October 5, 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.

Balancing act in big viral genomes

Viruses with super-sized RNA genomes — like the coronavirus family that includes the SARS virus — must perform quite a balancing act. They must generate enough genetic diversity to be able to adapt to changing environments while limiting excessive mutation that could cause their extinction. But the mechanisms that allow these viruses to evolve but maintain their large genomes are unclear.

Using mouse hepatitis virus (MHV) as a model coronavirus, postdoctoral fellow Lance Eckerle Ph.D., Mark Denison, M.D., and colleagues investigated the role of a nonstructural viral protein, nsp14, in maintaining genome stability. The investigators genetically engineered MHV with mutations in nsp14. When allowed to replicate in culture, the mutant virus replicated and grew but had 15 times more mutations than normal MHV.

The findings, reported early online in the Journal of Virology, suggest that coronavirus nsp14 plays a critical role in the prevention or repair of errors to the viral genome during replication — a feature that may have important implications for understanding the evolution of RNA viruses.

— Melissa Marino

Host genes sway vaccine response

Vaccines don't always work as intended. Sometimes they fail to spark a protective immune response, leaving an individual vulnerable to the infectious disease, and sometimes they cause serious adverse reactions. Yi-Wei Tang, M.D., Ph.D., and colleagues are turning to the genome to identify predictors of individual responses to vaccination.

The investigators evaluated eight polymorphisms (variants) in three immune response-related host genes in archived serum samples from a previous influenza vaccine trial. Based on data from that trial, they classified subjects by their immune responses — normal or poor — and by the presence or absence of an adverse reaction. The researchers report in the Oct. 1 Journal of Infectious Diseases that polymorphisms in two genes, MBL-2 and IL-10, are associated with a decreased risk for poor and adverse responses to influenza vaccination.

The study demonstrates the value of using specimens from previous vaccine trials to assess the contribution of genetic factors to vaccine responses.

— Leigh MacMillan

Heavy metal not toxic to brain cells

Depleted uranium (DU) — the heavy metal “left-overs” from the enrichment of uranium for nuclear fuel and weapons — is used in radiation shielding, military vehicle armor, and ammunition. Studies suggesting that DU is carcinogenic and potentially toxic have prompted suspicion that the neurological aspects of Gulf War Syndrome may be linked to DU exposure.

To examine DU's neurotoxic potential, Michael Aschner, Ph.D., and colleagues exposed cultured rat neurons and live worms to uranyl acetate, a chemical derived from DU. Except at very high levels not easily reached in realistic exposure situations, DU was not toxic to cultured neurons. Also, although uranium accumulated in worm neurons, the worms showed little corresponding neurodegeneration.

The limited toxicity of acute DU exposure suggests that it is not likely responsible for the neurological damage associated with Gulf War Syndrome, the authors suggest in the October issue of Toxicological Sciences.

— Melissa Marino

Gaps in research integrity knowledge

Responsible conduct of research (RCR) instruction has become a routine part of biomedical science graduate education. Elizabeth Heitman, Ph.D., and colleagues developed a multiple choice test to assess new biomedical science graduate students' baseline knowledge of core RCR concepts and standards. Scores for 251 trainees ranged from 26.7 percent to 83.3 percent, with a mean of 59.5 percent (passing is 80 percent or above). Even trainees who indicated they had prior graduate-level RCR instruction averaged only 67.7 percent.

The investigators conclude in the September Academic Medicine — which featured a special section on RCR education edited by Heitman and Lida Anestidou, D.V.M., Ph.D. — that new biomedical science graduate students have inadequate and inconsistent knowledge of RCR, regardless of prior education or experience. They suggest that graduate programs consider ongoing or advanced level RCR instruction.

— 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