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Molecular and cellular reorganization of neural circuits in the human lineage

  • Sousa, André M. M.
  • Zhu, Ying
  • Raghanti, Mary Ann
  • Kitchen, Robert R.
  • Onorati, Marco
  • Tebbenkamp, Andrew T. N.
  • Stutz, Bernardo
  • Meyer, Kyle A.
  • Li, Mingfeng
  • Kawasawa, Yuka Imamura
  • Liu, Fuchen
  • García Pérez, Raquel
  • Mele, Marta
  • Carvalho, Tiago Loureiro de, 1987-
  • Skarica, Mario
  • Gulden, Forrest O.
  • Pletikos, Mihovil
  • Shibata, Akemi
  • Stephenson, Alexa R.
  • Edler, Melissa K.
  • Ely, John J.
  • Elsworth, John D.
  • Horvath, Tamas L.
  • Hof, Patrick R.
  • Hyde, Thomas M.
  • Kleinman, Joel E.
  • Weinberger, Daniel R.
  • Reimers, Mark
  • Lifton, Richard P.
  • Mane, Shrikant M.
  • Noonan, James P.
  • State, Matthew W.
  • Lein, Ed S.
  • Knowles, James A.
  • Marquès i Bonet, Tomàs, 1975-
  • Sherwood, Chet C.
  • Gerstein, Mark B.
  • Sestan, Nenad
To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease., Data was generated as part of the PsychENCODE Consortium, supported by MH103339, MH106934, and MH110926. Additional support was provided by the NIH grant MH109904, the Kavli Foundation, the James S. McDonnell Foundation, NSF grant BCS-1316829, and ERC Starting Grant 260372, and MICINN BFU2011-28549

Effects of virgin olive oils differing in their bioactive compound contents on metabolic syndrome and endothelial functional risk biomarkers in healthy adults: a randomized double-blind controlled trial

  • Sánchez-Rodriguez, Estefanía
  • Lima-Cabello, Elena
  • Biel-Glesson, Sara
  • Fernández-Navarro, Jose-Ramón
  • Calleja, Miguel Angel
  • Roca Bigorra, Maria
  • Espejo-Calvo, Juan A.
  • Gil-Extremera, Blas
  • Soria-Florido, Maria
  • Torre Fornell, Rafael de la
  • Fitó Colomer, Montserrat
  • Covas Planells, Maria Isabel
  • Alche, Juan de Dios
  • Martínez de Victoria, Emilio
  • Gil, Angel
  • Mesa, Maria-Dolores
The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739).

Health-related quality of life inequalities by sexual orientation: results from the Barcelona health interview survey

  • Martí-Pastor, Marc
  • Pérez Albarracín, Glòria
  • German, Danielle
  • Pont Acuña, Àngels
  • Garin Boronat, Olatz, 1979-
  • Alonso Caballero, Jordi
  • Gotsens Miquel, Mercè, 1983-
  • Ferrer Forés, Maria Montserrat
Background: Studies on health-related quality of life (HRQoL) inequalities according to sexual orientation are scarce. The aim of this study was to assess HRQoL inequalities between lesbian, gay, and bisexual (LGB) people and heterosexuals in the 2011 Barcelona population, to describe the extent to which sociodemographic characteristics, health-related behaviors, and chronic conditions could explain such inequalities, and to understand if they are sexual orientation inequities. Methods: In the 2011 Barcelona Health Interview Survey 3277 adults answered the EQ-5D, which measures five dimensions of HRQoL summarized into a single utility index (1 = perfect health, 0 = death). To assess HRQoL differences by sexual orientation we constructed Tobit models for the EQ-5D index, and Poisson regression models for the EQ-5D dimensions. In both cases, nested models were constructed to assess the mediator role of selected variables. Results: After adjusting by socio-demographic variables, the LGB group presented a significantly lower EQ-5D index than heterosexuals, and higher prevalence ratios of problems in physical EQ-5D dimensions among both genders: adjusted prevalence ratio (aPR) = 1.70 for mobility (p = 0.046) and 2.11 for usual activities (p = 0.019). Differences in mental dimensions were only observed among men: aPR = 3.15 for pain/discomfort (p = 0.003) and 2.49 for anxiety/depression (p = 0.030). All these differences by sexual orientation disappeared after adding chronic conditions and health-related behaviors in the models. Conclusion: The LGB population presented worse HRQoL than heterosexuals in the EQ-5D index and most dimensions. Chronic conditions, health-related behaviors and gender play a major role in explaining HRQoL differences by sexual orientation. These findings support the need of including sexual orientation into the global agenda of health inequities.

Análisis de las atribuciones de guarda y custodia de menores en las sentencias judiciales

  • Rodríguez Domínguez, Carles
  • Jarne, Adolfo
  • Carbonell, Xavier
Dada la trascendencia que tienen sobre la vida de los menores involucrados en los procesos de separación o divorcio de sus padres, la atribución de la guarda y custodia de menores está determinada en la jurispruden­cia española por la supremacía del Interés Superior del Menor. Aún son escasos en nuestro entorno los estudios de las resoluciones judiciales sobre las atri­buciones de la custodia de menores. A fin de analizar las sentencias emitidas en separaciones o divorcios ad litem por los tribunales de familia, se confeccionó un protocolo para dar a conocer en el presente estudio los razonamientos sobre la atribución de la guarda y custo­dia, y las medi­das reguladoras entre las partes emitidas por los tribu­nales así como para exponer la evolución de la custodia compartida versus exclusiva en el período 2007 a 2013 en siete juzgados de familia de la ciudad de Barcelona. Los resultados revelaron evidencias de que todas las sentencias analizadas fueron motivadas, mos­traron un incremento a favor de la atribución de la custodia com­partida y un decremento de la custodia exclusiva atri­buida a favor de la madre en dicho período., Given the significance on the lives of children in­volved in the processes of separation or divorce of their parents, the attribution of custody and child custody is determined in Spanish jurisprudence by the supremacy of the greater interest of the Child. Are still rare in our environment studies of judicial decisions on the powers of the custody of children. In order to analyze the judgments in separation or divorce ad litem by the family courts, a protocol was drawn to publicize in this study reasoning about the attribution of the custody, and regulatory measures among parts issued by the courts and for explaining the evolution of shared versus sole custody in the period 2007-2013 in seven courts in Barcelona city. The results revealed evidence that all the sentences analyzed were motivated, showed an increase in favor of the attribution of joint custody and a de­crease in sole custody attributed in favor of the mother in that period.

In Silico QT and APD prolongation assay for early screening of drug-induced proarrhythmic risk

  • Romero, Lucia
  • Cano, Jordi
  • Gomis-Tena, Julio
  • Trenor, Beatriz
  • Sanz, Ferran
  • Pastor Maeso, Manuel
  • Saiz, Javier
Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue. Multiple channel-drug interactions and state-of-the-art human ventricular action potential models ( O'Hara , T. , PLos Comput. Biol. 2011 , 7 , e1002061 ) were used in our simulations. Specifically, 206.766 cellular and 7072 tissue simulations were performed by blocking the slow and the fast components of the delayed rectifier current ( IKs and IKr, respectively) and the L-type calcium current ( ICaL) at different levels. The performance of our system was validated by classifying the proarrhythmic risk of 84 compounds, 40 of which present torsadogenic properties. On the basis of these results, we propose the use of a new index (Tx) for discriminating torsadogenic compounds, defined as the ratio of the drug concentrations producing 10% prolongation of the cellular endocardial, midmyocardial, and epicardial APDs and the QT interval, over the maximum effective free therapeutic plasma concentration (EFTPC). Our results show that the Tx index outperforms standard methods for early identification of torsadogenic compounds. Indeed, for the analyzed compounds, the Tx tests accuracy was in the range of 87-88% compared with a 73% accuracy of the hERG IC50 based test., L.R., J.C., J.G., B.T., J.S.: This work was partially supported by the Direccion General de Política Cientifíca de la Generalitat Valenciana (PROMETEU2016/088) as well as Ministerio de Economia y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) DPI2015-69125-R (MINECO/FEDER, UE). F.S, M.P.: received support from the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115002 (eTOX), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contributions

Behavioral profiles of children with Williams syndrome from Spain and the United States: cross-cultural similarities and differences

  • Pérez García, Débora, 1985-
  • Brun i Gasca, Carme
  • Pérez Jurado, Luis Alberto
  • Mervis, Carolyn B.
To identify similarities and differences in the behavioral profile of children with Williams syndrome from Spain (n = 53) and the United States (n = 145), we asked parents of 6- to 14-year-olds with Williams syndrome to complete the Child Behavior Checklist 6-18. The distribution of raw scores was significantly higher for the Spanish sample than the American sample for all of the higher-order factors and half of both the empirically based and Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scales. In contrast, analyses based on country-specific T-scores indicated that the distribution for the Spanish sample was significantly higher than for the American sample only on the Social Problems scale. No gender differences were found. Genetic and cultural influences on children's behavior and cultural influences on parental ratings of behavior are discussed., Débora Pérez-García was supported by a predoctoral fellowship from Instituto de Salud Carlos III (FI11/00656). Data collection for the Spanish sample was supported by grants from the Spanish Ministries of Science, Economy & Competitivity (SAF04/6382 & PI13/02481) and the European Community (EC-FP6-37627) to Luis A. Pérez-Jurado. Data collection for the US sample was supported by grants from the National Institute of Child Health and Human Development (R37 HD29957) and the National Institute of Neurological Disorders and Stroke (R01 NS35102) to Carolyn Mervis. Data analysis and manuscript preparation were supported by NICHD grant R37 HD29957 and grant WSA 0104 from the Williams Syndrome Association to Carolyn Mervis

Coupling between distant biofilms and emergence of nutrient time-sharing

  • Liu, Jintao
  • Martínez Corral, Rosa
  • Prindle, Arthur
  • Lee, Dong-yeon D.
  • Larkin, Joseph
  • Gabaldà Sagarra, Marçal,1988-
  • Garcia Ojalvo, Jordi
  • Süel, Gürol M.
Bacteria within communities can interact to organize their behavior. It has been unclear whether such interactions can extend beyond a single community to coordinate the behavior of distant populations. We discovered that two Bacillus subtilis biofilm communities undergoing metabolic oscillations can become coupled through electrical signaling and synchronize their growth dynamics. Coupling increases competition by also synchronizing demand for limited nutrients. As predicted by mathematical modeling, we confirm that biofilms resolve this conflict by switching from in-phase to antiphase oscillations. This results in time-sharing behavior, where each community takes turns consuming nutrients. Time-sharing enables biofilms to counterintuitively increase growth under reduced nutrient supply. Distant biofilms can thus coordinate their behavior to resolve nutrient competition through time-sharing, a strategy used in engineered systems to allocate limited resources., This work was in part supported by the San Diego Center for Systems Biology (NIH grant P50 GM085764), the National Institute of General Medical Sciences (grant R01 GM121888 to G.M.S.), the Defense Advanced Research Projects Agency (grant HR0011-16-2-0035 to G.M.S.), the Howard Hughes Medical Institute–Simons Foundation Faculty Scholars program (to G.M.S.), a Simons Foundation Fellowship of the Helen Hay Whitney Foundation (to A.P.), a Career Award at the Scientific Interface from the Burroughs Wellcome Fund (to A.P.), the Spanish Ministry of Economy and Competitiveness and FEDER (European Regional Development Fund) (project FIS2015-66503-C3-1-P, to J.G.-O.), the Generalitat de Catalunya (project 2014SGR0947, to J.G.-O.), the ICREA (Catalan Institution for Research and Advanced Studies) Academia program (to J.G.-O.), the “Maria de Maeztu” Programme for Units of Excellence in Research and Development (Spanish Ministry of Economy and Competitiveness, grant MDM-2014-0370 to J.G.-O.), the La Caixa foundation (to R.M.-C.), and a doctoral grant from the Formacion del Profesorado Universitario program of the Ministerio de Educacion, Cultura y Deportes, Spain (to M.G.-S.)

Comorbidity between obsessive-compulsive disorder and body dysmorphic disorder: prevalence, explanatory theories, and clinical characterization

  • Frías, Álvaro
  • Palma Sevillano, Carolina
  • Farriols Hernando, Núria
  • González, Laura
Background: With the advent of the fifth edition of Diagnostic and Statistical Manual of Mental Disorders, body dysmorphic disorder (BDD) has been subsumed into the obsessive-compulsive disorders and related disorders (OCDRD) category. Objective: We aimed to determine the empirical evidence regarding the potential relationship between BDD and obsessive-compulsive disorder (OCD) based on the prevalence data, etiopathogenic pathways, and clinical characterization of patients with both disorders. Method: A comprehensive search of databases (PubMed and PsycINFO) was performed. Published manuscripts between 1985 and May 2015 were identified. Overall, 53 studies fulfilled inclusion criteria. Results: Lifetime comorbidity rates of BDD–OCD are almost three times higher in samples with a primary diagnosis of BDD than those with primary OCD (27.5% vs 10.4%). However, other mental disorders, such as social phobia or major mood depression, are more likely among both types of psychiatric samples. Empirical evidence regarding the etiopathogenic pathways for BDD–OCD comorbidity is still inconclusive, whether concerning common shared features or one disorder as a risk factor for the other. Specifically, current findings concerning third variables show more divergences than similarities when comparing both disorders. Preliminary data on the clinical characterization of the patients with BDD and OCD indicate that the deleterious clinical impact of BDD in OCD patients is greater than vice versa. Conclusion: Despite the recent inclusion of BDD within the OCDRD, data from comparative studies between BDD and OCD need further evidence for supporting this nosological approach. To better define this issue, comparative studies between BDD, OCD, and social phobia should be carried out.

The influence of psychosocial factors on human behaviour in emergency

  • Saccinto, Elisa
  • Pérez Testor, Carles
  • Pietrantoni, Luca
Lo scopo di questo studio e ` esplorare l’effetto di alcuni fattori psicosociali sul comportamento umano durante una situazione d’emergenza. In accordo con le osservazioni della teoria dell’Attaccamento Sociale nei disastri (Mawson 2005, 2007), le persone che si trovano in pericolo sperimentano sentimenti di attaccamento verso persone o luoghi familiari. Questi sentimenti hanno un effetto rassicurante, riducendo o ritardando i comportamenti di evacuazione. I partecipanti allo studio sono 173 superstiti di diverse situazioni d’emergenza, tra questi 42.4% sono uomini e 57.6% donne con un’eta ` media di 32.52 anni (DS 13.68). I risultati hanno evidenziato un’associazione negativa tra l’essere con persone familiari e il ritardo nel cominciare l’evacuazione, mentre non e ` emersa una relazione significativa tra la presenza di persone familiari e l’essere nella propria casa durante l’emergenza e i comportamenti di evacuazione. I risultati hanno inoltre rilevato associazioni significative tra la risposta emotiva del partecipante e il luogo: i partecipanti che si trovavano nella propria abitazione durante la situazione di pericolo hanno sperimentato piu` sintomi di panico, maggior disagio e piu` elevata percezione di pericolo nei diversi momenti dell’emergenza, rispetto a coloro che erano in luoghi pubblici. Infine, la presenza di persone familiari influenza i livelli di distress alla fine dell’emergenza. Si discutono alcune implicazioni di questi risultati per migliorare i progetti di prevenzione ed educazione sul comportamento umano in emergenza e migliorare la preparazione dei cittadini., The aim of this study is to explore the effect of some psychosocial factors on human behaviour during an emergency situation. In agreement with the observations of the theory of social attachment in disasters (Mawson 2005, 2007), people in danger experience feelings of attachment for familiar persons and places. These feelings have a reassuring effect, reducing or delaying the behaviour of evacuation. Participants were 173 survivors of several emergency situations: 42.4% were men and 57.6% were women with mean age 32.52 years (SD 13.68). Results evidenced a negative association between being with familiar people and delay in starting the evacuation, whereas the presence of familiar people or being at home during the danger situation were not significantly associated with evacuation. Findings also highlighted significant associations between participants’ emotional response and place: participants who were at home during the danger situation experienced more panic symptoms, distress, and perception of threat in the different moments of the evacuation in comparison with those who were in public buildings. Finally, it was concluded that the presence of familiar people had an influence on the level of distress during emergency situation. Here, we discuss some implications of these results for prevention and education programs on human behaviour during emergencies and for improving citizens’ preparedness.

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