February 20, 2009

Aliquots — research highlights from VMC laboratories

(Image by Dominic Doyle)

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.


HIV infectivity factors

HIV primarily infects immune cells like the CD4+ T lymphocytes (helper T cells). The two main types of helper T cells – Th1 and Th2 – differ in their ability to produce infectious HIV particles, but the reasons behind this difference are unclear.

In the February PLoS Pathogens, Michael Vetter, Richard D’Aquila, M.D., and colleagues show that T cell expression of the host proteins APOBEC3G and APOBEC3F– antiviral enzymes that decrease HIV’s ability to replicate – influences HIV infectivity. They found that Th1 cells expressed greater amounts of these enzymes, and produced less infective HIV particles, than Th2 cells regardless of the presence of vif (HIV-1 virion infectivity factor), a molecular countermeasure evolved by HIV to degrade these enzymes.

They further showed that overexpressing APOBEC3G in Th2 cells decreased infectivity and that reducing APOBEC3G expression in Th1 cells increased infectivity, demonstrating a causal role for APOBEC3G in the infectivity difference.

The authors suggest that these proteins might represent attractive targets for new therapeutic or preventive strategies against HIV.

Melissa Marino


Maintaining the stem cell pool

Poor nutrition and aging can reduce the viability and number of tissue stem cells, suggesting that systemic factors play critical roles in stem cell maintenance. Daniela Drummond-Barbosa, Ph.D., and colleagues previously showed that systemic insulin-like signals regulate the proliferation rate of germline stem cells in fruit fly ovaries.

In the Jan. 27 issue of the Proceedings of the National Academy of Sciences, the researchers detail how diet and aging – factors that affect insulin levels – interact to regulate germline stem cell maintenance. They show that insulin influences the activity of two key signaling pathways that maintain the number of supportive (cap) cells and interactions between these cap cells and germline stem cells – an interaction important for stem cell fate and activity. They also showed that increasing levels of insulin-like peptides could suppress the normal aging-induced loss of germline stem cells.

The findings may have important implications for stem cell research as well as help explain some of the observed links between restricted diet and longevity.

Melissa Marino


Fat-soluble pesticides more toxic

Dithiocarbamates are a class of chemicals widely useful in industry, agriculture (pesticides) and medicine. But they have neurotoxic potential, which past studies have suggested may result from copper accumulation and oxidative stress in the nervous system.

In the Jan. 19 issue of Chemical Research in Toxicology, William Valentine, DVM, Ph.D., and colleagues report that the ability of a dithiocarbamate-copper complex to promote lipid peroxidation correlates with the lipid solubility of the complex. To study how fat solubility affects neurotoxicity, they exposed rats to two dithiocarbamates: N,N-diethyldithiocarbamate (DEDC), which forms a fat-soluble copper complex, or sarcosine dithiocarbamate (SADC), which forms a water-soluble complex. They found that DEDC, but not SADC, caused significant increases in copper accumulation, oxidative injury and myelin lesions in brain and peripheral nerves.

The results support the hypothesis that neurotoxicity requires the formation of a fat-soluble dithiocarbamate-copper complex and could aid in the design of safer dithiocarbamates for therapeutic and pesticide applications.

Leigh MacMillan


Blueprints for a pancreatic islet

The endocrine pancreas, composed of “islets” that include the insulin-secreting beta cells, is involved in maintaining glucose balance in the body. Disruption of this balance can lead to diabetes.

Maureen Gannon, Ph.D., and colleagues are exploring the factors involved in normal pancreatic islet development – factors that could find therapeutic use for diabetes. In studies featured on the cover of the March issue of Molecular Endocrinology, they report that a protein called connective tissue growth factor (CTGF) plays a role in islet development. They showed that CTGF is expressed in the developing pancreas and that it participates in establishing normal ratios of the various islet cell types and normal islet architecture. They also found that this factor is required for beta cell proliferation during embryonic development.

The investigators suggest that CTGF may be a good candidate for expanding beta cell populations – in vivo or in vitro – to increase insulin production and potentially treat diabetes.

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