Medicine and Health Sciences | Open Access Articles

Alpha-Amino-Beta-Carboxy-Muconate-Semialdehyde Decarboxylase Controls Dietary Niacin Requirements For Nad+ Synthesis, Laura Palzer, Jessica J. Bader, Frances Angel, Megan Witzel, Sydney Blaser, Alexis Mcneil, Miles K. Wandersee, N. Adrian Leu, Christopher J. Lengner, Clara E. Cho, Kevin D. Welch, James B. Kirkland, Ralph G. Meyer, Mirella L. Meyer-Ficca

Animal, Dairy, and Veterinary Science Faculty Publications

NAD⁺ is essential for redox reactions in energy metabolism and necessary for DNA repair and epigenetic modification. Humans require sufficient amounts of dietary niacin (nicotinic acid, nicotinamide, and nicotinamide riboside) for adequate NAD⁺ synthesis. In contrast, mice easily generate sufficient NAD⁺ solely from tryptophan through the kynurenine pathway. We show that transgenic mice with inducible expression of human alpha-amino-beta-carboxy-muconate-semialdehyde decarboxylase (ACMSD) become niacin dependent similar to humans when ACMSD expression is high. On niacin-free diets, these acquired niacin dependency (ANDY) mice developed reversible, mild-to-severe NAD⁺ deficiency, depending on the nutrient composition of the diet. NAD deficiency …

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Dietary Docosahexaenoic Acid Prevents Silica-Induced Development Of Pulmonary Ectopic Germinal Centers And Glomerulonephritis In The Lupus-Prone Nzbwf1 Mouse, Melissa A. Bates, Peyman Akbari, Kristen N. Gilley, James G. Wagner, Ning Li, Anna K. Kopec, Kathryn A. Wierenga, Daven Jackson-Humbles, Christina Brandenberger, Andrij Holian, Abby D. Benninghoff, Jack R. Harkema, James J. Pestka

Animal, Dairy, and Veterinary Science Faculty Publications

Ectopic lymphoid structures (ELS) consist of B-cell and T-cell aggregates that are initiated de novo in inflamed tissues outside of secondary lymphoid organs. When organized within follicular dendritic cell (FDC) networks, ELS contain functional germinal centers that can yield autoantibody-secreting plasma cells and promote autoimmune disease. Intranasal instillation of lupus-prone mice with crystalline silica (cSiO₂), a respirable particle linked to human lupus, triggers ELS formation in the lung, systemic autoantibodies, and early onset of glomerulonephritis. Here we tested the hypothesis that consumption of docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid with anti-inflammatory properties, influences the temporal profile …

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Functional Genomics And Immunologic Tools: The Impact Of Viral And Host Genetic Variations On The Outcome Of Zika Virus Infection, Sang-Im Yun, Byung-Hak Song, Jordan C. Frank, Justin G. Julander, Aaron L. Olsen, Irina A. Polejaeva, Christopher J. Davies, Kenneth L. White, Young-Min Lee

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To investigate the importance of viral and host genetic variations in determining ZIKV infection outcomes, we created three full-length infectious cDNA clones as bacterial artificial chromosomes for each of three spatiotemporally distinct and genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire viral protein-coding region, we made three conceptual advances: (i) We created a comprehensive genome-wide portrait of ZIKV gene products and their related species, with several previously …

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Fetal Demise And Failed Antibody Therapy During Zika Virus Infection Of Pregnant Macaques, Diogo M. Magnani, Thomas F. Rogers, Nicholas J. Maness, Nathan D. Grubaugh, Nathan Beutler, Varian K. Bailey, Lucas Gonzalez-Nieto, Martin J. Gutman, Núria Pedreño-Lopez, Jaclyn M. Kwal, Michael J. Ricciardi, Tereance A. Myers, Justin G. Julander, Rudolf P. Bohm, Margaret H. Gilbert, Faith Schiro, Pyone P. Aye, Robert V. Blair, Mauricio A. Martins, Kathrine P. Falkenstien, Amitinder Kaur, Christine L. Curry, Esper G. Kallas, Ronald C. Desrosiers, Pascal J. Goldschmidt-Clermont, Stephen S. Whitehead, Kristian G. Andersen, Myrna C. Bonaldo, Andrew A. Lackner, Antonito T. Panganiban, Dennis R. Burton, David I. Watkins

Animal, Dairy, and Veterinary Science Faculty Publications

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from …

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Animal, Dairy, and Veterinary Science Faculty Publications

Animal, Dairy, and Veterinary Science Faculty Publications

Functional Genomics And Immunologic Tools: The Impact Of Viral And Host Genetic Variations On The Outcome Of Zika Virus Infection, Sang-Im Yun, Byung-Hak Song, Jordan C. Frank, Justin G. Julander, Aaron L. Olsen, Irina A. Polejaeva, Christopher J. Davies, Kenneth L. White, Young-Min Lee

Animal, Dairy, and Veterinary Science Faculty Publications

Animal, Dairy, and Veterinary Science Faculty Publications