Inhibition of PMCA activity by tau as a function of aging and Alzheimer's neuropathology

© 2015 Elsevier B.V.. Ca2+-ATPases are plasma membrane and intracellular membrane transporters that use the energy of ATP hydrolysis to pump cytosolic Ca2+ out of the cell (PMCA) or into internal stores. These pumps are the main high-affinity Ca2+ systems involved in the maintenance of intracellular free Ca2+ at the properly low level in eukaryotic cells. The failure of neurons to keep optimal intracellular Ca2+ concentrations is a common feature of neurodegeneration by aging and aging-linked neuropathologies, such as Alzheimer's disease (AD). This disease is characterized by the accumulation of β-amyloid senile plaques and neurofibrillary tangles of tau, a protein that plays a key role in axonal transport. Here we show a novel inhibition of PMCA activity by tau which is concentration-dependent. The extent of inhibition significantly decreases with aging in mice and control human brain membranes, but inhibition profiles were similar in AD-affected brain membrane preparations, independently of age. No significant changes in PMCA expression and localization with aging or neuropathology were found. These results point out a link between Ca2+-transporters, aging and neurodegeneration mediated by tau protein.Ministerio de Economía y Competitividad and Fundación Marcelino Botín (to A.M.M.); Junta de Extremadura and FEDERPeer Reviewe

Affective domain and multiple intelligences among pre-service teachers of University of Extremadura

En este estudio se realiza un análisis descriptivo e inferencial de las emociones experimentadas por una muestra de maestros en formación hacia la enseñanza de las ciencias, la identificación de su estilo de aprendizaje según la teoría de las inteligencias múltiples de Gardner (2011), el estudio de la percepción de autoeficacia hacia los distintos contenidos científicos y el establecimiento de correlaciones entre las variables. Los resultados obtenidos muestran que los maestros en formación sienten mayor rechazo hacia la física y química que hacia la biología y geología y que es posible establecer diferencias en las emociones hacia las ciencias según sus estudios de procedencia. Con respecto a la autoeficacia, se encuentran correlaciones entre sentir emociones positivas hacia la ciencia y tener una mayor autoeficacia frente a la enseñanza de los contenidos. También entre poseer determinados estilos de inteligencia, emociones y autoeficacia.This study presents a descriptive and inferential analysis of pre-service teachers’ emotions towards teaching science, their learning styles (based on Gardner’s theory of multiple intelligences), their perception of self-efficacy concerning the scientific content they will have to teach, and the correlations between these variables. The results showed a greater feeling of rejection towards Physics and Chemistry than towards Biology and Geology, and a link between participants’ emotional responses to science and their pre-university studies. Correlations were found between positive emotions towards science and greater self-efficacy in teaching scientific topics, and between certain types of intelligences, emotions and self-efficacy

Aprendizaje sobre las aves mediante el uso de una incubadora de huevos en un aula de Primaria

En este trabajo se presenta una experiencia didáctica para los primeros cursos de la Educación Primaria, con el objetivo de aprender, de forma activa y participativa, sobre las aves domésticas, especialmente la gallina. El eje central es una actividad de incubación de huevos de gallina en el aula, para seguir el desarrollo embrionario durante 21 días. Este eje se apoya, a su vez, en una serie de actividades participativas que giran en torno al desarrollo embrionario, y el conocimiento de los animales vertebrados, especialmente las aves, a través del ejemplo de la gallina. De esta forma se consigue un aprendizaje significativo mediante la observación y la indagación por parte de los alumnos

Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction

Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been associated with age-related cellular damage and dysfunction with reports of increased levels of apoptosis, necrosis, and inflammation in the aged kidney. Bioactive sphingolipids have been shown to regulate these same cellular processes, and have also been suggested to play a role in aging and cellular senescence.We hypothesized that alterations in kidney sphingolipids play a role in the declining kidney function that occurs during aging. To begin to address this, the sphingolipid profile was measured in young (3 mo), middle aged (9 mo) and old (17 mo) C57BL/6 male mice. Interestingly, while modest changes in ceramides and sphingoid bases were evident in kidneys from older mice, the most dramatic elevations were seen in long-chain hexosylceramides (HexCer) and lactosylceramides (LacCer), with C14- and C16-lactosylceramides elevated as much as 8 and 12-fold, respectively. Increases in long-chain LacCers during aging are not exclusive to the kidney, as they also occur in the liver and brain. Importantly, caloric restriction, previously shown to prevent the declining kidney function seen in aging, inhibits accumulation of long-chain HexCer/LacCers and prevents the age-associated elevation of enzymes involved in their synthesis. Additionally, long-chain LacCers are also significantly elevated in human fibroblasts isolated from elderly individuals.This study demonstrates accumulation of the glycosphingolipids HexCer and LacCer in several different organs in rodents and humans during aging. In addition, data demonstrate that HexCer and LacCer metabolism is regulated by caloric restriction. Taken together, data suggest that HexCer/LacCers are important mediators of cellular processes fundamental to mammalian aging

Microbes, good or bad?: “Microorganisms in our lifes” board game

El eje central de la propuesta didáctica descrita en esta contribución es el abordaje educativo de la pregunta: ¿los microbios son buenos o malos? Los escolares de todos los niveles sufren un bombardeo constante familiar, social y, especialmente, mediático sobre los peligros de los microbios y la necesidad de eliminarlos. Esto genera una biofobia hacia los microbios sobredimensionada, que no se contrarresta con los exiguos contenidos de microbiología de los currículos educativos. Dada esta situación, es necesario desarrollar nuevos materiales educativos innovadores para la enseñanza de los microorganismos y su relación (tanto positiva como negativa) con los seres humanos. En esta contribución se describe un juego de mesa didáctico sobre microbiología, que aborda, además de los virus, diferentes tipos de microorganismos, tanto beneficiosos como perjudiciales y oportunistas, así como sus características y su relación con el ser humano. Esta relación se aborda a través de una serie de eventos que comprenden vacunas, antibióticos, sexo, higiene, alimentación, medio ambiente, biotecnología, etc. Se trata de un recurso educativo versátil, fácilmente adaptable a distintos niveles de enseñanza, con el que es posible abordar los microorganismos desde la Educación Primaria hasta la Educación Superior, incluyendo dentro de esta la formación inicial del profesorado.The central axis of the didactic proposal described in this contribution is the educational approach to the question: are microbes good or bad? Schoolchildren of all levels suffer a constant family, social and, especially media, bombardment about the dangers of microbes and the need to eliminate them. This generates an oversized biophobia towards microbes, which is not counteracted by the meager content of microbiology in educational curricula. Given this situation, it is necessary to develop new innovative educational materials for the teaching of microorganisms and their relationship (both positive and negative) with human beings. This contribution describes a didactic board game on microbiology, which addresses, in addition to viruses, different types of microorganisms, both beneficial and harmful, and opportunistic, as well as their characteristics and their relationship with humans. This relationship is addressed through a series of events that include vaccines, antibiotics, sex, hygiene, food, environment, biotechnology, etc. It is a versatile educational resource, easily adaptable to different levels of education, with which it is possible to approach microorganisms from Primary Education to Higher Education, including initial teacher training

Estudio de los edificios religiosos y objetos de culto de la ciudad de Sevilla saqueados y destruídos por los marxistas

Localització de l'original : Fundació AmatllerForma part del projecte: Biblioteca Digital d'Història de l'Art Hispànic (UAB)Monografia sobre el saqueig d'edificis religiosos a Sevilla durant la guerra civil.Monografía sobre el saqueo de edificios religiosos en Sevilla durante la guerra civil.Monography on destrucion and pillaging of religious buildings in Seville during the Civil War

Microbes, good or bad? : “Microorganisms in our lifes” board game

[ES] El eje central de la propuesta didáctica descrita en esta contribución es el abordaje educativo de la pregunta: ¿los microbios son buenos o malos? Los escolares de todos los niveles sufren un bombardeo constante familiar, social y, especialmente, mediático sobre los peligros de los microbios y la necesidad de eliminarlos. Esto genera una biofobia hacia los microbios sobredimensionada, que no se contrarresta con los exiguos contenidos de microbiología de los currículos educativos. Dada esta situación, es necesario desarrollar nuevos materiales educativos innovadores para la enseñanza de los microorganismos y su relación (tanto positiva como negativa) con los seres humanos. En esta contribución se describe un juego de mesa didáctico sobre microbiología, que aborda, además de los virus, diferentes tipos de microorganismos, tanto beneficiosos como perjudiciales y oportunistas, así como sus características y su relación con el ser humano. Esta relación se aborda a través de una serie de eventos que comprenden vacunas, antibióticos, sexo, higiene, alimentación, medio ambiente, biotecnología, etc. Se trata de un recurso educativo versátil, fácilmente adaptable a distintos niveles de enseñanza, con el que es posible abordar los microorganismos desde la Educación Primaria hasta la Educación Superior, incluyendo dentro de esta la formación inicial del profesorado.[EN] The central axis of the didactic proposal described in this contribution is the educational approach to the question: are microbes good or bad? Schoolchildren of all levels suffer a constant family, social and, especially media, bombardment about the dangers of microbes and the need to eliminate them. This generates an oversized biophobia towards microbes, which is not counteracted by the meager content of microbiology in educational curricula. Given this situation, it is necessary to develop new innovative educational materials for the teaching of microorganisms and their relationship (both positive and negative) with human beings. This contribution describes a didactic board game on microbiology, which addresses, in addition to viruses, different types of microorganisms, both beneficial and harmful, and opportunistic, as well as their characteristics and their relationship with humans. This relationship is addressed through a series of events that include vaccines, antibiotics, sex, hygiene, food, environment, biotechnology, etc. It is a versatile educational resource, easily adaptable to different levels of education, with which it is possible to approach microorganisms from Primary Education to Higher Education, including initial teacher training

Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish

Sight depends on the tight cooperation between photoreceptors and pigmented cells, which derive from common progenitors through the bifurcation of a single gene regulatory network into the neural retina (NR) and retinal-pigmented epithelium (RPE) programs. Although genetic studies have identified upstream nodes controlling these networks, their regulatory logic remains poorly investigated. Here, we characterize transcriptome dynamics and chromatin accessibility in segregating NR/RPE populations in zebrafish. We analyze cis-regulatory modules and enriched transcription factor motives to show extensive network redundancy and context-dependent activity. We identify downstream targets, highlighting an early recruitment of desmosomal genes in the flattening RPE and revealing Tead factors as upstream regulators. We investigate the RPE specification network dynamics to uncover an unexpected sequence of transcription factors recruitment, which is conserved in humans. This systematic interrogation of the NR/RPE bifurcation should improve both genetic counseling for eye disorders and hiPSCs-to-RPE differentiation protocols for cell-replacement therapies in degenerative diseases.This work is supported by the following grants: (I) To J.-R.M.-M.: From the Spanish Ministry of Science, Innovation, and Universities (MICINN): BFU2017-86339P with FEDER funds, MDM-2016-0687 and PY20_00006/Junta de Andalucía. (II) To O.B. Australian Research Council (ARC) Discovery Project (DP190103852). (III) To F.-J.D.-C.: Andalusian Ministry of Health, Equality and Social Policies (PI-0099-2018). (IV) To P.B.: BFU2016-75412-R with FEDER funds; PCIN-2015-176-C02-01/ERA-Net Neuron ImprovVision, and a CBMSO Institutional grant from the Fundación Ramón Areces. (V) To both J.-R.M.-M. and P.B.: BFU2016-81887-REDT, as well as Fundación Ramón Areces-2016 (Supporting L.B.)

Involvement of stanniocalcins in the deregulation of glycaemia in obese mice and type 2 diabetic patients

Las estanniocalcinas se expresan en el tejido del páncreas, y se sugirió una correlación directa entre la insulina circulante y las concentraciones de STC2 en el ser humano. Aquí, mostramos una correlación significativa entre STC1 y tanto la glucemia como la hemoglobina glicosilada entre los pacientes con DM2, mientras que los pacientes con DM2 que presentan los mayores valores de hemoglobina glicosilada exhibieron la menor expresión de STC2. Sin embargo, el tratamiento de los pacientes con fármacos antiglicémicos no modifica significativamente la expresión de ambas STC. Por otra parte, los ratones STC2-/- que mostraron sobrepeso neonatal y adulto presentaron además una glucemia desregulada cuando fueron alimentados con una dieta hipercalórica (pellet de cría, BP). Esta alteración es más evidente en las primeras etapas de la vida animal. La glucemia desregulada en estos ratones se confirmó mediante una prueba oral de glucosa. Además, los ratones STC2-/- presentan un aumento del tamaño del páncreas; así, el análisis histológico revela que los ratones WT responden a la dieta BP aumentando el tamaño de los islotes pancreáticos a través de la inducción de la división celular, y los ratones STC2-/- carecen de este mecanismo compensatorio. Contrariamente, los ratones alimentados con STC2-/- muestran un mayor número de islotes pero de tamaño similar a los alimentados con el pellet regular. El análisis histopatológico demuestra la alteración de la estructura de los tejidos y las infiltraciones de eritrocitos en los ratones STC2-/-, posiblemente debido al estrés evocado por la dieta BP. Por último, se observó una mayor inmunotinción de glucagón en el islote de los ratones STC2-/-, y el ensayo ELISA de glucagón confirmó el aumento del glucagón circulante. En resumen, presentamos pruebas del papel de los STC, principalmente el STC2, como posible marcador temprano durante el desarrollo de la diabetes mellitus.Stanniocalcins are expressed in the pancreas tissue, and it was suggested a direct correlation between circulating insulin and STC2 concentrations in human. Here, we show a significant correlation between STC1 and both glycaemia and glycosylated haemoglobin among DM2 patients, while DM2 patients who present the greatest glycosylated haemoglobin values exhibited the lowest STC2 expression. However, treatment of patients with antiglycaemic drugs does not significantly modify the expression of both STCs. On the other hand, STC2-/- mice that exhibited neonatal and adult overweight further presented deregulated glycaemia when they were feed with a hypercaloric diet (breeding pellet, BP). This alteration is more evident at the early stages of the animal life. Deregulated glycaemia in these mice was confirmed using glucose oral test. In addition, STC2-/- mice present enhanced pancreas size; thus, the histological analysis reveals that WT mice respond to BP diet by increasing the size of the pancreatic islets through inducing cell division, and STC2-/- mice lack this compensatory mechanism. Contrary, BP fed STC2-/- mice show enhanced number of islets but of similar size than those fed with regular pellet. Histopathological analysis demonstrates tissue structure disruption and erythrocytes infiltrations in STC2-/- mice, possibly due to the stress evoked by the BP diet. Finally, enhanced glucagon immunostaining was observed in the islet of STC2-/- mice, and the glucagon ELISA assay confirmed the increase in the circulating glucagon. Summarizing, we present evidence of the role of STCs, mainly STC2, as a possible early marker during development of diabetes mellitus.• Ministerio de Economía y Competitividad. Becas 2013‐45564C2‐1‐P, BFU‐2016‐74932‐C2‐1‐P • Programa Juan de la Cierva. Becas IJCI‐2015‐25665, JC‐2012‐ 2934 • Junta de Extremadura. Beca PRIIB16046peerReviewe

Post-Hospital Syndrome and Hyponatremia

Introduction: Post-hospital syndrome (PHS) is defined as a period of vulnerability during the first 30 days after a patient is discharged from hospital, in which multiple factors come into play. Hyponatremia is the most frequent hydroelectrolytic disorder in hospitalized patients and may be related to the appearance of PHS. Objective: The objective is to estimate the prevalence of PHS that is assessed as the rate of readmissions in the first 30 days after discharge, in patients with hyponatremia. Material and Methods: It is a descriptive observational study of patients with hyponatremia who were discharged from 1 September 2010 to 2 February 2020 at the Internal Medicine Service of the Hospital University of San Juan (Alicante, Spain). Results: Of the 25 included patients, 5 (20%) were readmitted within a month of discharge, after a mean of 11.4 days (standard deviation [SD] 5.1). The overall mortality of the study was 20% (n = 5), with one case of death in the first 30 days post-hospitalization (4%). In 12 patients (48%) the origin of the hyponatremia was undetermined. The most frequently recorded etiology for the condition was pharmacological (n = 7, 28%), and there was pronounced variability in its clinical and laboratory study. The most widely used corrective measure was drug withdrawal, in 16 patients (64%). Water intake restriction was the most common treatment after discharge (5 patients, 20%), followed by urea (2 patients, 8%), while tolvaptan was not used. Conclusion: Hyponatremia may be the cause of PHS, which could increase the rate of early readmission. Hyponatremia is an underdiagnosed and undertreated entity, so it is necessary to apply an appropriate system to optimize its management and, in future studies, to assess its impact on PHS