Daily Rhythm of Melanopsin-Expressing Cells in the Mouse Retina

In addition to some other functions, melanopsin-expressing retinal ganglion cells (RGCs) constitute the principal mediators of the circadian photoentrainment, a process by which the suprachiasmatic nucleus (the central clock of mammals), adjusts daily to the external day/night cycle. In the present study these RGCs were immunohistochemically labelled using a specific polyclonal antiserum raised against mouse melanopsin. A daily oscillation in the number of immunostained cells was detected in mice kept under a light / dark (LD) cycle. One hour before the lights were on (i.e., the end of the night period) the highest number of immunopositive cells was detected while the lowest was seen 4 h later (i.e., within the first hours of the light period). This finding suggests that some of the melanopsin-expressing RGCs “turn on” and “off” during the day/night cycle. We have also detected that these daily variations already occur in the early postnatal development, when the rod/cone photoreceptor system is not yet functional. Two main melanopsin-expressing cell subpopulations could be found within the retina: M1 cells showed robust dendritic arborization within the OFF sublamina of the inner plexiform layer (IPL), whilst M2 cells had fine dendritic processes within the ON sublamina of the IPL. These two cell subpopulations also showed different daily oscillations throughout the LD cycle. In order to find out whether or not the melanopsin rhythm was endogenous, other mice were maintained in constant darkness for 6 days. Under these conditions, no defined rhythm was detected, which suggests that the daily oscillation detected either is light-dependent or is gradually lost under constant conditions. This is the first study to analyze immunohistochemically the daily oscillation of the number of melanopsin-expressing cells in the mouse retina

El mejillón invasor: una actividad didáctica lúdica dentro del marco “ciencia para todos/as”

La versión preprint es subida al repositorio el 20/12/2018, tras la finalización del congreso.III Congreso Virtual Internacional de Educación, Innovación y TIC, EDUNOVATIC2018, 17 a 19 de diciembre de 2018, Madrid (España)En este trabajo se presentan los resultados de una actividad práctica de naturaleza lúdica realizada con alumnado de educación secundaria (4º Educación Secundaria Obligatoria y 1º y 2º Bachillerato), destinada a favorecer la alfabetización científica y a ayudar a crear ciudadanos y ciudadanas responsables y que puedan tomar decisiones fundamentadas sobre diferentes problemáticas medioambientales actuales. En concreto, esta experiencia se centró en el aprendizaje del problema medioambiental y social causado por la proliferación de especies invasoras a escala global. Para ello se ha diseñado una actividad siguiendo los principios del Aprendizaje Basado en Problemas para cuya resolución debían responder a preguntas de niveles cognitivos superiores desempeñando el papel de un gestor de infraestructura afectada. Aunque todos los grupos alcanzaron un alto grado de comprensión de la problemática que entrañan las especies invasoras tras realizar la actividad, el nivel de adecuación / precisión / reflexión de respuesta varió para cada una de las preguntas planteadas, siendo distinto también entre cursos

Propuesta de utilización del role-playing como medio de evaluación en el Grado en Biología

Las nuevas técnicas de enseñanza introducen estrategias en las que el alumnado adquiere más protagonismo, desarrollando su propio aprendizaje bajo la tutela del docente. Una de estas herramientas es el juego de roles, o role-playing, en el que los alumnos interpretan el papel de personajes, combinando nuevos conocimientos con los previamente adquiridos. Numerosos estudios avalan esta herramienta, cuyos beneficios para el alumnado son entre otras cosas el desarrollo del pensamiento crítico, de la capacidad analítica, argumentativa y reflexiva, así como el fomento de las competencias de comunicación oral. En el presente trabajo se propone la utilización de un juego de rol en las Jornadas de Puertas Abiertas de la Universidad de Oviedo, en el que participarán alumnos/as de la asignatura de Zoología del Grado en Biología. Dicha actividad sería considerada como actividad práctica y evaluable de la asignatura

Deficiency in p53 is required for doxorubicin induced transcriptional activation of NF-кB target genes in human breast cancer

NF-кB has been linked to doxorubicin resistance in breast cancer patients. NF- кB nuclear translocation and DNA binding in doxorubicin treated-breast cancer cells have been extensively examined; however its functional relevance at transcriptional level on NF-кB -dependent genes and the biological consequences are unclear. We studied NF-кB -dependent gene expression induced by doxorubicin in breast cancer cells and fresh human cancer specimens with different genetic backgrounds focusing on their p53 status. NF-кB –dependent signature of doxorubicin was identified by gene expression microarrays in breast cancer cells treated with doxorubicin and the IKKβ-inhibitor MLN120B, and confirmed ex vivo in human cancer samples. The association with p53 was functionally validated. Finally, NF-кB activation and p53 status was determined in a cohort of breast cancer patients treated with adjuvant doxorubicin-based chemotherapy. Doxorubicin treatment in the p53-mutated MDA-MB-231 cells resulted in NF NF- кB driven-gene transcription signature. Modulation of genes related with invasion, metastasis and chemoresistance (ICAM-1, CXCL1, TNFAIP3, IL8) were confirmed in additional doxorubicin-treated cell lines and fresh primary human breast tumors. In both systems, p53-deficient background correlated with the activation of the NF-кB –dependent signature. Furthermore, restoration of p53WT in the mutant p53 MDAMB- 231 cells impaired NF-кB driven transcription induced by doxorubicin. Moreover, a p53 deficient background and nuclear NF-кB /p65 in breast cancer patients correlated with reduced disease free-survival. This study supports that p53 deficiency is necessary for a doxorubicin driven NF-кB -response that limits doxorubicin cytotoxicity in breast cancer and is linked to an aggressive clinical behavior.Financial support: This work was supported by RD12/0036/0051 (J.A.), RD09/0076/0101, RD09/0076/0036, RD12/0036/0054 (A.B), RD12/0036/0070 (A. Ll), PI12/00680 (J.A.), PI12/01552 (F.R.), PI12/01421 (A.Ll.), 2009 SGR 321 (J.A.), FMM 9757/002 (F.R.), and the “Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC). J.A. and F.R. are recipients of intensification program ISCIII/FEDER. We thank Fundació Cellex (Barcelona) for a generous donation to the Hospital del Mar Medical Oncology Service. We thank Millenium for generously providing MLN120B

El desarrollo urbano sostenible y las energías renovables: legislación comparada en la República Argentina y España

La Universidad del Salvador y la Universidad de Oviedo, España, firmaron un Convenio de Colaboración académica, científica y de cooperación para el desarrollo, publicado en el Boletín Oficial del Principado de Asturias número 180, del 3 de agosto del 2016. En el marco de dicho convenio, se desarrolló el presente proyecto de investigación en el que se buscó caracterizar, identificar y analizar la legislación argentina y española relativa a las fuentes de energías renovables y la forma en que aquellas fomentan y permiten un desarrollo sostenible de las ciudades. De las diferencias detectadas en ambos ordenamientos, se buscaron elementos comparativos capaces de ser analizados a la luz de la información recolectada. Finalmente, se buscó visibilizar posibles propuestas de políticas, modelos de gestión y metodologías jurídicas de intervención para el cumplimiento de tales objetivos.En Argentina, se evaluaron las leyes nacionales N. ° 26.190 y N. ° 27.191, y un total de cincuenta y tres (53) leyes provinciales sobre la temática. Del análisis del universo normativo relevado, se pudo concluir que la diversidad de conceptos, la falta de actualización normativa y de reglamentación no permite la posibilidad de generar una política de Estado tendiente a la utilización de fuentes de energías renovables.La cantidad y variedad de fuentes de energías renovables reguladas en las leyes argentinas imposibilitan su correcta regulación, como también la generación de una matriz energética capaz de ser aplicada como política pública tendiente a generar energías renovables en pos de un desarrollo urbano sostenible.En España, se evaluó el marco comunitario europeo, el sistema energético español y las principales normas que permiten la gestión de políticas encaminadas a alcanzar los compromisos asumidos tanto a nivel internacional como por su condición de miembro de la Unión Europea.Se determinó que es fundamental garantizar la coordinación de todos los instrumentos normativos y de planificación sectorial relacionados con el cambio climático y la coordinación de las distintasAdministraciones Públicas. Que las Administraciones Públicas apuesten decididamente por el establecimiento de un marco claro, estable y único que recoja todas las reformas y medidas de una nuevaimplementación para alcanzar la descarbonización de la economía española y la transición energética para posibilitar un verdadero desarrollo urbano sostenible. Debe contener medidas tendientes a la sustitución progresiva del consumo municipal de energías de origen fósil por energías renovablesproducidas in situ, promocionando el autoconsumo eléctrico; se debe seguir potenciando la mejora de la calidad del aire y continuar con medidas que fomenten la eficiencia energética y las energías renovables en las instalaciones de alumbrado público, agua y residuos, y de la gestión inteligente deespacios urbanos. Es necesario educar a los ciudadanos en los patrones de consumo actuales hacia vectores menos emisores y de mayor eficiencia energética.Los resultados obtenidos de ambos países dan cuenta de que es imperioso establecer normas que, atendiendo a las realidades propias de cada región, permitan de una manera coherente y coordinada la protección de fuentes de energías renovables, en pos de lograr la transición energética hacia unaeconomía descarbonizada, promovida e impulsada no solo desde las políticas públicas sino también con sustento en las leyes y normativas que las regulen adecuada y uniformemente

Smoking is associated with age at disease onset in Parkinson's disease

[Background] Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients.[Objective] The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to determine how these variables interact to define the overall risk.[Methods] We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic, gPD or idiopathic, iPD) and three genetic variants rs5848- GRN, rs1042522- TP53 and APOE. We studied two cohorts (PPMI and IPDGC) to replicate positive results.[Results] Regarding age at onset, male smokers PD had a significantly lower mean age compared to non-smoker (p = 0.001). APOE-Ɛ4 carriers had a younger onset-age compared to non-carriers (p = 0.03) in the Spanish cohort, but these results were not replicated in the other cohorts. Concerning survival, PD patients with an early onset (below 50 years) had an increased survival rate (p < 0.001).[Conclusions] Our study showed how several genetic and non-genetic risk factors influenced the age at onset and survival in PD.Irene Rosas was supported by a grant from Fundación Jose Luis Castaño-SEQC. Sergio Pérez-Oliveira is supported by Fundación Parkinson Asturias-Obra Social Cajastur. This study was supported by grant PI 15/00878 (Fondos Feder) to VA.Peer reviewe

Residual pulmonary infiltrates, symptoms and diffusion impairment at one‐year after severe COVID‐19 infection have different associated factors

Menendez R, Mendez R, Latorre A, Gonzalez-Jimenez P, Peces-Barba G, Molina M, et al. Residual pulmonary infiltrates, symptoms and diffusion impairment at 1-year after severe COVID-19 infection have different associated factors. J Intern Med. 2023;00:1-13. Introduction. After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, patients may show lung sequelae on radiology and functional impairment at the 1-year followup. We aimed to describe the persistence of symptoms, radiological alterations, or reduced diffusing capacity of the lung for carbon monoxide (DLCO) at 1-year follow-up in patients from the Spanish Registry RECOVID. Methods. RECOVID collected symptom and radiological and functional lung tests data on hospitalized patients with coronavirus disease 2019 during the acute phase and at the 6- and 12-month follow-up visits. Results. Of the 2500 enrolled survivors (90% admitted to the ward), 1874 had follow-up visits for up to a year. Of these, 42% continued to present with symptoms, 27% had radiological sequelae and 31% had reduced DLCO. Independently associated factors included female sex, asthma and the requirement for invasive or non-invasive mechanical ventilation. Complete radiological resolution was 72.2% at 12 months; associated factors with incomplete recovery were age, male sex, oxygen or respiratory support, corticosteroids and an initial SpO(2)/FiO(2) = 2. Reduced D-LCO was observed in 31% of patients at 12 months; associated factors were older age, female sex, smoking habit, SpO(2)/FiO(2) = 2 and the requirement of respiratory support.At 12 months, a proportion of the asymptomatic patients showed reduced D-LCO (9.5%), radiological findings (25%) or both (11%). Conclusions. The factors associated with symptom persistence, incomplete radiological resolution and D-LCO <80% differed according to age, sex, comorbidities and respiratory support. The burden of symptoms, reduced D-LCO and incomplete radiological resolution were considerable in patients with SARS-CoV-2 pneumonia at the 1-year follow-up after hospitalisation

The Mediating Role of Impulsivity in the Relationship Between Suicidal Behavior and Early Traumatic Experiences in Depressed Subjects

Background: Depressed patients with early traumatic experiences may represent a clinically and biologically distinct subtype, with worse clinical outcomes and greater risk of suicide. Since early traumatic experiences alter development of systems that regulate the stress response, increasing sensitivity to stress and mood disorders later in life, certain personality features may influence coping strategies, putting individuals with depression and a history of early traumatic experiences at greater risk of suicidal behavior.Objective: To determine whether impulsivity mediates the relationship between early traumatic experiences and suicidal behavior in patients with major depressive disorder (MDD).Methods: The total sample consists of 190 patients [mean age (SD) = 53.71 (10.37); females: 66.3%], with current MDD (DSM-5 criteria). The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the List of Threatening Experiences (LTE), and the Barratt Impulsiveness Scale-11 (BIS-11) were used to assess childhood and adulthood adverse life events and impulsivity, respectively. We developed mediation models by bootstrap sampling methods.Results: Eighty-one (42.6%) patients had a history of previous suicide attempts (SA). CTQ-SF-Total and BIS-11-Total scores were significantly higher in MDD patients with previous SA. Correlation analyses revealed significant correlations between the CTQ-SF-Total and BIS-11-Total, CTQ-SF-Total and HDRS-Total, and BIS-11-Total and HDRS-Total scores. Regression models found that CTQ-SF-Total, BIS-11-Total, and HDRS-Total scores were associated with SA. Mediation analyses further revealed the association between CTQ-SF-Total and SA was mediated by the indirect effect of the BIS-11-Total score (b = 0.007, 95% CI = 0.001, 0.015), after statistically controlling for sex, the HDRS-Total, and the LTE-Total.Discussion: Data suggest that impulsivity could mediate the influence of childhood trauma on suicidal behavior. This will help understand the role of risk factors in suicidal behavior and aid in the development of prevention interventions focused on modifiable mediators when risk factors are non-modifiable.2020-2

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis