Estudio comparativo de la calidad de la información ofrecida sobre los servicios en las webs de las bibliotecas virtuales de universidades a distancia

Exponemos el resultado de un estudio comparativo sobre la comunicación web de los servicios de las bibliotecas virtuales universitarias de una selección de universidades a distancia entre las que se encuentran la UNED, la UOC y la Open University. Este estudio se hace observando las diferencias cualitativas de diversos aspectos, tales como la organización, la accesibilidad, los formatos, el redactado, la utilidad y la presentación de la información sobre los servicios de la biblioteca ofrecida en la web a los usuarios de aquellas universidades y/o Bibliotecas que han realizado el proceso de gestión de calidad o han confeccionado la carta de servicios y las que no. Entre varias recomendaciones y ejemplos de buenas prácticas, el estudio concluye que aquellas universidades y bibliotecas que no muestran ningún tipo de proceso de calidad en su institución podemos ver que son las que olvidan algunos elementos esenciales y muchos detalles por lo que a la descripción de la oferta de servicios se refiere. Conclusión y recomendaciones extensibles a cualquier biblioteca universitaria que ofrezca información en línea sobre sus servicios. A partir de la elaboración de fichas que recogen los diversos aspectos a observar de cada una de las bibliotecas hemos ponderado, en base a la diversa bibliografía consultada, cada uno como desaconsejable, recomendable y excelente resultando un informe que muestra todas las recomendaciones para cada uno de los elementos.Ebsco, Libera, Elsevier, Emerald, Asociación Andaluza de Bibliotecarios, Springer, Cambridge University Press, RSC Publishing, ISOTool

New microRNA biomarkers for drug-induced steatosis and their potential to predict the contribution of drugs to non-alcoholic fatty liver disease

Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis. Methods: Human HepG2 cells were treated with drugs and changes in miRNA levels were measured by microarray and qRT-PCR. Drug-induced fat accumulation in HepG2 was analyzed by high-content screening and enzymatic methods. miRNA biomarkers were also analyzed in the sera of 44 biopsy-proven NAFLD patients and in 10 controls. Results: We found a set of 10 miRNAs [miR-22-5p, -3929, -24-2-5p, -663a, -29a-3p, -21 (5p and 3p), -27a-5p, -1260 and -202-3p] that were induced in human HepG2 cells and secreted to the culture medium upon incubation with model steatotic drugs (valproate, doxycycline, cyclosporin A and tamoxifen). Moreover, cell exposure to 17 common drugs for NAFLD patients showed that some of them (e.g., irbesartan, fenofibrate, and omeprazole) also induced these miRNAs and increased intracellular triglycerides, particularly in combinations. Finally, we found that most of these miRNAs (60%) were detected in human serum, and that NAFLD patients under fibrates showed both induction of these miRNAs and a more severe steatosis grade. Conclusion: Steatotic drugs induce a common set of hepatic miRNAs that could be used in drug screening during preclinical development. Moreover, most of these miRNAs are serum circulating biomarkers that could become useful in the diagnosis of iatrogenic steatosis

Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-Regulated in Nonalcoholic Fatty Liver

Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance

Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations

Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. This method can be used to estimate DILI risk if the maximal blood concentration (Cmax) of the test compound is known. Moreover, an ADI can be estimated even for compounds without information on blood concentrations. To systematically optimize the in vitro system, two novel test performance metrics were introduced, the toxicity separation index (TSI) which quantifies how well a test differentiates between hepatotoxic and non-hepatotoxic compounds, and the toxicity estimation index (TEI) which measures how well hepatotoxic blood concentrations in vivo can be estimated. In vitro test performance was optimized for a training set of 28 compounds, based on TSI and TEI, demonstrating that (1) concentrations where cytotoxicity first becomes evident in vitro (EC10) yielded better metrics than higher toxicity thresholds (EC50); (2) compound incubation for 48 h was better than 24 h, with no further improvement of TSI after 7 days incubation; (3) metrics were moderately improved by adding gene expression to the test battery; (4) evaluation of pharmacokinetic parameters demonstrated that total blood compound concentrations and the 95%-population-based percentile of Cmax were best suited to estimate human toxicity. With a support vector machine-based classifier, using EC10 and Cmax as variables, the cross-validated sensitivity, specificity and accuracy for hepatotoxicity prediction were 100, 88 and 93%, respectively. Concentrations in the culture medium allowed extrapolation to blood concentrations in vivo that are associated with a specific probability of hepatotoxicity and the corresponding oral doses were obtained by reverse modeling. Application of this in vitro/in silico method to the rat hepatotoxicant pulegone resulted in an ADI that was similar to values previously established based on animal experiments. In conclusion, the proposed method links oral doses and blood concentrations of test compounds to the probability of hepatotoxicity

Unraveling the role of dopamine signaling in the extended amygdala during defensive behaviors

La sélection et l’exécution d’une réponse comportementale adéquate reposent sur l’utilisation d’informations (stimuli sensoriels et/ou contextuels) prédictives d’évènements motivationnels positifs ou aversifs. Les mécanismes d’apprentissage contrôlé par la récompense conduisant à l’optimisation de ces comportements motivés requièrent l’intégrité de la transmission dopaminergique (DA). L’amygdale étendue (AE), composée de l’écorce (shell) du noyau accumbens, de l'amygdale centrale (CEA) et du noyau du lit de la strie terminale (BNST), joue un crucial dans le contrôle de la motivation, l’intégration de stimuli sensori-émotionnels, et dans les apprentissages associés à la peur et l’anxiété. Des dérégulations au sein de ces circuits neuronaux précipitent l’apparition de troubles anxieux généralisés caractérisés entre autre par une réaction exacerbée de peur en l’absence de danger. De manière intéressante, des études récentes suggèrent que la transmission DA joue un rôle essentiel dans l’optimisation de réponses comportementales adaptées pour faire face à un danger. Récemment, mon laboratoire d’accueil a mise en évidence que l’activation des D2R au niveau du BNST et du CEA, joue un rôle critique dans la mise en place des apprentissages associés à la discrimination de stimuli prédictifs d’évènements aversifs. Si ces résultats montrent clairement un rôle de la transmission DA dans le contrôle de la peur généralisée, les circuits neuronaux au sein desquels la signalisation D2R contrôlent ces apprentissages sont encore peu connus.Pour répondre à cette question, nous avons généré des souris mutantes conditionnelles nous permettant d'inactiver sélectivement les D2R dans les neurones de l’amygdale étendue (D2R-cKO) ainsi que dans les neurones DA du mésencéphale (autoD2R-cKO). Mes résultats ont permis de mettre en évidence que la signalisation D2R de l'amygdale étendue 1) module l'expression des stratégies de défense passives (immobilité) en réponse à la présentation des stimuli auditifs et contextuels associés à un danger, 2) facilite l'extinction d’une peur conditionnée, et 3) est nécessaire pour l'apprentissage d’évitement actif du danger. Ces phénotypes ne résultent pas d’une altération des systèmes sensoriels puisque les seuils auditifs ainsi que la sensibilité mécanique et thermique sont intactes chez les souris D2R-cKO. L’analyse de ces mêmes comportements chez les souris autoD2R m’a permis de révéler que les D2R exprimés par les neurones DA jouent un rôle clé dans la discrimination entre les stimuli neutres et ceux prédictifs d’un évènement aversif ou en danger. L’ensemble de mon travail suggère que la signalisation DA via les D2R exprimés par des populations neuronales distinctes contribue à l'optimisation des comportements de défense passifs et actifs mis en jeu pour faire face à situations dangereuses.Learning appropriate defensive behavioral responses to threatening situations is tightly controlled and requires a fine balance between memory specificity and generalization. However, inappropriate processing of threat learning can lead to excessive generalization resulting in the emergence of strong defensive reactions towards neutral cues. The central extended amygdala (EA) is a neuronal continuum critically involved in the control of behavioral responses towards threatening stimuli. Its core components, the nucleus accumbens, the central amygdala (CEA) and the bed nucleus of the stria terminalis (BNST), share similar inputs/outputs connectivity, and serve complementary roles in the integration of threat relevant information and the orchestration of fear- and anxiety-related behaviors. By conveying salience and valence, dopamine (DA) facilitate the encoding of discriminative learning between stimuli representing safety or threat and recent studies indicate that distortion of DA signaling is associated with maladaptive threat processing. We recently uncovered that DA gates overgeneralization of conditioned threat responses through concomitant activation of DA D2 type receptors (D2R) in both the CEA and the BNST. Despite these evidences, genetically-identified neural circuits of the extended amygdala in which, D2R signaling control threat processing, remain largely unknown.To tackle this issue, we have generated to D2R conditional knock-out mice allowing us to inactivate selectively D2R in extended D2R-expressing neurons (D2R-cKO) as well as in midbrain DA neurons (autoD2R-cKO). Our results revealed that extended amygdala D2R signaling modulates the expression of passive responses (i.e. freezing) to threat-conditioning auditory and contextual stimuli. We also found that extended amygdala D2R signaling facilitates extinction of threat conditioned stimulus and is required for active avoidance learning. Such impairments are not a consequence of sensory defaults since auditory brainstem response-evoked thresholds as well as Mechanical and thermal sensitivity are intact in D2R-cKO. On the other hand, we uncovered that autoD2R tunes the discrimination between stimuli representing safety or threat in discriminative auditory threat learning. Together our work suggest that, extended amygdala D2R signaling in distinct neural circuits contribute to the optimization of passive and active defensive behaviors in responses to threatening situations

Art pop i curtmetratges a una biblioteca penitencià ria : tallers de dinamització cultural a la Biblioteca del Centre Penitenciari de Joves de Barcelona

Es descriuen i sâanalitzen dues activitats dâextensió cultural dutes a terme a la Biblioteca del Centre Penitenciari de Joves de Barcelona a partir dâuna col·laboració externa. Sâinclou una descripció del Centre, de la Biblioteca i del perfil dâusuari a qui sâhan dirigit les activats. Seguidament, es resumeixen els diferents passos duts a terme per a la confecció de les activitats, com sâhan desenvolupat i la posterior valoració. Les activitats es van presentar com a tallers i se centraven en el fet visual i de la imatge: pintura dâestètica art pop i cinefòrum dâun curtmetratge. | Two activities of cultural extension are described and analysed. These were carried out, with external collaboration, at the library of the Juvenile Penitentiary Centre of Barcelona. The description covers the Centre, the library, and the profile of the users to whom the activities are directed. The article then explains the different steps undertaken to set up the activities, how they developed, and their subsequent evaluation. The activities took the form of workshops centred on visual happenings and images: pop art style painting and a forum on a short-length movie. | Se describen y analizan dos actividades de extensión cultural realizadas en la Biblioteca del Centre Penitenciari de Joves de Barcelona a partir de una colaboración externa. Se incluye una descripción del Centro, de la Biblioteca y del perfil del usuario al que van destinadas las actividades. Seguidamente, se resumen las diferentes fases de preparación de la actividad, su desarrollo y valoración posterior. Las actividades se presentaron como talleres y estaban centradas en el hecho visual y de la imagen: pintura de estética art pop y cineforum de un cortometraje

Estudio comparativo de la calidad de la información ofrecida sobre los servicios en las webs de las bibliotecas virtuales de universidades a distancia

S'exposa el resultat d'un estudi comparatiu sobre la comunicació web dels serveis de les biblioteques virtuals universitàries d'una selecció d'universitats a distància entre les quals hi ha la UNED, la UOC i l'Open University. Aquest estudi es fa observant les diferències qualitatives de diversos aspectes, com ara l'organització, l'accessibilitat, els formats, el redactat, la utilitat i la presentació de la informació sobre els serveis de la biblioteca oferta en la web als usuaris d'aquelles universitats i/o Biblioteques que han realitzat el procés de gestió de qualitat o han confeccionat la carta de serveis i les que no. Entre diverses recomanacions i exemples de bones pràctiques, l'estudi conclou que les universitats i biblioteques que no mostren cap tipus de procés de qualitat en la seva institució podem veure que són les que obliden alguns elements essencials i molts detalls pel que fa a la descripció de la oferta de serveis es refereix. Conclusió i recomanacions extensibles a qualsevol biblioteca universitària que ofereixi informació en línia sobre els seus serveis. A partir de l'elaboració de fitxes que recullen els diversos aspectes a observar de cadascuna de les biblioteques hem ponderat, d'acord amb la diversa bibliografia consultada, cadascun com desaconsellable, recomanable i excel·lent amb el resultat d'un informe que mostra totes les recomanacions per a cadascun dels elements.Se expone el resultado de un estudio comparativo sobre la comunicación web de los servicios de las bibliotecas virtuales universitarias de una selección de universidades a distancia entre las que se encuentran la UNED, la UOC y la Open University. Este estudio se hace observando las diferencias cualitativas de diversos aspectos, tales como la organización, la accesibilidad, los formatos, el redactado, la utilidad y la presentación de la información sobre los servicios de la biblioteca ofrecida en la web a los usuarios de aquellas universidades y/o Bibliotecas que han realizado el proceso de gestión de calidad o han confeccionado la carta de servicios y las que no. Entre varias recomendaciones y ejemplos de buenas prácticas, el estudio concluye que aquellas universidades y bibliotecas que no muestran ningún tipo de proceso de calidad en su institución podemos ver que son las que olvidan algunos elementos esenciales y muchos detalles por lo que a la descripción de la oferta de servicios se refiere. Conclusión y recomendaciones extensibles a cualquier biblioteca universitaria que ofrezca información en línea sobre sus servicios. A partir de la elaboración de fichas que recogen los diversos aspectos a observar de cada una de las bibliotecas hemos ponderado, en base a la diversa bibliografía consultada, cada uno como desaconsejable, recomendable y excelente resultando un informe que muestra todas las recomendaciones para cada uno de los elementos.The results of a comparative research of web communication in virtual university library services are presented for a sample of distance universities among which there are the UNED, the Open University of Catalonia (UOC) and the Open University. This paper analyses the qualitative differences in several aspects such as information organization, accessibility, formats, composition, usefulness and presentation of the library services offered on the website to the users of those institutions and/or libraries that have a quality management process or have developed a list of services and the ones that have not. Among several recommendations and examples of good practices, the study concludes that those universities and libraries that do not state clearly any quality process in their institutions are those one which that forget essential elements and many details as to the description of range of services is concerned. Conclusion and recommendations extend to any university library that provides online information about its services. By writing cards that gather the different aspects to observe in each library we have weighted, based on the bibliography, each as unwise, desirable and excellent resulting in a report that collects recommendations for each element

Estudio comparativo de la calidad de la información ofrecida sobre los servicios en las webs de las bibliotecas virtuales de universidades a distancia

S'exposa el resultat d'un estudi comparatiu sobre la comunicació web dels serveis de les biblioteques virtuals universitàries d'una selecció d'universitats a distància entre les quals hi ha la UNED, la UOC i l'Open University. Aquest estudi es fa observant les diferències qualitatives de diversos aspectes, com ara l'organització, l'accessibilitat, els formats, el redactat, la utilitat i la presentació de la informació sobre els serveis de la biblioteca oferta en la web als usuaris d'aquelles universitats i/o Biblioteques que han realitzat el procés de gestió de qualitat o han confeccionat la carta de serveis i les que no. Entre diverses recomanacions i exemples de bones pràctiques, l'estudi conclou que les universitats i biblioteques que no mostren cap tipus de procés de qualitat en la seva institució podem veure que són les que obliden alguns elements essencials i molts detalls pel que fa a la descripció de la oferta de serveis es refereix. Conclusió i recomanacions extensibles a qualsevol biblioteca universitària que ofereixi informació en línia sobre els seus serveis. A partir de l'elaboració de fitxes que recullen els diversos aspectes a observar de cadascuna de les biblioteques hem ponderat, d'acord amb la diversa bibliografia consultada, cadascun com desaconsellable, recomanable i excel·lent amb el resultat d'un informe que mostra totes les recomanacions per a cadascun dels elements.Se expone el resultado de un estudio comparativo sobre la comunicación web de los servicios de las bibliotecas virtuales universitarias de una selección de universidades a distancia entre las que se encuentran la UNED, la UOC y la Open University. Este estudio se hace observando las diferencias cualitativas de diversos aspectos, tales como la organización, la accesibilidad, los formatos, el redactado, la utilidad y la presentación de la información sobre los servicios de la biblioteca ofrecida en la web a los usuarios de aquellas universidades y/o Bibliotecas que han realizado el proceso de gestión de calidad o han confeccionado la carta de servicios y las que no. Entre varias recomendaciones y ejemplos de buenas prácticas, el estudio concluye que aquellas universidades y bibliotecas que no muestran ningún tipo de proceso de calidad en su institución podemos ver que son las que olvidan algunos elementos esenciales y muchos detalles por lo que a la descripción de la oferta de servicios se refiere. Conclusión y recomendaciones extensibles a cualquier biblioteca universitaria que ofrezca información en línea sobre sus servicios. A partir de la elaboración de fichas que recogen los diversos aspectos a observar de cada una de las bibliotecas hemos ponderado, en base a la diversa bibliografía consultada, cada uno como desaconsejable, recomendable y excelente resultando un informe que muestra todas las recomendaciones para cada uno de los elementos.The results of a comparative research of web communication in virtual university library services are presented for a sample of distance universities among which there are the UNED, the Open University of Catalonia (UOC) and the Open University. This paper analyses the qualitative differences in several aspects such as information organization, accessibility, formats, composition, usefulness and presentation of the library services offered on the website to the users of those institutions and/or libraries that have a quality management process or have developed a list of services and the ones that have not. Among several recommendations and examples of good practices, the study concludes that those universities and libraries that do not state clearly any quality process in their institutions are those one which that forget essential elements and many details as to the description of range of services is concerned. Conclusion and recommendations extend to any university library that provides online information about its services. By writing cards that gather the different aspects to observe in each library we have weighted, based on the bibliography, each as unwise, desirable and excellent resulting in a report that collects recommendations for each element

Organisation spatio-moléculaire des neurones D2R du striatum dévoilée par le séquençage d’ARN à haut débit

International audienc

Cell-type and endocannabinoid specific synapse connectivity in the adult nucleus accumbens core

International audienceThe nucleus accumbens (NAc) is a mesocorticolimbic structure that integrates cognitive, emotional and motor functions. Although its role in psychiatric disorders is widely acknowledged, the understanding of its circuitry is not complete. Here we combined optogenetic and whole-cell recordings to draw a functional portrait of excitatory disambiguated synapses onto D1 and D2 medium spiny neurons (MSNs) in the adult male mouse NAc core. Comparing synaptic properties of ventral hippocampus (vHipp), basolateral amygdala (BLA) and prefrontal cortex (PFC) inputs revealed a hierarchy of synaptic inputs that depends on the identity of the postsynaptic target MSN. Thus, the BLA is the dominant excitatory pathway onto D1 MSNs (BLA > PFC = vHipp) while PFC inputs dominate D2 MSNs (PFC > vHipp > BLA). We also tested the hypothesis that endocannabinoids endow excitatory circuits with pathway- and cell-specific plasticity. Thus, while CB1 receptors (CB1R) uniformly depress excitatory pathways irrespective of MSNs identity, TRPV1 receptors (TRPV1R) bidirectionally control inputs onto the NAc core in a pathway-specific manner. Finally, we show that the interplay of TRPV1R/CB1R shapes plasticity at BLA-NAc synapses. Together these data shed new light on synapse and circuit specificity in the adult NAc core and illustrate how endocannabinoids contribute to pathway-specific synaptic plasticity