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Search Results: 1 - 10 of 206770 matches for " Mark D. Zabel "
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Detection of Sub-Clinical CWD Infection in Conventional Test-Negative Deer Long after Oral Exposure to Urine and Feces from CWD+ Deer
Nicholas J. Haley,Candace K. Mathiason,Mark D. Zabel,Glenn C. Telling,Edward A. Hoover
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007990
Abstract: Chronic wasting disease (CWD) of cervids is a prion disease distinguished by high levels of transmissibility, wherein bodily fluids and excretions are thought to play an important role. Using cervid bioassay and established CWD detection methods, we have previously identified infectious prions in saliva and blood but not urine or feces of CWD+ donors. More recently, we identified very low concentrations of CWD prions in urine of deer by cervid PrP transgenic (Tg[CerPrP]) mouse bioassay and serial protein misfolding cyclic amplification (sPMCA). This finding led us to examine further our initial cervid bioassay experiments using sPMCA.
Detection of CWD Prions in Urine and Saliva of Deer by Transgenic Mouse Bioassay
Nicholas J. Haley, Davis M. Seelig, Mark D. Zabel, Glenn C. Telling, Edward A. Hoover
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004848
Abstract: Chronic wasting disease (CWD) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role. Here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (CWD). Prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid PrP gene (Tg[CerPrP] mice). In addition, PrPCWD was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA). The concentration of abnormal prion protein in bodily fluids was very low, as indicated by: undetectable PrPCWD levels by traditional assays (western blot, ELISA) and prolonged incubation periods and incomplete TSE attack rates in inoculated Tg(CerPrP) mice (373±3days in 2 of 9 urine-inoculated mice and 342±109 days in 8 of 9 saliva-inoculated mice). These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections.
Estimating Prion Adsorption Capacity of Soil by BioAssay of Subtracted Infectivity from Complex Solutions (BASICS)
A. Christy Wyckoff, Krista L. Lockwood, Crystal Meyerett-Reid, Brady A. Michel, Heather Bender, Kurt C. VerCauteren, Mark D. Zabel
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058630
Abstract: Prions, the infectious agent of scrapie, chronic wasting disease and other transmissible spongiform encephalopathies, are misfolded proteins that are highly stable and resistant to degradation. Prions are known to associate with clay and other soil components, enhancing their persistence and surprisingly, transmissibility. Currently, few detection and quantification methods exist for prions in soil, hindering an understanding of prion persistence and infectivity in the environment. Variability in apparent infectious titers of prions when bound to soil has complicated attempts to quantify the binding capacity of soil for prion infectivity. Here, we quantify the prion adsorption capacity of whole, sandy loam soil (SLS) typically found in CWD endemic areas in Colorado; and purified montmorillonite clay (Mte), previously shown to bind prions, by BioAssay of Subtracted Infectivity in Complex Solutions (BASICS). We incubated prion positive 10% brain homogenate from terminally sick mice infected with the Rocky Mountain Lab strain of mouse-adapted prions (RML) with 10% SLS or Mte. After 24 hours samples were centrifuged five minutes at 200×g and soil-free supernatant was intracerebrally inoculated into prion susceptible indicator mice. We used the number of days post inoculation to clinical disease to calculate the infectious titer remaining in the supernatant, which we subtracted from the starting titer to determine the infectious prion binding capacity of SLS and Mte. BASICS indicated SLS bound and removed ≥ 95% of infectivity. Mte bound and removed lethal doses (99.98%) of prions from inocula, effectively preventing disease in the mice. Our data reveal significant prion-binding capacity of soil and the utility of BASICS to estimate prion loads and investigate persistence and decomposition in the environment. Additionally, since Mte successfully rescued the mice from prion disease, Mte might be used for remediation and decontamination protocols.
Intranasal Inoculation of White-Tailed Deer (Odocoileus virginianus) with Lyophilized Chronic Wasting Disease Prion Particulate Complexed to Montmorillonite Clay
Tracy A. Nichols, Terry R. Spraker, Tara D. Rigg, Crystal Meyerett-Reid, Clare Hoover, Brady Michel, Jifeng Bian, Edward Hoover, Thomas Gidlewski, Aru Balachandran, Katherine O'Rourke, Glenn C. Telling, Richard Bowen, Mark D. Zabel, Kurt C. VerCauteren
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062455
Abstract: Chronic wasting disease (CWD), the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte), lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.
Liposome-siRNA-Peptide Complexes Cross the Blood-Brain Barrier and Significantly Decrease PrPC on Neuronal Cells and PrPRES in Infected Cell Cultures
Bruce Pulford,Natalia Reim,Aimee Bell,Jessica Veatch,Genevieve Forster,Heather Bender,Crystal Meyerett,Scott Hafeman,Brady Michel,Theodore Johnson,A. Christy Wyckoff,Gino Miele,Christian Julius,Jan Kranich,Alan Schenkel,Steven Dow,Mark D. Zabel
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011085
Abstract: Recent advances toward an effective therapy for prion diseases employ RNA interference to suppress PrPC expression and subsequent prion neuropathology, exploiting the phenomenon that disease severity and progression correlate with host PrPC expression levels. However, delivery of lentivirus encoding PrP shRNA has demonstrated only modest efficacy in vivo.
Amyloid-β and Proinflammatory Cytokines Utilize a Prion Protein-Dependent Pathway to Activate NADPH Oxidase and Induce Cofilin-Actin Rods in Hippocampal Neurons
Keifer P. Walsh, Laurie S. Minamide, Sarah J. Kane, Alisa E. Shaw, David R. Brown, Bruce Pulford, Mark D. Zabel, J. David Lambeth, Thomas B. Kuhn, James R. Bamburg
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095995
Abstract: Neurites of neurons under acute or chronic stress form bundles of filaments (rods) containing 1:1 cofilin:actin, which impair transport and synaptic function. Rods contain disulfide cross-linked cofilin and are induced by treatments resulting in oxidative stress. Rods form rapidly (5–30 min) in >80% of cultured hippocampal or cortical neurons treated with excitotoxic levels of glutamate or energy depleted (hypoxia/ischemia or mitochondrial inhibitors). In contrast, slow rod formation (50% of maximum response in ~6 h) occurs in a subpopulation (~20%) of hippocampal neurons upon exposure to soluble human amyloid-β dimer/trimer (Aβd/t) at subnanomolar concentrations. Here we show that proinflammatory cytokines (TNFα, IL-1β, IL-6) also induce rods at the same rate and within the same neuronal population as Aβd/t. Neurons from prion (PrPC)-null mice form rods in response to glutamate or antimycin A, but not in response to proinflammatory cytokines or Aβd/t. Two pathways inducing rod formation were confirmed by demonstrating that NADPH-oxidase (NOX) activity is required for prion-dependent rod formation, but not for rods induced by glutamate or energy depletion. Surprisingly, overexpression of PrPC is by itself sufficient to induce rods in over 40% of hippocampal neurons through the NOX-dependent pathway. Persistence of PrPC-dependent rods requires the continuous activity of NOX. Removing inducers or inhibiting NOX activity in cells containing PrPC-dependent rods causes rod disappearance with a half-life of about 36 min. Cofilin-actin rods provide a mechanism for synapse loss bridging the amyloid and cytokine hypotheses for Alzheimer disease, and may explain how functionally diverse Aβ-binding membrane proteins induce synaptic dysfunction.
Josephson tunnel junctions with ferromagnetic $\Fe_{0.75}\Co_{0.25}$ barriers
D. Sprungmann,K. Westerholt,H. Zabel,M. Weides,H. Kohlstedt
Physics , 2009, DOI: 10.1088/0022-3727/42/7/075005
Abstract: Josephson tunnel junctions with the strong ferromagnetic alloy $\Fe_{0.75}\Co_{0.25}$ as the barrier material were studied. The junctions were prepared with high quality down to a thickness range of a few monolayers of Fe-Co. An oscillation length of $\xi_{F2}\approx 0.79\:{\rm {nm}}$ between 0 and $\pi$-Josephson phase coupling and a very short decay length $\xi_{F1}\approx 0.22\:{\rm {nm}}$ for the amplitude of the superconducting pair wave function in the Fe-Co layer were determined. The rapid damping of the pair wave function inside the Fe-Co layer is caused by the strong ferromagnetic exchange field and additional magnetic pair breaking scattering. Josephson junctions with Fe-Co barriers show a significantly increased tendency towards magnetic remanence and flux trapping for larger thicknesses $d_{F}$.
Evidence for triplet superconductivity in Josephson junctions with ferromagnetic Cu$_{2}$MnAl-Heusler barriers
D. Sprungmann,K. Westerholt,H. Zabel,M. Weides,H. Kohlstedt
Physics , 2010,
Abstract: We have studied Josephson junctions with barriers prepared from the Heusler compound Cu$_2$MnAl. In the as-prepared state the Cu$_2$MnAl layers are non ferromagnetic and the critical Josephson current density $j_{c}$ decreases exponentially with the thickness of the Heusler layers $d_{F}$. On annealing the junctions at 240\degree C the Heusler layers develop ferromagnetic order and we observe a dependence $j_{c}(d_{F}$) with $j_{c}$ strongly enhanced and weakly thickness dependent in the thickness range 7.0 nm < $d_{F}$ < 10.6 nm. We attribute this feature to a triplet component in the superconducting pairing function generated by the specific magnetization profile inside thin Cu$_2$MnAl layers.
Domain wall propagation in Permalloy nanowires with a thickness gradient
O. Petracic,P. Szary,H. Zabel,D. Goerlitz,K. Nielsch
Physics , 2008, DOI: 10.1016/j.spmi.2009.08.001
Abstract: The domain wall nucleation and motion processes in Permalloy nanowires with a thickness gradient along the nanowire axis have been studied. Nanowires with widths, w = 250 nm to 3 um and a base thickness of t = 10 nm were fabricated by electron-beam lithography. The magnetization hysteresis loops measured on individual nanowires are compared to corresponding nanowires without a thickness gradient. The Hc vs. t/w curves of wires with and without a thickness gradient are discussed and compared to micromagnetic simulations. We find a metastability regime at values of w, where a transformation from transverse to vortex domain wall type is expected.
NMR and NQR Fluctuation Effects in Layered Superconductors
D. Fay,J. Appel,C. Timm,A. Zabel
Physics , 2000, DOI: 10.1103/PhysRevB.63.064509
Abstract: We study the effect of thermal fluctuations of the s-wave order parameter of a quasi two dimensional superconductor on the nuclear spin relaxation rate near the transition temperature Tc. We consider both the effects of the amplitude fluctuations and the Berezinskii-Kosterlitz-Thouless (BKT) phase fluctuations in weakly coupled layered superconductors. In the treatment of the amplitude fluctuations we employ the Gaussian approximation and evaluate the longitudinal relaxation rate 1/T1 for a clean s-wave superconductor, with and without pair breaking effects, using the static pair fluctuation propagator D. The increase in 1/T1 due to pair breaking in D is overcompensated by the decrease arising from the single particle Green's functions. The result is a strong effect on 1/T1 for even a small amount of pair breaking. The phase fluctuations are described in terms of dynamical BKT excitations in the form of pancake vortex-antivortex (VA) pairs. We calculate the effect of the magnetic field fluctuations caused by the translational motion of VA excitations on 1/T1 and on the transverse relaxation rate 1/T2 on both sides of the BKT transitation temperature T(BKT)
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