March 19, 2010

Aliquots — research highlights from VUMC laboratories


Immune protein sparks psoriasis

IL-20, IL-22 and IL-24 are cytokines (proteins secreted by immune system cells) that transmit chemical signals between cells. While they signal through a shared set of receptors, it remains unclear whether these cytokines have redundant biological functions.

IL-20 and IL-22 are known to play important roles in the skin. To investigate IL-24’s role there, Peng Liang, Ph.D., – whose lab discovered IL-24 in colon cancer cells – and graduate student Miao He created transgenic mice that expressed IL-24 in the skin (IL-24 Tg mice).

These mice exhibited similar abnormalities in skin cell proliferation and differentiation as IL-20 and IL-22 Tg mice, suggesting redundant roles for the three cytokines. Interestingly, the IL-24 Tg mice exhibited features of a psoriatic skin condition consistent with previous studies showing elevated IL-24 expression in human psoriasis and chronic wounds.

Their Feb. 15 paper in the Journal of Immunology establishes the role of IL-24 in skin function and identifies IL-24 as a potential new therapeutic target for inflammatory skin ailments like psoriasis.

Melissa Marino


Fast test for tick-borne illness

Tick-borne diseases like ehrlichiosis (caused by Ehrlichia species bacteria) are difficult to diagnose clinically due to their nonspecific symptoms of fever, headache and muscle and joint pain. Lab tests for these infections – which include antibody tests, blood smears and blood cultures – also have limitations that may cause critical delays in treatment.

Yi-Wei Tang, M.D., Ph.D., and colleagues developed and evaluated a polymerase chain reaction/mass spectrometry assay (PCR/ESI-MS) in clinical blood and spinal fluid specimens. They found that this method – which uses a mix of primers for several tick-borne and non-tick-borne bacterial species – accurately detected Ehrlichia species and identified them with sensitivity and specificity similar to reference detection methods. PCR/ESI-MS also identified a variety of other pathogenic bacteria, and testing could be completed within six hours.

The results, reported in the February Journal of Clinical Microbiology, suggest that the rapid and correct detection and identification achieved by PCR/ESI-MS may facilitate the timely diagnosis and improve treatment of tick-borne illnesses.

Melissa Marino


Ecstasy blurs memory for words

More than 12 million Americans have likely used the recreational ‘club drug’ Ecstasy (MDMA), and it is popular throughout the world. The lasting impact of MDMA on the brain is not entirely clear.

MDMA users have impaired verbal memory – memory for words and their meanings. Previous studies by Ronald Cowan, M.D., Ph.D., and colleagues showed that MDMA users had decreased grey matter (neuronal cells) in brain areas associated with verbal memory. The investigators have now used functional MRI to study brain activity during verbal memory tasks in a group of polysubstance users enriched for MDMA exposure.

They report in the February Journal of Psychopharmacology that lifetime MDMA use was associated with decreased activation in some of those brain areas during the recognition portion of the verbal memory task. MDMA exposure did not change accuracy or response time. The findings suggest a locus for impaired verbal memory in MDMA users, and a potential role for MDMA in causing functional changes in the affected brain regions.

Leigh MacMillan


Decoding gene-gene interactions

Genes don’t often act in isolation. Their effects can be altered – even masked – by other genes. Identifying and understanding these “epistatic” interactions could be the key to understanding complex diseases such as Alzheimer’s disease, diabetes and cardiovascular disease.

To find gene-gene interactions associated with disease, geneticists rely on sophisticated statistical approaches. One approach, called Multifactor Dimensionality Reduction (MDR) (and the related MDR-PDT), is good at detecting epistatic effects in simulated data. But the gene- gene associations it detects could be due to true epistatic interactions that are associated with the disease trait, or they could be simply multiple independent (non-interacting) effects.

Marylyn Ritchie, Ph.D., and colleagues have now developed a statistical addition to the MDR algorithm that can distinguish between true gene-gene interactions and independent effects. Their approach, reported in the February issue of PLoS ONE, is not restricted to MDR and can be applied to any method that is used to search for gene-gene interactions.

Leigh MacMillan


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:

Past Aliquots

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