Structure-activity relationships based on 3D-QSAR CoMFA/CoMSIA and design of aryloxypropanol-amine agonists with selectivity for the human β3-adrenergic receptor and anti-obesity and anti-diabetic profiles

Indexación: Scopus.Acknowledgments: This work was supported by FONDECYT No. 11130701. We would also like to thank fDoTr CthLeafbr efeora vthaeil afrbeilei tayvoafiltahbeilsitoyf towfa trheer seoqfutwireadret orecqaulciureladt etothcealAcuDla(thet ttph:e/ A/dDt c(lhatbt.pw:/e/dbstc.cloabm.w/seobfst.wcoamre/-stoofotlws aarned-tools and http://teqip.jdvu.ac.in/QSAR_Tools/). SDG. Conflicts of Interest: The authors declare no conflict of interest. Conflicts of Interest: The authors declare no conflict of interest.The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB), and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques. This is the first combined comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) study in a series of selective aryloxypropanolamines displaying anti-diabetes and anti-obesity pharmacological profiles. The best CoMFA and CoMSIA models presented values of r2 ncv = 0.993 and 0.984 and values of r2 test = 0.865 and 0.918, respectively. The results obtained were subjected to extensive external validation (q2, r2, r2 m, etc.) and a final series of compounds was designed and their biological activity was predicted (best pEC50 = 8.561). © 2018 by the authors.https://www.mdpi.com/1420-3049/23/5/119

Status of carnivores in Biscay (N lberian peninsula)

The first study on the carnivore community of Biscay was published in 1985. The present study, made twelve years later, was carried out to assess the present situation of these mammals. In this work, data collected from 1990 to 1996 by trapping, sighting, and surveying road and other kills, as well as faeces and tracks are reported. Records of 12 species were obtained, of which American mink Mustela vison (Schreber, 1777) is cited for the first time, and the wolf reappears as a non-occasional species. The main trends observed during the last twelve years seem to be related to changes in land use and management of natural resources. The situation has turned favourable for the most opportunistic species, which have become very abundant in some areas, while populations of the most specialist or relictic species show a more restricted distribution. At the same time, the expansion of wolf and European mink, with the appearance of American mink for the first time, reflect a dynamic but very unstable scene. Key words: Carnivores, Population status, Distribution, Conservation, lberian peninsula.The first study on the carnivore community of Biscay was published in 1985. The present study, made twelve years later, was carried out to assess the present situation of these mammals. In this work, data collected from 1990 to 1996 by trapping, sighting, and surveying road and other kills, as well as faeces and tracks are reported. Records of 12 species were obtained, of which American mink Mustela vison (Schreber, 1777) is cited for the first time, and the wolf reappears as a non-occasional species. The main trends observed during the last twelve years seem to be related to changes in land use and management of natural resources. The situation has turned favourable for the most opportunistic species, which have become very abundant in some areas, while populations of the most specialist or relictic species show a more restricted distribution. At the same time, the expansion of wolf and European mink, with the appearance of American mink for the first time, reflect a dynamic but very unstable scene. Key words: Carnivores, Population status, Distribution, Conservation, lberian peninsula.The first study on the carnivore community of Biscay was published in 1985. The present study, made twelve years later, was carried out to assess the present situation of these mammals. In this work, data collected from 1990 to 1996 by trapping, sighting, and surveying road and other kills, as well as faeces and tracks are reported. Records of 12 species were obtained, of which American mink Mustela vison (Schreber, 1777) is cited for the first time, and the wolf reappears as a non-occasional species. The main trends observed during the last twelve years seem to be related to changes in land use and management of natural resources. The situation has turned favourable for the most opportunistic species, which have become very abundant in some areas, while populations of the most specialist or relictic species show a more restricted distribution. At the same time, the expansion of wolf and European mink, with the appearance of American mink for the first time, reflect a dynamic but very unstable scene. Key words: Carnivores, Population status, Distribution, Conservation, lberian peninsula

Nestling diet and fledgling production of eurasian kestrels (Falco tinnunculus) in eastern Spain.

We studied 81 Eurasian kestrel (Falco tinnunculus) nests in the Alto Palancia region (Castel16n, eastern Spain) from 1982-87. Fledgling production was recorded in routine visits to the nests, and the diet was determined by pellet analysis. The mean date of laying was 8 May (N -- 24, SD -- 11.5), similar to that of populations breeding further north in Europe. On average, each successful pair produced four fledglings per year (N = 47, SD = 0.7, range = 2-5), and no significant differences in fledging success were found among years. Grasshoppers formed the bulk of the diet during the nestling period. Mammals and birds were scarcely represented. The number of fledglings per successful pair was similar to or higher than that reported from Finland, Germany, and England where voles are the main prey brought to the nestlings. We suggest that a relative abundance of insects, and reduced energy requirements for thermoregulation in Mediterranean areas allow kestrels to successfully feed their young mainly on insects, without reducing fledgling production in relation to populations where voles form the bulk of the nestling diet. Se estudiaron 81 nidos de cernícalo vulgar (Falco tinnunculus) en la comarca del Alto Palancia (Castel16n, Este de España) entre 1982-87. La producci6n de pollos se estudió mediante visitas periódicas a los nidos, y la dieta analizando las egagrópilas recolectadas durante el periodo de permanencia de los pollos en el nido. La fecha media de inicio de la puesta fue el 8 de Mayo (N -- 24, SD -- 11.5), similar a las observadas en otros países de Europa. Cada pareja con éxito produce una media de cuatro pollos por año (N -- 47, SD = 0.7, rango -- 2-5), no habiendo diferencias significativas entre años. Los saltamontes forman la base de la dieta durante el periodo estudiado, estando los mamíferos y las aves escasamente representados. La producción de pollos por pareja con éxito es similar o mayor a las obtenidas en Finlandia, Alemania e Inglaterra, donde los topillos forman la base de la dieta de los pollos. Se sugiere que una mayor disponibilidad de insectos, y una reducción de los requerimientos energéticos de los pollos en las áreas mediterráneas, permiten a los cernícalos alimentar a los pollos con una dieta basada en insectos sin reducir su productividad con respecto a poblaciones donde los mamíferos son la base de la dieta

Cognitive function in childhood and lifetime cognitive change in relation to mental wellbeing in four cohorts of older people

Background: poorer cognitive ability in youth is a risk factor for later mental health problems but it is largely unknown whether cognitive ability, in youth or in later life, is predictive of mental wellbeing. The purpose of this study was to investigate whether cognitive ability at age 11 years, cognitive ability in later life, or lifetime cognitive change are associated with mental wellbeing in older people.Methods: we used data on 8191 men and women aged 50 to 87 years from four cohorts in the HALCyon collaborative research programme into healthy ageing: the Aberdeen Birth Cohort 1936, the Lothian Birth Cohort 1921, the National Child Development Survey, and the MRC National Survey for Health and Development. We used linear regression to examine associations between cognitive ability at age 11, cognitive ability in later life, and lifetime change in cognitive ability and mean score on the Warwick Edinburgh Mental Wellbeing Scale and meta-analysis to obtain an overall estimate of the effect of each.Results: people whose cognitive ability at age 11 was a standard deviation above the mean scored 0.53 points higher on the mental wellbeing scale (95% confidence interval 0.36, 0.71). The equivalent value for cognitive ability in later life was 0.89 points (0.72, 1.07). A standard deviation improvement in cognitive ability in later life relative to childhood ability was associated with 0.66 points (0.39, 0.93) advantage in wellbeing score. These effect sizes equate to around 0.1 of a standard deviation in mental wellbeing score. Adjustment for potential confounding and mediating variables, primarily the personality trait neuroticism, substantially attenuated these associations.Conclusion: associations between cognitive ability in childhood or lifetime cognitive change and mental wellbeing in older people are slight and may be confounded by personality trait difference

Evaluating the performance of model transformation styles in Maude

Rule-based programming has been shown to be very successful in many application areas. Two prominent examples are the specification of model transformations in model driven development approaches and the definition of structured operational semantics of formal languages. General rewriting frameworks such as Maude are flexible enough to allow the programmer to adopt and mix various rule styles. The choice between styles can be biased by the programmer’s background. For instance, experts in visual formalisms might prefer graph-rewriting styles, while experts in semantics might prefer structurally inductive rules. This paper evaluates the performance of different rule styles on a significant benchmark taken from the literature on model transformation. Depending on the actual transformation being carried out, our results show that different rule styles can offer drastically different performances. We point out the situations from which each rule style benefits to offer a valuable set of hints for choosing one style over the other

Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project

INTRODUCTION: Chronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. METHODS: A total of 107 children (10.0 ± 1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma: white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Munoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. RESULTS: IL-6 was inversely associated with adaptive skills (beta = -0.228; p = 0.030), while TNF-alpha was related to mathematics (beta = -0.198; p = 0.034). In addition, CRP was positively associated with externalizing (beta = 0.246; p = 0.046) and internalizing problems (beta = 0.234; p = 0.039), as well as the behavioural symptoms index (beta = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (beta = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (beta = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (beta = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (beta = 0.366; p < 0.001, k = 81) and TNF-alpha (beta = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (beta = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (beta ranging from -0.473 to -0.404; p < 0.001, k = 87). CONCLUSIONS: Inflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children's brain health

The mediterranean biotypes of Tylenchulus semipenetrans in Spanish citrus orchards

Les capacités de reproduction de quatorze populations du nématode des citrus (#Tylenchulus semipenetrans$) collectées dans la principale zone de citriculture de l'Espagne ont été comparées sur oranger amer et citrange Carrizo. Toutes les populations ont été identifiées comme appartenant au biotype méditerranéen. La capacité de reproduction varie considérablement en fonction des populations. Le pouvoir infestant et le taux de reproduction des populations collectées dans la rhizosphère des porte-greffes citranges Troyer ou Carrizo sont plus élevés (P supérieur ou égal à 0,05) que ceux des populations collectées sur oranger amer. (Résumé d'auteur

Functionalised graphene sheets as effective high dielectric constant fillers

A new functionalised graphene sheet (FGS) filled poly(dimethyl)siloxane insulator nanocomposite has been developed with high dielectric constant, making it well suited for applications in flexible electronics. The dielectric permittivity increased tenfold at 10 Hz and 2 wt.% FGS, while preserving low dielectric losses and good mechanical properties. The presence of functional groups on the graphene sheet surface improved the compatibility nanofiller/polymer at the interface, reducing the polarisation process. This study demonstrates that functionalised graphene sheets are ideal nanofillers for the development of new polymer composites with high dielectric constant values

The Relationship between Visual-Spatial and Auditory-Verbal Working Memory Span in Senegalese and Ugandan Children

BACKGROUND: Using the Kaufman Assessment Battery for Children (K-ABC) Conant et al. (1999) observed that visual and auditory working memory (WM) span were independent in both younger and older children from DR Congo, but related in older American children and in Lao children. The present study evaluated whether visual and auditory WM span were independent in Ugandan and Senegalese children. METHOD: In a linear regression analysis we used visual (Spatial Memory, Hand Movements) and auditory (Number Recall) WM along with education and physical development (weight/height) as predictors. The predicted variable in this analysis was Word Order, which is a verbal memory task that has both visual and auditory memory components. RESULTS: Both the younger (<8.5 yrs) and older (>8.5 yrs) Ugandan children had auditory memory span (Number Recall) that was strongly predictive of Word Order performance. For both the younger and older groups of Senegalese children, only visual WM span (Spatial Memory) was strongly predictive of Word Order. Number Recall was not significantly predictive of Word Order in either age group. CONCLUSIONS: It is possible that greater literacy from more schooling for the Ugandan age groups mediated their greater degree of interdependence between auditory and verbal WM. Our findings support those of Conant et al., who observed in their cross-cultural comparisons that stronger education seemed to enhance the dominance of the phonological-auditory processing loop for WM