September 21, 2007

Aliquots — Research highlights from VUMC laboratories

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Balancing water in withered worms

Life requires water and, perhaps even more critically, osmoregulation — the maintenance of the delicate balance of water and ion concentrations between a cell and its environment. In the September issue of the American Journal of Physiology – Cell Physiology, Keith Choe, Ph.D., and Kevin Strange, Ph.D., identify molecules critical to the maintenance of water balance and recovery from dehydration in a whole animal, the roundworm C. elegans.

The researchers knocked down the expression of an enzyme, GCK-3 kinase, and exposed the worms to high salt conditions that cause water loss and overall body shrinkage. Loss of this enzyme dramatically inhibited the worms' ability to recover their lost water volume and to survive in high salt. Additionally, they identified another enzyme, WNK-1, that interacts with GCK-3 in a common pathway. Based on phylogenetic analysis, the researchers suggest that the interaction between these enzymes is evolutionarily ancient and likely coincided with the need for early multicellular animals to tightly regulate the epithelial transport processes mediating water balance.

— Melissa Marino

Trauma: Life in the mitochondria

Traumatic injury launches a complex stress response that involves high energy demand and inflammation. Could a defect in the cellular “power plants” — the mitochondria — contribute to trauma mortality?

Mitochondria have their own genome (mtDNA), and variations in mitochondrial genes can impair energy production and increase free radical generation. Mitochondrial gene variants, or polymorphisms, have been associated with a variety of diseases including Parkinson's disease and cancer.

Jeffrey Canter, M.D., M.P.H., John Morris, M.D., and colleagues examined three mtDNA polymorphisms in a large cohort of patients admitted to the trauma ICU. They report in the September Annals of Surgery that a particular mtDNA variant, 4216T, appears to increase the risk of in-hospital mortality after severe traumatic injury. The findings suggest that this polymorphism should be considered a new genetic risk factor for trauma mortality and underscore the importance of including the mitochondrial genome in the search for factors involved in the response to trauma.

— Leigh MacMillan

Tea modifies cancer risk

For Asian women, rates of endometrial cancer increase when they emigrate to the United States, suggesting that lifestyle factors offer some protection against this disease. In particular, Asian diets include foods like tea and soy that are high in polyphenols — plant chemicals that inhibit the activity of aromatase, the enzyme encoded by the CYP19A1 gene. Variants in the gene have been linked to endometrial cancer.

Xiao Ou Shu, M.D., Ph.D., and colleagues examined the interaction of these dietary factors with genetic variations, or polymorphisms, in CYP19A1. They report in the American Journal of Epidemiology that higher intake of both soy and tea were associated with lower risk of endometrial cancer. However, only tea consumption modified endometrial cancer risk linked to three CYP19A1 polymorphisms. The findings suggest that tea polyphenols may modify the effect of polymorphisms in the CYP19A1 gene on the development of endometrial cancer and highlight the importance of gene-environment interactions on disease risk.

— Melissa Marino

Genes’ role in preterm birth disparity

Preterm birth — before 37 weeks of gestation — occurs in more than 10 percent of all pregnancies in the United States and is the largest contributor to infant morbidity and mortality. African-Americans (AA) experience preterm births at almost twice the rate of European-Americans (EA), a disparity that may result from genetic differences.

To explore this idea, Scott Williams, Ph.D., and colleagues, analyzed patterns of genetic variation in two previously proposed candidate genes — interleukin 6 (IL-6) and its receptor (IL-6R) — in mothers and fetuses from both preterm and term birth events. They report in the September Annals of Human Genetics that eight genetic variants in these two genes differ between the AA and EA populations. The investigators also examined IL-6 concentrations in amniotic fluid and found increased levels in EA preterm births, in association with microbial invasion. The findings support a role for the IL-6 and IL-6R genes in the preterm birth disparity between AA and EA.

— Leigh MacMillan

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.

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012