Variation in the FFAR1 gene modifies BMI, body composition and plasma lipids but not plasma insulin or Beta-cell function in overweight subjects

Background FFAR1 receptor is a long chain fatty acid G-protein coupled receptor which is expressed widely, but found in high density in the pancreas and central nervous system. It has been suggested that FFAR1 may play a role in insulin sensitivity, lipotoxicity and is associated with type 2 diabetes. Here we investigate the effect of three common SNPs of FFAR1 (rs2301151; rs16970264; rs1573611) on pancreatic function, BMI, body composition and plasma lipids. Methodology/Principal Findings For this enquiry we used the baseline RISCK data, which provides a cohort of overweight subjects at increased cardiometabolic risk with detailed phenotyping. The key findings were SNPs of the FFAR1 gene region were associated with differences in body composition and lipids, and the effects of the 3 SNPs combined were cumulative on BMI, body composition and total cholesterol. The effects on BMI and body fat were predominantly mediated by rs1573611 (1.06 kg/m2 higher (P = 0.009) BMI and 1.53% higher (P = 0.002) body fat per C allele). Differences in plasma lipids were also associated with the BMI-increasing allele of rs2301151 including higher total cholesterol (0.2 mmol/L per G allele, P = 0.01) and with the variant A allele of rs16970264 associated with lower total (0.3 mmol/L, P = 0.02) and LDL (0.2 mmol/L, P<0.05) cholesterol, but also with lower HDL-cholesterol (0.09 mmol/L, P<0.05) although the difference was not apparent when controlling for multiple testing. There were no statistically significant effects of the three SNPs on insulin sensitivity or beta cell function. However accumulated risk allele showed a lower beta cell function on increasing plasma fatty acids with a carbon chain greater than six. Conclusions/Significance Differences in body composition and lipids associated with common SNPs in the FFAR1 gene were apparently not mediated by changes in insulin sensitivity or beta-cell function.

Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids

Objective: SNPs identified from genome wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. Methods: Participants (n = 490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. Results: The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total(P = 0.02) and LDL (P = 0.002) cholesterol, triglycerides (P = 0.001) and apolipoprotein B (P = 0.004), and with lower baseline concentrations of HDL cholesterol (P < 0.001) and apolipoprotein A-I (P < 0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Conclusion: Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.

Means, motive and opportunity? Disentangling client influence on performance measurement appraisals

This paper investigates the extent to which clients were able to influence performance measurement appraisals during the downturn in commercial property markets that began in the UK during the second half of 2007. The sharp change in market sentiment produced speculation that different client categories were attempting to influence their appraisers in different ways. In particular, it was recognised that the requirement for open-ended funds to meet redemptions gave them strong incentives to ensure that their asset values were marked down to market. Using data supplied by Investment Property Databank, we demonstrate that, indeed, unlisted open ended funds experienced sharper drops in capital values than other fund types in the second half of 2007, after the market turning point. These differences are statistically significant and cannot simply be explained by differences in portfolio composition. Client influence on appraisal forms one possible explanation of the results observed: the different pressures on fund managers resulting in different appraisal outcomes.

Farm forestry in Pakistan: an application of Theory of Planned Behaviour by probing into the measurement issues

A research has been conducted over methodological issues concerning the Theory of Planned Behaviour (TPB) by determining an appropriate measurement (direct and indirect) of constructs and selection of a plausible scaling techniques (unipolar and bipolar) of constructs: attitude, subjective norm, perceived behavioural control and intention that are important in explaining farm level tree planting in Pakistan. Unipolar scoring of beliefs showed higher correlation among the constructs of TPB than bipolar scaling technique. Both direct and indirect methods yielded significant results in explaining intention to perform farm forestry except the belief based measure of perceived behavioural control, which were analysed as statistically non-significant. A need to examine more carefully the scoring of perceived behavioural control (PBC) has been expressed

Motivation, rationale and key results from the GERBILS Saharan dust measurement campaign

The Geostationary Earth Radiation Budget Intercomparison of Longwave and Shortwave radiation (GERBILS) was an observational field experiment over North Africa during June 2007. The campaign involved 10 flights by the FAAM BAe-146 research aircraft over southwestern parts of the Sahara Desert and coastal stretches of the Atlantic Ocean. Objectives of the GERBILS campaign included characterisation of mineral dust geographic distribution and physical and optical properties, assessment of the impact upon radiation, validation of satellite remote sensing retrievals, and validation of numerical weather prediction model forecasts of aerosol optical depths (AODs) and size distributions. We provide the motivation behind GERBILS and the experimental design and report the progress made in each of the objectives. We show that mineral dust in the region is relatively non-absorbing (mean single scattering albedo at 550 nm of 0.97) owing to the relatively small fraction of iron oxides present (1–3%), and that detailed spectral radiances are most accurately modelled using irregularly shaped particles. Satellite retrievals over bright desert surfaces are challenging owing to the lack of spectral contrast between the dust and the underlying surface. However, new techniques have been developed which are shown to be in relatively good agreement with AERONET estimates of AOD and with each other. This encouraging result enables relatively robust validation of numerical models which treat the production, transport, and deposition of mineral dust. The dust models themselves are able to represent large-scale synoptically driven dust events to a reasonable degree, but some deficiencies remain both in the Sahara and over the Sahelian region, where cold pool outflow from convective cells associated with the intertropical convergence zone can lead to significant dust production.

A study of the ethene-ozone reaction with photoelectron spectroscopy: measurement of product branching ratios and atmospheric implications

The ozone-ethene reaction has been investigated at low pressure in a flow-tube interfaced to a u.v. photoelectron spectrometer. Photoelectron spectra recorded as a function of reaction time have been used to estimate partial pressures of the reagents and products, using photoionization cross-sections for selected photoelectron bands of the reagents and products, which have been measured separately. Product yields compare favourably with results of other studies, and the production of oxygen and acetaldehyde have been measured as a function of time for the first time. A reaction scheme developed for the ozone-ethene reaction has been used to simulate the reagents and products as a function of time. The results obtained are in good agreement with the experimental measurements. For each of the observed products, the simulations allow the main reaction (or reactions) for production of that product to be established. The product yields have been used in a global model to estimate their global annual emissions in the atmosphere. Of particular interest are the calculated global annual emissions of formaldehyde (0.96 ± 0.10 Tg) and formic acid, (0.05 ± 0.01 Tg) which are estimated as 0.04% and 0.7% of the total annual emission respectively.

A study of the atmospherically relevant reaction between molecular chlorine and dimethylsulfide (DMS): establishing the reaction intermediate and measurement of absolute photoionization cross-sections

In a study using UV photoelectron spectroscopy (PES) of the atmospherically relevant reaction CH3SCH3 + Cl2 → CH3SCH2Cl + HCl bands associated with a reaction intermediate have been observed. These have been assigned to ionization of the covalently bound molecule (CH3)2SCl2 on the basis of the intensity of the observed bands as a function of reaction time, molecular orbital calculations of vertical ionization energies and evidence from infrared spectroscopy. A method has also been developed, with the flow-tube/PE spectrometer combination used, to measure photoionization cross-sections of the reagents and products at the photon energy utilized and this has allowed the photoionization cross-section of the intermediate to be estimated. This work augments an earlier study in which the rate constant of the reaction between CH3SCH3 (DMS) and Cl2 has been measured at room temperature.