Connexin-36 protects against suddent infant death syndrome

The sudden infant death syndrome (SIDS) is the main cause of postneonatal infant death; however the etiology of SIDS remains ill defined. The hypothesis that SIDS, or a subset of SIDS, is due to an abnormal brainstem mechanism is one of the current leading hypotheses on SIDS etiology. The brainstem is essential for cardiac and respiratory function, controlling autonomic and homeostatic responses including breathing, central chemosensitivity, heartbeat and blood pressure, all mechanisms that are thought to be involved in SIDS. Connexin-36 (Cx36), the principal component of neuron-to-neuron channels that form the electrical synapses, is present in the specific neural populations of brainstem region involved in the CO2 chemoreception and respiratory control, and its expression is unregulated during this critical period of life. Accordingly, we postulate that Cx36 would be a key element in the pathogenesis of SIDS. To address this issue we have studied how the genetic suppression of Cx36 expression affects to the respiratory pacemaker, central chemoreflexes, cardiorespiratory coupling, and risk for SIDS. Mice lacking Cx36 at postnatal day 14 showed in comparison with control wild-type greater variability in the respiratory rhythmicity, abnormally enhanced ventilatory responses to hypoxia and hypercapnia, more cardiorespiratory phase synchronization and less respiratory sinus arrhythmia. A combination of low O2 and high CO2 content in inspired air was used as exogenous stressor of SIDS; under these conditions all wild-type mice survived while the 40% of Cx36-knockout animals succumbed by respiratory failure

Myelinating oligodendrocytes generated by direct cell reprogramming from adult rat adipose tissue

Obtaining oligodendroglial cells from dispensable tissues would be of great interest for autologous or immunocompatible cell replacement in demyelinating diseases as well as for studying myelin pathologies. Recently, two laboratories have simultaneously reported that mouse fibroblasts could be converted into oligodendroglial cells by direct reprogramming with transcription factors involved in oligodendrocyte development (Najm et al., Nat. Biotechnol. 31:426, 2013, Yang et al., Nat. Biotechnol. 31:434, 2013). We have lentivirally transfected combinations of tetracycline-inducible sox10 (S), olig2 (O), zfp536 (Z) and/or nkx6.1 (N) transgenes in adult rat adipose tissue-derived stromal cells (ADSCs) and checked for the generation of functional oligodendrocytes. Immunostaining with the O4 monoclonal, which binds to oligodendrocyte progenitor cell membranes, was used as initial marker of oligodendroglial reprogramming. The first signs of ADSC conversion into oligodendrocytic cells were observed with the S-O-Z combination by 6 weeks and the O4+ cell population kept rising the following months, eventually constituting more than 50% of cells. Increasing numbers of O1 (galactocerebroside), p75 (low-affinity NGF receptor), and GFAP-positive cells appeared in that period. Cells expressed also myelin-associated proteins like MBP, MAG, MOG and PLP1/DM20. Transduction with the S-O-N-Z transgene combination also produced oligodendrocyte progenitors but did not improve the result; S-O-N, O-Z or O transductions did not consistently produce oligodendrocytes in our hands. After 3 months of continuous expansion, the reprogrammed cells became independent of transgene activation by doxycycline. Antibiotic selection of transduced cells (with zeocin) did not show to be more efficient for reprogrammed cell purity and proliferation than unselected cultures. Different pre-induction treatments were tried in an attempt to improve the efficiency or speed of reprogramming: of these, treatment with Repsox followed by retinoic acid or adipocytic pre-differentiation, appeared to increase reprogramming consistency or to slightly accelerate the process. When seeded onto rat dorsal root ganglion neurons, transdifferentiated cells were observed to cover lengths of one or several axons with typical myelin-like appearance. We propose that functional oligodendrocytes can be efficiently generated from adult mesenchymal cells in the rat by direct cell reprogramming

A model based on the combination of ifn-γ, ip-10, ferritin and 25-hydroxyvitamin d for discriminating latent from active tuberculosis in children

Altres ajuts: This work was supported by grants from: (i) the Isolana Foundation, (ii) the Maria Francisca de Roviralta Foundation expedient AT/MA 1-19/07/2017, AT/MA 70-27/04/2016, and AT/MA 3-22/10/2014 and (vi) Fundació Recerca i Docència Mútua Terrassa.In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Toxocara canis Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91-1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children

Social-ecological, motivational and volitional factors for initiating and maintaining physical activity in the context of HIV

Sport and exercise can have several health benefits for people living with HIV. These benefits can be achieved through different types of physical activity, adapting to disease progression, motivation and social-ecological options. However, physical activity levels and adherence to exercise are generally low in people living with HIV. At the same time, high drop-out rates in intervention studies are prevalent; even though they often entail more favourable conditions than interventions in the natural settings. Thus, in the framework of an intervention study, the present study aims to explore social-ecological, motivational and volitional correlates of South African women living with HIV with regard to physical activity and participation in a sport and exercise health promotion programme. The qualitative data was produced in the framework of a non-randomised pre-post intervention study that evaluated structure, processes and outcomes of a 10-week sport and exercise programme. All 25 participants of the programme were included in this analysis, independent of compliance. Data was produced through questionnaires, participatory group discussions, body image pictures, research diaries and individual semi-structured interviews. All participants lived in a low socioeconomic, disadvantaged setting. Hence, the psychological correlates are contextualised and social-ecological influences on perception and behaviour are discussed. The results show the importance of considering social-cultural and environmental influences on individual motives, perceptions and expectancies, the fear of disclosure and stigmatisation, sport and exercise-specific group dynamics and self-supporting processes. Opportunities and strategies to augment physical activity and participation in sport and exercise programmes in the context of HIV are discussed.Scopu

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

Información científica compleja y comprensibilidad del lenguaje

Probar que el lenguaje usado en la transmisión de conocimientos puede resultar incomprensible o dificultoso por: exceso de conceptos, utilización de un léxico hiperculto. Inadecuación de los programas, defectos metodológicos, clarificar y cuantificar los problemas planteados por la utilización del lenguaje conceptual en las explicaciones de los programas de tipo académico. Dos grupos de cada uno de los niveles del BUP, constituyendo un total de 200 sujetos para el cuestionario de evaluación conceptual y de 128 alumnos para el índice léxicocultural. Las variables medidas en esta investigación fueron: Identificación de conceptos. Aplicación inmediata de conceptos. Aplicación de conceptos, para la que se requiere una reflexión previa. Relación entre conceptos. Asociación de varios conceptos a uno genérico con el que guardan algún tipo de relación, etc. Cuestionarios de evaluación conceptual: con contenidos centrados en las áreas de Ciencias Naturales, Física y Química, Historia y Lengua. Indice léxicocultural de Secadas: en él se trata de asociar a una serie de términos dados, grupos de cuatro términos que el alumno puede elegir entre un conjunto de ellos desordenados que se le ofrecen. Los resultados se analizan utilizando frecuencias y porcentajes para describir el número de aciertos y errores de cada pregunta. Y representaciones gráficas como diagramas de barras. Los errores más frecuentes detectados en el área de Lengua son: el desconocimiento del léxico utilizado, lectura superficial del enunciado, uso de enunciados ambiguos. En Ciencias Naturales se manifiesta un escaso conocimiento del lenguaje y una gran inmediatez de las respuestas. Existe una gran dificultad para el alumno en la incorporación de los conocimientos adquiridos mediante el estudio a sus circuitos habituales de razonamiento. La progresión en el nivel de estudios no implica una mayor flexibilidad en la capacidad de respuesta. En el índice sociocultural el mayor número de aciertos recae sobre seres o acciones fuertemente conectados con la vida diaria. Los sustantivos abstractos de contenido moral siguen en la línea de aciertos. Los sustantivos abstractos de contenido social y académico tienen porcentajes inferiores. El menor grado de comprensión afecta a los términos técnicos afines al mundo artesanal, agrícola y comercial. Esta investigación se considera abierta aún, pues en ella no se han llegado a aplicar todos los instrumentos que se habían previsto: test etimológicos, formación de frases coherentes predeterminadas, localización en el texto de errores conceptuales, test de fluidez verbal y actitudes verbales primarias, análisis de léxico de los textos y las clases, análisis de la metodología docente habitual, estudio estructural de programas.AsturiasES