Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Systematic review of interventions targeting sickness absence among pregnant women in healthcare settings and workplaces

Objectives: The high rate of sickness absence from work during pregnancy is recognised as a problem, and may be higher than necessary from a health perspective. The aim was to evaluate the effectiveness of interventions in healthcare settings and workplaces targeting sickness absence among pregnant women. Methods: Studies were eligible if they included pregnant women participating in any intervention in healthcare settings or workplaces. The outcome was length of sickness absence in days or number of episodes. Study design had to be either randomised controlled trials (RCTs) or quasi-experimental studies. The search for studies was conducted in PubMed, Scopus, CINAHL, PsycINFO, ClinicalTrials.gov and WHO trial registry. Risk of bias was assessed by the Joanna Briggs Institute standardised quality assessment instrument. Results: A total of nine studies were quality assessed and of these, four were excluded due to insufficient methodological quality. Five RCTs conducted in healthcare settings in Sweden and Norway were included. Due to heterogeneity, meta-analysis was not performed. Two RCTs examined complementary and alternative medicine and three RCTs the effect of physical exercise. In general, the frequency of women on sickness absence was lower in the intervention groups than the control groups, however, only among pregnant women who participated in a 12-week exercise programme, the frequency was significantly lower (22% vs 30%, p=0.04). Conclusion: The evidence of interventions targeting sickness absence among pregnant women in healthcare settings is sparse, and no studies were conducted at workplaces. Future interventions including physical activity provided in collaboration with healthcare settings and workplaces are requested. Studies should measure sickness absence based on valid methods, measure compliance to the intervention and provide transparency of statistical methods

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Direct Evidence of an Excited-State Triplet Species upon Photoactivation of the Chlorophyll Precursor Protochlorophyllide

The chlorophyll precursor protochlorophyllide (Pchlide), which is the substrate for the light-driven enzyme protochlorophyllide oxidoreductase, has unique excited-state properties that facilitate photocatalysis. Previous time-resolved spectroscopy measurements have implied that a long-lived triplet state is formed during the excited-state relaxation of Pchlide, although direct evidence of its existence is still lacking. Here we use time-resolved electron paramagnetic resonance (EPR) in combination with time-resolved absorption measurements at a range of temperatures (10–290 K), solvents, and oxygen concentrations to provide a detailed characterization of the triplet state of Pchlide. The triplet decays in a biphasic, oxygen-dependent manner, while the first reported EPR signature of a Pchlide triplet displays both emissive and absorptive features and an antisymmetric spectrum similar to other porphyrin triplet states. This work demonstrates that the Pchlide triplet is accessible to various cryogenic spectroscopic probes over a range of time scales and paves the way for understanding its potential role in catalysis

Crystal Growth, Dynamic and Charge Transfer Properties of New Coronene Charge Transfer Complexes

© 2015 American Chemical Society. Two new coronene charge transfer complexes with F4-TCNQ of 2:1 and 1:1:1 (solvate with acetonitrile, MeCN) stoichiometry were obtained using crystal growth procedures from the solution and vapor phase. It was shown that mobility of coronene molecules in crystals is more affected by the asymmetry of its surrounding than by the composition and degree of charge transfer and interstack interactions. The combination of X-ray diffraction and electrochemistry in the solid state and a time-resolved one in solution allowed us to clarify the nucleation in solution showing that the formation of 2:1 coronene/F4-TCNQ complexes is thermodynamically preferable. The X-ray single crystal data for pristine coronene showed the crystal structure to be the same as at ambient temperature, raising doubt about the previously reported phase transitions at 140-180 K

Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults – The GOYA Study

Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ~1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations. Methodology/Principal Findings: From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ~212,000 individuals). We followed up novel (at the time of the study) association signals (