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Mutant Neurogenin-3 In Congenital Malabsorptive Diarrhea, Jiafang Wang, Galen Cortina, S. Vincent Wu, Robert Tran, Jang-Hyeon Cho, Ming-Jer Tsai, Travis J. Bailey, Milan Jamrich, Marvin E. Ament, William R. Treem, Ivor D. Hill, Jorge H. Vargas, George Gershman, Douglas G. Farmer, Laurie Reyen, Martin G. Martín
Mutant Neurogenin-3 In Congenital Malabsorptive Diarrhea, Jiafang Wang, Galen Cortina, S. Vincent Wu, Robert Tran, Jang-Hyeon Cho, Ming-Jer Tsai, Travis J. Bailey, Milan Jamrich, Marvin E. Ament, William R. Treem, Ivor D. Hill, Jorge H. Vargas, George Gershman, Douglas G. Farmer, Laurie Reyen, Martin G. Martín
Biology
Background: Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine. The NEUROG3 gene (NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells. Methods: We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3. We then tested the ability of the observed mutations to alter NEUROG3 function, using in vitro and in vivo assays. Results: The patients had few intestinal enteroendocrine cells positive for chromogranin A, but they had …
Modification Of Human Immunodeficiency Virus Type 1 Reverse Transcriptase To Target Cells With Elevated Cellular Dntp Concentrations, Varuni K. Jamburuthugoda, Pauline Chugh, Baek Kim
Modification Of Human Immunodeficiency Virus Type 1 Reverse Transcriptase To Target Cells With Elevated Cellular Dntp Concentrations, Varuni K. Jamburuthugoda, Pauline Chugh, Baek Kim
Biology
Retroviruses and DNA viruses utilize cellular dNTPs as substrates for their DNA polymerases during viral replication in infected cells. However, because of S phase-dependent dNTP biosynthesis, the availability of cellular dNTPs significantly varies among cell types (e.g. dividing versus nondividing cells and normal versus tumor cells). Here we tested whether alterations in the dNTP utilization efficiency and dNTP binding affinity of viral DNA polymerases can switch viral infection specificity to cell types with different dNTP concentrations. We employed an HIV-1 reverse transcriptase (RT) mutant (Q151N), which is catalytically active only at high dNTP concentrations because of its reduced dNTP binding …