The Role of Glia in Addiction: Dopamine as a Modulator of Glial Responses in Addiction

Cellular and Molecular Neurobiology - Addiction is a chronic and potentially deadly disease considered a global health problem. Nevertheless, there is still no ideal treatment for its management....     

Examining the behavior of crop-derived antibiotic resistance genes in anaerobic sludge batch reactors under thermophilic conditions

The consumption of transgenic crops and their by-products has become increasingly common in the United States. Yet, uncertainty remains regarding the fate and behavior of DNA within food matrices once it exits the digestive track and enters into wastewater treatment plants (WWTPs). Because many transgenic crops have historically contained antibiotic resistance genes as selection markers, understanding the behavior and uptake of these transgenes by environmental microbes is of critical importance. To investigate the behavior of free transgenic crop DNA, thermophilic anaerobic batch reactors were amended with varying concentrations of transgenic crop genes (i.e., LUG, nptII, and bla) and the persistence of those genes was monitored over 60 days using quantitative PCR. Significant levels of nptII and bla were detected in extracellular DNA (eDNA). Furthermore, LUG maize marker genes were also detected in the control reactors, suggesting that other crop-derived transgenes contained within digested transgenic foods may also enter WWTPs. Possible bacterial transformation events were detected within the highest dose treatments at Days 30 and 60 of incubation. These findings suggest that within the average conventional digester residence times in the United States (30 days), there is a potential for bacterial transformation events to occur with crop-derived transgenes found in eDNA.     

Environment changes epistasis to alter trade‐offs along alternative evolutionary paths

The fitness effect of a mutation can depend on both its genetic background, known as epistasis, and the prevailing external environment. Many examples of these dependencies are known, but few studies consider both aspects in combination, especially as they affect mutations that have been selected together. We examine interactions between five coevolved mutations in eight diverse environments. We find that mutations are, on average, beneficial across environments, but that there is high variation in their fitness effects, including many examples of mutations conferring a cost in some, but not other, genetic background‐environment combinations. Indeed, even when global interaction trends are accounted for, specific local mutation interactions are common and differed across environments. One consequence of this dependence is that the range of trade‐offs in genotype fitness across selected and alternative environments are contingent on the particular evolutionary path followed over the mutation landscape. Finally, although specific interactions were common, there was a consistent pattern of diminishing returns epistasis whereby mutation effects were less beneficial when added to genotypes of higher fitness. Our results underline that specific mutation effects are highly dependent on the combination of genetic and external environments, and support a general relationship between a genotype's current fitness and its potential to increase in fitness.     

Whole genome bisulfite sequencing of cell-free DNA and its cellular contributors uncovers placenta hypomethylated domains

BackgroundCirculating cell-free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the maternal and fetal DNA. Testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA; however, this depends on knowledge of the methylomes of circulating cell-free DNA and its cellular contributors.ResultsWe perform whole genome bisulfite sequencing on a set of unmatched samples including circulating cell-free DNA from non-pregnant and pregnant female donors and genomic DNA from maternal buffy coat and placenta samples. We find CpG cytosines within longer fragments are more likely to be methylated. Comparison of the methylomes of placenta and non-pregnant circulating cell-free DNA reveal many of the 51,259 identified differentially methylated regions are located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases. We find these placenta hypomethylated domains are consistently located within regions exhibiting low CpG and gene density. Differentially methylated regions identified when comparing placenta to non-pregnant circulating cell-free DNA are recapitulated in pregnant circulating cell-free DNA, confirming the ability to detect differential methylation in circulating cell-free DNA mixtures.ConclusionsWe generate methylome maps for four sample types at single-base resolution, identify a link between DNA methylation and fragment length in circulating cell-free DNA, identify differentially methylated regions between sample groups, and uncover the presence of megabase-size placenta hypomethylated domains.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0645-x) contains supplementary material, which is available to authorized users.