Mason Journals (George Mason Univ.)
Not a member yet
3256 research outputs found
Sort by
The NOCCA Integrated World History Curriculum: A New Paradigm for Teaching History in High School
No full text
Cole, Adrian and Stephen Ortega. The Thinking Past: Questions and Problems in World History to 1750
No full textKenneth R. Curtis and Jerry H. Bentley, eds., Architects of World History: Researching the Global Past
No full textLieutenant-General Antonio de la Caridad Maceo y Grajales: A Dual Case Study in Cuban Self Determination and Common Core/ World History Teaching
No full text
Computationally Exploring FKBP65’s Interaction with Collagen
No full textFKBP65, a 4-domain FK506-binding protein, acts as a peptidyl-prolyl cis/trans isomerase (PPIase). It catalyzes the cis/trans isomerization of proline in collagen and assists in collagen maturation. Overexpressed collagen creates a microenvironment favorable to tumors, promotes tumor growth, facilitates metastasis, and induces heavy fibrosis. Therefore, finding a chemical compound that can decrease FKBP65’s interaction with collagen might improve cancer outcomes. Despite this target's importance, relatively little is known about each putative PPIase domain. We used ChimeraX to evaluate each domain and found that domains 1, 2, and 3 have probable PPIase activity, while domain 4 likely did not. We then identified portions of the collagen sequence likely recognized by each domain. Next, we identified target regions on each domain for inhibition. Finally, we used small molecule docking to identify potential inhibitors. We discuss the prospects for these inhibitors as potential cancer drugs
Structure-Based Discovery of Lead Compounds to Prevent Neuronal Death in Venezuelan Equine Encephalitis Virus Infection
No full textThe Venezuelan Equine Encephalitis Virus (VEEV) is a positive, single-stranded RNA virus that causes severe neuronal damage by disrupting nuclear-cytoplasmic transport. The virus crosses the blood-brain barrier and produces the VEEV capsid protein. The N-terminus of the capsid, the H68 peptide, contains nuclear localization signals (NLS) and nuclear export signals (NES). These conflicting signals promote formation of a tetrameric complex involving the nuclear import protein, importin alpha (ImpA), and the nuclear export protein, CRM1. This complex then blocks the nuclear pores, ultimately leading to neuronal death. Previous studies found compounds that prevent nuclear pore blocking but also suffer from limited efficacy and potential off-target toxicity. We leveraged models of the tetrameric complex to apply structure-based drug design with pharmacophores to discover and evaluate candidate compounds based on their physical features, such as binding sites and contact residues. We will present some of the chemotypes found as well as the rationale for why we believe they offer better starting points than the current chemical leads