June 13, 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: aliquots@vanderbilt.edu.

The molecules that bind

The protein Bves – Blood vessel epicardial substance – is a member of a family of proteins identified because they are highly expressed in the developing and adult heart. Bves and its family members have been proposed to function as novel cell adhesion proteins, but the molecular mechanism accounting for such a role has remained unclear.

David Bader, Ph.D., and colleagues, who originally discovered and named Bves, report in the May 21 PLoS ONE that Bves interacts with itself – forming a Bves-Bves complex – and that this interaction is essential for cell-cell adhesion. The investigators found that two particular amino acids in the intracellular domain of Bves are critical to the interaction. Mutation of these amino acids in Bves abolished cell-cell contacts between human corneal cells, disrupting the normal epithelial sheets that these cells form. The findings suggest that Bves plays a role in epithelial cell adhesion and have implications for understanding Bves function in development and disease.

— Leigh MacMillan

Sensitivity training for lung cancer

Radiation may initially knock down lung cancer, but it often comes back with a vengeance – and an increased resistance to subsequent radiation therapy. Bo Lu, M.D., Ph.D., and colleagues previously showed that knocking down the expression of proteins that induce programmed cell “suicide” (apoptosis) actually increased another type of cell death (autophagy) and increased the sensitivity of lung cancer cells to radiation in vitro.

To further explore apoptosis inhibition as a radiosensitizing strategy, they administered a combination of radiation and an experimental apoptosis-inhibiting drug (M867) to mice with implanted lung tumors. The drug alone reduced survival of lung cancer cells, and the combination of M867 and radiation significantly reduced tumor proliferation, delayed tumor growth and inhibited blood vessel formation. They confirmed that autophagy contributed to the increased tumor cell death.

The enhanced toxic effects of such a combination therapy in culture and in animal models suggests a potential new strategy for treating locally advanced lung cancer, they report in the May 28 PLoS ONE.

— Melissa Marino

Diabetes: we got your number

The necessities of diabetes management – counting carbohydrates, glucose self-monitoring, and proper insulin dosage – are a well-mapped terrain. Many patients with diabetes, however, lack an essential skill for controlling their illness: numeracy, or the ability to use and understand numbers.

Kerri Cavanaugh M.D., M.P.H., Russell Rothman, M.D. M.P.P., and colleagues report that poor numeracy skills are common in patients with diabetes. They developed and used the Diabetes Numeracy Test (DNT) to show that lower diabetes-related numeracy skills are associated with lower diabetes knowledge, lower self-efficacy (e.g., a lower confidence in one’s ability to manage their diabetes), and poorer control of one’s diabetes. These findings, reported in the Annals of Internal Medicine, have driven the investigators to develop a numeracy-sensitive educational tool kit for diabetes patients, which is currently in trial. They have also developed and validated a shorter and more practical version of the DNT, called the Diabetes Numeracy Test-15, for clinical use.

— William Peters

TRIMming HIV infection

Retroviruses like HIV exhibit a restricted host range: for example, certain retroviruses (like HIV) cause disease in humans and not monkeys. After a retrovirus enters a cell, a host protein –TRIM5? – can attach to proteins of the viral core and restrict infection by a mechanism that may involve premature uncoating. Based on the protein structure of TRIM5?, Christopher Rold and Christopher Aiken, Ph.D., proposed that the proteasome – the cellular “garbage disposal” that degrades unwanted or damaged proteins – participates in viral restriction by degrading the TRIM5?-viral complex.

In the May PLoS Pathogens, they show that TRIM5? is rapidly degraded in cells exposed to a restriction-sensitive retrovirus but not in cells infected with an unrestricted virus. For example, the macaque TRIM5? – but not human TRIM5? – gets degraded upon encounter with HIV-1. Pretreating cells with proteasome inhibitors prevented the virus-induced loss of TRIM5?, supporting the role of the proteasome in retrovirus restriction. Additional studies of the restriction mechanism may aid the development of novel antiviral therapies targeting the viral core.

— 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