July 27, 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: aliquots@vanderbilt.edu.

EXALTation of gene expression

The widespread usage of microarray technologies has created a potential gold mine of gene expression data, much of which is available in public repositories. However, the many differences between the data sets make it difficult to compare and find meaningful associations among experiments.

To help researchers fully exploit the potential of such data, Yajun Yi, M.D., Ph.D., and colleagues have developed and validated a new bioinformatic system, called EXALT (Expression signature analysis tool) (http://seq.mc.vanderbilt.edu/exalt/).

In Genome Biology, the team details the features and potential uses of this new strategy. They show that EXALT can be used to compare data across different types of microarrays, different laboratories and even different species. This new approach could help researchers make use of the mountains of gene expression data in public databases, with potential applications in disease gene discovery, definition of biomarkers, drug discovery and toxicity studies.

— Melissa Marino

After the blaze

The dynamic molecular changes that follow burn injury to the skin are poorly understood. To explore these changes, Alonda Pollins, M.S., David Friedman, Ph.D., and Lillian Nanney, Ph.D., analyzed normal and burn skin samples using a proteomic technology called 2D-difference gel electrophoresis (DIGE) coupled with mass spectrometry. The investigators compared protein profiles from normal/unwounded skin and from wounds isolated from burn patients 1-3 days, 4-6 days, or 7-10 days after injury. They identified a set of 20 proteins with altered expression in burn samples. Some were predictable, such as certain inflammatory and cytoskeletal proteins, but half of the proteins were previously unassociated with either burn injury or wound healing.

The study, published in the Journal of Surgical Research, provides a proteomic snapshot of the temporal events that define the skin's response to burn injury. Proteins identified by DIGE/mass spectrometry and other methods may represent biomarkers for the wound healing process and new targets for burn treatment.

— Leigh MacMillan

NET blockade ups blood pressure

Atomoxetine and other norepinephrine transporter (NET) blockers are commonly used to treat attention deficit disorder, obesity and depression, conditions with high incidence in the United States. Because these drugs can increase sympathetic nervous system output — “fight or flight” responses — there is concern that they could worsen or induce hypertension.

Cyndya Shibao, M.D., intern in the Department of Medicine, working with Italo Biaggioni, M.D., and colleagues studied the response to atomoxetine in patients with impairment of the blood pressure-regulating autonomic nervous system. They report in the July Hypertension that low (pediatric) doses of atomoxetine induce hypertension in patients with impaired central autonomic regulation, increasing blood pressure by about 50 mm Hg.

This marked increase in blood pressure urges caution when using NET blockers, particularly in patients with milder forms of autonomic impairment. However, the findings also suggest that atomoxetine may be useful for improving standing blood pressure in patients with central autonomic disorders, such as orthostatic hypotension.

— Leigh MacMillan

IRES holds muscular dystrophy clue

Cells and viruses can take a “shortcut” from RNA to protein by initiating translation at an internal ribosome entry site (IRES) in the mRNA transcript. This shortcut requires the interaction of a large number of proteins with the IRES, many of which remain unidentified.

Vincent Gerbasi and Andrew Link, Ph.D., performed a proteomic screen to identify proteins that interact with an IRES sequence in a model gene. They found two IRES-interacting proteins — PCBP2 and ZNF9 — that associate with the IRES in a normal transcript, but did not bind to mutant sequence. While PCBP2 was known as an activator of viral and cellular IRESs, their study is the first to show IRES-activity of ZNF9, a protein associated with Myotonic Dystrophy Type 2. Along with Type 1, the disease is the most common form of muscular dystrophy in adults.

The results, published in the June Molecular and Cellular Proteomics, may reveal clues about the normal role of ZNF9 and how mutations in the gene lead to myotonic dystrophy.

— Melissa Marino

Past Aliquots

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