Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration.

Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein, for which there is still no effective treatment. Therefore, new pharmacological targets are being sought, such as elements of the endocannabinoid system (ECS). We analysed the occurrence of changes in the ECS in tauopathies and their implication in the pathogenesis. By integrating gene expression analysis, immunofluorescence, genetic and adeno-associated virus expressing TAU mouse models, we found a TAU-dependent increase in CB2 receptor expression in hippocampal neurons, that occurs as an early event in the pathology and was maintained until late stages. These changes were accompanied by alterations in the endocannabinoid metabolism. Remarkably, CB2 ablation in mice protects from neurodegeneration induced by hTAU P301L overexpression, corroborated at the level of cognitive behaviour, synaptic plasticity, and aggregates of insoluble TAU. At the level of neuroinflammation, the absence of CB2 did not produce significant changes in concordance with a possible neuronal location rather than its classic glial expression in these models. These findings were corroborated in post-mortem samples of patients with Alzheimer’s disease, the most common tauopathy. Our results show that neurons with accumulated TAU induce the expression of the CB2 receptor, which enhances neurodegeneration. These results are important for our understanding of disease mechanisms, providing a novel therapeutic strategy to be investigated in tauopathiespost-print8580 K

Rachas secas y gradiente pluviométrico en la cuenca del Duero

Ponencia presentada en: III Congreso de la Asociación Española de Climatología “El agua y el clima”, celebrado en Palma de Mallorca del 16 al 19 de junio de 2002.[ES]Se estudian las rachas secas a lo largo de un marcado gradiente pluviométrico entre el sector central de la cuenca del Duero, con una precipitación media anual inferior a 400 mm, y la Sierra de Salamanca con más de 1.000 mm. Los resultados, considerando el umbral de 0,1 mm en la definición de “día seco”, muestran la elevada duración y frecuencia de las rachas secas en el conjunto del transecto, con una racha media de 10 días y un valor medio de las rachas máximas anuales superior a 40 días, manifestando una marcada mediterraneidad a pesar de su ubicación en la mitad septentrional de la Península Ibérica y del carácter montañoso de parte del mismo. No obstante, sí se observa un comportamiento diferencial, de acuerdo con el gradiente, cuando se consideran umbrales de lluvia (=10 mm) que discriminan las precipitaciones que realmente inciden sobre la disponibilidad hídrica de los ecosistemas.[EN]The aim of the present work is to study the dry spells along a marked rainfall gradient from the central part of the Duero basin, with an average annual precipitation below 400 mm, to Salamanca Rangeland, with precipitation recordings above 1000 m. Considering as dry days those with precipitations of = 0.1 mm, the results of the analysis show a high duration and frequency of dry spells for the overall zone: mean duration over 10 days and the mean duration of maximum dry spells is higher than 40 days. Although the study area is located in the northern part of Iberian Peninsula and the mountainous sector is important, this analysis indicates the Mediterranean climatic characteristics of the transect. However, the differences were noteworthy, according with the rainfall gradient, when threshold rainfalls (= 10 mm) related with water availability of ecosystems are used.Los autores quieren expresar su agradecimiento al Ministerio de Ciencia y Tecnología (Proyecto REN2000-1157) y a la Junta de Castilla y León (Proyecto SA55/00A) por la financiación que ha hecho posible este trabajo

Beef quality differentiation in the framework of the Serrana de Teruel endangered breed conservation programme

La Serrana de Teruel es una raza bovina en peligro de extinción, criada tradicionalmente en áreas montañosas del Sur de Aragón (España). Con objeto de recuperar la raza, se realizó la caracterización morfológica, zootécnica y genética de la población existente. La raza presentó un grado medio-alto de armonía y homogeneidad, siendo la mayoría de individuos de perfil recto, eumétricos y sublongilíneos, aunque de menor tamaño al observado en otras razas filogenéticamente próximas. Los estudios de biodiversidad mostraron niveles altos de variabilidad genética y bajos de consanguinidad, a pesar del censo reducido (240 individuos en 2010), y proporcionaron las bases para llevar a cabo un programa sostenible de conservación. Para garantizar su mantenimiento a largo plazo, los bancos de germoplasma mantienen 6400 dosis de semen y 74 embriones. Paralelamente, se analizó la viabilidad comercial de la raza, a través del estudio de la calidad de canal y carne de las categorías comerciales de ternero, añojo y cebón (castrados con 9 meses), con edades a sacrificio de 12, 22 y 22 meses y pesos vivos de 470, 720 y 660 kg, respectivamente. Finalmente, se realizó un análisis prospectivo, según la opinión de expertos, de una nueva carne de vacuno con denominación de calidad, llamada ‘Serrana de Teruel’. Estos trabajos muestran la posibilidad de realizar una producción alternativa, tipo cebón, susceptible de acogerse a distintivos de calidad diferenciada, que podrían suponer un incentivo para la explotación de la Serrana de Teruel frente a otras razas, lo que favorecería su conservación a medio plazo.Serrana de Teruel is an endangered cattle breed raised traditionally in the mountainous areas of Southern Aragon (Spain). With the aim of recovering the breed, a characterization was carried out to determine the morphology, husbandry and genetic values of the Serrana de Teruel breed. Individuals showed a medium to high degree of homogeneity and harmony, most of the animals being of straight profile, and eumetrical and sublongilineal individuals, although smaller in size than other phylogenetically proximate breeds. Biodiversity studies showed good diversity values despite the breed’s low effective population size (240 individuals in 2010). These studies provided the basis for a sustainable programme of genetic conservation. In order to guarantee long-term maintenance, germplasm banks contain 6400 doses of semen and 74 embryos. Concurrently, the commercial viability of the breed was studied by means of an analysis of carcass and meat quality from three commercial categories – yearling, bull and steer (castrated at 9 months old) – with ages at slaughter of 12, 22 and 22 months and live weights of 470, 720 and 660 kg,, respectively. Good performances and high-quality products with no commercial constraints in the beef market were obtained. Finally, a prospective study for a new beef quality product labelled ‘Serrana de Teruel’ was performed, according to the opinions of experts. These studies provide the standard requirements for the alternative production of a labelled beef product that might create an incentive for the production of the Serrana de Teruel breed among other breeds, and thus favour the conservation of the breed in the medium termLa Serrana de Teruel est une race bovine rustique élevée dans les régions montagneuses du sud de l’Aragon (Espagne) qui est en danger d’extinction. Afin de récupérer cette race on a réalisé la caractérisation morphologique, génétique et zootechnique de la population existante. La race présente un degré moyen-élevé d’harmonie et d’uniformité, la plupart des animaux étant de profil droit, eumétrique et sublongiligne, bien que plus petit en taille que les autres races proches. Des études sur la biodiversité ont montré des niveaux élevés de diversité génétique et un faible niveau de consanguinité, malgré les effectifs limités d’animaux (240 individus en 2010), en fournissant les bases du programme de conservation. Afin de garantir le maintien à long terme, a été créée une banque de matériel génétique contenant 6400 doses de semence et 74 embryons. En parallèle, on a confirmé la viabilité commerciale de la race à travers l’étude de la qualité de la carcasse et de la viande pour les catégories commerciales de veau, taurillon et bouvillons (castrés à 9 mois), avec des âges à l’abattage de 12, 22 et 22 mois, et 470, 720 et 660 kg de poids vif, respectivement. Enfin, nous avons mené une analyse prospective, à dires d’experts, pour un nouveau label de qualité du boeuf appelé ‘Serrana de Teruel’. Ces travaux montrent la possibilité d’une production alternative, comme boeuf, susceptible de bénéficier d’une certification de qualité, ce qui pourrait créer une incitation pour l’exploitation de la Serrana de Teruel parmi les autres races, et ainsi favoriser sa préservation à long termePublishe

A Genetic Tuning to Improve the Performance of Fuzzy Rule-Based Classification Systems with Interval-Valued Fuzzy Sets: Degree of Ignorance and Lateral Position

Fuzzy Rule-Based Systems are appropriate tools to deal with classification problems due to their good properties. However, they can suffer a lack of system accuracy as a result of the uncertainty inherent in the definition of the membership functions and the limitation of the homogeneous distribution of the linguistic labels. The aim of the paper is to improve the performance of Fuzzy Rule-Based Classification Systems by means of the Theory of Interval-Valued Fuzzy Sets and a post-processing genetic tuning step. In order to build the Interval-Valued Fuzzy Sets we define a new function called weak ignorance for modeling the uncertainty associated with the definition of the membership functions. Next, we adapt the fuzzy partitions to the problem in an optimal way through a cooperative evolutionary tuning in which we handle both the degree of ignorance and the lateral position (based on the 2-tuples fuzzy linguistic representation) of the linguistic labels. The experimental study is carried out over a large collection of data-sets and it is supported by a statistical analysis. Our results show empirically that the use of our methodology outperforms the initial Fuzzy Rule-Based Classification System. The application of our cooperative tuning enhances the results provided by the use of the isolated tuning approaches and also improves the behavior of the genetic tuning based on the 3-tuples fuzzy linguistic representation.Spanish Government TIN2008-06681-C06-01 TIN2010-1505

Males and females with first episode psychosis present distinct profiles of social cognition and metacognition

Altres ajuts: Royal Society of New Zealand - Marsden (E2987-3648) ; Obra Social La Caixa (RecerCaixa call 2013) ; Obra Social Sant Joan de Déu BML (RTI2018-100927-J-I00) ; Ministerio Regional de Salud AndaluzDeficits in social cognition and metacognition impact the course of psychosis. Sex diferences in social cognition and metacognition could explain heterogeneity in psychosis. 174 (58 females) patients with frst-episode psychosis completed a clinical, neuropsychological, social cognitive, and metacognitive assessment. Subsequent latent profle analysis split by sex yielded two clusters common to both sexes (a Homogeneous group, 53% and 79.3%, and an Indecisive group, 18.3% and 8.6% of males and females, respectively), a specifc male profle characterized by presenting jumping to conclusions (28.7%) and a specifc female profle characterized by cognitive biases (12.1%). Males and females in the homogeneous profle seem to have a more benign course of illness. Males with jumping to conclusions had more clinical symptoms and more neuropsychological defcits. Females with cognitive biases were younger and had lower self-esteem. These results suggest that males and females may beneft from specifc targeted treatment and highlights the need to consider sex when planning interventions

Evaluation of a New Monoclonal Chemiluminescent Immunoassay Stool Antigen Test for the Diagnosis of Helicobacter pylori Infection: A Spanish Multicentre Study

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON(R) Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard C-13-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients >= 18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naive, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT = 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON(R) Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection

Paradigmatic de novo GRIN1 variants recapitulate pathophysiological mechanisms underlying GRIN1-related disorder clinical spectrum

Background: GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting GRIN genes (mostly GRIN1, GRIN2A and GRIN2B genes), which encode for the GluN subunit of the N-methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present. Methods: In this study, we aimed to delineate the structural and functional alterations of GRIN1 disease-associated variants, and their correlations with clinical symptoms in a Spanish cohort of 15 paediatric encephalopathy patients harbouring these variants. Results: Patients harbouring GRIN1 disease-associated variants have been clinically deeplyphenotyped. Further, using computational and in vitro approaches, we identified different critical checkpoints affecting GluN1 biogenesis (protein stability, subunit assembly and surface trafficking) and/or NMDAR biophysical properties, and their association with GRD clinical symptoms. Conclusions: Our findings show a strong correlation between GRIN1 variants-associated structural and functional outcomes. This structural-functional stratification provides relevant insights of genotypephenotype association, contributing to future precision medicine of GRIN1-related encephalo

Validation and psychometric analysis of the Internet Addiction Test in Spanish among college students

BACKGROUND: The wide use of the Internet in the workplace, academic or social field, can have an impact on daily life. One of the most used questionnaires worldwide to analyse these problems is the Internet Addiction Test (IAT). Our aim was to validate a Spanish version of the IAT and analyse its psychometric properties. METHODS: Population of study were college students participating in the uniHcos project (Universities of Granada, Huelva, Jaén, León, Salamanca, and Vigo). The questionnaire was translated and back-translated by two native English speakers. Reliability of scores was analysed using Pearson's correlation coefficient and agreement was analysed using the Bland-Altman and Kappa techniques. Test dimensions were analysed by exploratory and confirmatory factor analysis. RESULTS: The reliability of scores was good (r = 0.899, Kappa = 0.650 and mean difference using Bland-Altman = -3.5). The psychometric assessment identified two factors (Emotional Investment; Performance and Time Management) which explained 55 % of the variance (total internal consistency of 0.91) and only 19 items. The confirmatory analysis showed an acceptable goodness of fit, especially when items 6 and 8 were related (RMSEA = 0.07 90%IC = 0.06 - 0.08; WRMR = 1.01, CFI = 0.96; TLI = 0.95). The two dimensions were negatively correlated with age and positively correlated with time spent online, especially for the purposes of leisure and entertainment. DISCUSSION: The results show good reliability and psychometric properties of the Spanish version of IAT with a two-dimensional solution. This result is partially in concordance with previous validations of the IAT in other languages that have found uni- and multi-dimensional solutions using different methodologies. Moreover, we want to highlight the possibility that some item of this questionnaire is outdated due to the technological and lifestyles changes and should be not taken into account. CONCLUSION: The reliability and psychometric properties obtained in this study support the conclusion that this Spanish short version of the IAT represents a useful tool for the analysis of problems arising from misuse of the Internet

Impact of the Spanish Smoking Law on Exposure to Second-Hand Smoke and Respiratory Health in Hospitality Workers: A Cohort Study

A smoke-free law came into effect in Spain on 1st January 2006, affecting all enclosed workplaces except hospitality venues, whose proprietors can choose among totally a smoke-free policy, a partial restriction with designated smoking areas, or no restriction on smoking on the premises. We aimed to evaluate the impact of the law among hospitality workers by assessing second-hand smoke (SHS) exposure and the frequency of respiratory symptoms before and one year after the ban