Dietary Plant Sterol Esters Must Be Hydrolyzed to Reduce Intestinal Cholesterol Absorption in Hamsters

Background: Elevated concentrations of LDL cholesterol are associated with the development of atherosclerosis and therefore are considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is addressed by drug therapy as well as dietary supplementation with plant sterols and plant sterol esters (PSEs). Objective: This study was conducted to test the hypothesis that the cholesterol-lowering effects of PSE require hydrolysis to free sterols (FSs). Methods: Male Syrian hamsters were fed atherogenic diets (AIN-93M purified diet containing 0.12% cholesterol and 8% coconut oil) to which one of the following was added: no PSEs or ethers (control), 5% sterol stearate esters, 5% sterol palmitate esters (PEs), 5% sterol oleate esters (OEs), 5% sterol stearate ethers (STs; to mimic nonhydrolyzable PSE), or 3% FSs plus 2% sunflower oil. The treatments effectively created a spectrum of PSE hydrolysis across which cholesterol metabolism could be compared. Metabolic measurements included cholesterol absorption, plasma and liver lipid concentration, and fecal neutral sterol and bile acid excretion. Results: The STs and the PEs and SEs were poorly hydrolyzed (1.69–4.12%). In contrast,OEs were 88.3% hydrolyzed. The percent hydrolysis was negatively correlated with cholesterol absorption (r=20.85; P \u3c 0.0001) and positively correlated with fecal cholesterol excretion (r = 0.92; P \u3c 0.0001), suggesting that PSE hydrolysis plays a central role in the cholesterol-lowering properties of PSE. Conclusions: Our data on hamsters suggest that PSE hydrolysis and the presence of FSs is necessary to induce an optimum cholesterol-lowering effect and that poorly hydrolyzed PSEs may lower cholesterol through an alternative mechanism than that of competition with cholesterol for micelle incorporation

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10−8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10−5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.</p

Paper Trails: Following the Money

In many recent elections, the candidates who raise the most money have a better shot at winning, so candidates must raise millions of dollars to win an election. A top question to consider in all elections: Where is the money coming from? Posting about the financing behind federal elections from In All Things - an online hub committed to the claim that the life, death, and resurrection of Jesus Christ has implications for the entire world. http://inallthings.org/paper-trails-following-the-money

Searching for eV-scale sterile neutrinos with eight years of atmospheric neutrinos at the IceCube neutrino telescope

We report in detail on searches for eV-scale sterile neutrinos, in the context of a 3+1 model, using eight years of data from the IceCube neutrino telescope. By analyzing the reconstructed energies and zenith angles of 305,735 atmospheric $\nu_\mu$ and $\bar{\nu}_\mu$ events we construct confidence intervals in two analysis spaces: $\sin^2 (2\theta_{24})$ vs. $\Delta m^2_{41}$ under the conservative assumption $\theta_{34}=0$; and $\sin^2(2\theta_{24})$ vs. $\sin^2 (2\theta_{34})$ given sufficiently large $\Delta m^2_{41}$ that fast oscillation features are unresolvable. Detailed discussions of the event selection, systematic uncertainties, and fitting procedures are presented. No strong evidence for sterile neutrinos is found, and the best-fit likelihood is consistent with the no sterile neutrino hypothesis with a p-value of 8\% in the first analysis space and 19\% in the second.Comment: This long-form paper is a companion to the letter "An eV-scale sterile neutrino search using eight years of atmospheric muon neutrino data from the IceCube Neutrino Observatory". v2: update other experiments contours on results plo

An eV-scale sterile neutrino search using eight years of atmospheric muon neutrino data from the IceCube Neutrino Observatory

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305,735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01\,eV$^2$ and 100\,eV$^2$. The best-fit point is found to be at $\sin^2(2\theta_{24})=0.10$ and $\Delta m_{41}^2 = 4.5{\rm eV}^2$, which is consistent with the no sterile neutrino hypothesis with a p-value of 8.0\%.Comment: 11 pages, 5 figures. This letter is supported by the long-form paper "Searching for eV-scale sterile neutrinos with eight years of atmospheric neutrinos at the IceCube neutrino telescope," also appearing on arXiv. Digital data release available at: https://github.com/icecube/HE-Sterile-8year-data-releas

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57