Human metastable epiallele candidates link to common disorders

Metastable epialleles (MEs) are mammalian genomic loci where epigenetic patterning occurs before gastrulation in a stochastic fashion leading to systematic interindividual variation within one species. Importantly, periconceptual nutritional influences may modulate the establishment of epigenetic changes, such as DNA methylation at MEs. Based on these characteristics, we exploited Infinium HumanMethylation450 BeadChip kits in a 2-tissue parallel screen on peripheral blood leukocyte and colonic mucosal DNA from 10 children without identifiable large intestinal disease. This approach led to the delineation of 1776 CpG sites meeting our criteria for MEs, which associated with 1013 genes. The list of ME candidates exhibited overlaps with recently identified human genes (including CYP2E1 and MGMT, where methylation has been associated with Parkinson disease and glioblastoma, respectively) in which perinatal DNA methylation levels where linked to maternal periconceptual nutrition. One hundred 18 (11.6%) of the ME candidates overlapped with genes where DNA methylation correlated (r > 0.871; p < 0.055) with expression in the colon mucosa of 5 independent control children. Genes involved in homophilic cell adhesion (including cadherin-associated genes) and developmental processes were significantly overrepresented in association with MEs. Additional filtering of gene expression-correlated MEs defined 35 genes, associated with 2 or more CpG sites within a 10 kb genomic region, fulfilling the ME criteria. DNA methylation changes at a number of these genes have been linked to various forms of human disease, including cancers, such as asthma and acute myeloid leukemia (ALOX12), gastric cancer (EBF3), breast cancer (NAV1), colon cancer and acute lymphoid leukemia (KCNK15), Wilms tumor (protocadherin gene cluster; PCDHAs) and colorectal cancer (TCERG1L), suggesting a potential etiologic role for MEs in tumorigenesis and underscoring the possible developmental origins of these malignancies. The presented compendium of ME candidates may accelerate our understanding of the epigenetic origins of common human disorders.     

Tracking the physical aging of poly(ethylene oxide): A technical note

Physical aging of 2 types of PEO could be tracked by the combination of PALS, DSC, and SEM methods. After storing the samples at 40°C±2°C and 75%±5% RH, a decrease in the o-Ps lifetime values and an increase in the melting enthalpies as a function of storage time indicated a reorientation of the polymer chains. The limitations of monitoring enthalpy relaxation confirm the importance of methods that track volume relaxation, such as PALS. Structural changes could be observed even after a short storage time (4 weeks), which highlights the effect of further investigations of the influence of physical aging on the properties of PEO-containing dosage forms.     

In the Same Boat? A Comparative Analysis of the Approaches of Russia and Canada in the Negotiation of the IMO’s Mandatory Polar Code

Abstract

In the field of Arctic shipping, Canada and the Russian Federation have enacted extensive unilateral national regulations cognizant of Article 234, UN Convention on the Law of the Sea. On the global level, both states have been important actors in negotiating the International Maritime Organization’s mandatory Polar Code, a legal instrument with implications for regulations at the national level. This article compares and contrasts the approaches, positions, and arguments of Canada and Russia especially regarding national systems to control navigation and vessel-source pollution. The results suggest different emphases stemming from the two states’ political and economic realities and capacities.