Role of mTOR-regulated autophagy in spine pruning defects and memory impairments induced by binge-like ethanol treatment in adolescent mice

Adolescence is a brain maturation developmental period during which remodeling and changes in synaptic plasticity and neural connectivity take place in some brain regions. Different mechanism participates in adolescent brain maturation, including autophagy that plays a role in synaptic development and plasticity. Alcohol is a neurotoxic compound and its abuse in adolescence induces neuroinflammation, synaptic and myelin alterations, neural damage and behavioral impairments. Changes in synaptic plasticity and its regulation by mTOR have also been suggested to play a role in the behavioral dysfunction of binge ethanol drinking in adolescence. Therefore, by considering the critical role of mTOR in both autophagy and synaptic plasticity in the developing brain, the present study aims to evaluate whether binge ethanol treatment in adolescence would induce dysfunctions in synaptic plasticity and cognitive functions and if mTOR inhibition with rapamycin is capable of restoring both effects. Using C57BL/6 adolescent female and male mice (PND30) treated with ethanol (3 g/kg) on two consecutive days at 48-hour intervals over 2 weeks, we show that binge ethanol treatment alters the density and morphology of dendritic spines, effects that are associated with learning and memory impairments and changes in the levels of both transcription factor CREB phosphorylation and miRNAs. Rapamycin administration (3 mg/kg) prior to ethanol administration restores ethanol-induced changes in both plasticity and behavior dysfunctions in adolescent mice. These results support the critical role of mTOR/autophagy dysfunctions in the dendritic spines alterations and cognitive alterations induced by binge alcohol in adolescence

Selective expression of the neurexin substrate for presenilin in the adult forebrain causes deficits in associative memory and presynaptic plasticity

Presenilins (PS) form the active subunit of the gamma-secretase complex, which mediates the proteolytic clearance of a broad variety of type-I plasma membrane proteins. Loss-of-function mutations in PSEN1/2 genes are the leading cause of familial Alzheimer's disease (fAD). However, the PS/gamma-secretase substrates relevant for the neuronal deficits associated with a loss of PS function are not completely known. The members of the neurexin (Nrxn) family of presynaptic plasma membrane proteins are candidates to mediate aspects of the synaptic and memory deficits associated with a loss of PS function. Previous work has shown that fAD-linked PS mutants or inactivation of PS by genetic and pharmacological approaches failed to clear Nrxn C-terminal frag-ments (NrxnCTF), leading to its abnormal accumulation at presynaptic terminals. Here, we generated transgenic mice that selectively recreate the presynaptic accumulation of NrxnCTF in adult forebrain neurons, leaving unaltered the function of PS/gamma-secretase complex towards other substrates. Behavioral characterization identified selective impairments in NrxnCTF mice, including decreased fear-conditioning memory. Electro-physiological recordings in medial prefrontal cortex-basolateral amygdala (mPFC-BLA) of behaving mice showed normal synaptic transmission and uncovered specific defects in synaptic facilitation. These data functionally link the accumulation of NrxnCTF with defects in associative memory and short-term synaptic plasticity, pointing at impaired clearance of NrxnCTF as a new mediator in ADMinisterio de Ciencia, Innovación y Universidades (RTI2018-101886-B-100)Junta de Andalucía (PY18-823)Junta de Andalucía (P11- CVI-7599)Ministerio de Economía, Industria y Competitividad (BES-2016-076579)Garantía Juvenil contract from Universidad de Sevill

La informática en los centros de infantil y primaria en Extremadura: datos y propuestas

Este documento constituye el informe de investigación final del proyecto “Estado de la Informática en los centros de Educación Infantil y Primaria de Extremadura”. Se recogen en él los aspectos más destacables de los datos obtenidos a partir de los cuestionarios cumplimentados por el profesorado de los centros públicos de nuestra Región, con objeto de conocer sus competencias tecnológicas y pedagógicas, la utilización que hacen de los recursos de que disponen en los centros y las características de su formación. Por el volumen de datos recogidos y el nivel de profundización, permite obtener una imagen fiable y precisa de la situación de estos recursos en los centros públicos de nuestra Comunidad, algo que hasta ahora ha sido realizado, pero con menor detalle en algunos estudios parciales anteriores, que describiremos más adelante. Se ofrecen igualmente propuestas de actuación que contribuyan a mejorar la integración de las Nuevas Tecnologías en el aula.This document constitutes the final investigation report of the project "State of the computing centers in the infant and primary education of Extremadura". Are reflected in the salient aspects of the data obtained from the questionnaires filled out by the teachers of public centers of our region, in order to know their technological and pedagogical skills, the use of the resources available in the centers and the characteristics of their training. By the volume of data collected and the level of deepening, allows you to obtain a reliable and accurate picture of the situation of these resources in the public schools of our Community, something that until now has been carried out, but with less detail in some past partial studies, which are described later. There are also proposals for action which contribute to improve the integration of new technologies in the classroom.Esta investigación ha sido realizada con cargo al Proyecto PRI09A005 según la “Orden de 17 de diciembre de 2008, DOE nº 2, de 5 de enero de 2009, por la que se convocan subvenciones para la realización de proyectos de investigación, desarrollo e innovación del Gobierno de Extremadura

All about (nk cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity

NK cells are key mediators of immune cell-mediated cytotoxicity toward infected and transformed cells, being one of the main executors of cell death in the immune system. NK cells recognize target cells through an array of inhibitory and activating receptors for endogenous or exogenous pathogen-derived ligands, which together with adhesion molecules form a structure known as immunological synapse that regulates NK cell effector functions. The main and best characterized mechanisms involved in NK cell-mediated cytotoxicity are the granule exocytosis pathway (perforin/granzymes) and the expression of death ligands. These pathways are recognized as activators of different cell death programmes on the target cells leading to their destruction. However, most studies analyzing these pathways have used pure recombinant or native proteins instead of intact NK cells and, thus, extrapolation of the results to NK cell-mediated cell death might be difficult. Specially, since the activation of granule exocytosis and/or death ligands during NK cell-mediated elimination of target cells might be influenced by the stimulus received from target cells and other microenvironment components, which might affect the cell death pathways activated on target cells. Here we will review and discuss the available experimental evidence on how NK cells kill target cells, with a special focus on the different cell death modalities that have been found to be activated during NK cell-mediated cytotoxicity; including apoptosis and more inflammatory pathways like necroptosis and pyroptosis. In light of this new evidence, we will develop the new concept of cell death induced by NK cells as a new regulatory mechanism linking innate immune response with the activation of tumour adaptive T cell responses, which might be the initiating stimulus that trigger the cancer-immunity cycle. The use of the different cell death pathways and the modulation of the tumour cell molecular machinery regulating them might affect not only tumour cell elimination by NK cells but, in addition, the generation of T cell responses against the tumour that would contribute to efficient tumour elimination and generate cancer immune memory preventing potential recurrences

New archaeological excavations at Cova Gran and Cova Freda de Montserrat (Collbató, Barcelona) after almost 100 years

[spa] En este trabajo se presentan los primeros datos estratigráficos, radiocarbónicos y de cultura material de las recientes excavaciones en las Coves de Montserrat (Cova Gran y Cova Freda). Estos emblemáticos yacimientos fueron excavados el año 1922 y proporcionaron uno de los primeros conjuntos cardiales de la península ibérica. Desde entonces, no volvieron a ser intervenidos de forma oficial y quedaron abandonados. En el año 2018 se han reiniciado los trabajos con sondeos en ambas cuevas, determinando la preservación de depósitos arqueológicos estratificados en algunos de ellos. En la Cova Freda se ha reconocido la existencia de un tramo de la cavidad probablemente usado como redil durante el Neolítico Antiguo Cardial y, en la Cova Gran, se han documentado un nivel y una estructura negativa de esa misma cronología, así como un potente nivel finipaleolítico.[eng] This work presents the first stratigraphic, chronologic and cultural results of the archaeological works in the Coves de Montserrat (Cova Gran and Cova Freda). These emblematic sites that were excavated in 1922 and that provided one of the first cardial assemblages of the Iberian Peninsula. They were not intervened again and they were abandoned. These works have been restarted in 2018 by means of different test pits in both caves. These have determined the preservation of stratified archaeological deposits in some of these tests: in the Cova Freda it has been determined the existence of a section of the cavity probably used as a fold during the Early Neolithic; while, in the Cova Gran, a layer and a negative structure of that same chronology have been documented, as well as a finipaleolithic layer. This paper presents the first stratigraphic, radiocarbon and material culture data of these emblematic sites of Iberian historiography

Revista de Vertebrados de la Estación Biológica de Doñana

Captura de Petromyzon marinus lo en las Marismas del GuadalquivirEstudio sobre la Lagartiia de Valverde Algyroides marchi (Reptilia, Lacertidae)Dimorfismo sexual en Psammodromuus algirus (Reptilia, Lacertidae)Mecanismos de parasitización por Clamator glandarius y defensa por Pica pica.Nidificación de Cyanopica cyana en Doñana.Reproducción de la Urraca (P.pica) en DoñanaNesting relationship between Columba palambus and Milvus migransBiometría y dimorfismo sexual en el Calamón (Polphyrio porphyrio).Sobre sexo, mecanismos y proceso de reproducciónen el Buitre Leonado (Gyps fulvus)Aves anilladas por la Estación Biológica de Doñana. Informe Nº 1. (Años 1964 a 1971)Dimorfismo sexual y diferenciación de edades en Sturnus unicolor Temm.Contribución al estudio de la biología y ecología del Lirón Careto, Eliomys quercinus Linnaeus 1766, en Iberia Central, Parte 1: Crecimiento, Reproducción y Nidificación.Sobre el Lobo (Canis lupus) ibérico:1. Dimorfismo sexual en cráneosMorfología y dimorfismo sexual de la pelvis de Pitymys duodecimcostatusAlgunos aspectos del diformismo sexual en el cráneo de las Ginetas españolas, (Genetta genetta) (L.) 1758Peer reviewe

Experiencias de actividades de extensión en temas relacionados con la alimentación y su impacto en los alumnos participantes

La Organización Mundial de la Salud (2013) define a la salud, como el “estado de completo bienestar físico, mental y social y no la sola ausencia de enfermedad”, siendo el accionar nutricional uno de los más elementales factores sanitarios, a fin de mantener buenas condiciones de salud de la comunidad. En las provincias de Corrientes y Resistencia, hay problemas serios de malnutrición en los niños y cada vez son más evidentes las enfermedades asociadas a la desnutrición y obesidad en la población. Entre los años 2006 y 2018, los docentes del Área de Bromatología del Departamento de Bioquímica de la LACENA (UNNE), desarrollaron proyectos de extensión y voluntariado, con el objetivo de aportar soluciones a esta problemática. Se realizaron actividades de capacitación nutricional y educación de la población dirigida a niños en edad escolar y adolescentes, brindando conocimientos sobre principios de nutrición, procesamiento de alimentos e higiene alimentaria y capacitando al público en general en la preparación de alimentos con importantes aportes nutricionales e interpretación del rotulado. De las actividades desarrolladas a lo largo de estos años y según las consultas realizadas, las experiencias fueron consideradas muy enriquece- doras por todos los involucrados, alumnos, docentes y representantes institucionales, permitiendo un mayor acercamiento de la universidad al medio. Se detectó una avidez de conocimientos y de interacción entre los representantes de la instituciones y la satisfacción de los docentes de la Universidad con la tarea realizada. Para los los alumnos fue importante el aprendizaje logrado, no solo en lo académico, sino en lo social al tener la oportunidad de tomar contacto con la realidad del entorno

Etología. Introducción a la ciencia del comportamiento

1ª ed., 3ª reimp.El objetivo de este libro es proporcionar una introducción a la Etología. Ésta ciencia responde al interés por profundizar en el conocimiento de las costumbres animales; por comprender la variedad de comportamientos que en diferentes situaciones exhiben los individuos de diferentes especies. Una posible definición de Etología podría ser: el estudio científico del comportamiento de los seres vivos. A lo largo de esta obra se analizan todos los aspectos que tienen que ver con el comportamiento animal, desde las causas y mecanismos de actuación o la adaptación y evolución y el bienestar animal.The purpose of this book is to provide an introduction to Ethology. This science responds to the interest in deepening the knowledge of animal customs; to understand the variety of behaviour that in different situations exhibit individuals of different species. A possible definition of ethology could be: the scientific study of the behavior of living beings. Throughout this book all aspects related to animal behavior, from the causes and mechanisms of action or adaptation and evolution and animal welfare, are analyzed

PD-1 is expressed in cytotoxic granules of NK cells and rapidly mobilized to the cell membrane following recognition of tumor cells

5 figures.-- Supplementary information available.The contribution of the T cell-related inhibitory checkpoint PD-1 to the regulation of NK cell activity is still not clear with contradictory results concerning its expression and role in the modulation of NK cell cytotoxicity. We provide novel key findings on the mechanism involved in the regulation of PD-1 expression on NK cell membrane and its functional consequences for the elimination of cancer cells. In contrast to freshly isolated NK cells from cancer patients, those from healthy donors did not express PD-1 on the cell membrane. However, when healthy NK cells were incubated with tumor target cells, membrane PD-1 expression increased, concurrent with the CD107a surface mobilization. This finding suggested that PD-1 was translocated to the cell membrane during NK cell degranulation after contact with target cells. Indeed, cytosolic PD-1 was expressed in freshly-isolated-NK cells and partly co-localized with CD107a and GzmB, confirming that membrane PD-1 corresponded to a pool of preformed PD-1. Moreover, NK cells that had mobilized PD-1 to the cell membrane presented a significantly reduced antitumor activity on PD-L1-expressing-tumor cells in vitro and in vivo, which was partly reversed by using anti-PD-1 blocking antibodies. Our results indicate that NK cells from healthy individuals express cytotoxic granule-associated PD-1, which is rapidly mobilized to the cell membrane after interaction with tumor target cells. This novel finding helps to understand how PD-1 expression is regulated on NK cell membrane and the functional consequences of this expression during the elimination of tumor cells, which will help to design more efficient NK cell-based cancer immunotherapies.Work in the JP laboratory is funded by FEDER (Fondo Europeo de Desarrollo Regional), Gobierno de Aragón (Group B29_20R), Ministerio de Ciencia, Innovación y Universidades (MCUN), Agencia Estatal de Investigación (SAF2017-83120-C2-1-R; PID2020-113963RBI00), Fundación Inocente Inocente, ASPANOA, and Carrera de la Mujer de Monzón. Postdoctoral Juan de la Cierva Contract (MA and LS) and Predoctoral Grant from AECC (CP). JP is supported by ARAID Foundation; Fundación Agencia Aragonesa para la investigación y el Desarrollo; Fundación Científica Asociación Española Contra el Cáncer.Peer reviewe

Extreme and long-term drought in the La Plata Basin: event evolution and impact assessment until September 2022

The current drought conditions across the Parana-La Plata Basin (LPB) in Brazil-Argentina have been the worst since 1944. While this area is characterized by a rainy season with a peak from October to April, the hydrological year 2020-2021 was very deficient in rainfall, and the situation extended into the 2021-2022 hydrological year. Below-normal rainfall was dominant in south-eastern Brazil, northern Argentina, Paraguay, and Uruguay, suggesting a late onset and weaker South American Monsoon and the continuation of drier conditions since 2021. In fact, in 2021 Brazilian south and south-east regions faced their worst droughts in nine decades, raising the spectre of possible power rationing given the grid dependence on hydroelectric plants. The Paraná-La Plata Basin drought induced damages to agriculture and reduced crop production, including soybeans and maize, with effects on global crop markets. The drought situation continued in 2022 in the Pantanal region. Dry meteorological conditions are still present in the region at the end of September 2022 with below-average precipitation anomalies. Soil moisture anomaly and vegetation conditions are worst in the lower part of the La Plata Basin, in the southern regions. Conversely, upper and central part of the basin show partial and temporary recovery