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

Multifunction hexagonal liquid-crystal containing modified surface TiO2 nanoparticles and terpinen-4-ol for controlled release

Eloísa Berbel Manaia,1 Renata Cristina Kiatkoski Kaminski,2 Anselmo Gomes de Oliveira,1 Marcos Antonio Corrêa,1 Leila Aparecida Chiavacci1 1Drugs and Medicines Department, Faculty of Pharmaceutical Sciences, 2Physical-Chemistry Department, Chemistry Institute, São Paulo State University – UNESP, Araraquara, Brazil Abstract: Multifunctional products have been developed to combine the benefits of functional components and terpinen-4-ol (TP) delivery systems. In this way, p-toluene sulfonic acid modified titanium dioxide (TiO2) nanoparticles and TP, an antioxidant, have been incorporated in liquid-crystalline formulations for photoprotection and controlled release of the TP, respectively. By X-ray powder diffraction and diffuse reflectance spectroscopy, we noted that using p-toluene sulfonic acid as a surface modifier made it possible to obtain smaller and more transparent TiO2 nanoparticles than those commercially available. The liquid-crystalline formulation containing the inorganic ultraviolet filter was classified as broad-spectrum performance by the absorbance spectroscopy measurements. The formulations containing modified TiO2 nanoparticles and TP were determined to be in the hexagonal phase by polarized light microscopy and small-angle X-ray scattering, which makes possible the controlled released of TP following zero-order kinetics. The developed formulations can control the release of TP. Constant concentrations of the substance have been released per time unit, and the modified TiO2 nanoparticles can act as a transparent inorganic sunscreen. Keywords: titanium dioxide, sol-gel, drug delivery, sunscree

Physicochemical characterization of drug nanocarriers

Eloísa Berbel Manaia,1 Marina Paiva Abuçafy,1 Bruna Galdorfini Chiari-Andréo,1,2 Bruna Lallo Silva,1 João Augusto Oshiro Junior,1 Leila Aparecida Chiavacci1 1Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil, 2Department of Biological and Health Sciences, Centro Universitário de Araraquara, UNIARA, Araraquara, SP, Brazil Abstract: Pharmaceutical design has enabled important advances in the prevention, treatment, and diagnosis of diseases. The use of nanotechnology to optimize the delivery of drugs and diagnostic molecules is increasingly receiving attention due to the enhanced efficiency provided by these systems. Understanding the structures of nanocarriers is crucial in elucidating their physical and chemical properties, which greatly influence their behavior in the body at both the molecular and systemic levels. This review was conducted to describe the principles and characteristics of techniques commonly used to elucidate the structures of nanocarriers, with consideration of their size, morphology, surface charge, porosity, crystalline arrangement, and phase. These techniques include X-ray diffraction, small-angle X-ray scattering, dynamic light scattering, zeta potential, polarized light microscopy, transmission electron microscopy, scanning electron microcopy, and porosimetry. Moreover, we describe some of the commonly used nanocarriers (liquid crystals, metal–organic frameworks, silica nanospheres, liposomes, solid lipid nanoparticles, and micelles) and the main aspects of their structures. Keywords: nanoparticles, drug delivery, physicochemical properties, controlled drug releas

Common genetic variants on 5p14.1 associate with autism spectrum disorders

Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)—two genes encoding neuronal cell-adhesion molecules—revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 × 10(−8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 × 10(−8) to 2.1 × 10(−10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs