Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface

Plasma concentrations of biologically active vitamin D (1,25- (OH)2D) are tightly controlled via feedback regulation of renal 1-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)2D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitaminDderegulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface

The association between low level exposures to ambient air pollution and term low birth weight: a retrospective cohort study

BACKGROUND: Studies in areas with relatively high levels of air pollution have found some positive associations between exposures to ambient levels of air pollution and several birth outcomes including low birth weight (LBW). The purpose of this study was to examine the association between LBW among term infants and ambient air pollution, by trimester of exposure, in a region of lower level exposures. METHODS: The relationship between LBW and ambient levels of particulate matter up to 10 um in diameter (PM(10)), sulfur dioxide (SO(2)) and ground-level ozone (O(3)) was evaluated using the Nova Scotia Atlee Perinatal Database and ambient air monitoring data from the Environment Canada National Air Pollution Surveillance Network and the Nova Scotia Department of Environment. The cohort consisted of live singleton births (≥37 weeks of gestation) between January1,1988 and December31,2000. Maternal exposures to air pollution were assigned to women living within 25 km of a monitoring station at the time of birth. Air pollution was evaluated as a continuous and categorical variable (using quartile exposures) for each trimester and relative risks were estimated from logistic regression, adjusted for confounding variables. RESULTS: There were 74,284 women with a term, singleton birth during the study period and with exposure data. In the analyses unadjusted for year of birth, first trimester exposures in the highest quartile for SO(2 )and PM(10)suggested an increased risk of delivering a LBW infant (relative risk = 1.36, 95% confidence interval = 1.04 to 1.78 for SO(2 )exposure and relative risk = 1.33, 95% confidence interval = 1.02 to 1.74 for PM(10)). After adjustment for birth year, the relative risks were attenuated somewhat and not statistically significant. A dose-response relationship for SO(2 )was noted with increasing levels of exposure. No statistically significant effects were noted for ozone. CONCLUSION: Our results suggest that exposure during the first trimester to relatively low levels of some air pollutants may be associated with a reduction in birth weight in term-born infants. These findings have implications for the development of effective risk management strategies to minimize the public health impacts for pregnant women

Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo-controlled trial

BACKGROUND: Maternal micronutrient deficiencies are commonly associated with clinical indicators of placental dysfunction. OBJECTIVE: We tested the hypothesis that periconceptional multiple-micronutrient supplementation (MMS) affects placental function. DESIGN: We conducted a double-blind, randomized, placebo-controlled trial of MMS in 17- to 45-y-old Gambian women who were menstruating regularly and within the previous 3 mo. Eligible subjects were pre-randomly assigned to supplementation with the UNICEF/WHO/United Nations University multiple micronutrient preparation (UNIMMAP) or placebo on recruitment and until they reached their first antenatal check-up or for 1 y if they failed to conceive. Primary outcome measures were midgestational indexes of utero-placental vascular-endothelial function [ratio of plasminogen-activator inhibitor (PAI) 1 to PAI-2 and mean uterine-artery resistance index (UtARI)] and placental active transport capacity at delivery [fetal to maternal measles antibody (MMA) ratio]. RESULTS: We recruited 1156 women who yielded 415 pregnancies, of which 376 met all of the inclusion criteria. With adjustment for gestational age at sampling, there were no differences in PAI-1 to PAI-2 or MMA ratios between trial arms, but there was a 0.02-unit reduction in UtARI between 18 and 32 wk of gestation (95% CI: -0.03, -0.00; P = 0.040) in women taking UNIMMAP. CONCLUSIONS: Placental vascular function was modifiable by periconceptional micronutrient supplementation. However, the effect was small and supplementation did not further affect other variables of placental function. This trial was registered at www.controlled-trials.com as ISRCTN 13687662

A population-based phenome-wide association study of cardiac and aortic structure and function

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart–brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers

Asymptotic Performance of Vector Quantizers with a Perceptual Distortion Measure

Gersho's bounds on the asymptotic performance of vector quantizers are valid for vector distortions which are powers of the Euclidean norm. Yamada, Tazaki and Gray generalized the results to distortion measures that are increasing functions of the norm of their argument. In both cases, the distortion is uniquely determined by the vector quantization error, i.e., the Euclidean difference between the original vector and the codeword into which it is quantized. We generalize these asymptotic bounds to input-weighted quadratic distortion measures, a class of distortion measure often used for perceptually meaningful distortion. The generalization involves a more rigorous derivation of a fixed rate result of Gardner and Rao and a new result for variable rate codes. We also consider the problem of source mismatch, where the quantizer is designed using a probability density different from the true source density. The resulting asymptotic performance in terms of distortion increase in dB is shown..

NMR Analysis of a Conformational Transition in an Acyclic Peptide. Model System for Studying Helix Unfolding

The stabilization of helical structures in short apolar peptides is readily achieved by introduction of alpha,alpha-dialkylamino acids. The use of stereochemically constrained residues in conjunction with conformationally flexible segments permits the design of peptides that are poised to undergo structural transitions. The octapeptide Boc-Leu-Ac(8)c-Val-Gly-Gly-Leu-Ac(8)c-Val-OMe (Ac(8)c = 1-aminocyclooctane-1-carboxylic acid) incorporates residues with contradictory conformational tendencies. NMR analysis in CDCl3, using nuclear Overhauser effects and delineation of hydrogen-bonded NH groups establishes a 3(10)-helical conformation. In a polar strongly solvating medium, like DMSO, the helix unfolds. Studies in CDCl3/DMSO mixtures provide clear evidence for a solvent dependent conformational transition. Amide NH chemical shifts and temperature coefficients at varying solvent composition allow a detailed structural analysis of the unfolding process. The intrinsic fragility of the octapeptide helix provides an opportunity to examine invasion of the helix backbone by water molecules. Studies in DMSO solution containing low concentrations of water establish that preferential water peptide interactions may indeed be present

Multiresolution Tree Structured Vector Quantization

In some applications of progressive image transmission, the images are viewed at several resolutions with fewer bits at lower resolutions. A multiresolution tree structured vector quantizer is developed to produce an embedded code, so that the quality of the image is optimized for the corresponding resolution at any number of bits. The resolution at which the image is viewed given a particular number of bits is determined by the specific decoder. The multiresolution tree structured vector quantizer presented in the paper generates the codebook by greedy tree growing, which is an extension of the generalized BFOS algorithm. The tree is grown one step further by splitting the node which will yield the best ratio of the change in distortion at the corresponding resolution of current bit rate to the change in rate. The decoder has codewords of all resolutions obtained by optimal centroiding for a given resolution and a given encoder partition. The encoding of an image is essentially the sa..

Utilization of red mud for making bricks

‘Red mud’ or ‘bauxite residue’ is a highly alkaline waste generated from alumina refinery with a pH of 10.5–12.5. Red mud poses serious environmental problems such as alkali seepage in ground water and alkaline dust generation. Most of the environmental hazards related to disposal of red mud can be reduced by its safe treatment and efficient utilization. Sintering of red mud along with a silicate material at a very high temperature fixes nearly all the leachable soda and the mixture can be utilized as a building material. Fired and non-fired bricks can be developed by mixing red mud with fly ash and other materials. In this way, red mud can be utilized in bulk in building and construction industry. Review of utilization of red mud in manufacture of fired and non-fired bricks is presented in the paper.by Jyoti Mukhopadhyay et al.