Epigenetic Regulation of B Lymphocyte Differentiation, Transdifferentiation, and Reprogramming

B cell development is a multistep process that is tightly regulated at the transcriptional level. In recent years, investigators have shed light on the transcription factor networks involved in all the differentiation steps comprising B lymphopoiesis. The interplay between transcription factors and the epigenetic machinery involved in establishing the correct genomic landscape characteristic of each cellular state is beginning to be dissected. The participation of "epigenetic regulator-transcription factor" complexes is also crucial for directing cells during reprogramming into pluripotency or lineage conversion. In this context, greater knowledge of epigenetic regulation during B cell development, transdifferentiation, and reprogramming will enable us to understand better how epigenetics can control cell lineage commitment and identity. Herein, we review the current knowledge about the epigenetic events that contribute to B cell development and reprogramming

In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

Class IIa histone deacetylase (HDAC) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. In this study, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while also leading to pro-B cell lineage promiscuity. We find that HDAC7 represses myeloid and T lymphocyte genes in B cell progenitors through interaction with myocyte enhancer factor 2C (MEFC2). In B cell progenitors, HDAC7 is recruited to promoters and enhancers of target genes, and its absence leads to increased enrichment of histone active marks. Our results prove that HDAC7 is a bona fide transcriptional repressor essential for B cell development

Methodology applied in the study of the language development in children with early detection of neonatal hearing loss.

Introducción y objetivo: Dado que el potencial discapacitante que causa la deficiencia auditiva neonatal disminuye con una detección e intervención tempranas, hemos elaborado un proyecto de investigación, con el que nos proponemos conocer el grado de desarrollo del lenguaje de los niños y niñas que procedentes del cribado auditivo universal, han sido diagnosticados/as por nosotros de hipoacusia prelingual en estos últimos 15 años y analizar las variables determinantes y las que son modificables. El objeto de esta comunicación consistirá en presentar la metodología que vamos a utilizar. Método: Partimos de los datos almacenados en nuestro Servicio de ORL, que comprende a 282 niños con hipoacusia. Hemos tenido la oportunidad de crear un grupo de investigación en el que coincidimos especialistas de la audición infantil y del lenguaje, por lo que contamos con medios suficientes para el estudio. Resultados: Describimos los elementos que configuran este proyecto, en relación al equipo de trabajo y a su desarrollo. Tras aplicar unos criterios de exclusión/inclusión, hemos seleccionado a un grupo de 45 niños entre 3 y 15 años, definiendo sus características auditivas. Mediante pruebas específicas, adaptadas a la edad, estudiaremos los diferentes aspectos del lenguaje; y a través de una entrevista estructurada realizada a los padres, intentaremos determinar las variables que influyen en el proceso re-habilitador. Finalmente, los datos serán analizados estadísticamente. Discusión: La variabilidad y la escasa prevalencia de la hipoacusia infantil, dificultan la realización de estudios con población suficiente para obtener resultados estadísticamente significativos. Sin embargo, creemos que el grupo de niños seleccionado y la metodología utilizada nos permitirán conocer mejor las variables influyentes en el desarrollo del lenguaje. Conclusiones: El programa de cribado auditivo universal ha permitido una intervención más precoz, lo que debería mejorar los niveles de lenguaje de los niños detectados/as con hipoacusia. Aunque el desarrollo normalizado de la comunicación depende de otros factores difíciles de determinar, a través del protocolo presentado pretendemos equiparar estos resultados, validando el proceso de cribado/diagnóstico e intervención de nuestro medio.Introduction and objective: Given that the disabling potential causing neonatal hearing impairment decreases with early detection and intervention, we have drawn up a research project, with which we intend to know the degree of development of the language of children and girls than from the universal hearing screening, have been diagnosed for us of prelingual hearing loss in the last 15 years and analyze the determining variables and which are modifiable. The object of this communication will be to present the methodology that we use. Method: We assume the data stored on our ENT service, including 282 children with hearing loss. We have had the opportunity to create a research group in which we agree ENT and language specialists so we have resources sufficient for the study. Results: We describe the elements that make up this project in relation to the team and to its development. After applying inclusion/exclusion criteria, we have selected a group of 45 children between 3 and 15 years, defining their auditory characteristics. Through specific tests, adapted to the age, we will study the different aspects of the language; and through a structured interview parents, we try to determine the variables that influence the rehabilitator process. Finally, the data will be analyzed statistically. Discussion: The variability and the low prevalence of infant hearing loss, make it difficult studies with sufficient population to obtain statistically significant results. However, we believe that the group of children and the methodology selected will allow us to learn more about the influential in the development of the language variables. Conclusions: The hearing screening program allowed us to earlier intervention, which should improve the levels of language of children detected with hearing loss. Although the standard development of communication depends on other factors difficult to determine, through the presented protocol we equate these findings, validating the process of screening/diagnosis and intervention of our environment

HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages

B lymphopoiesis is the result of several cell-commitment, lineage-choice, and differentiation processes. Every differentiation step is characterized by the activation of a new, lineage-specific, genetic program and the extinction of the previous one. To date, the central role of specific transcription factors in positively regulating these distinct differentiation processes to acquire a B cell-specific genetic program is well established. However, the existence of specific transcriptional repressors responsible for the silencing of lineage inappropriate genes remains elusive. Here we addressed the molecular mechanism behind repression of non-lymphoid genes in B cells. We report that the histone deacetylase HDAC7 was highly expressed in pre-B cells but dramatically down-regulated during cellular lineage conversion to macrophages. Microarray analysis demonstrated that HDAC7 re-expression interfered with the acquisition of the gene transcriptional program characteristic of macrophages during cell transdifferentiation; the presence of HDAC7 blocked the induction of key genes for macrophage function, such as immune, inflammatory, and defense response, cellular response to infections, positive regulation of cytokines production, and phagocytosis. Moreover, re-introduction of HDAC7 suppressed crucial functions of macrophages, such as the ability to phagocytose bacteria and to respond to endotoxin by expressing major pro-inflammatory cytokines. To gain insight into the molecular mechanisms mediating HDAC7 repression in pre-B cells, we undertook co-immunoprecipitation and chromatin immunoprecipitation experimental approaches. We found that HDAC7 specifically interacted with the transcription factor MEF2C in pre-B cells and was recruited to MEF2 binding sites located at the promoters of genes critical for macrophage function. Thus, in B cells HDAC7 is a transcriptional repressor of undesirable genes. Our findings uncover a novel role for HDAC7 in maintaining the identity of a particular cell type by silencing lineage-inappropriate genes

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Innovación en las enseñanzas universitarias: experiencias presentadas en las III Jornadas de Innovación Educativa de la ULL

En este libro se recoge un conjunto de experiencias de innovación educativa desarrolladas en la ULL en el curso 2011-12. Se abordan distintos ámbitos y ramas del conocimiento, y ocupan temáticas variadas que han sido desarrolladas con rigor, y con un claro potencial para su extrapolación a efectos de la mejora educativa en el ámbito universitario. Esta publicación constituye una primera edición de una serie que irá recogiendo las experiencias de innovación educativa de la ULL. Este es un paso relevante para su impulso en nuestra institución, como lo es el de su vinculación con la investigación educativa, para potenciar su publicación en las revistas científicas en este ámbito cada vez más pujante y relevante para las universidades. Sobre todo representan el deseo y el compromiso del profesorado de la ULL para la mejora del proceso educativo mediante la investigación, la evaluación y la reflexión compartida de nuestras prácticas y planteamientos docentes

One-year changes in fruit and vegetable variety intake and cardiometabolic risk factors changes in a middle-aged Mediterranean population at high cardiovascular risk

Background and aims Previous studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome. Methods a one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (β-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors. Results Two points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (−0.33 mg/dL (0.58, −0.07)), body weight (−0.07 kg (−0.13, −0.02)) and waist circumference (WC) (−0.08 cm (−0.16, −10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (−0.50 mg/dL (−0.93, −0.08)), glucose (−0.21 mg/dL (−0.32, −0.11)), body weight (−0.11 kg (−0.15, −0.07)) and WC (−0.10 cm (−0.14, −0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (−1.26 mg/dL (−2.09, −0.43)), body weight (−0.40 kg (−0.58, −0.23)) and WC (−0.50 cm (−0.73, −0.28)). Conclusion Greater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk

¿Qué queda de mí?

Este libro es una reclamación a quienes hemos sido, somos o seremos docentes. A quienes no hemos respetado a las personas que se han puesto junto a nosotros y nosotras, confiando su bien más preciado: la libertad. Estas páginas denuncian cada vez que convertimos una visión en la visión, una emoción en la emoción, un saber en el saber, un comportamiento en el comportamiento. Es un grito contra la imposición, la normalización, la neutralización y la universalización de una perspectiva particular. Una pugna contra cada proceso que no se ha conectado con las vidas de los aprendices. Un texto colaborativo realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga y coordinado por Ignacio Calderón Almendros

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

Proyecto, investigación e innovación en urbanismo, arquitectura y diseño industrial

Actas de congresoLas VII Jornadas de Investigación “Encuentro y Reflexión” y I Jornadas de Investigación de becarios y doctorandos. Proyecto, investigación e innovación en Urbanismo, Arquitectura y Diseño Industrial se centraron en cuatro ejes: el proyecto; la dimensión tecnológica y la gestión; la dimensión social y cultural y la enseñanza en Arquitectura, Urbanismo y Diseño Industrial, sustentados en las líneas prioritarias de investigación definidas epistemológicamente en el Consejo Asesor de Ciencia y Tecnología de esta Universidad Nacional de Córdoba. Con el objetivo de afianzar continuidad, formación y transferencia de métodos, metodología y recursos se incorporó becarios y doctorandos de los Institutos de investigación. La Comisión Honoraria la integraron las tres Secretarias de Investigación de la Facultad, arquitectas Marta Polo, quien fundó y María del Carmen Franchello y Nora Gutiérrez Crespo quienes continuaron la tradición de la buena práctica del debate en la cotidianeidad de la propia Facultad. Los textos que conforman las VII Jornadas son los avances y resultados de las investigaciones realizadas en el bienio 2016-2018.Fil: Novello, María Alejandra. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Repiso, Luciana. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Mir, Guillermo. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Brizuela, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Herrera, Fernanda. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Períes, Lucas. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Romo, Claudia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Gordillo, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Andrade, Elena Beatriz. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; Argentin