Biochemistry Commons^™

Dynamics On Multiple Timescales In The Rna-Directed Rna Polymerase From The Cystovirus Φ6, Zhen Ren, Hsin Wang, Ranajeet Ghose

Publications and Research

The de novoinitiating RNA-directed RNA polymerase (RdRP), P2, forms the central machinery in the infection cycle of the bacteriophage ϕ6 by performing the dual tasks of replication and transcription of the double-stranded RNA genome in the host cell. By measurement and quantitative analysis of multiple-quantum spin-relaxation data for the δ1 positions of Ile residues that are distributed over the 3D-fold of P2, we find that the enzyme is dynamic both on the fast (ps–ns) and slow (µs–ms) timescales. The characteristics of several motional modes including those that coincide with the catalytic timescale (500–800/s) are altered in the presence of …

Morphological Changes And Immunohistochemical Expression Of Rage And Its Ligands In The Sciatic Nerve Of Hyperglycemic Pig (Sus Scrofa), Judyta K. Juranek, Alexey Aleshin, Eileen M. Rattigan, Lynne Johnson, Wu Qu, Fei Song, Radha Ananthakrishnan, Nosirudeen Quadri, Shi Du Yan, Ravichandran Ramasamy, Ann Marie Schmidt, Matthew S. Geddis

Publications and Research

The aim of our project was to study the effect of streptozotocin (STZ)—induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products), and its ligands—S100B and Carboxymethyl Lysine (CML)-advanced glycation endproduct (AGE) in the laboratory pig. Six months after STZ—injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products—methyl-glyoxal (MG) were performed. The results of our study revealed that …

Involvement Of Inflammation In Tau Pathology And Mechanisms That Drive Neurodegeneration In Alzheimer's Disease, Lisette T. Arnaud

Dissertations, Theses, and Capstone Projects

Two of the hallmarks of neurodegenerative disorders, such as Alzheimer's disease (AD), are (1) the appearance of proteinaceous deposits in inclusion bodies containing aggregates of ubiquitinated proteins and (2) activated microglia and astrocytes surrounding the diseased neurons. In Alzheimer's disease, the intracellular inclusion bodies are known as neurofibrilary tangles (NFT). The mechanisms leading to inclusion body formation and their role in the progression of neurodegeneration are still largely unknown.

Many of the proteins that accumulate in inclusion bodies depend on the ubiquitin/proteasome pathway (UPP) for their degradation. This pathway is responsible for the bulk (∼80%) of intracellular protein degradation. Because …

Pldb, A Putative Phospholipase D Homologue, Mediates Quorum Sensing In Dictyostelium Discoideum Development, Yi Chen

Dissertations, Theses, and Capstone Projects

Quorum sensing, the ability to measure the local cell density, is required for animal cells to achieve proper cell growth, differentiation and development. However, because of the genetic intractability of mammalian cells, we study quorum sensing in the genetically pliable unicellular eukaryote Dictyostelium discoideum. D. discoideum cells live as individual cells under vegetative conditions. Starvation sets off development to a multicellular organism. But cells won't develop unless enough cells are under starvation conditions. Approximately 10⁵ cells are needed to form a fruiting body, the final stage of the development. When starved, cells are able to calculate the concentration …

I. Comparison Of Translesion Bypass Of Guanine–N2 Monoadducts Of Mitomycin C And Guanine-N7 Monoadducts Of 2,7-Diaminomitosene By T7 Exo-, Klenow Exo-, Eta And Klenow Exo+ Dna Polymerases. Ii. Structure-Based Design, Synthesis, Structure-Conformation And Structure-Activity Relationships Studies Of D-Phe-Pro-D-Arg-P1’-Conh2 Tetrapeptides With Inhibitory Activity For Thrombin., Cristina C. Clement

Dissertations, Theses, and Capstone Projects

The guanine (G)-N² DNA monoadduct of mitomycin C (MC), a cytotoxic anticancer drug, inhibits translesion bypass by DNA polymerases. 2,7-Diaminomitosene (2,7-DAM) is the major metabolite of MC in tumor cells, generated by the reduction of MC. 2,7-DAM alkylates DNA in the cell in situ, forming an adduct at the N7 position of 2'-deoxyguanosine (2,7-DAM-dG) and is noncytotoxic. In part I of this study we tested a potential correlation between the lack of cytotoxicity of 2,7-DAM and the relative ease of bypass of this adduct as compared with the MC adduct. 24-mer and 27-mer templates, adducted at a single …

Aspects Of Mitochondrial Oxidative Metabolism, Leslie Kushner

Dissertations, Theses, and Capstone Projects

The effects of metabolic intermediates and coenzymes on the activities of fatty acyl-CoA synthetase and carnitine palmitoyltransferase (CPT) in rat heart mitochondria were studied. ADP and palmitoyl-l-carnitine were weak inhibitors of fatty acyl-CoA synthetase. CPT A was inhibited 59.3% by 100 (mu)M succinyl-CoA. However, succinate thiokinase activity in rat heart cytosol was too low to maintain a succinyl-CoA concentration sufficient to affect the activity of CPT A. There was no indication that fatty acid oxidation in rat heart mitochondria is controlled via the regulation of either CPT A or fatty acyl-CoA synthetase.

The dependence of the oxidation of unsaturated fatty …