Excitabilidad intrínseca y su plasticidad en el hipocampo de rata

Durante las primeras semanas del desarrollo postnatal se producen cambios en las propiedades electrofisiológicas y morfológicas (Pokorny & Yamamoto 1981a; Pokorny & Yamamoto 1981b; Schwartzkroin & Kunkel 1982; Liao et al. 1999), así como en la conectividad sináptica (Hsia et al. 1998; Groc et al. 2003) de las neuronas piramidales de CA1. Además, aumenta el comportamiento exploratorio que depende de la actividad hipocampal en las ratas (Langston et al. 2010). La propagación de la información dentro de un circuito neuronal como el hipocampal, depende de la conectividad sináptica dentro del circuito y de las propiedades intrínsecas de cada neurona. Cambios en la actividad del circuito pueden provocar plasticidades en: la eficacia sináptica, la integración de la señal de entrada y la generación de una señal de salida (Daoudal & Debanne 2003; Debanne et al. 2003; Remy et al. 2010). Diversos estudios han demostrado la existencia de plasticidades de la excitabilidad intrínseca en respuesta a variaciones de la actividad previa (Fan et al. 2005; O’Leary et al. 2010; Cudmore et al. 2010; Campanac et al. 2013). El calcio es un ion fundamental en el mantenimiento de la excitabilidad neuronal. La disminución de su concentración extracelular se relaciona con crisis epilépticas (Heinemann et al. 1977) y con un comportamiento epileptiforme en estudios in vitro (Bikson et al. 2002; Isaev et al. 2012; Aivar et al. 2014). Además, el calcio está implicado en gran parte de las plasticidades sinápticas e intrínsecas descritas (Katz & Miledi 1968; Lynch et al. 1983; Zucker & Regehr 2002; Fan et al. 2005; Grubb & Burrone 2010)..

Propuesta constructivista para la enseñanza del campo eléctrico

Se presenta una propuesta didáctica para enseñar el concepto de campo eléctrico en ingeniería. Se sigue un planteamiento teórico basado en el enfoque constructivista partiendo de los conocimientos previos de los alumnos, identificados mediante un diagnóstico inicial y un mapa cognitivo, y se propone emplear una serie de experimentos sencillos de fenómenos eléctricos para que ellos reflexionen sobre las interacciones observadas. Con la propuesta también se aspira a que los estudiantes den una explicación del porqué de los fenómenos a través de preguntas dirigidas que inducen a considerar la posibilidad de incluir conceptos científicos en sus explicaciones. Lo anterior permitirá que los estudiantes adquieran un aprendizaje significativo de los conceptos estudiados, haciéndolos propios e integrándolos a sus conocimientos existentes

Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer

Background: Wnt factors control cell differentiation through semi-independent molecular cascades known as the beta-catenin-dependent (canonical) and -independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood. Results: Here we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2), a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring ROR2 promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic. Conclusions: Our data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour

Proyecto FIDO: La Educación STEAM en las aulas del Grado de Educación Primaria. (ESTeam)

Este proyecto persigue el objetivo principal de introducir la educación STEAM en el alumnado de Educación Primaria. La educación STEAM supone un enfoque en el cual se trabajan conjuntamente Ciencias, Tecnología, Ingeniería, Arte y Matemáticas. Los trabajos del futuro cada vez están más unidos a la tecnología. Además, tienen una visión holística donde las distintas disciplinas tienen un aporte que encaja como un engranaje. La metodología usada en este proyecto es el Aprendizaje Basado en Proyectos (ABP) (Barrows, 1986). En este tipo de aprendizaje el alumno tiene un rol activo y el docente lo guía. Además, en el proyecto inicial se propuso conformar un “MakerSpace”. En este sentido, hay que indicar que nos tuvimos que adaptar a las condiciones impuestas con la pandemia del COVID-19 y procedimos como explicaremos a continuación. Este proyecto implementó en la asignatura de Ciencias Experimentales y su Transversalidad (CET en adelante). Se dedicaron varios seminarios al desarrollo de las actividades propuestas. Cuando se hizo la propuesta del proyecto, no se conocía cómo iba a ser la actividad docente debido a la situación sanitaria derivada del Covid-19, así que se pensó en presencial. Como esto no fue posible, el desarrollo de la primera actividad introductoria fue la siguiente: El profesor Rafael Gómez desarrolló una actividad (Escapada del planeta Gorogoa, reconstruyendo nuestro robot Joan Carlo, (ANEXO Ia y Ib donde se adjuntan guión y vídeos) donde el alumnado tenía que usar un robot tipo Mbot para desarrollar la actividad. El alumnado entregó un pequeño informe donde mostraba cómo había desarrollado esta tarea. Además, se invitaron a dos profesores que dieron dos charlas por videoconferencia. La primera conferencia llamada “El enfoque educativo STEM: un gran desconocido en boca de todos” (presentación en ANEXO IIa) la realizó el profesor experto en STEAM David Aguilera Morales, coautor, junto con F. Javier Perales Palacios, del artículo “Ciencia-Tecnología-Sociedad vs. STEM: ¿evolución, revolución o disyunción? “ (Perales Palacios y Aguilera, 2020). En esta charla el alumnado pudo conocer qué es STEAM e interactuar con el conferenciante. La segunda charla impartida fue “Docencia en STEAMs: Mi experiencia como ingeniera y profesora de ingeniería”, por la profesora de la Escuela de Informática y Telecomunicaciones de la Universidad de Granada Luz García Martínez (Presentación en ANEXO IIb). La segunda actividad que tuvieron que realizar los alumnos fue la elaboración de un proyecto con enfoque STEAM. Para ello se les dieron unas directrices (se adjunta guion en ANEXO III) y se les ofrecieron dos tipos de kits de robótica educativa: Makey Makey y Microbit. (Inicialmente en el presupuesto se incluía una partida para conferenciantes invitados y pósteres. Al pasar la docencia a virtual, este dinero se gastó en más material, para que el alumnado se lo pudiera llevar a casa y pudieran trabajar en grupos más pequeños, intentando así facilitar el trabajo online del alumnado). Como producto, cada grupo entregó un informe de su proyecto e hizo una presentación virtual del mismo. This project pursues the main objective of introducing STEAM education in Primary Education students. STEAM education is an approach in which Science, Technology, Engineering, Art and Mathematics work together. The jobs of the future are increasingly linked to technology. In addition, they have a holistic vision where the different disciplines have a contribution that fits like a gear. The methodology used in this project is Project Based Learning (PBL) (Barrows, 1986). In this type of learning the student has an active role and the teacher guides him/her. In addition, in the initial project it was proposed to create a “MakerSpace”. In this sense, it should be noted that we had to adapt to the conditions imposed with the COVID-19 pandemic and we proceeded as we will explain below. This project was implemented in the subject of Experimental Sciences and its Transversality (CET). Several seminars were devoted to the development of the proposed activities. When the project proposal was made, it was not known what the teaching activity was going to be like, so it was thought in person. As this was not possible, the development of the first introductory activity was as follows: Professor Rafael Gómez developed an activity (Getaway from the planet Gorogoa, rebuilding our Joan Carlo robot, (ANNEX Ia and Ib where script and videos are attached) where the students had to use an Mbot-type robot to develop the activity. The students gave a small report showing how they had developed this task. In addition, two teachers were invited to give two talks by videoconference. The first conference called "The STEM educational approach: a great unknown on everyone's lips" (presentation in ANNEX IIa) was held the expert professor in STEAM David Aguilera Morales, co-author, together with F. Javier Perales Palacios, of the article “Science-Technology-Society vs. STEM: evolution, revolution or disjunction?” (Perales Palacios and Aguilera, 2020). The second talk given was "Teaching in STEAMs: My experience as an engineer and engineering teacher", by the Professor at the School of Informatics and Telecommunications of the University of Granada Luz García Martínez (Presentation in ANNEX IIb). The second activity, that the students had to carry out, was the elaboration of a project with a STEAM approach. For this, they were given guidelines (script is attached in ANNEX III) and two types of educational robotics kits were offered: Makey Makey and Microbit. (Initially, the budget included an item for invited speakers and posters. When teaching went virtual, this money was spent on more material, so that students could take it home and they could work in smaller groups, thus trying to facilitate students' online work). As a product, each group delivered a report on their project and made a virtual presentation of it.Universidad de Granad

Synthesis, characterization, and antibacterial activities of a heteroscorpionate derivative platinum complex against methicillin-resistant Staphylococcus aureus

Staphylococcus aureus is one of the species with the greatest clinical importance and greatest impact on public health. In fact, methicillin-resistant S. aureus (MRSA) is considered a pandemic pathogen, being essential to develop effective medicines and combat its rapid spread. This study aimed to foster the translation of clinical research outcomes based on metallodrugs into clinical practice for the treatment of MRSA. Bearing in mind the promising anti-Gram-positive effect of the heteroscorpionate ligand 1,1’-(2-(4-isopropylphenyl)ethane-1,1-diyl)bis(3,5-dimethyl-1H-pyrazole) (2P), we propose the coordination of this compound to platinum as a clinical strategy with the ultimate aim of overcoming resistance in the treatment of MRSA. Therefore, the novel metallodrug 2P-Pt were synthetized, fully characterized and its antibacterial effect against the planktonic and biofilm state of S. aureus evaluated. In this sense, three different strains of S. aureus were studied, one collection strain of S. aureus sensitive to methicillin and two clinical MRSA strains. To appraise the antibacterial activity, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) were determined. Moreover, successful outcomes on the development of biofilm in a wound-like medium were obtained. The mechanism of action for 2P-Pt was proposed by measuring the MIC and MBC with EDTA (cation mediated mechanism) and DMSO (exogenous oxidative stress mechanism). Moreover, to shed light on the plausible antistaphylococcal mechanism of this novel platinum agent, additional experiments using transmission electron microscopy were carried out. 2P-Pt inhibited the growth and eradicated the three strains evaluated in the planktonic state. Another point worth stressing is the inhibition in the growth of MRSA biofilm even in a wounded medium. The results of this work support this novel agent as a promising therapeutic alternative for preventing infections caused by MRSA

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

La enseñanza en el máster de abogacía a través del análisis de casos reales de carácter multidisciplinar. Aprendizaje "a partir del estudio de razonamientos parciales temáticos"

Generar blog para publicaciones de alumnos del Máster Abogacía, con "entradas" dirigidas. Habría análisis desde varias disciplinas añadiéndose estudios con enfoque basado en otras áreas de conocimiento, generando interdisciplinariedad

Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival.

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long-term follow-up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32-44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18-26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow-up of 4.5 years, 91 deaths accounted for 4.21 higher-than-expected mortality in the age-matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance-either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six-month changes in the composite clinical score and in the 6-minute walk test distance were related to survival. Conclusions Persistent valvular heart disease-pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.This study was funded by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain, the European Union–European Regional Development Fund (EC07/90772 and PI19/00649), and the Consorcio de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV).S

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

[EN]Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the Red Temática de Investigación Cooperativa en Cáncer (RTICC); grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain