Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Tissue engineering techniques in cardiac repair and disease modelling

Cell therapy has been proposed to treat patients with end-stage heart failure. However, it has been suggested that the significant mechanical forces in an often ischaemic, inflamed, biochemically hostile environment may cause poor cell survival and retention. It is hypothesised that tissue engineering techniques could be used to modify the environment to improve the efficacy of cell therapy. Similarly, it has been suggested that tissue engineering technology could be used to mature the phenotype of immature cardiomyocytes in vitro, making them more useful disease models. In this review we will briefly discuss key tissue engineering techniques and principles that can be used to facilitate cell therapy, and modify the phenotype of immature cardiomyocytes and stem cells

Research data supporting "Electrospun aniline-tetramer-co-polycaprolactone fibres for conductive, biodegradable scaffolds"

Research data supporting the publication: Guex, A.G. et al., 2017, "Electrospun aniline-tetramer-co-polycaprolactone fibres for conductive, biodegradable scaffolds", MRS Communications. https://doi.org/10.1557/mrc.2017.4

[Increase of potassium conductance and spontaneous electric activity in vitro: comparison of nicorandil and cicletanine].

Nicorandil (N) increases potassium conductance in vascular smooth muscle and so induces vasodilation; N also dose-dependently reduces action potential duration (APD). However, it is unclear whether increased potassium conductance, and concomitant APD shortening, might be arrhythmogenic, particularly when myocardial ischemia (where potassium efflux is increased) concurs. Data on the anti-arrhythmic effectiveness of N have also been published: N reduced the spontaneous discharge of sino-atrial node and so reduced heart rate, both in vitro and man. On the other hand, among other vasodilators, cicletanine (C) has been reported to increase potassium conductance, an effect which was advocated to explain its antiarrhythmic potency. In the present investigation the direct myocardial effects of N were compared to those following C in 63 experiments (from 13 Guinea-pigs), using atrial strips (containing sino-atrial node) superfused in 1-compartment bath with normal Tyrode's solution. Using glass microelectrodes, standard electrophysiologic variables were recorded (APA, RMP, APD50%, Vmax) in spontaneously beating atrial tissue, either in Tyrode, dimethyl-sulfoxide (DMSO 1:100, as solvent), C 10(-5) M (in DMSO 1:100), and N 10(-3) M (in DMSO 1:100), whose respective perfusion periods (15 min) were randomized, always following 15 min of washout with Tyrode. Only N was tested in experiments of both 15 and 30 min duration.(ABSTRACT TRUNCATED AT 250 WORDS

A DROP-IN beta probe for robot-assisted Ga-68-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens

Background Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-IN beta) detector. Methods Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of similar to 70 MBq(68)Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-IN(beta)probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments. Results After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-IN(beta)probe prototype was tested in a robotic setting. In the ex vivo setting, the probe-positioned by the robot-was able to identify(68)Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing. Conclusions This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-IN(beta)detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Bivariate genome-wide association study of depressive symptoms with type 2 diabetes and quantitative glycemic traits.

Objective: Shared genetic background may explain phenotypic associations between depression and Type 2 diabetes (T2D). We aimed to study, on a genome-wide level, if genetic correlation and pleiotropic loci exist between depressive symptoms and T2D or glycemic traits. Methods: We estimated single-nucleotide polymorphism (SNP)-based heritability and analyzed genetic correlation between depressive symptoms and T2D and glycemic traits with the linkage disequilibrium score regression by combining summary statistics of previously conducted meta-analyses for depressive symptoms by CHARGE consortium (N = 51,258), T2D by DIAGRAM consortium (N = 34,840 patients and 114,981 controls), fasting glucose, fasting insulin, and homeostatic model assessment of β-cell function and insulin resistance by MAGIC consortium (N = 58,074). Finally, we investigated pleiotropic loci using a bivariate genome-wide association study approach with summary statistics from genome-wide association study meta-analyses and reported loci with genome-wide significant bivariate association p value (p < 5 10−8). Biological annotation and function of significant pleiotropic SNPs were assessed in several databases. Results: The SNP-based heritability ranged from 0.04 to 0.10 in each individual trait. In the linkage disequilibrium score regression analyses, depressive symptoms showed no significant genetic correlation with T2D or glycemic traits (p > 0.37). However, we identified pleiotropic genetic variations for depressive symptoms and T2D (in the IGF2BP2, CDKAL1, CDKN2B-AS, and PLEKHA1 genes), and fasting glucose (in the MADD, CDKN2B-AS, PEX16, and MTNR1B genes). Conclusions: We found no significant overall genetic correlations between depressive symptoms, T2D, or glycemic traits suggesting major differences in underlying biology of these traits. However, several potential pleiotropic loci were identified between depressive symptoms, T2D, and fasting glucose, suggesting that previously established phenotypic associations may be partly explained by genetic variation in these specific loci