico, innovación y uso de TIC con una muestra por conveniencia a un total de 30 MiPymes entre ambos países en donde se observa que estas empresas son conscientes de los beneficios que tiene la implementación de las TIC por ello se incluyen en la mayoría de las acciones empresariales. Identificando que respecto a la comparación de medias el desempeño es el que presenta mayor nivel y la innovación menor en ambos países, de la misma forma el país influye de manera significativa en el Uso de TIC con significancia de 0.012 y no lo hace en los elementos de innovación con significancia de .335, desempeño con significancia de 0.069 y factor económico el que menos influye con 0.421

Changes in PRC1 activity during interphase modulate lineage transition in pluripotent cells

We thank the core facilities at GENYO for excellent technical support. We also thank the genomics unit at the CRG for assistance with RNA-seq and ChIP-seq experiments. The Landeira lab is supported by the Spanish ministry of science and innovation (PID2019-108108-100, EUR2021- 122005), the Andalusian regional government (PIER-0211-2019, PY20_00681) and the University of Granada (A-BIO-6-UGR20) grants. Research in the Klose lab is supported by the Wellcome Trust (209400/ Z/17/Z) and the European Research Council (681440). A.F. was sup- ported by a Sir Henry Wellcome Post-doctoral fellowship (110286/Z/15/ Z). Work in the Rada-Iglesias lab is funded by the Ministerio de Ciencia e Innovación, the Agencia Española de Investigación and the European Regional Development Fund (PGC2018-095301-B-I00 and RED2018- 102553-T); by the European Research Council (862022); and by the European Commission (H2020-MSCA-ITN-2019-860002).The online version contains supplementary material available at https://doi.org/10.1038/s41467-023-35859-9The potential of pluripotent cells to respond to developmental cues and trigger cell differentiation is enhanced during the G1 phase of the cell cycle, but the molecular mechanisms involved are poorly understood. Variations in polycomb activity during interphase progression have been hypothesized to regulate the cell-cycle-phase-dependent transcriptional activation of differentiation genes during lineage transition in pluripotent cells. Here, we show that recruitment of Polycomb Repressive Complex 1 (PRC1) and associated molecular functions, ubiquitination of H2AK119 and three-dimensional chromatin interactions, are enhanced during S and G2 phases compared to the G1 phase. In agreement with the accumulation of PRC1 at target promoters upon G1 phase exit, cells in S and G2 phases show firmer transcriptional repression of developmental regulator genes that is drastically perturbed upon genetic ablation of the PRC1 catalytic subunit RING1B. Importantly, depletion of RING1B during retinoic acid stimu- lation interferes with the preference of mouse embryonic stem cells (mESCs) to induce the transcriptional activation of differentiation genes in G1 phase. We propose that incremental enrolment of polycomb repressive activity during interphase progression reduces the tendency of cells to respond to develop- mental cues during S and G2 phases, facilitating activation of cell differentiation in the G1 phase of the pluripotent cell cycle.Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2019-108108-100, EUR2021-122005Andalusian regional government PIER-0211-2019, PY20_00681University of Granada A-BIO-6-UGR20Wellcome Trust 209400/Z/17/ZEuropean Research Council (ERC) European Commission 862022Wellcome Trust PGC2018-095301-B-I00Ministry of Science and Innovation, Spain (MICINN) Instituto de Salud Carlos III Spanish GovernmentEuropean Commission RED2018-102553-T, H2020-MSCA-ITN-2019-860002European Commission European Commission Joint Research Centre 681440Agencia Española de Investigación110286/Z/15/

Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9–8.6) months, with a 4-year OS probability of 18% (95% CI, 9%–27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109–3.362), 2.958 (1.640–5.334), and 2.976 (1.157–7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.La Caixa" Foundation and ISCIII, Grant/ Award Number: PI19/01828; Generalitat de Catalunya (GRC), Grant/Award Number: 2017 SGR28

Ética profesional en educación superior : finalidades, estrategias y desafíos de la formación

Todo proyecto educativo que no responde a su época se expone a problemas de legitimidad y al duro escrutinio y sanción de los usuarios. Las instituciones de educación superior no son la excepción de esta premisa clásica, incluso más validada por eldinamismos, la versatilidad y ojo crítico en el mundo contemporáneo. La ética se ha convertido en el baremo principal para someter a juicio a las instituciones y a las personas que ahí actuan, como a las finalidades que se pretenden en sus acciones. En esta perspectiva, debe examinarse la función de las instituciones de educación superior.Este libro es el esfuerzo colectivo por acercarnos a esa problemática, en especial a las finalidades, estrategias y relaciones en juego para cumplir la tarea de la formación y sus nexos inevitables con la ética profesional

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

A new microbial gluten-degrading prolyl endopeptidase: Potential application in celiac disease to reduce gluten immunogenic peptides.

Gluten is a complex of proteins present in barley, wheat, rye and several varieties of oats that triggers celiac disease in genetically predisposed subjects. Gluten is notoriously difficult to digest by mammalian proteolytic enzymes and therefore, proline-rich digestion-resistant peptides contain multiple immunogenic epitopes. Prolyl endopeptidases (PEP) hydrolyse internal proline residues on the carboxyl side of peptides and have been proposed for food gluten detoxification and as oral enzyme supplementation for celiacs. The aim of this study was to identify new gluten-degrading microbial enzymes with the potential to reduce gluten immunogenicity by neutralizing its antigenic epitopes. Using a gluten-degrading colony screening approach, a bacterial isolate (2RA3) displaying the highest glutenase activity was selected, characterized and its genome completely sequenced. The identification through 16S rDNA gene sequencing showed a 99,1% similarity to Chryseobacterium taeanense. Hydrolysis of gluten immunogenic peptides (GIP) was further monitored, over a 48-hour period, by colony encapsulation in gliadin-containing microspheres, followed by detection with the G12 anti-GIP monoclonal antibody. Glutenase activity was detected in the extracellular medium of 2RA3 cultures, where gel electrophoresis and gliadin zymography revealed the presence of a ~50 kDa gluten-degrading enzyme. Nano-ESI-Q-TOF of the excised active band identified 7 peptides contained in the protein product predicted for an open reading frame (ORF) in the 2RA3 genome. Based on sequence similarity to the PEP family, the new enzyme was named PEP 2RA3. The PEP 2RA3 coding sequence was PCR-amplified from C. taeanense 2RA3, cloned and expressed in Escherichia coli as a C-terminally His-tagged recombinant protein and purified by Ni-NTA affinity chromatography. The recombinant protein, with predicted molecular mass and isoelectric point of 78.95 kDa and 6.8, respectively, shows PEP activity with standard chromogenic substrates, works optimally at pH 8.0 and 30°C and remains stable at pH 6.0 and 50°C, indicating a potential use in gluten-containing food process applications. The ability of the recombinant enzyme to degrade GIP in beer into smaller peptides was confirmed

Hábitos alimenticios y su impacto en el rendimiento académico de estudiantes de la Licenciatura en Farmacia

Introduction. According to the United Nations Food and Agriculture Organization (FAO), human food is defined as a consistent and educatable voluntary process. Objective. To identify the impact of eating habits on the academic performance of students of the ICSa Pharmacy degree. Methodology. A cross-sectional, observational and prospective study was carried out. The MAPFRE Foundation's Healthy Eating survey was adapted and the sampling was non-probabilistic. Results. We  applied 102 surveys, predominated the female sex, with an average age of 20 (± 1) years. About 50%, he  mentioned bringing food from his home and having the habit of having breakfast, however, less than half  of the sample consumes at least one fruit and/or vegetable a day. A 76% believe their food if it impacts  their academic performance. Conclusions. It is important to make students aware of the correct way to eat and the impact on their academic performance, as well as to promote healthy lifestyles and provide them with necessary and correct information to properly select their food and drinks, otherwise that food selection will not be positive, that is, negative.  Introducción. De acuerdo a la organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO), la alimentación humana se define como un proceso voluntario consistente y educable. Objetivo. Determinar hábitos alimenticios y su impacto en el rendimiento académico de los estudiantes de la Licenciatura en Farmacia del ICSa. Metodología. Se realizó un estudio observacional transversal. Se adaptó la encuesta sobre alimentación saludable de la fundación MAPFRE y el muestreo fue no probabilístico. Resultados. Se aplicaron 102 encuestas, predomino el sexo femenino, con un promedio de edad de 20(±1)  años. Cerca del 50%, mencionó traer alimentos de su casa y tener el hábito de desayunar, sin embargo,  menos de la mitad de la muestra consume al menos una fruta y/o verdura al día. Un 76% considera que su  alimentación si impacta en su rendimiento académico. Conclusiones. Es importante concienciar a los estudiantes sobre la manera correcta de alimentarse y el impacto en su rendimiento académico, así como fomentar estilos de vida saludables y brindarles información necesaria y correcta para seleccionar adecuadamente sus alimentos y bebidas, de lo contrario  esa selección de alimentos será no positiva, es decir, negativa.