scholarly journals Long-Term Incubation PrPCWD with Soils Affects Prion Recovery but Not Infectivity

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 311
Author(s):  
Alsu Kuznetsova ◽  
Debbie McKenzie ◽  
Catherine Cullingham ◽  
Judd M. Aiken
Keyword(s):  
Prion Disease ◽  
Soil Type ◽  
Infectious Agent ◽  
Brain Homogenate ◽  
Wasting Disease ◽  
Soil Minerals ◽  
Prion Infectivity ◽  
Incubation Periods ◽  
Clinical Stages

Chronic wasting disease (CWD) is a contagious prion disease of cervids. The infectious agent is shed from animals at the preclinical and clinical stages of disease where it persists in the environment as a reservoir of CWD infectivity. In this study, we demonstrate that long-term incubation of CWD prions (generated from tg-mice infected with deer or elk prions) with illite, montmorillonite (Mte) and whole soils results in decreased recovery of PrPCWD, suggesting that binding becomes more avid and irreversible with time. This continual decline of immunoblot PrPCWD detection did not correlate with prion infectivity levels. Bioassay showed no significant differences in incubation periods between mice inoculated with 1% CWD brain homogenate (BH) and with the CWD-BH pre-incubated with quartz or Luvisolic Ae horizon for 1 or 30 weeks. After 55 weeks incubation with Chernozem and Luvisol, bound PrPCWD was not detectable by immunoblotting but remained infectious. This study shows that although recovery of PrPCWD bound to soil minerals and whole soils with time become more difficult, prion infectivity is not significantly altered. Detection of prions in soil is, therefore, not only affected by soil type but also by length of time of the prion–soil interaction.

scholarly journals Failure To Detect Prion Infectivity in Ticks following Prion-Infected Blood Meal

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Ronald A. Shikiya ◽  
Anthony E. Kincaid ◽  
Jason C. Bartz ◽  
Travis J. Bourret
Keyword(s):  
Prion Disease ◽  
Blood Meal ◽  
Red Deer ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Geographic Range ◽  
Lymphoid Tissues ◽  
Wasting Disease ◽  
Prion Infection ◽  
Prion Infectivity

ABSTRACT Chronic wasting disease (CWD) is an emerging and fatal contagious prion disease that affects cervids, including mule deer, white-tailed deer, black-tailed deer, red deer reindeer, elk, and moose. CWD prions are widely distributed throughout the bodies of CWD-infected animals and are found in the nervous system, lymphoid tissues, muscle, blood, urine, feces, and antler velvet. The mechanism of CWD transmission in natural settings is unknown. Potential mechanisms of transmission include horizontal, maternal, or environmental routes. Due to the presence of prions in the blood of CWD-infected animals, the potential exists for invertebrates that feed on mammalian blood to contribute to the transmission of CWD. The geographic range of the Rocky Mountain Wood tick, Dermancentor andersoni, overlaps with CWD throughout the northwest United States and southwest Canada, raising the possibility that D. andersoni parasitization of cervids may be involved in CWD transmission. We investigated this possibility by examining the blood meal of D. andersoni that fed upon prion-infected hamsters for the presence of prion infectivity by animal bioassay. None of the hamsters inoculated with a D. andersoni blood meal that had been ingested from prion-infected hamsters developed clinical signs of prion disease or had evidence for a subclinical prion infection. Overall, the data do not demonstrate a role for D. andersoni in the transmission of prion disease. IMPORTANCE Chronic wasting disease (CWD) is an emerging prion disease that affects cervids, including mule deer, white-tailed deer, black-tailed deer, red deer reindeer, elk, and moose. The mechanism of CWD transmission in unknown. Due to the presence of prions in the blood of CWD-infected animals, it is possible for invertebrates that feed on cervid blood to contribute to the transmission of CWD. We examined the blood meal of D. andersoni, a tick with a similar geographic range as cervids, that fed upon prion-infected hamsters for the presence of prion infectivity by animal bioassay. None of the D. andersoni blood meals that had been ingested from prion-infected hamsters yielded evidence of prion infection. Overall, the data do not support a role of D. andersoni in the transmission of prion disease.

scholarly journals Detection of Prions in Brain Homogenates and CSF Samples Using a Second-Generation RT-QuIC Assay: A Useful Tool for Retrospective Analysis of Archived Samples

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 750
Author(s):  
Tibor Moško ◽  
Soňa Galušková ◽  
Radoslav Matěj ◽  
Magdalena Brůžová ◽  
Karel Holada
Keyword(s):  
Retrospective Analysis ◽  
Prion Disease ◽  
Second Generation ◽  
Prion Diseases ◽  
Neuropsychiatric Symptoms ◽  
Final Diagnosis ◽  
Post Mortem ◽  
Long Term Storage ◽  
Archived Samples

The possibilities for diagnosing prion diseases have shifted significantly over the last 10 years. The RT-QuIC assay option has been added for neuropsychiatric symptoms, supporting biomarkers and final post-mortem confirmation. Samples of brain homogenates used for final diagnosis, archived for many years, provide the possibility for retrospective studies. We used a second-generation RT-QuIC assay to detect seeding activity in different types of sporadic and genetic prion diseases in archival brain homogenates and post-mortem CSF samples that were 2 to 15 years old. Together, we tested 92 archival brain homogenates: 39 with definite prion disease, 28 with definite other neurological disease, and 25 with no signs of neurological disorders. The sensitivity and specificity of the assay were 97.4% and 100%, respectively. Differences were observed in gCJD E200K, compared to the sporadic CJD group. In 52 post-mortem CSF samples—24 with definite prion disease and 28 controls—we detected the inhibition of seeding reaction due to high protein content. Diluting the samples eliminated such inhibition and led to 95.8% sensitivity and 100% specificity of the assay. In conclusion, we proved the reliability of archived brain homogenates and post-mortem CSF samples for retrospective analysis by RT-QuIC after long-term storage, without changed reactivity.

scholarly journals Chimeric elk/mouse prion proteins in transgenic mice

2013 ◽  
Vol 94 (2) ◽  
pp. 443-452 ◽  
Author(s):  
Gültekin Tamgüney ◽  
Kurt Giles ◽  
Abby Oehler ◽  
Natrina L. Johnson ◽  
Stephen J. DeArmond ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Prion Proteins ◽  
Second Line ◽  
Mouse Line ◽  
Wasting Disease ◽  
C Terminus ◽  
Incubation Periods ◽  
N Terminus ◽  
Mouse Lines

Chronic wasting disease (CWD) of deer and elk is a highly communicable neurodegenerative disorder caused by prions. Investigations of CWD are hampered by slow bioassays in transgenic (Tg) mice. Towards the development of Tg mice that will be more susceptible to CWD prions, we created a series of chimeric elk/mouse transgenes that encode the N terminus of elk PrP (ElkPrP) up to residue Y168 and the C terminus of mouse PrP (MoPrP) beyond residue 169 (mouse numbering), designated Elk3M(SNIVVK). Between codons 169 and 219, six residues distinguish ElkPrP from MoPrP: N169S, T173N, V183I, I202V, I214V and R219K. Using chimeric elk/mouse PrP constructs, we generated 12 Tg mouse lines and determined incubation times after intracerebral inoculation with the mouse-passaged RML scrapie or Elk1P CWD prions. Unexpectedly, one Tg mouse line expressing Elk3M(SNIVVK) exhibited incubation times of <70 days when inoculated with RML prions; a second line had incubation times of <90 days. In contrast, mice expressing full-length ElkPrP had incubation periods of >250 days for RML prions. Tg(Elk3M,SNIVVK) mice were less susceptible to CWD prions than Tg(ElkPrP) mice. Changing three C-terminal mouse residues (202, 214 and 219) to those of elk doubled the incubation time for mouse RML prions and rendered the mice resistant to Elk1P CWD prions. Mutating an additional two residues from mouse to elk at codons 169 and 173 increased the incubation times for mouse prions to >300 days, but made the mice susceptible to CWD prions. Our findings highlight the role of C-terminal residues in PrP that control the susceptibility and replication of prions.

scholarly journals Human Prion Disease and Relative Risk Associated with Chronic Wasting Disease

2006 ◽  
Vol 12 (10) ◽  
pp. 1527-1535 ◽  
Author(s):  
Samantha MaWhinney ◽  
W. John Pape ◽  
Jeri E. Forster ◽  
C. Alan Anderson ◽  
Patrick Bosque ◽  
...  
Keyword(s):  
Relative Risk ◽  
Prion Disease ◽  
Chronic Wasting Disease ◽  
Human Prion Disease ◽  
Wasting Disease

scholarly journals Effect of serotonin modulation on dystrophin-deficient zebrafish

Biology Open ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. bio053363 ◽  
Author(s):  
Janelle M. Spinazzola ◽  
Matthias R. Lambert ◽  
Devin E. Gibbs ◽  
James R. Conner ◽  
Georgia L. Krikorian ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Dystrophic Muscle ◽  
Wasting Disease ◽  
Term Survival ◽  
Reversible Inhibitors ◽  
Restoration Strategies ◽  
Muscle Wasting Disease ◽  
Improve Patient ◽  
Serotonin Pathway

ABSTRACTDuchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutation of the dystrophin gene. Pharmacological therapies that function independently of dystrophin and complement strategies aimed at dystrophin restoration could significantly improve patient outcomes. Previous observations have suggested that serotonin pathway modulation ameliorates dystrophic pathology, and re-application of serotonin modulators already used clinically would potentially hasten availability to DMD patients. In our study, we used dystrophin-deficient sapje and sapje-like zebrafish models of DMD for rapid and easy screening of several classes of serotonin pathway modulators as potential therapeutics. None of the candidate drugs tested significantly decreased the percentage of zebrafish exhibiting the dystrophic muscle phenotype in the short-term birefringence assay or lengthened the lifespan in the long-term survival assay. Although we did not identify an effective drug, we believe our data is of value to the DMD research community for future studies, and there is evidence that suggests serotonin modulation may still be a viable treatment strategy with further investigation. Given the widespread clinical use of selective serotonin reuptake inhibitors, tricyclic antidepressants and reversible inhibitors of monoamine oxidase, their reapplication to DMD is an attractive strategy in the field's pursuit to identify pharmacological therapies to complement dystrophin restoration strategies.

Influence of Long Term Tillage, Crop Rotation, and Soil Type Combinations on Corn Yield

1976 ◽  
Vol 40 (1) ◽  
pp. 100-105 ◽  
Author(s):  
D. M. Van Doren ◽  
G. B. Triplett ◽  
J. E. Henry
Keyword(s):  
Crop Rotation ◽  
Soil Type ◽  
Corn Yield

scholarly journals Post-Traumatic Exogenous Endophthalmitis Caused By Nocardia Farcinica

2021 ◽  
Author(s):  
Marie Česká Burdová ◽  
Kateřina Donátová ◽  
Gabriela Mahelková ◽  
Vanda Chrenková ◽  
Dagmar Dotřelová
Keyword(s):  
Anterior Chamber ◽  
Infectious Agent ◽  
Corneal Injury ◽  
Nocardia Farcinica ◽  
Complicated Course ◽  
Post Traumatic ◽  
Exogenous Endophthalmitis ◽  
Treatment Procedures

Abstract A case report of post-traumatic exogenous endophthalmitis caused by Nocardia farcinica, including treatment procedures, microbiology examination, and systemic medications. A 23-year-old male suffered a penetrating corneal injury that was treated with sutures. The sutures were individually removed during the 4th and 5th months after surgery. On the thirteenth day after the final suture was removed, an anterior uveitis developed and progressed to whitish, plump, nodular, and tufted exudates within the anterior chamber over the next 10 days; this led to an indication for intraocular surgery. Anterior chamber lavage and resection of solid fibrinous exudates (using a vitrectomy knife) for a complete microbiological examination were performed. Nocardia farcinica was identified. Systemic medications were chosen according to sensitivity, and a fixed combination of sulfamethoxazole 400 mg/trimethoprim 80 mg was administered long-term (months). After a complicated course, the final visual acuity was 0.5. In this case, accurate, early detection of an atypical infectious agent and determination of its sensitivity to antibiotic treatment enabled effective treatment that achieved the best functional and anatomical results under the circumstances.

Estimates of short- and long-term incubation periods of Plasmodium vivax malaria in the Republic of Korea

2007 ◽  
Vol 101 (4) ◽  
pp. 338-343 ◽  
Author(s):  
Hiroshi Nishiura ◽  
Hyeong-Woo Lee ◽  
Shin-Hyeong Cho ◽  
Wook-Gyo Lee ◽  
Tae-Suk In ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Republic Of Korea ◽  
Incubation Periods ◽  
Plasmodium Vivax Malaria ◽  
Short And Long Term ◽  
The Republic

scholarly journals Dehydration of Prions on Environmentally Relevant Surfaces Protects Them from Inactivation by Freezing and Thawing

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Qi Yuan ◽  
Glenn Telling ◽  
Shannon L. Bartelt-Hunt ◽  
Jason C. Bartz
Keyword(s):  
Prion Disease ◽  
Disease Transmission ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Control Strategies ◽  
Horizontal Transmission ◽  
Freezing And Thawing ◽  
Wasting Disease ◽  
Live Animal ◽  
Weathering Processes

ABSTRACTChronic wasting disease (CWD) is an emerging prion disease in North America. Recent identification of CWD in wild cervids from Norway raises the concern of the spread of CWD in Europe. CWD infectivity can enter the environment through live animal excreta and carcasses where it can bind to soil. Well-characterized hamster prion strains and CWD field isolates in unadsorbed or soil-adsorbed forms that were either hydrated or dehydrated were subjected to repeated rounds of freezing and thawing. We found that 500 cycles of repeated freezing and thawing of hydrated samples significantly decreased the abundance of PrPScand reduced protein misfolding cyclic amplification (PMCA) seeding activity that could be rescued by binding to soil. Importantly, dehydration prior to freezing and thawing treatment largely protected PrPScfrom degradation, and the samples maintained PMCA seeding activity. We hypothesize that redistribution of water molecules during the freezing and thawing process alters the stability of PrPScaggregates. Overall, these results have significant implications for the assessment of prion persistence in the environment.IMPORTANCEPrions excreted into the environment by infected animals, such as elk and deer infected with chronic wasting disease, persist for years and thus facilitate horizontal transmission of the disease. Understanding the fate of prions in the environment is essential to control prion disease transmission. The significance of our study is that it provides information on the possibility of prion degradation and inactivation under natural weathering processes. This information is significant for remediation of prion-contaminated environments and development of prion disease control strategies.

scholarly journals Change in tau phosphorylation associated with neurodegeneration in the ME7 model of prion disease

2010 ◽  
Vol 38 (2) ◽  
pp. 545-551 ◽  
Author(s):  
Ayodeji A. Asuni ◽  
V. Hugh Perry ◽  
Vincent O'Connor
Keyword(s):  
Axonal Transport ◽  
Prion Disease ◽  
Neuronal Loss ◽  
Brain Homogenate ◽  
Tau Phosphorylation ◽  
Synaptic Dysfunction ◽  
Normal Brain ◽  
Hyperphosphorylated Tau ◽  
Ad Alzheimer’S Disease ◽  
End Stage

Hyperphosphorylation of the microtubule-associated protein tau is a significant determinant in AD (Alzheimer's disease), where it is associated with disrupted axonal transport and probably causes synaptic dysfunction. Although less well studied, hyperphosphorylation has been observed in prion disease. We have investigated the expression of hyperphosphorylated tau in the hippocampus of mice infected with the ME7 prion agent. In ME7-infected animals, there is a selective loss of CA1 synapse, first discernable at 13 weeks of disease. There is a potential that dysfunctional axonal transport contributes to this synaptopathy. Thus investigating hyperphosphorylated tau that is dysfunctional in AD could illuminate whether and how they are significant in prion disease. We observed no differences in the levels of phosphorylated tau (using MC1, PHF-1 and CP13 antibodies) in detergent-soluble and detergent-insoluble fractions extracted from ME7- and NBH- (normal brain homogenate) treated animals across disease. In contrast, we observed an increase in phospho-tau staining for several epitopes using immunohistochemistry in ME7-infected hippocampal sections. Although the changes were not of the magnitude seen in AD tissue, clear differences for several phospho-tau species were seen in the CA1 and CA3 of ME7-treated animals (pSer199−202>pSer214>PHF-1 antibody). Temporally, these changes were restricted to animals at 20 weeks and none of the disease-related staining was associated with the axons or dendrites that hold CA1 synapses. These findings suggest that phosphorylation of tau at the epitopes examined does not underpin the early synaptic dysfunction. These data suggest that the changes in tau phosphorylation recorded here and observed by others relate to end-stage prion pathology when early dysfunctions have progressed to overt neuronal loss.

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