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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 Jan 2006

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 Jan 2006

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 …


Identification Of The Heparin-Binding Determinants Within Fibronectin Repeat Iii1: Role In Cell Spreading And Growth, Liqiong Gui, Katherine Wojciechowski, Candace D. Gildner, Hristina Nedelkovska, Denise C. Hocking Jan 2006

Identification Of The Heparin-Binding Determinants Within Fibronectin Repeat Iii1: Role In Cell Spreading And Growth, Liqiong Gui, Katherine Wojciechowski, Candace D. Gildner, Hristina Nedelkovska, Denise C. Hocking

Biology

Fibronectins are high molecular mass glycoproteins that circulate as soluble molecules in the blood, and are also found in an insoluble, multimeric form in extracellular matrices throughout the body. Soluble fibronectins are polymerized into insoluble extracellular matrix (ECM) fibrils via a cell-dependent process. Recent studies indicate that the interaction of cells with the ECM form of fibronectin promotes actin organization and cell contractility, increases cell growth and migration, and enhances the tensile strength of artificial tissue constructs; ligation of integrins alone is insufficient to trigger these responses. Evidence suggests that the effect of ECM fibronectin on cell function is mediated …


Krepa4, An Rna Binding Protein Essential For Editosome Integrity And Survival Of Trypanosoma Brucei, Rezaq Salavati, Nancy Lewis Ernst, Jeffrey O'Rear, Troy Gilliam, Salvador Tarun Jr., Kenneth Stuart, K. Jan 2006

Krepa4, An Rna Binding Protein Essential For Editosome Integrity And Survival Of Trypanosoma Brucei, Rezaq Salavati, Nancy Lewis Ernst, Jeffrey O'Rear, Troy Gilliam, Salvador Tarun Jr., Kenneth Stuart, K.

Biology

The 20S editosome, a multiprotein complex, catalyzes the editing of most mitochondrial mRNAs in trypanosomatids by uridylate insertion and deletion. RNAi mediated inactivation of expression of KREPA4 (previously TbMP24), a component of the 20S editosome, in procyclic form Trypanosoma brucei resulted in inhibition of cell growth, loss of RNA editing, and disappearance of 20S editosomes. Levels of MRP1 and REAP-1 proteins, which may have roles in editing but are not editosome components, were unaffected. Tagged KREPA4 protein is incorporated into 20S editosomes in vivo with no preference for either insertion or deletion subcomplexes. Consistent with its S1-like motif, recombinant KREPA4 …