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Accelerated High Fidelity Prion Amplification Within And Across Prion Species Barriers, Kristi M. Green, Joaquín Castilla, Tanya S. Seward, Dana L. Napier, Jean E. Jewell, Claudio Soto, Glenn C. Telling
Accelerated High Fidelity Prion Amplification Within And Across Prion Species Barriers, Kristi M. Green, Joaquín Castilla, Tanya S. Seward, Dana L. Napier, Jean E. Jewell, Claudio Soto, Glenn C. Telling
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier …
Cd5 Plays An Inhibitory Role In The Suppressive Function Of Murine Cd4+ Cd25+ TReg Cells, Trivikram Dasu, Joseph E. Qualls, Halide Tuna, Chander Raman, Donald A. Cohen, Subbarao Bondada
Cd5 Plays An Inhibitory Role In The Suppressive Function Of Murine Cd4+ Cd25+ TReg Cells, Trivikram Dasu, Joseph E. Qualls, Halide Tuna, Chander Raman, Donald A. Cohen, Subbarao Bondada
Microbiology, Immunology, and Molecular Genetics Faculty Publications
A subset of CD4+ T cells, the CD4+ CD25+ regulatory T (Treg) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such ‘natural regulatory (Treg) cells’ and for activation of the effector function of CD4+ CD25+ regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, …
Sumoylation Regulates Lamin A Function And Is Lost In Lamin A Mutants Associated With Familial Cardiomyopathies, Yu-Qian Zhang, Kevin D. Sarge
Sumoylation Regulates Lamin A Function And Is Lost In Lamin A Mutants Associated With Familial Cardiomyopathies, Yu-Qian Zhang, Kevin D. Sarge
Molecular and Cellular Biochemistry Faculty Publications
Lamin A mutations cause many diseases, including cardiomyopathies and Progeria Syndrome. The covalent attachment of small ubiquitin-like modifier (SUMO) polypeptides regulates the function of many proteins. Until now, no examples of human disease-causing mutations that occur within a sumoylation consensus sequence and alter sumoylation were known. We show that lamin A is sumoylated at lysine 201 and that two lamin A mutants associated with familial dilated cardiomyopathy, E203G and E203K, exhibit decreased sumoylation. E203 occupies the conserved +2 position in the sumoylation consensus Psi KXE. Lamin A mutants E203G, E203K, and K201R all exhibit a similar aberrant subcellular localization and …
Assessment Of A Non-Invasive High-Throughput Classifier For Behaviours Associated With Sleep And Wake In Mice, Kevin D. Donohue, Dharshan C. Medonza, Eli R. Crane, Bruce F. O'Hara
Assessment Of A Non-Invasive High-Throughput Classifier For Behaviours Associated With Sleep And Wake In Mice, Kevin D. Donohue, Dharshan C. Medonza, Eli R. Crane, Bruce F. O'Hara
Biology Faculty Publications
This work presents a non-invasive high-throughput system for automatically detecting characteristic behaviours in mice over extended periods of time, useful for phenotyping experiments. The system classifies time intervals on the order of 2 to 4 seconds as corresponding to motions consistent with either active wake or inactivity associated with sleep. A single Polyvinylidine Difluoride (PVDF) sensor on the cage floor generates signals from motion resulting in pressure. This paper develops a linear classifier based on robust features extracted from normalized power spectra and autocorrelation functions, as well as novel features from the collapsed average (autocorrelation of complex spectrum), which characterize …
Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty
Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty
Saha Cardiovascular Research Center Faculty Publications
The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …
Sr-Bi Protects Against Endotoxemia In Mice Through Its Roles In Glucocorticoid Production And Hepatic Clearance, Lei Cai, Ailing Ji, Frederick C. De Beer, Lisa R. Tannock, Deneys R. Van Der Westhuyzen
Sr-Bi Protects Against Endotoxemia In Mice Through Its Roles In Glucocorticoid Production And Hepatic Clearance, Lei Cai, Ailing Ji, Frederick C. De Beer, Lisa R. Tannock, Deneys R. Van Der Westhuyzen
Internal Medicine Faculty Publications
Septic shock results from an uncontrolled inflammatory response, mediated primarily by LPS. Cholesterol transport plays an important role in the host response to LPS, as LPS is neutralized by lipoproteins and adrenal cholesterol uptake is required for antiinflammatory glucocorticoid synthesis. In this study, we show that scavenger receptor B-I (SR-BI), an HDL receptor that mediates HDL cholesterol ester uptake into cells, is required for the normal antiinflammatory response to LPS-induced endotoxic shock. Despite elevated plasma HDL levels, SR-BI–null mice displayed an uncontrollable inflammatory cytokine response and a markedly higher lethality rate than control mice in response to LPS. In addition, …