Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children

Background

The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).

Methods and Findings

All studies identified to have data on the FTO rs9939609 variant (or any proxy [r ²>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A−) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but PA attenuated this effect (p _interaction  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents.

Conclusions

The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. Please see later in the article for the Editors'' Summary     

Exine ontogeny in Borago officinalis pollen

The primexine matrix is finely granulo-fibrillar up to callose digestion; it becomes distinctly fibrillar at the free microspore stage. The columellae and the tectum are initiated at the middle tetrad stage, the foot layer and the endexine are initiated when the callose wall digestion begins. The columellae are initiated by the deposition of spiral elements around a clear central zone. This hollow aspect of columella disappears when thickening. The foot layer and the endexine are built by the expansion of plasmalemma derived components. The foot layer appears first at the poles, then at the interapertural levels and at last at the apertures while the endexine appears first at the mesoapertures, then it spreads laterally towards the interapertural levels and, at last, at the poles. The gemmae are formed at the free microspore stage over all the tectum. The thickening of the exine takes place essentially during the free microspore stage and continues during the vacuolate microspore one. Apertures are entirely formed before the complete digestion of the callose wall. The ectoapertures are determined by the lacking of the columellae; the sites of the pericolpal cavities and the mesoapertures result from the plasmalemma retraction even before the setting up of the foot layer and the endexine by which they will be delimited respectively afterwards. The endoapertures are determined by the lacking of compact endexine at their level, and merge into a continuous equatorial belt.     

The Perils of Pathogen Discovery: Origin of a Novel Parvovirus-Like Hybrid Genome Traced to Nucleic Acid Extraction Spin Columns

Next-generation sequencing was used for discovery and de novo assembly of a novel, highly divergent DNA virus at the interface between the Parvoviridae and Circoviridae. The virus, provisionally named parvovirus-like hybrid virus (PHV), is nearly identical by sequence to another DNA virus, NIH-CQV, previously detected in Chinese patients with seronegative (non-A-E) hepatitis. Although we initially detected PHV in a wide range of clinical samples, with all strains sharing ∼99% nucleotide and amino acid identity with each other and with NIH-CQV, the exact origin of the virus was eventually traced to contaminated silica-binding spin columns used for nucleic acid extraction. Definitive confirmation of the origin of PHV, and presumably NIH-CQV, was obtained by in-depth analyses of water eluted through contaminated spin columns. Analysis of environmental metagenome libraries detected PHV sequences in coastal marine waters of North America, suggesting that a potential association between PHV and diatoms (algae) that generate the silica matrix used in the spin columns may have resulted in inadvertent viral contamination during manufacture. The confirmation of PHV/NIH-CQV as laboratory reagent contaminants and not bona fide infectious agents of humans underscores the rigorous approach needed to establish the validity of new viral genomes discovered by next-generation sequencing.     

Daily activity patterns of coyotes (Canis latrans) in a tropical deciduous forest of western Mexico

We studied the activity patterns of the coyote (Canis latrans) in a tropical deciduous forest in the Mexican Pacific coast over 3 years. Fifteen coyotes (six females, nine males) were fitted with radio-collars equipped with activity sensors to determine the influence of seasonality (dry vs. wet), gender (males vs. females) and diel intervals (dusk, night, dawn, and day) on activity patterns. We found differences in activity patterns between diel intervals, but the only pair of diel intervals that showed significant differences was dawn (more active) vs. day (less active). We found no differences due to sex or season on any of the four studied diel intervals. Coyote activity patterns in this tropical forest could be responding to prey availability, human avoidance or thermoregulation.     

Acquisition of HIV by African-Born Residents of Victoria,Australia: Insights from Molecular Epidemiology

African-born Australians are a recognised “priority population” in Australia''s Sixth National HIV/AIDS Strategy. We compared exposure location and route for African-born people living with HIV (PLHIV) in Victoria, Australia, with HIV-1 pol subtype from drug resistance assays and geographical origin suggested by phylogenetic analysis of env gene. Twenty adult HIV positive African-born Victorian residents were recruited via treating doctors. HIV exposure details were obtained from interviews and case notes. Viral RNA was extracted from participant stored plasma or whole blood. The env V3 region was sequenced and compared to globally representative reference HIV-1 sequences in the Los Alamos National Library HIV Database. Twelve participants reported exposure via heterosexual sex and two via iatrogenic blood exposures; four were men having sex with men (MSM); two were exposed via unknown routes. Eight participants reported exposure in their countries of birth, seven in Australia, three in other countries and two in unknown locations. Genotype results (pol) were available for ten participants. HIV env amplification was successful in eighteen cases. HIV-1 subtype was identified in all participants: eight both pol and env; ten env alone and two pol alone. Twelve were subtype C, four subtype B, three subtype A and one subtype CRF02_AG. Reported exposure location was consistent with the phylogenetic clustering of env sequences. African Australians are members of multiple transnational social and sexual networks influencing their exposure to HIV. Phylogenetic analysis may complement traditional surveillance to discern patterns of HIV exposure, providing focus for HIV prevention programs in mobile populations.     

Sterilization and protection of protein in combinations of Camellia sinensis green tea extract and gamma irradiation

Sterilization of milk protein without heating is of great interest. Gamma irradiation is a very powerful method to decontaminated casein. Gamma-irradiation of proteins in aqueous media at doses higher than 5kGy is known to induce their aggregation (without oxygen) or degradation (in presence of oxygen). Camellia sinensis green tea extract addition before irradiation of caseins cow milk proteins was examined. It was found that the presence of C. sinensis green tea extract during irradiation in the presence of oxygen conditions prevented the protein aggregation even at doses higher than 10kGy, probably by scavenging oxygen radicals produced by irradiation. The protective role of C. sinensis green tea extract allowing the gamma-irradiation treatment of caseins cow milk proteins in solution, was asserted by sodium dodecyl-sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and by high performance liquid chromatography inverse phase (RP-HPLC). The total viable microorganisms content evaluated by Plate Count Agar (PCA) incubation for 12h at 37°C, showed that caseins protein preparations gamma-irradiated remained sterile at a dose 2kGy in absence of C. sinensis green tea extract and at a dose lower than 2kGy in the presence of C. sinensis green tea extract.     

Ligand entry pathways in the ligand binding domain of PPARγ receptor

To address the question of ligand entry process, we report targeted molecular dynamics simulations of the entry of the flexible ionic ligand GW0072 in the ligand binding domain of the nuclear receptor PPARγ. Starting with the ligand outside the receptor the simulations led to a ligand docked inside the binding pocket resulting in a structure very close to the holo-form of the complex. The results showed that entry process is guided by hydrophobic interactions and that entry pathways are very similar to exit pathways. We suggest that TMD method may help in discriminating between ligands generated by in silico docking.     

Plasticity of Ly-6C(hi) myeloid cells in T cell regulation

CD11b(+)Ly-6C(hi) cells, including inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs), are important in infectious, autoimmune, and tumor models. However, their role in T cell regulation is controversial. In this article, we show that T cell regulation by IMCs and IDCs is determined by their activation state and is plastic during an immune response. Nonactivated IMCs and IDCs function as APCs, but activated IMCs and IDCs suppress T cells through NO production. Suppressive IMCs are induced by IFN-γ, GM-CSF, TNF-α, and CD154 derived from activated T cells during their interaction. In experimental autoimmune encephalomyelitis, CD11b(+)Ly-6C(hi) cells in the CNS are increasingly activated from disease onset to peak and switch their function from Ag presentation to T cell suppression. Furthermore, transfer of activated IMCs or IDCs enhances T cell apoptosis in the CNS and suppresses experimental autoimmune encephalomyelitis. These data highlight the interplay between innate and adaptive immunity: immunization leads to the expansion of Ly-6C(hi) myeloid cells initially promoting T cell function. As T cells become highly activated in the target tissue, they induce activation and NO production in Ly-6C(hi) myeloid cells, which in turn suppress T cells and lead to the contraction of local immune response.     

Tdp1 protects against oxidative DNA damage in non‐dividing fission yeast

In humans, a mutation in the tyrosyl‐DNA phosphodiesterase (Tdp1) is responsible for the recessively inherited syndrome spinocerebellar ataxia with axonal neuropathy (SCAN1). Tdp1 is a well‐conserved DNA repair enzyme, which processes modified 3′ phospho‐DNA adducts in vitro. Here, we report that in the yeast Schizosaccharomyces pombe, tdp1 mutant cells progressively accumulate DNA damage and rapidly lose viability in a physiological G0/quiescent state. Remarkably, this effect is independent of topoisomerase I function. Moreover, we provide evidence that Tdp1, with the polynucleotide kinase (Pnk1), processes the same naturally occurring 3′‐ends, produced from oxidative DNA damage in G0. We also found that one half of the dead cells lose their nuclear DNA. Nuclear DNA degradation is genetically programmed and mainly depends on the two DNA damage checkpoint responses, ATM/Tel1 and ATR/Rad3, reminiscent to programmed cell death. Diminishing the respiration rate or treating cells with a low concentration of antioxidants rescues the quiescent tdp1 mutant cells. These findings suggest that mitochondrial respiration causes neuronal cell death in the SCAN1 syndrome and in other neurological disorders.