A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

Análise do processo de formação como mediadora entre o público e a arte

The proposed work is located in education field in exhibition spaces of art and seeks to analyze a process of formation as a mediator focusing on the public's relationship with art, taking into account the fact that often the general public does not dominate the codes of this area, being incumbent upon mediator introduce them. One of the main points to be analyzed is the impact that can be generated by the contact of the visitor with the mediator in the exhibition space, considering a spectrum of possibilities, where at one end focuses the belonging and in the other the symbolic violence. In this direction this research aims to build a relationship of emancipation and autonomy of both, the educator and the visitor. It is known that the concept of public is a generalization, therefore, the analysis of the mediation process, are having as support the experiences lived by the mediator, especially, in the relationship with the lay public. The locations of the experiences lived, were the SESC Pompéia and the Pavilion of the Bienal of São Paulo, different places, but both with the potential to generate reception and / or distances, shot through space (architecture), bodies, codes, accesses, works of art, repertoires, expographic and especially through the mobilization of educator front of all these issues. The cutting of the research covers the experience of the educator (as an intern and professional) in six exhibitions, in these two spaces, between the years 2010 to 2015.O trabalho proposto se situa no âmbito da educação em espaços expositivos de arte e busca analisar um processo de formação como mediadora com foco na relação do público com a arte, levando em consideração o fato de que muitas vezes o público leigo não domina os códigos desse espaço, cabendo ao mediador apresentá-los. Um dos pontos principais a ser analisado é o impacto que pode ser gerado pelo contato do visitante com o mediador no espaço expositivo, dentro de um espectro de possibilidades, no qual em uma ponta concentra-se o pertencimento e na outra a violência simbólica. Nesta direção, buscou-se construir uma relação de emancipação e autonomia tanto do educador quanto do visitante. Sabe-se que o conceito de público é uma generalização, portanto, as análises sobre os processos de mediação, estão tendo como suporte as experiências vivenciadas pela mediadora na relação, especialmente, com o público leigo. Os locais das experiências vivenciadas foram o SESC Pompéia e o Pavilhão da Bienal de São Paulo, lugares distintos, mas ambos com potencialidades para gerar acolhimentos e/ou distanciamentos, disparados através do espaço (arquitetura), dos corpos, dos códigos, dos acessos, das obras de arte, dos repertórios, da expografia e principalmente através da mobilização do educador diante de todos estes fatores. O recorte da pesquisa abrange a experiência da educadora (como estagiária e profissional) em seis exposições, nesses dois espaços, entre os anos de 2010 até 2015

Modulation of Charge Transport Across Double-Stranded DNA by the Site-Specific Incorporation of Copper Bis-Phenanthroline Complexes

The site-specific incorporation of transition-metal complexes within DNA duplexes, followed by their immobilization on a gold surface, was studied by electrochemistry to characterize their ability to mediate charge. Cyclic voltammetry, square-wave voltammetry, and control experiments were carried out on fully matched and mismatched DNA strands that are mono- or bis-labeled with transition-metal complexes. These experiments are all consistent with the ability of the metal centers to act as a redox probe that is well coupled to the DNA π-stack, allowing DNA-mediated charge transport

Molecular diagnosis and novel genes and phenotypes in a pediatric thoracic insufficiency cohort

Abstract Thoracic insufficiency syndromes are a genetically and phenotypically heterogeneous group of disorders characterized by congenital abnormalities or progressive deformation of the chest wall and/or vertebrae that result in restrictive lung disease and compromised respiratory capacity. We performed whole exome sequencing on a cohort of 42 children with thoracic insufficiency to elucidate the underlying molecular etiologies of syndromic and non-syndromic thoracic insufficiency and predict extra-skeletal manifestations and disease progression. Molecular diagnosis was established in 24/42 probands (57%), with 18/24 (75%) probands having definitive diagnoses as defined by laboratory and clinical criteria and 6/24 (25%) probands having strong candidate genes. Gene identified in cohort patients most commonly encoded components of the primary cilium, connective tissue, and extracellular matrix. A novel association between KIF7 and USP9X variants and thoracic insufficiency was identified. We report and expand the genetic and phenotypic spectrum of a cohort of children with thoracic insufficiency, reinforce the prevalence of extra-skeletal manifestations in thoracic insufficiency syndromes, and expand the phenotype of KIF7 and USP9X-related disease to include thoracic insufficiency

A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations

Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes

Varia

Ce numéro varia revient sur une question d’ontologie qui mit aux prises deux jeunes philosophes français à la fin du xixe siècle : nominaliste, Jean-Marie Guyau voyait ainsi dans la religion une transposition altruiste d’aspirations et de craintes individuelles ; réaliste, Émile Durkheim y entrevoyait plutôt une production sociale sui generis aux formes historiques diversifiées. Remontant à la forme biblique, une analyse structurale du sacrifice d’Abraham montre comment ses transformations scripturaires marquent différemment les traditions judaïque et islamique. Retour en aval, dans la Chine contemporaine où le culte ancien des saints musulmans, ravivé au Xinjiang depuis la Révolution culturelle, produit de nouveaux repères pour un temps de transition. Sous les mêmes latitudes, mais tout autour du monde, s’alignent les pays cibles des missions évangéliques qui en dressent la carte, la Spiritual Mapping, en vue de nouvelles conquêtes. Mais comme le montre parmi tant d’autres le pèlerinage de la Vierge de San Juan au Mexique, la ferveur populaire ne se commande pas à distance. Plus bas sur la carte, au Brésil, les petits arrangements avec le ciel se poursuivent face aux questions de contraception ou de procréation assistée. Là comme partout l’individu choisit sa religion au gré de ses expériences : la croyance se fait ressource.  Deux notes critiques accompagnent ce varia : l’une sur les liens et conflits de parenté entre sociologie et anthropologie des religions au travers de récents manuels de poche ; l’autre sur les tribulations des missions en Asie au xixe siècle. Sans oublier pour finir un bulletin bibliographique marqué par divers thèmes récurrents : nationalisme et religion en Asie, identité juive et Occident, ecclésiologie catholique, islam et modernité