Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 6 of 6
Full-Text Articles in Medicine and Health Sciences
Med5(Nut1) And Med17(Srb4) Are Direct Targets Of Mediator Histone H4 Tail Interactions, Zhongle Liu, Lawrence C. Myers
Med5(Nut1) And Med17(Srb4) Are Direct Targets Of Mediator Histone H4 Tail Interactions, Zhongle Liu, Lawrence C. Myers
Dartmouth Scholarship
The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone …
Isolation Of Phosphatidylethanolamine As A Solitary Cofactor For Prion Formation In The Absence Of Nucleic Acids, Nathan R. Deleault, Justin R. Piro, Daniel J. Walsh, Fei Wang, Jiyan Ma, James C. Geoghegan, Surachai Supattapone
Isolation Of Phosphatidylethanolamine As A Solitary Cofactor For Prion Formation In The Absence Of Nucleic Acids, Nathan R. Deleault, Justin R. Piro, Daniel J. Walsh, Fei Wang, Jiyan Ma, James C. Geoghegan, Surachai Supattapone
Dartmouth Scholarship
Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of …
Propentofylline Targets Troy, A Novel Microglial Signaling Pathway, Valerie L. Jacobs, Yingna Liu, Joyce A. De Leo
Propentofylline Targets Troy, A Novel Microglial Signaling Pathway, Valerie L. Jacobs, Yingna Liu, Joyce A. De Leo
Dartmouth Scholarship
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer, with a median survival of less than 2 years after diagnosis with current available therapies. The tumor microenvironment serves a critical role in tumor invasion and progression, with microglia as a critical player. Our laboratory has previously demonstrated that propentofylline, an atypical methylxanthine with central nervous system glial modulating and anti-inflammatory actions, significantly decreases tumor growth in a GBM rodent model by preferentially targeting microglia. In the present study, we used the CNS-1 rat glioma model to elucidate the mechanisms of propentofylline. Here we demonstrate that propentofylline targets …
Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan
Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan
Dartmouth Scholarship
PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …
Mitogen Activated Protein Kinase Phosphatase-1 Prevents The Development Of Tactile Sensitivity In A Rodent Model Of Neuropathic Pain, Christian Ndong, Russell P. Landry, Joyce A. Deleo, Edgar A. Romero-Sandoval
Mitogen Activated Protein Kinase Phosphatase-1 Prevents The Development Of Tactile Sensitivity In A Rodent Model Of Neuropathic Pain, Christian Ndong, Russell P. Landry, Joyce A. Deleo, Edgar A. Romero-Sandoval
Dartmouth Scholarship
Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK) family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs) limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of …
Ovarian Cancer Progression Is Controlled By Phenotypic Changes In Dendritic Cells, Uciane K. Scarlett, Melanie R. Rutkowski, Adam M. Rauwerdink, Jennifer Fields, Ximena Escovar-Fadul, Jason Baird, Juan R. Cubillos-Ruiz, Ana C. Jacobs, Jorge L. Gonzalez, John Weaver, Steven Fiering, Jose R. Conejo-Garcia
Ovarian Cancer Progression Is Controlled By Phenotypic Changes In Dendritic Cells, Uciane K. Scarlett, Melanie R. Rutkowski, Adam M. Rauwerdink, Jennifer Fields, Ximena Escovar-Fadul, Jason Baird, Juan R. Cubillos-Ruiz, Ana C. Jacobs, Jorge L. Gonzalez, John Weaver, Steven Fiering, Jose R. Conejo-Garcia
Dartmouth Scholarship
We characterized the initiation and evolution of the immune response against a new inducible p53-dependent model of aggressive ovarian carcinoma that recapitulates the leukocyte infiltrates and cytokine milieu of advanced human tumors. Unlike other models that initiate tumors before the development of a mature immune system, we detect measurable antitumor immunity from very early stages, which is driven by infiltrating dendritic cells (DCs) and prevents steady tumor growth for prolonged periods. Coinciding with a phenotypic switch in expanding DC infiltrates, tumors aggressively progress to terminal disease in a comparatively short time. Notably, tumor cells remain immunogenic at advanced stages, but …