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Two alternative pathways for generating transmissible prion disease de novo

Overview of attention for article published in Acta Neuropathologica Communications, November 2015
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Title
Two alternative pathways for generating transmissible prion disease de novo
Published in
Acta Neuropathologica Communications, November 2015
DOI 10.1186/s40478-015-0248-5
Pubmed ID
Authors

Natallia Makarava, Regina Savtchenko, Ilia V. Baskakov

Abstract

Previous studies established that prion disease with unique strain-specific phenotypes could be induced by in vitro-formed recombinant PrP (rPrP) fibrils with structures different from that of authentic prions, or PrP(Sc). To explain the etiology of prion diseases, new mechanism proposed that in animals the transition from rPrP fibrils to PrP(Sc) consists of two main steps: the first involves fibril-induced formation of atypical PrPres, a self-replicating but clinically silent state, and the second consists of atypical PrPres-dependent formation of PrP(Sc) via rare deformed templating events. In the current study, atypical PrPres with characteristics similar to those of brain-derived atypical PrPres was generated in vitro. Upon inoculation into animals, in vitro-generated atypical PrPres gave rise to PrP(Sc) and prion disease with a phenotype similar to those induced by rPrP fibrils. Significant differences in the sialylation pattern between atypical PrPres and PrP(Sc) suggested that only a small sub-fraction of the PrP(C) that is acceptable as a substrate for PrP(Sc) could be also recruited by atypical PrPres. This can explain why atypical PrPres replicates slower than PrP(Sc) and why PrP(Sc) outcompetes atypical PrPres. This study illustrates that transmissible prion diseases with very similar disease phenotypes could be produced via two alternative procedures: direct inoculation of recombinant PrP amyloid fibrils or in vitro-produced atypical PrPres. Moreover, this work showed that preparations of atypical PrPres free of PrP(Sc) can give rise to transmissible diseases in wild type animals and that atypical PrPres generated in vitro is an adequate model for brain-derived atypical PrPres.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 42%
Researcher 5 19%
Student > Bachelor 2 8%
Professor 2 8%
Other 2 8%
Other 4 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 46%
Agricultural and Biological Sciences 5 19%
Pharmacology, Toxicology and Pharmaceutical Science 2 8%
Neuroscience 2 8%
Nursing and Health Professions 1 4%
Other 2 8%
Unknown 2 8%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 27 November 2015.
All research outputs
#14,240,855
of 22,832,057 outputs
Outputs from Acta Neuropathologica Communications
#1,074
of 1,375 outputs
Outputs of similar age
#146,238
of 282,792 outputs
Outputs of similar age from Acta Neuropathologica Communications
#22
of 26 outputs
Altmetric has tracked 22,832,057 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,375 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.9. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 282,792 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.