GEIRA: gene-environment and gene–gene interaction research application

The GEIRA (Gene-Environment and Gene–Gene Interaction Research Application) algorithm and subsequent program is dedicated to genome-wide gene-environment and gene–gene interaction analysis. It implements concepts of both additive and multiplicative interaction as well as calculations based on dominant, recessive and co-dominant genetic models, respectively. Estimates of interactions are incorporated in a single table to make the output easily read. The algorithm is coded in both SAS and R. GEIRA is freely available to non-commercial users at http://www.epinet.se. Additional information, including user’s manual and example datasets is available online at http://www.epinet.se

Insufficient sun exposure has become a real public health problem

This is the final version. Available on open access from MDPI via the DOI in this recordThis article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer’s disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5–30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.Sunshine Health Foundation (SHF

GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL–associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, Pcombined = 2×10−21) located 962 bp away from rs10484561 (r2<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:ORadjusted = 0.70, Padjusted = 4×10−12; rs10484561:ORadjusted = 1.64, Padjusted = 5×10−15). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, Pcombined = 1.4×10−7). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL

Silent chromatin at the middle and ends: lessons from yeasts

Eukaryotic centromeres and telomeres are specialized chromosomal regions that share one common characteristic: their underlying DNA sequences are assembled into heritably repressed chromatin. Silent chromatin in budding and fission yeast is composed of fundamentally divergent proteins tat assemble very different chromatin structures. However, the ultimate behaviour of silent chromatin and the pathways that assemble it seem strikingly similar among Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe) and other eukaryotes. Thus, studies in both yeasts have been instrumental in dissecting the mechanisms that establish and maintain silent chromatin in eukaryotes, contributing substantially to our understanding of epigenetic processes. In this review, we discuss current models for the generation of heterochromatic domains at centromeres and telomeres in the two yeast species

Turbulent Flow Over Large Roughness Elements: Effect of Frontal and Plan Solidity on Turbulence Statistics and Structure

Wind-tunnel experiments were carried out on fully-rough boundary layers with large roughness (δ/h≈10 δ/h≈10, where h is the height of the roughness elements and δ δ is the boundary-layer thickness). Twelve different surface conditions were created by using LEGO™ bricks of uniform height. Six cases are tested for a fixed plan solidity (λ P λP) with variations in frontal density (λ F λF), while the other six cases have varying λ P λP for fixed λ F λF. Particle image velocimetry and floating-element drag-balance measurements were performed. The current results complement those contained in Placidi and Ganapathisubramani (J Fluid Mech 782:541–566, 2015), extending the previous analysis to the turbulence statistics and spatial structure. Results indicate that mean velocity profiles in defect form agree with Townsend’s similarity hypothesis with varying λ F λF, however, the agreement is worse for cases with varying λ P λP. The streamwise and wall-normal turbulent stresses, as well as the Reynolds shear stresses, show a lack of similarity across most examined cases. This suggests that the critical height of the roughness for which outer-layer similarity holds depends not only on the height of the roughness, but also on the local wall morphology. A new criterion based on shelter solidity, defined as the sheltered plan area per unit wall-parallel area, which is similar to the ‘effective shelter area’ in Raupach and Shaw (Boundary-Layer Meteorol 22:79–90, 1982), is found to capture the departure of the turbulence statistics from outer-layer similarity. Despite this lack of similarity reported in the turbulence statistics, proper orthogonal decomposition analysis, as well as two-point spatial correlations, show that some form of universal flow structure is present, as all cases exhibit virtually identical proper orthogonal decomposition mode shapes and correlation fields. Finally, reduced models based on proper orthogonal decomposition reveal that the small scales of the turbulence play a significant role in assessing outer-layer similarity