Testing the predictive validity of the healthy eating index-2015 in the multiethnic cohort: Is the score associated with a reduced risk of all-cause and cause-specific mortality?

The Healthy Eating Index-2015 (HEI-2015) was created to assess conformance of dietary intake with the Dietary Guidelines for Americans (DGA) 2015–2020. We assessed the association between the HEI-2015 and mortality from all-cause, cardiovascular disease (CVD), and cancer in the Multiethnic Cohort (MEC). White, African American, Native Hawaiian, Japanese American, and Latino adults (n > 215,000) from Hawaii and California completed a quantitative food-frequency questionnaire at study enrollment. HEI-2015 scores were divided into quintiles for men and women. Radar graphs were used to demonstrate how dietary components contributed to HEI-2015 scores. Mortality was documented over 17–22 years of follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards models. High HEI-2015 scores were inversely associated with risk of mortality from all-cause, CVD, and cancer for men and women (p-trend <0.0001 for all models). For men, the HRs (CIs) for all-cause, CVD, and cancer comparing the highest to the lowest quintile were 0.79 (0.76, 0.82), 0.76 (0.71, 0.82), and 0.80 (0.75, 0.87), respectively. For women, the HRs were 0.79 (0.76, 0.82), 0.75 (0.70, 0.81), and 0.84 (0.78, 0.91), respectively. These results, in a multiethnic population, demonstrate that following a diet aligned with the DGAs 2015–2020 recommendations is associated with lower risk of mortality from all-cause, CVD, and cancer

Quantification of the Calcification Phenotype of Abcc6-Deficient Mice with Microcomputed Tomography

Pseudoxanthoma elasticum in humans and dystrophic cardiac calcification in mice are heritable disorders characterized by dystrophic calcification of soft connective tissues related to the defective function of the ABCC6 (human)/Abcc6 (mouse) transporter. Of particular interest is the finding of calcified vibrissae in Abcc6−/− mice, which facilitates the study of dystrophic calcification by histological techniques. We aimed to determine whether mice prone to dystrophic cardiac calcification (C3H/HeOuJ and DBA/2J strains) presented similar vibrissae changes and to evaluate the value of microcomputed tomography to quantify the extent of mystacial vibrissae calcifications. These calcifications were absent in DBA/2J and C57BL/6J control mice. In both Abcc6−/− and C3H/HeOuJ mice, calcifications progressed in a caudal-rostral direction with aging. However, the calcification process was delayed in C3H/HeOuJ mice, indicating an incomplete expression of the calcification phenotype. We also found that the calcification process in the cephalic region was not limited to mystacial vibrissae but was also present in other periorbital sensorial vibrissae. The vibrissae calcification was circular and encompassed the medial region of the vibrissae capsule, adjacent to the ring and cavernous sinuses (the areas adjacent to blood and lymphatic vessels). Collectively, our findings confirm that Abcc6 acts as an inhibitor of spontaneous chronic mineralization and that microcomputed tomography is a valuable noninvasive tool for the assessment of the calcification phenotype in Abcc6-deficient mice

Identifying cooperative transcriptional regulations using protein–protein interactions

Cooperative transcriptional activations among multiple transcription factors (TFs) are important to understand the mechanisms of complex transcriptional regulations in eukaryotes. Previous studies have attempted to find cooperative TFs based on gene expression data with gene expression profiles as a measure of similarity of gene regulations. In this paper, we use protein–protein interaction data to infer synergistic binding of cooperative TFs. Our fundamental idea is based on the assumption that genes contributing to a similar biological process are regulated under the same control mechanism. First, the protein–protein interaction networks are used to calculate the similarity of biological processes among genes. Second, we integrate this similarity and the chromatin immuno-precipitation data to identify cooperative TFs. Our computational experiments in yeast show that predictions made by our method have successfully identified eight pairs of cooperative TFs that have literature evidences but could not be identified by the previous method. Further, 12 new possible pairs have been inferred and we have examined the biological relevances for them. However, since a typical problem using protein–protein interaction data is that many false-positive data are contained, we propose a method combining various biological data to increase the prediction accuracy

Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

BACKGROUND: Mammographic density is a strong predictor of breast cancer risk and is increased by hormone replacement therapy (HRT). Some associations with genetic polymorphisms in enzymes involved in estrogen metabolism have been described. This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val(58 )Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort. METHODS: Mammographic density, before diagnosis in cases, was quantified by using a validated computer-assisted method. Blood samples were genotyped by standard PCR/RFLP methods. Adjusted mean percent density was calculated by genotype using mixed models with the unstructured covariance option. RESULTS: A positive association between the C allele in the CYP1A2*1F gene and percent density, but not the dense area, was suggested (p = 0.11). The relation was limited to controls (p = 0.045), postmenopausal women not using HRT (p = 0.08), and normal weight subjects (p = 0.046). We did not observe any relation between the COMT Val(58 )Met polymorphism and breast density. CONCLUSION: The lack of an association between the CYP1A2 genotype and the size of the dense areas suggests an effect on the non-dense, i.e., fatty breast tissue. The discrepancies among studies may be due to differential susceptibility; changes in enzyme activity as a result of the CYP1A2*1F polymorphism may influence breast tissue differently depending on hormonal status. Larger studies with the ability to look at interactions would be useful to elucidate the influence of genetic variation in CYP1A2 and COMT on the risk of developing breast cancer

Nuclear structure studies with the 7Li(e,e'p) reaction

Experimental momentum distributions for the transitions to the ground state and first excited state of 6He have been measured via the reaction 7Li(e,e'p)6He, in the missing momentum range from -70 to 260 MeV/c. They are compared to theoretical distributions calculated with mean-field wave functions and with variational Monte Carlo (VMC) wave functions which include strong state-dependent correlations in both 7Li and 6He. These VMC calculations provide a parameter-free prediction of the momentum distribution that reproduces the measured data, including its normalization. The deduced summed spectroscopic factor for the two transitions is 0.58 +/- 0.05, in perfect agreement with the VMC value of 0.60. This is the first successful comparison of experiment and ab initio theory for spectroscopic factors in p-shell nuclei.Comment: 4 pages, 3 figure

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin