Styrene‐Maleic Acid (SMA) Nanodisc Technology: A Novel Approach for Isolation and Purification of the Infectious Prion Protein (PrP <sup>Sc</sup> )
Bibliographic record
Abstract
Understanding the structure of infectious prion proteins (PrPSc) and their arrangement within the native lipid bilayer has been a daunting task. The challenge arose largely due to an extensive use of conventional detergents such as Sarkosyl and phosphotungstic acid (PTA) derivatives during the purification of PrPSc, which in turn can exclude physiological lipids and induces fibrillization of PrPSc into amyloid. Hence, studies based on conventional PrPSc preparations result in a distorted representation of the in vivo PrPSc-lipid interactions. We demonstrated, for the first time, a novel and fast method for the isolation and purification of PrPSc from Syrian hamster brains infected with the Hyper prion strain using a number of styrene-maleic acid (SMA) copolymers. Western blots and silver stained SDS-PAGEs of the samples (highly enriched in lipids) confirm the presence of PrPSc in different glycosylation states. The samples were further analyzed by negative stain electron microscopy highlighting key features of the detergent-free purified PrPSc including 1) fairly ordered arrays of lipid-PrPSc fibrils, 2) formation of 2D crystals under certain experimental conditions and lipid:protein ratios, 3) the appearance of the PrPSc fibrils is similar to those of detergent purified samples. The SMA platform promises new avenues towards an in-depth structural, biochemical, and pathological characterization of PrPSc and its assortment of strains. Support or Funding Information This work has been generously supported by Alberta Innovate BioSolution Different oligomeric structures of isolated PrPsc Silver stained and western blotting of isolated PrPSc using Nanodisc technology Coherent interaction of PrPSc and lipid membranes A glimpse of PrPSc prions dissociated from lipid membranes Different oligomeric structures of isolated PrPsc Silver stained and western blotting of isolated PrPSc using Nanodisc technology Coherent interaction of PrPSc and lipid membranes A glimpse of PrPSc prions dissociated from lipid membranes
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".