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Red-Backed Vole Brain Promotes Highly Efficient In Vitro Amplification of Abnormal Prion Protein from Macaque and Human Brains Infected with Variant Creutzfeldt-Jakob Disease Agent

Overview of attention for article published in PLOS ONE, October 2013
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Title
Red-Backed Vole Brain Promotes Highly Efficient In Vitro Amplification of Abnormal Prion Protein from Macaque and Human Brains Infected with Variant Creutzfeldt-Jakob Disease Agent
Published in
PLOS ONE, October 2013
DOI 10.1371/journal.pone.0078710
Pubmed ID
Authors

Julie Nemecek, Nabanita Nag, Christina M. Carlson, Jay R. Schneider, Dennis M. Heisey, Christopher J. Johnson, David M. Asher, Luisa Gregori

Abstract

Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrP(TSE)) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE) in tissues and blood. Macaque vCJD PrP(TSE) did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrP(TSE). The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE). Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE) was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE) demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE) was more permissive than human PrP(TSE) in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE) from brains of humans and macaques with vCJD. PrP(TSE) signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE) from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrP(TSE) in vCJD-infected human and macaque blood.

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Mendeley readers

The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 20 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 35%
Student > Ph. D. Student 6 30%
Professor 2 10%
Other 1 5%
Professor > Associate Professor 1 5%
Other 1 5%
Unknown 2 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 35%
Agricultural and Biological Sciences 4 20%
Medicine and Dentistry 2 10%
Environmental Science 1 5%
Immunology and Microbiology 1 5%
Other 3 15%
Unknown 2 10%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 November 2013.
All research outputs
#16,559,153
of 20,587,020 outputs
Outputs from PLOS ONE
#138,728
of 177,689 outputs
Outputs of similar age
#152,916
of 208,318 outputs
Outputs of similar age from PLOS ONE
#3,139
of 4,164 outputs
Altmetric has tracked 20,587,020 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 177,689 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.4. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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We're also able to compare this research output to 4,164 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.