We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.
Edit for a change
RNA editing – a process that changes the coding potential of mature mRNAs – is an increasingly recognized strategy for modulating the function of proteins involved in neuronal excitability, such as the GABAA receptor. Andre Lagrange, M.D., Ph.D., Elizabeth Rula, Ph.D., and colleagues have characterized the editing of the mouse GABAA receptor alpha3 subunit.
They report in the June 11 Journal of Neuroscience that editing of this subunit, called Gabra3, is low at embryonic day 15 and increases to about 90 percent by seven days after birth. Only the hippocampus in adult mouse brains had low levels of edited Gabra3. Using electrophysiological techniques, the researchers found that editing results in GABAA receptor channels that pass less current, activate more slowly and deactivate more quickly. The studies suggest that RNA editing introduces functional flexibility that allows GABAA receptors (non-edited) to play an excitatory role and promote neuronal growth and connectivity during development and then switch (edited) to inhibitory functions in mature animals. To see the study, go <a href="http://www.jneurosci.org/cgi/content/abstract/28/24/6196?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=lagrange&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT">here</a>.
— Leigh MacMillan
A molecular path to arteries
Well before blood begins coursing through an embryo, genetic factors establish which cells will become the arteries and veins that carry the blood. Vascular endothelial growth factor (VEGF) and the Notch signaling pathway play critical roles in determining the fate of arterial cells. Tsutomu Kume, Ph.D., and colleagues recently found essential roles for two transcription factors – Foxc1 and Foxc2 – in arterial cell specification. But whether and how Foxc transcription factors interact with VEGF and Notch signaling in vascular development remains unclear.
In the June issue of PLoS ONE, Kume and Hisaki Hayashi, Ph.D., provide further details of the molecular mechanisms by which Foxc transcription factors control arterial gene expression. They show that Foxc proteins directly activate a Notch target gene, Hey2, and that these transcription factors cooperate with VEGF to activate genes in the Notch pathway. This detailed mechanism could offer clues about how abnormal vascular development can lead to congenital defects in arteries and veins. To see the study, go <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002401">here</a>.
— Melissa Marino
Many faces of depression
As with other cognitive disorders, the root cause of major depressive disorder (MDD) is difficult to identify, with many genetic and environmental factors impacting disease risk. The disorder can include disturbances in mood, sleep, appetite and motor function, and differences in pattern and duration of illness. While typically diagnosed based on clinical symptoms, MDD may be better understood by identifying specific genetic variants responsible for particular symptoms.
To determine the relationship between certain genetic variants and specific MDD features, Maureen Hahn, Ph.D., and colleagues analyzed common gene variants in the brain’s monoaminergic and cholinergic pathways in 110 individuals with unipolar MDD. They identified specific genetic variants in the norepinephrine and choline transporters associated with symptoms like recurrent depression, appetite increase, and overall depression severity. The results, reported in the June issue of Genes, Brain and Behavior, suggest that such “genotype-phenotype” analysis can differentiate clinical subpopulations of MDD, which may help identify groups that can benefit from more targeted drug therapy. To see the study, go <a href="http://www3.interscience.wiley.com/journal/119424399/abstract">here</a>.
— William Peters
Too many chromosomes spark tumors
Polyploidy – an increase in the number of a cell’s whole set of chromosomes – has been proposed to contribute to cancer development by promoting genomic instability. But it is unclear whether this instability is a driving force for tumorigenesis, or a consequence of it.
Meejeon Roh, Ph.D., Sarki Abdulkadir, M.D., Ph.D., and colleagues report in the July issue of PLoS ONE that polyploidy causes genomic instability and has a direct role in tumor development in human cells. They expressed the oncogene Pim-1, which has been implicated in the development of various tumors, in human prostate and breast epithelial cells. Pim-1 expression in the cells caused the gradual emergence of polyploidy, allowing the investigators to sort the cells into diploid (normal chromosomal content) and polyploid populations. The polyploid cells were tumorigenic in vitro and in vivo, and they showed chromosomal abnormalities. The findings suggest that polyploid cells in human tumors may be attractive targets for novel therapeutics. To see the study, go <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002572">here</a>.
— Leigh MacMillan
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June 22, 2012
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