Lymphoma factor amps up metabolism
The functions of most members of the enzyme family known as poly(ADP-ribose)polymerases (PARPs) are unclear. Some PARP-related proteins are in a B aggressive lymphoma (BAL) protein family, which are highly expressed in certain types of B cell lymphomas – malignancies of the antibody-producing B lymphocytes.
Sung Hoon Cho, Ph.D., Mark Boothby, M.D., Ph.D., and colleagues, in a collaboration with Christine Eischen, Ph.D., and Owen McGuinness, Ph.D., have discovered that the BAL-family protein PARP14 is vital to interleukin-4 regulation of glycolysis (a metabolic pathway whose activity is commonly increased in cancer), and influences the oncogenic and developmental effect of the Myc pathway.
The results, reported in the Sept. 20 Proceedings of the National Academy of Sciences, suggest that PARP-14’s ability to increase cellular metabolic rates may play a role in the susceptibility to B cell lymphomas. The findings also point to such metabolic pathways as potential targets for treating these types of malignancies.
The research was supported by grants from the National Cancer Institute, the National Institute of General Medical Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases.
— Melissa Marino
Diversity key in antibody repertoire
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James Crowe, Jr., M.D., and colleagues previously isolated an antibody to 1918 influenza (called 2D1) that could also neutralize the 2009 H1N1 strain. In the Oct. 1 Journal of Immunology, they report the isolation and characterization of a panel of five antibodies from a survivor of the 2009 H1N1 pandemic. Although the 2009 antibodies bound the same region of the virus (the Sa site) as 2D1, they inhibited a broader panel of H1N1 strains than did 2D1. The 2009 antibodies also shared a gene segment in the antibodies’ “heavy chains” – which differed from the gene segment identified in 2D1. High throughput gene sequencing suggested that the antibodies arose independently, but converged toward similar amino acid sequences.
The findings provide new insights into how antibody diversity forms and functions – and could potentially lead to better methods of designing flu vaccines rationally.
The research was supported by grants from the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Disorders, and the National Eye Institute.
— Melissa Marino
Parkinson’s deep brain target fired up
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David Charles, M.D., Peter Konrad, M.D., Ph.D., and colleagues are conducting a pilot clinical trial to test DBS in individuals with early-stage Parkinson’s disease. This trial provides the team with a unique opportunity to evaluate neuronal activity in the subthalamic nucleus in early-stage disease (prior to this trial, such recordings have only been possible in patients undergoing DBS for advanced disease).
They report in Movement Disorders that subthalamic nucleus neurons had a significantly lower firing rate – and the region had lower overall activity – in early versus advanced Parkinson’s disease. The findings suggest that neuronal firing in the subthalamic nucleus increases with disease progression.
This study was supported by Medtronic, Inc., the National Center for Research Resources, and the Parkinson’s and Movement Disorder Foundation.
— Leigh MacMillan
Fungus toxin gets in the way in DNA
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A metabolite of aflatoxin B1 reacts with DNA, forming adducts that cause mutations. To understand how different chemical forms of such adducts induce differing levels of mutations, Surajit Banerjee, Ph.D., Kyle Brown, Ph.D., Martin Egli, Ph.D., and Michael Stone, Ph.D., examined how a DNA polymerase replicated DNAs that included different aflatoxin adducts. They obtained the first structures showing how aflatoxin B1 adducts interact with a DNA polymerase.
They report in the Aug. 17 Journal of the American Chemical Society how the ability of the polymerase to bypass aflatoxin-induced DNA damage depends upon its specific chemical form, and how this relates to the structure of the adduct within the enzyme active site. The findings could provide insight into aflatoxin’s cancer-causing mechanisms.
This research was supported by the National Cancer Institute, the Vanderbilt University Center in Molecular Toxicology, and the Vanderbilt-Ingram Cancer Center.
— 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: aliquots@vanderbilt.edu.
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