The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Chemisorption working capacity and kinetics of CO2 and H2O of hydrotalcite-based adsorbents for sorption-enhanced water-gas-shift applications

The adsorption behavior of carbon dioxide and water on a K-promoted hydrotalcite based adsorbent has been studied by thermogravimetric analysis with the aim to better understand the kinetic behavior and mechanism of such material in sorption enhanced water-gas shift reactions. The cyclic adsorption capacity was measured as a function of temperature (300–500 °C), pressure (0–8 bar) and the cycle time. Both species interact at elevated temperatures with the adsorbent. The history of the adsorbent (pretreatment/desorption conditions) has a profound influence on its sorption capacity. Slow desorption kinetics determine the sorption capacity during cyclic operation, where a high temperature during the desorption and long half-cycle times can increase the cyclic working capacity for both CO2 and H2O significantly. Accounting for the sorbent history and the definition of adsorption capacity are very important features when comparing sorption capacities to values reported in literature. The adsorbent shows very high capacities for H2O compared to CO2 which has not been reported in the literature up to now. The mechanism for H2O and CO2 adsorption seems to be a different one. Whereas H2O adsorption seems to follow the principles of a simple physisorption mechanism, CO2 adsorption can only be explained by a chemical reaction with the adsorbent. Working isotherms (cyclic working capacity at isothermal conditions at different pressures) of both CO2 and H2O were measured up to 8 bar total pressure. Higher partial pressures increase the cyclic working capacity of the adsorbent up to 0.47 mmol/g for CO2View the MathML source(PCO2=8bar) and 1.06 mmol/g for H2O (View the MathML sourcePH2O=4.2bar) at 400 °C after 30 min of adsorption followed by 30 min of dry regeneration with N2

Influence of material composition on the CO2 and H2O adsorption capacities and kinetics of potassium-promoted sorbents

Two different potassium-promoted hydrotalcite (HTC)-based adsorbents and a potassium-promoted alumina sorbent were investigated using thermogravimetric analysis (TGA) and different characterization methods in order to study CO2 and H2O adsorption capacity and kinetics. A higher Mg content improves the cyclic working capacity for CO2 due to the higher basicity of the material. The initial adsorption rate for CO2 is very fast for all sorbents, but for sorbents with higher MgO content, this fast-initial adsorption is followed by a slower CO2 uptake probably caused by the slow formation of bulk carbonates. A longer half-cycle time can therefore increase the CO2 cyclic working capacity for sorbents with a higher MgO content. Potassium-promoted alumina has a very stable CO2 cyclic working capacity at different operating temperatures compared to the potassium-promoted HTC's. Usually a higher operating temperature increases the desorption kinetics for a HTC-based adsorbent, but not for potassium-promoted alumina. HTC-based adsorbents show the highest cyclic working capacity for H2O. The adsorption kinetics for H2O are not influenced by the material composition, indicating that the mechanism behind the adsorption of H2O is different compared to CO2. Depending on the material composition, adsorption of steam at high operating temperatures (>500 °C) results in an irreversible decomposition of carbonate species. Steam can reduce the temperature where usually K2CO3 is irreversibly decomposed resulting in a significantly reduced cyclic working capacity, which is very important concerning the use of these sorbents for sorption-enhanced water-gas shift processes

Chemisorption of H2O and CO2 on hydrotalcites for sorptionenhanced water-gas-shift processes

Thermogravimetric analysis and breakthrough experiments in a packed bed reactor were used to validate a developed adsorption model to describe the cyclic working capacity of CO2 and H2O on a potassium-promoted hydrotalcite, a very promising adsorbent for sorption-enhanced water-gas-shift applications. Four different adsorption sites (two sites for CO2, one site for H2O and one equilibrium site for both species) were required to describe the mass changes observed in the TGA experiments. The TGA experiments were carried out at operating temperatures between 300 and 500 °C, while the total pressure in the reactor was kept at atmospheric pressure. Cyclic working capacities for different sites and the influence of the operating conditions on the cyclic working capacity were studied using the developed model. A higher operating temperature leads to a significant increase in the cyclic working capacity of the sorbent for CO2 attributed to the increase in the desorption kinetics for CO2. The model was successfully validated with experiments in a packed bed reactor at different operating temperatures

On the CO2 and H2O chemisorption on hydrotalcite-based adsorbents for sorption-enhanced water-gas-shift processes.

Thermogravimetric analysis (TGA) was used to study the adsorption phenomena of CO2 and H2O on a hydrotalcite-based adsorbent to be used for sorption-enhanced Water-Gas-Shift (SEWGS). The adsorption of CO2 and H2O and the interaction between the two can be described when considering the presence of at least three different sites (2 for CO2 and 1 for H2O) participating in the adsorption phenomena at elevated temperatures. The experiments confirm that the regeneration conditions are crucial for activating more sites for CO2 adsorption and are therefore the limiting factor for the cyclic working capacity of the adsorbent

Sorption-enhanced water-gas shift

Sorption-enhanced water-gas shift (SEWGS) is a promising technology for precombustion CO2 capture with high energy efficiency. Hydrotalcite-based adsorbents were studied as possible solid sorbents for pressure swing adsorption under SEWGS conditions. They show high thermal and mechanical stability with sufficiently high cyclic working capacity and fast adsorption kinetics. The regenerations step (desorption of CO2 by feeding steam to the adsorbent) is slower and limits the cyclic working capacity of the adsorbent. It was found that a higher operating temperature is beneficial because of enhanced desorption kinetics. Steam induces the desorption of a second adsorption site available for CO2 which cannot be desorbed with N2. Different adsorption sites are present on the hydrotalcite material. On the basis of a dedicated set of high-pressure breakthrough experiments an adsorption isotherm has been developed which describes the interaction of CO2 and H2O with the hydrotalcite-based adsorbent over the relevant range of partial pressures. Based on the isotherm and a linear driving force approximation for intraparticle mass transfer, a reactor model has been constructed for the simulation and optimization of SEWGS cycles. A parameter study of SEWGS cycles shows that the high-pressure rinse steam improves the CO2 product purity, while the low-pressure steam purge mainly serves to improve the CO2 capture ratio. Finally, a comparative analysis of the required work of precombustion separation of CO2 and H2 shows that SEWGS outperforms conventional technologies for hydrogen-carbon dioxide separation, partly because of its inherently high CO2 capture ratio

On the influence of steam on the CO2 chemisorption capacity of a hydrotalcite-based adsorbent for SEWGS applications

Hydrotalcite-based adsorbents have shown great potential for use in sorption-enhanced water-gas-shift applications. A combination of thermogravimetric experiments and breakthrough experiments have been carried out to elucidate the effect of steam on the CO2 cyclic sorption capacity on a K-promoted hydrotalcite-based adsorbent. Different TGA cycles have been designed to study the mass change on sorbents exposed to different sequences of different CO2/H2O/N2 mixtures. Because the complex sorption/desorption and replacement phenomena cannot be explained by TGA experiments only, additional information from breakthrough experiments in a packed bed reactor was used to correlate the observed total mass change in the TGA cycles to the phenomena prevailing on the sorbent. A mechanism has been developed which is able to describe the cyclic working capacity, for both CO2 and H2O under different experimental conditions. It was found that at least four different adsorption sites participate in the sorption/desorption of CO2 and H2O. Two adsorption sites can be regenerated with N2, whereas the other adsorption sites require the presence of H2O or CO2 to be desorbed. Regeneration of the adsorbent with steam leads to a significant increase in the CO2 cyclic working capacity from 0.3 to 0.53 mmol/g compared to a dry regeneration with N2 using the same cycle times

Differential modulation of enterocyte-like Caco-2 cells after exposure to short-chain fatty acids

The response of intestinal epithelial cells to short-chain fatty acids, which are increasingly used as food additives, was investigated. Human small intestinal epithelial cell model Caco-2 cells were exposed to formate, propionate and butyrate to assess their effect on cellular growth, metabolism, differentiation and protection against bacteria. The Caco-2 cells were entirely grown in the different short-chain fatty acids and respective growth patterns were determined. Differentiated cells were exposed to 0-20 mM short-chain fatty acids for 48 h and changes in DNA, RNA, (glyco)protein syntheses, sucrase isomaltase activity, transepithelial electrical resistance and protection against Salmonella enteritidis were measured. The short-chain fatty acids, altered linearly and differentially the growth pattern ranging from stimulation by formate to inhibition by butyrate. Formate inhibited cellular metabolism. Low concentrations of up to 5 mM propionate and 2 mM butyrate stimulated metabolism, while higher doses were inhibitory. Formate had no effect on sucrase isomaltase enzyme activity and transepithelial electrical resistance, whereas propionate and butyrate increased these markers of differentiation. Infection with S. enteritidis did not benefit from the short-chain fatty acid-induced transepithelial electrical resistance. It is concluded that formate, propionate and butyrate selectively and differentially modulate growth characteristics, cellular metabolism, sucrase isomaltase activity and transepithelial electrical resistance in a concentration- and carbon atom-related fashion. The short-chain fatty acid-induced transepithelial electrical resistance does not confer protection against S. enteritidis