November 30, 2007

Aliquots — Research highlights from VUMC laboratories

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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:

A sound peek at tumor molecules

“Seeing” — in a non-invasive way — the molecules that participate in a cancer's progression would be ideal for evaluating tumor responses to therapy and guiding treatment decisions. Andrej Lyshchik, M.D., Ph.D., and colleagues evaluated high-frequency ultrasonography coupled with a targeted contrast agent as a tool for imaging angiogenesis (blood vessel growth) in a mouse breast cancer model.

The investigators were able to detect signals from the experimental breast cancer tumors using a contrast agent targeted to VEGFR2, a receptor that is highly expressed in new tumor blood vessels. The intensity of the ultrasound signal in the tumors correlated with the expression of VEGFR2, as confirmed by immunoblotting and histologic evaluation. The authors suggest in the November Journal of Ultrasound in Medicine that the technology may enable in vivo imaging of VEGFR2 in tumor blood vessels, which could be used to evaluate early tumor responses to anti-angiogenic drugs.

— Leigh MacMillan

Fatty acids with strained relations

Polyunsaturated fatty acids, like the fatty acids required from our diets, are converted by enzymes in the body to highly reactive products that act as signaling molecules with diverse bodily functions — from inflammation to nervous system processes.

In the Nov. 27 issue of the Proceedings of the National Academy of Sciences, Alan Brash, Ph.D., and colleagues report their discovery of an unusual fatty acid product — never before observed in nature — produced by an enzyme found in the blue-green algae Anabaena.

The researchers isolated and identified the reaction products of the algal enzyme and determined that the major fatty acid contained a substituted bicyclobutane — a high-energy double four-carbon ring structure known previously only as a model compound for mechanistic studies in chemistry.

The existence of this unique molecule suggests that other similar enzymatic reactions should be scrutinized for the formation of these highly strained and unstable products, which might function in biochemical signaling in microbes.

— Melissa Marino

Lining up nucleic acids

DNA's double-helical structure quite easily reveals secrets about “how” the molecule transmits genetic information. Decades of research on the composition and construction of nucleic acids is now revealing “why” they are built as they are.

In the October issue of Nucleic Acids Research, Martin Egli, Ph.D., Pradeep Pallan, Ph.D., and colleagues define a new parameter that measures the angle, or inclination, between a nucleic acid's sugar-phosphate backbone and the bases (A, T(U), C, and G). They calculated this parameter for complexes of DNA, RNA, p-RNA (artificial RNA analog), and homo-DNA (artificial DNA analog).

Their analysis revealed that backbone-base inclination determines whether strands of the same nucleic acid can align themselves in a parallel or antiparallel orientation and whether strands of different nucleic acids can bind to one another. Deciphering such properties is central to understanding the origin of nucleic acids and life on Earth.

— Melissa Marino

Death by membrane penetration

Cell suicide (apoptosis) is a common outcome of infections by many viruses — in some cases, it's a defensive move by the host cell to limit viral replication; in other cases, the virus causes apoptosis in order to spread the infection. Little is known about the viral “pro-death” signals that contribute to disease.

The reovirus mu-1 protein pierces the host cell's membranes to enter the cell interior and has been linked to reovirus-induced apoptosis. Pranav Danthi, Ph.D., Terence Dermody, M.D., and colleagues analyzed a panel of mu-1 mutant viruses to identify domains that promote cell suicide. They report in the Journal of Virology that single amino acid changes in mu-1 reduce the efficiency of membrane penetration, diminish the capacity of the virus to elicit apoptosis, and reduce virulence in a mouse model of reovirus-induced encephalitis.

The results show that the membrane-piercing activity of mu-1 is critical to its ability to evoke pro-death signaling pathways that regulate reovirus pathogenesis.

— Leigh MacMillan

Past Aliquots

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