- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Infectious Encephalopathies and Encephalitis
- RNA regulation and disease
- Alzheimer's disease research and treatments
- Amino Acid Enzymes and Metabolism
- Animal Genetics and Reproduction
- Bacteriophages and microbial interactions
- Enzyme Structure and Function
- Animal Disease Management and Epidemiology
- Olfactory and Sensory Function Studies
- Animal Ecology and Behavior Studies
- Metallurgy and Material Science
- Effects and risks of endocrine disrupting chemicals
- Genetic Neurodegenerative Diseases
- Advanced Biosensing Techniques and Applications
- Cellular Mechanics and Interactions
- S100 Proteins and Annexins
- Monoclonal and Polyclonal Antibodies Research
- Cancer Treatment and Pharmacology
- Digestive system and related health
- Alcoholism and Thiamine Deficiency
- Ion Transport and Channel Regulation
- Pancreatic function and diabetes
Creighton University
2016-2025
CHI Health Creighton University Medical Center - Bergan Mercy
2015-2024
University of Minnesota
2022-2024
Colorado State University
2024
University Hospital Ulm
2016
Indiana University School of Medicine
2008-2014
University of Nebraska at Omaha
2008-2014
Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie
2014
University of Nebraska–Lincoln
2008-2012
Stanford University
2012
Understanding protein adsorption kinetics to surfaces is of importance for various environmental and biomedical applications. Adsorption bovine serum albumin self-assembled monolayer including neutral charged hydrophilic hydrophobic was investigated using in-situ combinatorial quartz crystal microbalance with dissipation spectroscopic ellipsometry. varied as a function surface properties, concentration pH value. Charged exhibited greater quantity adsorption, larger layer thickness, increased...
ABSTRACT Food-borne transmission of prions can lead to infection the gastrointestinal tract and neuroinvasion via splanchnic vagus nerves. Here we report that transmissible mink encephalopathy (TME) is 100,000-fold more efficient by inoculation into tongues hamsters than oral ingestion. The incubation period following TME agent (hereinafter referred as TME) lingual muscles was shortest among five nonneuronal routes inoculation, including another intramuscular route. Deposition abnormal...
Chronic wasting disease (CWD) is an emerging prion of deer and elk. The risk CWD transmission to humans following exposure CWD-infected tissues unknown. To assess the susceptibility nonhuman primates CWD, two squirrel monkeys were inoculated with brain tissue from a mule deer. CWD-inoculated developed progressive neurodegenerative euthanized at 31 34 months postinfection. Brain contained abnormal isoform protein, PrP-res, displayed spongiform degeneration. This first reported primates.
ABSTRACT Interspecies transmission of the transmissible spongiform encephalopathies (TSEs), or prion diseases, can result in adaptation and selection TSE strains with an expanded host range increased virulence such as case bovine encephalopathy variant Creutzfeldt-Jakob disease. To investigate strain adaptation, we serially passaged a biological clone mink (TME) into Syrian golden hamsters examined distinct phenotypes conformations disease-specific isoform protein (PrP Sc ). The...
The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of prion protein is conformational. Because disruption PrPSc structure decreases scrapie infectivity, restoration disease-specific conformation should restore infectivity. In this study, (as monitored by loss proteinase K resistance) guanidine hydrochloride (GdnHCl) resulted in decreased Upon dilution GdnHCl, protease resistance PrP was restored infectivity regained. addition copper facilitated both a...
Prion strains are characterized by differences in the outcome of disease, most notably incubation period and neuropathological features. While it is established that disease specific isoform prion protein, PrPSc, an essential component infectious agent, strain-specific relationship between PrPSc properties biological features resulting not clear. To investigate this relationship, we examined amplification efficiency conformational stability from eight hamster-adapted compared to processing...
Blood-borne transmission of infectious prions during the symptomatic and asymptomatic stages disease occurs for both human animal transmissible spongiform encephalopathies (TSEs). The geographical distribution cervid TSE, chronic wasting (CWD), continues to spread across North America prospective number individuals harboring an infection variant Creutzfeldt-Jakob Disease (vCJD) in United Kingdom has been projected be ~1 3000 residents. Thus, it is important monitor blood products ensure herd...
Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie (PrP(Sc)), a beta-sheet rich isoform normal cell-surface glycoprotein, protein (PrP(C)). Limited reports suggest imbalance brain iron homeostasis as significant associated cause neurotoxicity prion-infected cell and mouse models. However, systematic studies on generality this phenomenon underlying mechanism(s) leading dyshomeostasis diseased brains are lacking. In report, we demonstrate that...
Animals that naturally acquire the prion diseases have a well-developed olfactory sense they utilize for variety of basic behaviors. To assess potential nasal cavity to serve as point entry diseases, small amount prion-infected brain homogenate was placed inferior nostrils hamsters, where it immediately sniffed into cavity. Hamsters extra-nasally inoculated with HY strain transmissible mink encephalopathy (TME) agent had an incubation period not significantly different from per os...
Prion strain interference can influence the emergence of a dominant from mixture; however, mechanisms underlying prion are poorly understood. In our model interference, inoculation sciatic nerve with drowsy (DY) transmissible mink encephalopathy (TME) agent prior to superinfection hyper (HY) TME completely block HY causing disease. We show here that deposition PrP(Sc), in absence neuronal loss or spongiform change, central nervous system corresponds ability DY infection. This suggests...
Significance To study mechanisms of interspecies prion transmission, we used transgenic mice that recapitulate natural disease susceptibilities. Predictably, prions from a particular species inefficiently caused in expressing proteins different species. However, contrast to the expected adaptation allows efficient replication new host, discovered process which pathogenic prions, despite causing on primary passage, failed adapt for sustained propagation instead preserving strain and host...
ABSTRACT While prion infection of the lymphoreticular system (LRS) is necessary for neuroinvasion in many diseases, bovine spongiform encephalopathy and atypical cases sheep scrapie there evidence to challenge that LRS required neuroinvasion. Here we investigated role tissues following extraneural inoculation with HY DY strains transmissible mink (TME) agent. TME agent infectivity was not detected spleen or lymph nodes intraperitoneal clinical disease observed into peritoneum nodes, after...
Prion sorption to soil is thought play an important role in the transmission of scrapie and chronic wasting disease (CWD) via environment. Sorption PrP minerals influenced by strain species PrP(Sc) characteristics. However, ability soil-bound prions convert PrP(c) under these wide-ranging conditions remains poorly understood. We developed a semiquantitative protein misfolding cyclic amplification (PMCA) protocol evaluate replication efficiency prions. Binding hyper (HY) transmissible mink...
ABSTRACT Infectious prions traverse epithelial barriers to gain access the circulatory system, yet temporal parameters of transepithelial transport and persistence in blood over time remain unknown. We used whole-blood real-time quaking-induced conversion (wbRT-QuIC) analyze whole collected from transmissible spongiform encephalopathy (TSE)-inoculated deer hamsters throughout incubation period for presence common prion protein-conversion competent amyloid (PrP C -CCA). observed PrP -CCA...
Prion strains are characterized by strain-specific differences in neuropathology but can also differ incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) drowsy (DY) of hamster-adapted transmissible mink encephalopathy (TME) tropism susceptibility to infection extraneural routes infection. Notably, DY TME is not detected the secondary lymphoreticular system (LRS) tissues infected hosts regardless route inoculation. We found that similar lymphotropic strain HY...
Chronic wasting disease (CWD) has been identified in 30 states the United States, four provinces Canada, and recently emerged Scandinavia. The association of CWD prions with environmental materials such as soil, plants, surfaces may enhance persistence prion infectivity environment exacerbating transmission. Identifying quantifying is significant for monitoring transmission control. A systematic method quantification from associated materials, however, does not exist. In this study, we...
Abstract Prion diseases, including chronic wasting disease (CWD), are caused by prions, which misfolded aggregates of normal cellular prion protein. Prions possess many characteristics that distinguish them from conventional pathogens, in particular, an extraordinary recalcitrance to inactivation and a propensity avidly bind surfaces. In mid late stages CWD, prions begin accumulating cervid muscle tissues. These features collectively create scenarios where occupational hazards arise for...
Transmission of iatrogenic prion disease has occurred from contaminated neurosurgical tools, transplant materials, and occupational exposure to prion-contaminated laboratory tools. Prions cause by the templated misfolding normal cellular form protein, PrPC, into misfolded pathogenic PrPSc are invariably fatal. Reducing transmission is challenging. First, prions can bind persist on surfaces for long periods time. Second, highly resistant inactivation. Given this, retain infectivity time...