Pennsylvania Folklife Vol. 11, No. 1

• A Dunker Weekend Love Feast of 100 Years Ago • The Peacock in Pennsylvania • The Get-Togethers of the Young Amish Folk • Church and Meetinghouse Stables and Sheds • Abraham Harley Cassel - Dunkard Bibliophile • Mennonite Folklore • Springs and Springhouses • Finishing Wooden Surfaces • Early Funeral Notices • Collecting Dialect Folk Songshttps://digitalcommons.ursinus.edu/pafolklifemag/1006/thumbnail.jp

Herpes Simplex Virus-1 Infection in Human Primary Corneal Epithelial Cells is Blocked by a Stapled Peptide that Targets Processive DNA Synthesis

Purpose: Acyclovir is most commonly used for treating ocular Herpes Keratitis, a leading cause of infectious blindness. However, emerging resistance to Acyclovir resulting from mutations in the thymidine kinase gene of Herpes Simplex Virus −1 (HSV-1), has prompted the need for new therapeutics directed against a different viral protein. One novel target is the HSV-1 Processivity Factor which is essential for tethering HSV-1 Polymerase to the viral genome to enable long-chain DNA synthesis. Methods: A series of peptides, based on the crystal structure of the C-terminus of HSV-1 Polymerase, were constructed with hydrocarbon staples to retain their alpha-helical conformation. The stapled peptides were tested for blocking both HSV-1 DNA synthesis and infection. The most effective peptide was further optimized by replacing its negative N-terminus with two hydrophobic valine residues. This di-valine stapled peptide was tested for inhibiting HSV-1 infection of human primary corneal epithelial cells. Results: The stapled peptides blocked HSV-1 DNA synthesis and HSV-1 infection. The unstapled control peptide had no inhibitory effects. Specificity of the stapled peptides was confirmed by their inabilities to block infection by an unrelated virus. Significantly, the optimized di-valine stapled peptide effectively blocked HSV-1 infection in human primary corneal epithelial cells with selectivity index of 11.6. Conclusions: Hydrocarbon stapled peptides that simulate the α-helix from the C-terminus of HSV-1 DNA polymerase can specifically block DNA synthesis and infection of HSV-1 in human primary corneal epithelial cells. These stapled peptides provide a foundation for developing a topical therapeutic for treating human ocular Herpes Keratitis. © 202

Plasma Dynamics

Contains reports on ten research projects split into two sections.National Science Foundation (Grant ENG77-00340)U.S. Department of Energy (Contract EY-76-S-02-2766)U.S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U.S. Department of Energy (Contract ET-78-C-01-3019)U.S. Department of Energy (Contract ET-78-S-02-4681)U.S. Department of Energy (Contract ET-78-S-02-4682)U.S. Department of Energy (Grant EG-77-G-01-4107)U.S. Department of Energy (Contract ET-78-S-02-4714)U.S. Department of Energy (Contract ET-78-S-02-4886)U.S. Department of Energy (Contract ET-78-S-02-4690

Plasma Dynamics

Contains reports on ten research projects divided into two sections.National Science Foundation (Grant ENG79-07047)U.S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U.S. Department of Energy (Contract DE-ACO2-78ET51013)U.S. Department of Energy (Contract DE-ASO2-78ET53073.AO02)U.S. Department of Energy (Contract ET-78-S-02-4682)U.S. Department of Energy (Contract DE-AS02-78ET53074)U.S. Department of Energy (Contract DE-ASO2-78ET53050)U.S. Department of Energy (Contract DE-AS02-78ET51002)U.S. Department of Energy (Contract DE-ASO2-78ET53076

Plasma Dynamics

Contains research objectives and summary of research on nineteen research projects split into five sections.National Science Foundation (Grant ENG75-06242-A01)U.S. Energy Research and Development Administration (Contract E(11-1)-2766)U.S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U.S. Energy Research and Development Administration (Contract EY-76-C2-02-3070.*000

Plasma Dynamics

Contains reports on seventeen research projects split into two sections.National Science Foundation (Grant ENG77-00340)U. S. Energy Research and Development Administration (Contract E(11-1)-2766)U. S. Energy Research and Development Administration (Contract EY-76-S-02-2766)U. S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U. S. Department of Energy (Grant EG-77-G-01-4107

Plasma Dynamics

Contains research objectives and summary of research on eighteen research projects split into seven sections and reports on four research projects.U.S. Atomic Energy Commission (Contract AT(l1-1)-3070)National Science Foundation (Grant GK-37979X1

Plasma Dynamics

Contains research objectives and summary of research on twenty-one projects split into three sections, with four sub-sections in the second section and reports on twelve research projects.National Science Foundation (Grant ENG75-06242)U.S. Energy Research and Development Administration (Contract E(11-1)-2766)U.S. Energy Research and Development Agency (Contract E(11-1)-3070)U.S. Energy Research and Development Administration (Contract E(11-1)-3070)Research Laboratory of Electronics, M.I.T. Industrial Fellowshi

The Novel Deacetylase Inhibitor AR-42 Demonstrates Pre-Clinical Activity in B-Cell Malignancies In Vitro and In Vivo

While deacetylase (DAC) inhibitors show promise for the treatment of B-cell malignancies, those introduced to date are weak inhibitors of class I and II DACs or potent inhibitors of class I DAC only, and have shown suboptimal activity or unacceptable toxicities. We therefore investigated the novel DAC inhibitor AR-42 to determine its efficacy in B-cell malignancies.In mantle cell lymphoma (JeKo-1), Burkitt's lymphoma (Raji), and acute lymphoblastic leukemia (697) cell lines, the 48-hr IC(50) (50% growth inhibitory concentration) of AR-42 is 0.61 microM or less. In chronic lymphocytic leukemia (CLL) patient cells, the 48-hr LC(50) (concentration lethal to 50%) of AR-42 is 0.76 microM. AR-42 produces dose- and time-dependent acetylation both of histones and tubulin, and induces caspase-dependent apoptosis that is not reduced in the presence of stromal cells. AR-42 also sensitizes CLL cells to TNF-Related Apoptosis Inducing Ligand (TRAIL), potentially through reduction of c-FLIP. AR-42 significantly reduced leukocyte counts and/or prolonged survival in three separate mouse models of B-cell malignancy without evidence of toxicity.Together, these data demonstrate that AR-42 has in vitro and in vivo efficacy at tolerable doses. These results strongly support upcoming phase I testing of AR-42 in B-cell malignancies