Tobacco exposure-related alterations in DNA methylation and gene expression in human monocytes: the Multi-Ethnic Study of Atherosclerosis (MESA)

Alterations in DNA methylation and gene expression in blood leukocytes are potential biomarkers of harm and mediators of the deleterious effects of tobacco exposure. However, methodological issues, including the use of self-reported smoking status and mixed cell types have made previously identified alterations in DNA methylation and gene expression difficult to interpret. In this study, we examined associations of tobacco exposure with DNA methylation and gene expression, utilizing a biomarker of tobacco exposure (urine cotinine) and CD14+ purified monocyte samples from 934 participants of the community-based Multi-Ethnic Study of Atherosclerosis (MESA). Urine cotinine levels were measured using an immunoassay. DNA methylation and gene expression were measured with microarrays. Multivariate linear regression was used to test for associations adjusting for age, sex, race/ethnicity, education, and study site. Urine cotinine levels were associated with methylation of 176 CpGs [false discovery rate (FDR)<0.01]. Four CpGs not previously identified by studies of non-purified blood samples nominally replicated (P value<0.05) with plasma cotinine-associated methylation in 128 independent monocyte samples. Urine cotinine levels associated with expression of 12 genes (FDR<0.01), including increased expression of P2RY6 (Beta ± standard error = 0.078 ± 0.008, P = 1.99 × 10^?22), a gene previously identified to be involved in the release of pro-inflammatory cytokines. No cotinine-associated (FDR<0.01) methylation profiles significantly (FDR<0.01) correlated with cotinine-associated (FDR<0.01) gene expression profiles. In conclusion, our findings i) identify potential monocyte-specific smoking-associated methylation patterns and ii) suggest that alterations in methylation may not be a main mechanism regulating gene expression in monocytes in response to cigarette smoking.     

The Role of Grandmothers in the Lives of Preschoolers Growing Up in Urban Poverty

Abstract

Little is known about how grandmothers may influence children's development, although they may frequently assist parents in the raising of their children, especially among low-income families. Data from Welfare, Children, and Families: A Three-City Study were used to explore how preschoolers function academically and psychologically over time based on grandmothers' residential status and level of caretaking responsibility. Longitudinal regression analyses suggest that children who consistently have custodial grandmothers lag behind their peers in the development of their academic achievement, whereas those in multigenerational households consistently have more socioemotional problems over time. However, many of these differences are accounted for by co-occurring family characteristics. Furthermore, children transitioning into the care of custodial grandmothers were found to have positive changes in self-regulation and socioemotional functioning, and those transitioning into multigenerational households had more problems with self-regulation over time.     

Evidence of differential pH regulation of the Arabidopsis vacuolar Ca2+/H+ antiporters CAX1 and CAX2.

The Arabidopsis Ca(2+)/H(+) antiporters cation exchanger (CAX) 1 and 2 utilise an electrochemical gradient to transport Ca(2+) into the vacuole to help mediate Ca(2+) homeostasis. Previous whole plant studies indicate that activity of Ca(2+)/H(+) antiporters is regulated by pH. However, the pH regulation of individual Ca(2+)/H(+) antiporters has not been examined. To determine whether CAX1 and CAX2 activity is affected by pH, Ca(2+)/H(+) antiport activity was measured in vacuolar membrane vesicles isolated from yeast heterologously expressing either transporter. Ca(2+) transport by CAX1 and CAX2 was regulated by cytosolic pH and each transporter had a distinct cytosolic pH profile. Screening of CAX1/CAX2 chimeras identified an amino acid domain within CAX2 that altered the pH-dependent Ca(2+) transport profile so that it was almost identical to the pH profile of CAX1. Results from mutagenesis of a specific His residue within this domain suggests a role for this residue in pH regulation.     

Factors Affecting Ethanol Induced Luminescence in Dark-Treated Chloroplasts

Dark-treated chloroplasts emit light when treated with a high ethanol concentration. The ethanol treatment causes chlorophyll solvation. The light is red and emanates from a singlet excited molecule, probably a chlorophyll peroxide. It is quenched by acetone, sodium dodecyl sulfate treatment of the chloroplasts before the addition of ethanol, boiling, reducing substances and low pH. It is enhanced by ferricyanide and high pH. This is interpreted as a requirement for an organized structure and for an energy transfer system for light emission to occur.     

THE INTRINSIC MECHANISM OF CHROMATIN DECONDENSATION AND ITS ACTIVATION IN HUMAN SPERMATOZOA*

In vitro decondensation of human sperm chromatin induced by the activation of an intrinsic mechanism was studied by light microscopy, scanning and transmission electron microscopy. Morphological evidence was provided to support the concept that this mechanism is essential for the chromatin decondensation occurring in vivo. Prostatic zinc is hypothesized to preserve this potential decondensation ability from oxidative destruction, by reversibly binding to free thiol-groups. The unique occurrence of disulphide-stabilized structures in eutherian spermatozoa may serve to protect the spermatozoon from structural degradation by its own proteolytic activity during the relatively slow passage through the eutherian egg investments.     

SEDIMENTARY STRUCTURES IN CAMBRIAN LIMESTONES STUDIED BY RADIOGRAPHY

The paper deals with radiographic studies of Middle Cambrian 'fragment limestone', and Upper Cambrian anthraconite concretions from Bornholm (Denmark). A very simple method provides good insight into the sedimentary structures of the rocks and hence a good foundation for interpretation of the lithogenesis.