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Full-Text Articles in Medical Sciences
Tryptophan Hydroxylase-1 Regulates Immune Tolerance And Inflammation, Elizabeth C. Nowak, Victor C. De Vries, Anna Wasiuk, Cory Ahonen, Kathryn A. Bennett, Isabelle Le Mercier, Dae-Gon Ha, Randolph J. Noelle
Tryptophan Hydroxylase-1 Regulates Immune Tolerance And Inflammation, Elizabeth C. Nowak, Victor C. De Vries, Anna Wasiuk, Cory Ahonen, Kathryn A. Bennett, Isabelle Le Mercier, Dae-Gon Ha, Randolph J. Noelle
Dartmouth Scholarship
Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control in ammatory responses and immune tolerance. Here we report the novel nding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 de ciency breaks allograft tolerance, induces tumor remission, and intensi es neuroin ammation, respectively. All of these effects of Tph-1 de ciency are independent of its downstream product serotonin. Because …
Cofactor Molecules Maintain Infectious Conformation And Restrict Strain Properties In Purified Prions, Nathan R. Deleault, Daniel J. Walsh, Justin R. Piro, Fei Wang, Xinhe Wang, Jiyan Ma, Judy R. Rees, Surachai Supattapone
Cofactor Molecules Maintain Infectious Conformation And Restrict Strain Properties In Purified Prions, Nathan R. Deleault, Daniel J. Walsh, Justin R. Piro, Fei Wang, Xinhe Wang, Jiyan Ma, Judy R. Rees, Surachai Supattapone
Dartmouth Scholarship
No abstract provided.
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 …
Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib
Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib
Dartmouth Scholarship
Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.
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 …
Caveolae, Fenestrae And Transendothelial Channels Retain Pv1 On The Surface Of Endothelial Cells, Eugene Tkachenko, Dan Tse, Olga Sideleva, Sophie J. Deharvengt, Marcus R. Luciano, Yan Xu, Caitlin L. Mcgarry, John Chidlow, Paul F. Pilch, William C. Sessa, Derek K. Toomre, Radu V. Stan
Caveolae, Fenestrae And Transendothelial Channels Retain Pv1 On The Surface Of Endothelial Cells, Eugene Tkachenko, Dan Tse, Olga Sideleva, Sophie J. Deharvengt, Marcus R. Luciano, Yan Xu, Caitlin L. Mcgarry, John Chidlow, Paul F. Pilch, William C. Sessa, Derek K. Toomre, Radu V. Stan
Dartmouth Scholarship
PV1 protein is an essential component of stomatal and fenestral diaphragms, which are formed at the plasma membrane of endothelial cells (ECs), on structures such as caveolae, fenestrae and transendothelial channels. Knockout of PV1 in mice results in in utero and perinatal mortality. To be able to interpret the complex PV1 knockout phenotype, it is critical to determine whether the formation of diaphragms is the only cellular role of PV1. We addressed this question by measuring the effect of complete and partial removal of structures capable of forming diaphragms on PV1 protein level. Removal of caveolae in mice by knocking …