Sedimentary Iron Cycling and the Origin and Preservation of Magnetization in Platform Carbonate Muds, Andros Island, Bahamas

Carbonate muds deposited on continental shelves are abundant and well-preserved throughout the geologic record because shelf strata are difficult to subduct and peritidal carbonate units often form thick, rheologically strong units that resist penetrative deformation. Much of what we know about pre-Mesozoic ocean chemistry, carbon cycling, and global change is derived from isotope and trace element geochemistry of platform carbonates. Paleomagnetic data from the same sediments would be invaluable, placing records of paleolatitude, paleogeography, and perturbations to the geomagnetic field in the context and relative chronology of chemostratigraphy. To investigate the depositional and early diagenetic processes that contribute to magneitzation in carbonates, we surveyed over 500 core and surface samples of peritidal, often microbially bound carbonate muds spanning the last not, vert, similar 1000 yr and deposited on top of Pleistocene aeolianites in the Triple Goose Creek region of northwest Andros Island, Bahamas. Sedimentological, geochemical, magnetic and ferromagnetic resonance properties divide the sediment columns into three biogeochemical zones. In the upper sediments, the dominant magnetic mineral is magnetite, produced by magnetotactic bacteria and dissimiliatory microbial iron metabolism. At lower depths, above or near mean tide level, microbial iron reduction dissolves most of the magnetic particles in the sediment. In some cores, magnetic iron sulfides precipitate in a bottom zone of sulfate reduction, likely coupled to the oxidation of decaying mangrove roots. The remanent magnetization preserved in all oriented samples appears indistinguishable from the modern local geomagnetic field, which reflects the post-depositional origin of magnetic particles in the lower zone of the parasequence. While we cannot comment on the effects of late-stage diagenesis or metamorphism on remanence in carbonates, we postulate that early-cemented, thin-laminated parasequence tops in ancient peritidal carbonates are mostly likely to preserve syn-depositional paleomagnetic directions and magnetofossil stratigraphies

Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans

Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW p(FDR) = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.Peer reviewe

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Dose-Dependent Associations of Dietary Glycemic Index, Glycemic Load, and Fiber With 3-Year Weight Loss Maintenance and Glycemic Status in a High-Risk Population : A Secondary Analysis of the Diabetes Prevention Study PREVIEW

OBJECTIVE To examine longitudinal and dose-dependent associations of dietary glycemic index (GI), glycemic load (GL), and fiber with body weight and glycemic status during 3-year weight loss maintenance (WLM) in adults at high risk of type 2 diabetes. RESEARCH DESIGN AND METHODS In this secondary analysis we used pooled data from the PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) randomized controlled trial, which was designed to test the effects of four diet and physical activity interventions. A total of 1,279 participants with overweight or obesity (age 25-70 years and BMI >= 25 kg . m(-2)) and prediabetes at baseline were included. We used multiadjusted linear mixed models with repeated measurements to assess longitudinal and dose-dependent associations by merging the participants into one group and dividing them into GI, GL, and fiber tertiles, respectively. RESULTS In the available-case analysis, each 10-unit increment in GI was associated with a greater regain of weight (0.46 kg . year(-1); 95% CI 0.23, 0.68; P < 0.001) and increase in HbA(1c). Each 20-unit increment in GL was associated with a greater regain of weight (0.49 kg . year(-1); 0.24, 0.75; P < 0.001) and increase in HbA(1c). The associations of GI and GL with HbA(1c) were independent of weight change. Compared with those in the lowest tertiles, participants in the highest GI and GL tertiles had significantly greater weight regain and increases in HbA(1c). Fiber was inversely associated with increases in waist circumference, but the associations with weight regain and glycemic status did not remain robust in different analyses. CONCLUSIONS Dietary GI and GL were positively associated with weight regain and deteriorating glycemic status. Stronger evidence on the role of fiber is needed.Peer reviewe

What Is the Profile of Overweight Individuals Who Are Unsuccessful Responders to a Low-Energy Diet? A PREVIEW Sub-study

This study was performed to evaluate the profile of overweight individuals with pre-diabetes enrolled in PREVIEW who were unable to achieve a body weight loss of >= 8% of the baseline value in response to a 2-month low-energy diet (LED). Their baseline profile reflected potential stress-related vulnerability that predicted a reduced response of body weight to a LED programme. The mean daily energy deficit maintained by unsuccessful weight responders of both sexes was less than the estimated level in successful female (656 vs. 1,299 kcal, p < 0.01) and male (815 vs. 1,659 kcal, p < 0.01) responders. Despite this smaller energy deficit, unsuccessful responders displayed less favorable changes in susceptibility to hunger and appetite sensations. They also did not benefit from the intervention regarding the ability to improve sleep quality. In summary, these results show that some individuals display a behavioral vulnerability which may reduce the ability to lose weight in response to a diet-based weight loss program. They also suggest that this vulnerability may be accentuated by a prolonged diet restriction.Peer reviewe

Compositional analysis of the associations between 24-h movement behaviours and cardio-metabolic risk factors in overweight and obese adults with pre-diabetes from the PREVIEW study: cross-sectional baseline analysis

Background: Physical activity, sedentary time and sleep have been shown to be associated with cardio-metabolic health. However, these associations are typically studied in isolation or without accounting for the effect of all movement behaviours and the constrained nature of data that comprise a finite whole such as a 24 h day. The aim of this study was to examine the associations between the composition of daily movement behaviours (including sleep, sedentary time (ST), light intensity physical activity (LIPA) and moderate-to-vigorous activity (MVPA)) and cardio-metabolic health, in a cross-sectional analysis of adults with pre-diabetes. Further, we quantified the predicted differences following reallocation of time between behaviours. Methods: Accelerometers were used to quantify daily movement behaviours in 1462 adults from eight countries with a body mass index (BMI) ≥25 kg·m− 2 , impaired fasting glucose (IFG; 5.6–6.9 mmol·l − 1 ) and/or impaired glucose tolerance (IGT; 7.8–11.0 mmol•l − 1 2 h following oral glucose tolerance test, OGTT). Compositional isotemporal substitution was used to estimate the association of reallocating time between behaviours. Results: Replacing MVPA with any other behaviour around the mean composition was associated with a poorer cardio-metabolic risk profile. Conversely, when MVPA was increased, the relationships with cardiometabolic risk markers was favourable but with smaller predicted changes than when MVPA was replaced. Further, substituting ST with LIPA predicted improvements in cardio-metabolic risk markers, most notably insulin and HOMA-IR. Conclusions: This is the first study to use compositional analysis of the 24 h movement composition in adults with overweight/obesity and pre-diabetes. These findings build on previous literature that suggest replacing ST with LIPA may produce metabolic benefits that contribute to the prevention and management of type 2 diabetes. Furthermore, the asymmetry in the predicted change in risk markers following the reallocation of time to/from MVPA highlights the importance of maintaining existing levels of MVPA. Trial registration: ClinicalTrials.gov (NCT01777893)

Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs

<p>Each cryotolerance index was calculated as follows:.</p><p>(m.p.: membrane permeability; o.a.m.: outer acrosome membrane; GMFI: Geometric mean of fluorescence intensity; arbitrary units).</p