August 15, 2008

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:

Pop goes the virus

Respiratory syncytial virus (RSV) – the most common viral cause of serious lower respiratory illness in children under age 5 – is especially dangerous for premature infants, the elderly and immunocompromised patients.

James Crowe, M.D., and colleagues are studying the RSV life cycle, particularly late steps including assembly and “budding” of new virus particles from an infected cell’s surface. They previously established a link between a cellular cargo-moving compartment – the ARE – and RSV assembly. Now, they have tested the role of a major ARE-associated protein, FIP2, in the RSV life cycle.

They report in the July 22 Proceedings of the National Academy of Sciences that inhibiting FIP2 function blocks RSV budding and causes retention of assembled virus particles in cultured cells. They also show that blocking a different, well-defined mechanism for budding of RNA viruses (like RSV) does not affect RSV budding. The findings suggest that RSV uses a novel budding mechanism controlled by FIP2 and may point to new therapeutic targets.

To see the study, go <a href="">here</a>.

— Leigh MacMillan

Some mice are sweeter than others

Targeted gene modification in mice is an invaluable tool for probing the role of genes in vivo. But a variety of inbred mouse strains have been used to produce these new mouse models, and it is widely recognized that physiological characteristics vary among mouse strains.

Eric Berglund, Alvin Powers, M.D., David Wasserman, Ph.D., and colleagues have taken the first comprehensive look at glucose metabolism in four commonly used inbred mouse strains (C57BL/6, 129X1/Sv, FVB/N, DBA/2). They used glucose clamps – a gold standard for assessing glucose metabolism – to study insulin action, insulin secretion, and counter-regulatory responses to low blood sugar. They also assessed insulin secretion in isolated pancreatic islets. The team reports in the July issue of Diabetes that parameters related to glucose metabolism vary considerably in the four strains. The findings emphasize the importance of considering genetic background in experimental design and interpretation and will be a resource for selecting inbred mice to study glucose metabolism.

To see the study, go <a href="">here</a>.

— Leigh MacMillan

Needles in the microarray haystack

Microarrays allow researchers to identify not just single genes, but entire genetic pathways affected by disease or drug treatment. While the thousands of genes on each microarray make analysis difficult, several specialized statistical methods have been developed to tackle the complex data analysis, all with various limitations.

In the July issue of PLoS Genetics, Lily Wang, Ph.D., and colleagues propose an alternative “mixed model” approach for analyzing microarray data and compare their approach to other popular methods. Compared to another common analysis method (called GSEA), the mixed model approach identifies the same pathway as the most significantly changed pathway in muscle samples from diabetic patients. However, the mixed model identified six additional affected pathways missed by GSEA analysis. The researchers also illustrated the mixed model’s application in a dose-response dataset. This flexible and powerful approach, which can be easily performed with common statistical software, could provide a new way to identify affected gene pathways from microarray experiments.

To see the study, go <a href="">here</a>.

— Melissa Marino

Stroke injury scars brain

Much like the skin, the brain can “scar” when damaged. This scarring, or gliosis, barricades the injured area to prevent the damage from spreading to healthy brain regions. But the scar also can limit healing, preventing neuronal regeneration and leading to the death of neurons and long-term brain dysfunction.

Antonis Hatzopoulos, Ph.D., and colleagues are investigating the molecular signals underlying the gliosis that follows a stroke. In the July issue of The American Journal of Pathology, they report that a protein, called Egr-1, is highly expressed in astrocytes (the scar-forming cells) that accumulate around the site of injury after an experimental “stroke” in mice. In cultured human astrocytes, Egr-1 regulated the production of the main protein components of the scar. Mice lacking Egr-1 showed lower levels of these proteins than normal mice in the scar tissue around the damaged area. The findings suggest that Egr-1 is an important regulator of gliosis after stroke and may offer new avenues for stroke therapies.

To see the study, go <a href="">here</a>.

— 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