Regulation of Cortico-Thalamic JNK1/2 and ERK1/2 MAPKs and Apoptosis-Related Signaling Pathways in PDYN Gene-Deficient Mice Following Acute and Chronic Mild Stress

The crosstalk between the opioidergic system and mitogen-activated protein kinases (MAPKs) has a critical role in mediating stress-induced behaviors related to the pathophysiology of anxiety. The present study evaluated the basal status and stress-induced alterations of cortico-thalamic MAPKs and other cell fate-related signaling pathways potentially underlying the anxiogenic endophenotype of PDYN gene-deficient mice. Compared to littermates, PDYN knockout (KO) mice had lower cortical and or thalamic amounts of the phospho-activated MAPKs c-Jun N-terminal kinase (JNK1/2) and extracellular signal-regulated kinase (ERK1/2). Similarly, PDYN-KO animals displayed reduced cortico-thalamic densities of total and phosphorylated (at Ser191) species of the cell fate regulator Fas-associated protein with death domain (FADD) without alterations in the Fas receptor. Exposure to acute restraint and chronic mild stress stimuli induced the robust stimulation of JNK1/2 and ERK1/2 MAPKs, FADD, and Akt-mTOR pathways, without apparent increases in apoptotic rates. Interestingly, PDYN deficiency prevented stress-induced JNK1/2 and FADD but not ERK1/2 or Akt-mTOR hyperactivations. These findings suggest that cortico-thalamic MAPK- and FADD-dependent neuroplasticity might be altered in PDYN-KO mice. In addition, the results also indicate that the PDYN gene (and hence dynorphin release) may be required to stimulate JNK1/2 and FADD (but not ERK1/2 or Akt/mTOR) pathways under environmental stress conditions.This joint research was funded by Red Temática de Investigación Cooperativa en Salud–Red de Trastornos Adictivos (RETICS–RTA, Instituto de Salud Carlos III [ISCIII], MCIU/AEI/FEDER), Grupos RD06/0001/0004 (J.M.) and RD06/0001/0003 (J.A.G.-S.). J.M. also received financial support from Proyectos de Investigación en Salud—ISCIII (grant RD. PI18/00576), Red de Investigación en Atención Primaria de Adicciones (grant RD21/0009/0008), and Delegación del Gobierno para el Plan Nacional Sobre Drogas (PNSD, grant 2019I012) from the Spanish Ministry of Health (MSC). This study was also supported by MCIU/AEI/FEDER (grants RTI2018-094414-A-I00 to A.R.-M., PID2019-109323RA-I00 to T.F., and SAF2008-01311 to J.A.G.-S.), and MSC/FEDER (FIS 05/0429 to J.M). A.R.-M. (grant RYC-2016-19282) and T.F. (grant RYC-2017-22666) are ‘Ramón y Cajal’ Researchers

Disrupted neuroglial metabolic coupling after peripheral surgery

Immune-related events in the periphery can remotely affect brain function, contributing to neurodegenerative processes and cognitive decline. In mice, peripheral surgery induces a systemic inflammatory response associated with changes in hippocampal synaptic plasticity and transient cognitive decline, however, the underlying mechanisms remain unknown. Here we investigated the effect of peripheral surgery on neuronal-glial function within hippocampal neuronal circuits of relevance to cognitive processing in male mice at 6, 24, and72hpostsurgery. At 6hwedetect theproinflammatorycytokineIL-6inthehippocampus, followedupbyalterations in them RNA and protein expression of astrocyticandneuronal proteinsnecessaryfor optimal energysupplytothebrainandfor thereuptakeandrecycling of glutamate in the synapse. Similarly, at 24 h postsurgery the mRNA expression of structural proteins (GFAP and AQP4) was compromised. At this time point, functional analysis in astrocytes revealed a decrease in resting calcium signaling. Examination of neuronal activity by whole-cell patch-clamp shows elevated levels of glutamatergic transmission and changes in AMPA receptor subunit composition at 72 h postsurgery. Finally, lactate, an essential energy substrate produced by astrocytes and critical for memory formation, decreases at 6 and 72 h after surgery. Based on temporal parallels with our previous studies, we propose that the previously reported cognitive decline observed at 72 h postsurgery in mice might be the consequence of temporal hippocampal metabolic, structural, and functional changes in astrocytes that lead to a disruption of the neuroglial metabolic coupling and consequently to a neuronal dysfunction.This work was supported by a “Ramón y Cajal” fellowship (RYC-2014-15792 to A.G.-C.) from Spanish “Ministerio de Economía y Competitividad”, the Swedish Research Council, the confocal microscope used in the study by Knut and Alice Wallenberg Foundation (Grant KAW2008.0149), and NIH/NIA R01AG057525 to N.T

Infiltration sintering of WCu alloys from copper-coated tungsten composite powders for superior mechanical properties and arc-ablation resistance

W70Cu30(W-30 wt.% Cu) alloys were fabricated using cold pressing and infiltration sintering methods from two types of powders, i.e., mixed copper-tungsten (M-Cu-W) powders and our newly developed copper-coated tungsten composite (Cu@W) powders. Microstructure, mechanical and arc-ablation properties of the W70Cu30 alloys were investigated, and the mechanism of enhanced physical/mechanical properties and arc-erosion resistance of the W70Cu30 alloys was discussed. For the W70Cu30 alloys prepared using the Cu@W powders, their physical properties, including hardness, electrical conductivity and relative density were much better than those prepared from the M-Cu-W powders. The W70Cu30 alloys fabricated from the Cu@W powders were free of cracks, and showed homogenous distributions of W and Cu network structures. Whereas for the alloys prepared from the M-Cu-W powders, segregation of Cu was observed and the segregation size was about 40–100 μm. Characterization of arc-erosion morphologies of the W70Cu30 alloys prepared with the Cu@W powders revealed the occurrence of evaporation of Cu phase; whereas that of W70Cu30 alloys prepared with the M-Cu-W powders revealed the occurrence of the sputtering of Cu. After arc breakdown for 200 times, mass loss of alloys made using the mixed powders was twice as much as those made using the coated composite powders. Based on the experimental results and theoretical analysis, an arc breakdown mechanism of the WCu-C alloys using the composite powders was proposed which is attributed to the formation of a homogeneous Cu-Cu network structure to uniformly disperse arc energy and dissipate the generated heat, thus prolonging the service life of the WCu alloy contacts

GCAT|Genomes for life: a prospective cohort study of the genomes of Catalonia

PURPOSE: The prevalence of chronic non-communicable diseases (NCDs) is increasing worldwide. NCDs are the leading cause of both morbidity and mortality, and it is estimated that by 2030, they will be responsible for 80% of deaths across the world. The Genomes for Life (GCAT) project is a long-term prospective cohort study that was designed to integrate and assess the role of epidemiological, genomic and epigenomic factors in the development of major chronic diseases in Catalonia, a north-east region of Spain. PARTICIPANTS: At the end of 2017, the GCAT Study will have recruited 20 000 participants aged 40-65 years. Participants who agreed to take part in the study completed a self-administered computer-driven questionnaire, and underwent blood pressure, cardiac frequency and anthropometry measurements. For each participant, blood plasma, blood serum and white blood cells are collected at baseline. The GCAT Study has access to the electronic health records of the Catalan Public Healthcare System. Participants will be followed biannually at least 20 years after recruitment. FINDINGS TO DATE: Among all GCAT participants, 59.2% are women and 83.3% of the cohort identified themselves as Caucasian/white. More than half of the participants have higher education levels, 72.2% are current workers and 42.1% are classified as overweight (body mass index ≥25 and <30 kg/m2). We have genotyped 5459 participants, of which 5000 have metabolome data. Further, the whole genome of 808 participants will be sequenced by the end of 2017. FUTURE PLANS: The first follow-up study started in December 2017 and will end by March 2018. Residences of all subjects will be geocoded during the following year. Several genomic analyses are ongoing, and metabolomic and genomic integrations will be performed to identify underlying genetic variants, as well as environmental factors that influence metabolites

GCAT|Genomes for life : A prospective cohort study of the genomes of Catalonia

The prevalence of chronic non-communicable diseases (NCDs) is increasing worldwide. NCDs are the leading cause of both morbidity and mortality, and it is estimated that by 2030, they will be responsible for 80% of deaths across the world. The Genomes for Life (GCAT) project is a long-term prospective cohort study that was designed to integrate and assess the role of epidemiological, genomic and epigenomic factors in the development of major chronic diseases in Catalonia, a north-east region of Spain. Participants At the end of 2017, the GCAT Study will have recruited 20 000 participants aged 40-65 years. Participants who agreed to take part in the study completed a self-administered computer-driven questionnaire, and underwent blood pressure, cardiac frequency and anthropometry measurements. For each participant, blood plasma, blood serum and white blood cells are collected at baseline. The GCAT Study has access to the electronic health records of the Catalan Public Healthcare System. Participants will be followed biannually at least 20 years after recruitment. Findings to date Among all GCAT participants, 59.2% are women and 83.3% of the cohort identified themselves as Caucasian/white. More than half of the participants have higher education levels, 72.2% are current workers and 42.1% are classified as overweight (body mass index ≥25 and <30 kg/m 2). We have genotyped 5459 participants, of which 5000 have metabolome data. Further, the whole genome of 808 participants will be sequenced by the end of 2017. Future plans The first follow-up study started in December 2017 and will end by March 2018. Residences of all subjects will be geocoded during the following year. Several genomic analyses are ongoing, and metabolomic and genomic integrations will be performed to identify underlying genetic variants, as well as environmental factors that influence metabolites

Coordinación y seguimiento en la implementación eficaz de las titulaciones de Grado en la Facultad de Derecho

El trabajo de esta Red docente ha consistido en el seguimiento de las acciones de calidad que se pretenden implantar en las titulaciones de Grado y de los mecanismos de coordinación docente aplicables, con el objetivo de mejorar la implementación de las titulaciones en aquellos aspectos esenciales en el procedimiento de acreditación de las distintas titulaciones. Los resultados de los Informes de Seguimiento de cada titulación de la Facultad, muestran la necesidad de establecer instrumentos de coordinación del profesorado de cada titulación para unificar y armonizar criterios en lo relativo al volumen total del trabajo exigido al estudiante, la distribución temporal adecuada del mismo y el trabajo colectivo de todos los profesores para conseguir los objetivos plasmados en la Memoria Verificada por ANECA para cada título. El objetivo de esta Red ha sido analizar los datos necesarios para el Informe que será necesario para la evaluación externa de la renovación de la acreditación de la titulación de acuerdo con los distintos criterios que han sido objeto del procedimiento de acreditación: gestión del título, información y transparencia, sistema interno de garantía de calidad, recursos, resultados, satisfacción y rendimiento

Retos del Programa de Acción Tutorial: la adaptación curricular y nuevas vías de interacción con los estudiantes

El programa de adaptación curricular pretende adaptar el proceso de enseñanza-aprendizaje tanto a las necesidades específicas del alumnado universitario (movilidad, deporte de élite, violencia de género, vida laboral) como a las características particulares de los estudiantes con necesidades educativas especiales derivadas de una situación de discapacidad, física o psíquica, para que puedan acceder al currículo y alcanzar los objetivos de las distintas asignaturas y planes de estudio en igualdad de condiciones que el resto de estudiantes. En este sentido, la Facultad de Derecho ha resuelto varias solicitudes del alumnado de adaptación curricular durante el curso 2015-2016, en cuyo procedimiento se han implicado distintos agentes: la dirección del Centro, el voluntariado, el profesorado afectado y el CAE, junto con los tutores del PAT. La revisión por la Red del procedimiento de actuación previsto en el artículo 5 del Reglamento de Adaptación curricular en la Universidad de Alicante y su implementación en la Facultad de Derecho ha puesto de manifiesto la necesidad de acomodar las medidas de adaptación sobre las solicitudes presentadas por alumnos con discapacidad psíquica que requieren la intervención del Centro de Apoyo al Estudiante de la Universidad de Alicante

Body-brain-microbiome interaction

Brain function is influenced by internal inputs from many parts of the body, including chemicals in the blood and bacteria in the gut. The gut microbiota is a fundamental component of the body that can be transferred across generations and contribute to the unique features of the human phenotype influencing both health and disease. Deciphering the controlling mechanisms of microbiome-bodybrain interactions may help in identifying new molecular targets to prevent and/or treat a range of psychiatric and neurologic disorders as well as their physical comorbidities. Here we provide an update on the functioning of the gut microbiome-body-brain axis and outline open scientific challenges and future research directions.Peer reviewe

Análisis de experiencia previa y propuestas de mejora en el Máster Universitario en Gestión de la Edificación

Tras los acontecimientos ocurridos en el sector edificatorio durante los últimos años, es preciso establecer ciertas mejoras en la estructura del Máster Universitario en Gestión de la Edificación, perteneciente a la Escuela Politécnica Superior de la Universidad de Alicante, tanto en relación a la organización de los estudios a nivel de programa así como a los conceptos específicos estudiados en cada materia. Por ello, el propósito del presente trabajo es reflexionar sobre la experiencia previa desarrollada en el Máster con el fin de establecer determinadas medidas que proporcionen una mayor coordinación y seguimiento entre los departamentos implicados. Así, esta situación permitirá desarrollar las acciones propuestas en el Plan de Acciones de Mejora para la Renovación de la Acreditación del citado Máster en relación a su estructura organizativa, introducción de mejoras tecnológicas, así como la propuesta de innovaciones metodológicas y de evaluación docente adaptadas a los condicionantes actuales del sector de la edificación. Se propone mantener una metodología docente basada en la Evaluación Continua, mediante un temario donde los conocimientos adquiridos por el estudiante sean graduales y de aplicación sucesiva en prácticas y temas teóricos de actualidad en el sector, apostando por la clase participativa como estrategia de aprendizaje

A first update on mapping the human genetic architecture of COVID-19

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