Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Long-term effects of tongue piercing — a case control study

The aim of this study was to evaluate tooth and periodontal damage in subjects wearing a tongue piercing (TP) in comparison to matched control subjects without tongue piercing. Members of the German Federal Armed Forces who had TP (group TP) and a matched control group (group C) volunteered to take part in the study. The time in situ, localization and material of TP were documented. Dental examinations included DMF-T, oral hygiene, enamel fissures (EF), enamel cracks (EC) and recessions. Statistical analysis was determined by χ2 test and the t test. Both groups had 46 male subjects (mean age 22.1 years). The piercings had been in situ for 3.8 ± 3.1 years. Subjects in the TP group had a total of 1,260 teeth. Twenty-nine subjects had 115 teeth (9.1%) with EF (67% lingual). In group C (1,243 teeth), 30 subjects had 60 teeth with EF (4.8%, 78% vestibular) (p < 0.01). Thirty-eight subjects belonging to group TP had EC in 186 teeth (15%). In group C, 26 subjects with 56 teeth (4.5%) were affected by EC (p < 0.001). Twenty-seven subjects in group TP had 97 teeth (7.7%) with recessions. Lingual surfaces of anterior teeth in the lower jaw were affected most frequently (74%). In group C, 8 subjects had 19 teeth (1.5%) with recessions (65% vestibular). Differences between the two groups were statistically significant (p < 0.001). Tongue piercing is correlated with an increased occurrence of enamel fissures, enamel cracks and lingual recessions. Patients need better information on the potential complications associated with tongue piercing

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

© The Author 2015.Background: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. Patients and methods: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. Conclusion: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC

Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel

Genetic imputation is a cost-efficient way to improve the power and resolution of genome-wide association (GWA) studies. Current publicly accessible imputation reference panels accurately predict genotypes for common variants with minor allele frequency (MAF) >= 5% and low-frequency variants (0.5Peer reviewe

Novel, Meso-Substituted Cationic Porphyrin Molecule for Photo-Mediated Larval Control of the Dengue Vector Aedes aegypti

Dengue is a life-threatening viral disease of growing importance, transmitted by Aedes mosquito vectors. The control of mosquito larvae is crucial to contain or prevent disease outbreaks, and the discovery of new larvicides able to increase the efficacy and the flexibility of the vector control approach is highly desirable. Porphyrins are a class of molecules which generate reactive oxygen species if excited by visible light, thus inducing oxidative cell damage and cell death. In this study we aimed at assessing the potential of this photo-mediated cytotoxic mechanism to kill Aedes (Stegomyia) aegypti mosquito larvae. The selected porphyrin molecule, meso-tri(N-methylpyridyl),meso-mono(N-tetradecylpyridyl)porphine (C14 for simplicity), killed the larvae at doses lower than 1 µM, and at light intensities 50–100 times lower than those typical of natural sunlight, by damaging their intestinal tissues. The physicochemical properties of C14 make it easily adsorbed into organic material, and we exploited this feature to prepare an ‘insecticidal food’ which efficiently killed the larvae and remained active for at least 14 days after its dispersion in water. This study demonstrated that photo-sensitizing agents are promising tools for the development of new larvicides against mosquito vectors of dengue and other human and animal diseases

Hydrothermal alteration of andesitic lava domes can lead to explosive volcanic behaviour

Dome-forming volcanoes are among the most hazardous volcanoes on Earth. Magmatic outgassing can be hindered if the permeability of a lava dome is reduced, promoting pore pressure augmentation and explosive behaviour. Laboratory data show that acid-sulphate alteration, common to volcanoes worldwide, can reduce the permeability on the sample lengthscale by up to four orders of magnitude and is the result of pore- and microfracture-filling mineral precipitation. Calculations using these data demonstrate that intense alteration can reduce the equivalent permeability of a dome by two orders of magnitude, which we show using numerical modelling to be sufficient to increase pore pressure. The fragmentation criterion shows that the predicted pore pressure increase is capable of fragmenting the majority of dome-forming materials, thus promoting explosive volcanism. It is crucial that hydrothermal alteration, which develops over months to years, is monitored at dome-forming volcanoes and is incorporated into real-time hazard assessments

Friend versus foe: Neural correlates of prosocial decisions for liked and disliked peers

Although the majority of our social interactions are with people we know, few studies have investigated the neural correlates of sharing valuable resources with familiar others. Using an ecologically valid research paradigm, this functional magnetic resonance imaging study examined the neural correlates of prosocial and selfish behavior in interactions with real-life friends and disliked peers in young adults. Participants (N = 27) distributed coins between themselves and another person, where they could make selfish choices that maximized their own gains or prosocial choices that maximized outcomes of the other. Participants were more prosocial toward friends and more selfish toward disliked peers. Individual prosociality levels toward friends were associated negatively with supplementary motor area and anterior insula activity. Further preliminary analyses showed that prosocial decisions involving friends were associated with heightened activity in the bilateral posterior temporoparietal junction, and selfish decisions involving disliked peers were associated with heightened superior temporal sulcus activity, which are brain regions consistently shown to be involved in mentalizing and perspective taking in prior studies. Further, activation of the putamen was observed during prosocial choices involving friends and selfish choices involving disliked peers. These findings provide insights into the modulation of neural processes that underlie prosocial behavior as a function of a positive or negative relationship with the interaction partner