Distinct patterns of prion strain deposition and toxicity in a novel whole brain organotypic slice culture system
Bibliographic record
Abstract
Prion diseases are fatal transmissible neurodegenerative diseases that affect many mammals, including humans, caused by the templated misfolding of the prion protein. Different conformations of misfolded prions can occur, leading to distinct disease phenotypes or strains and the accumulation of prions in distinct brain regions. How prion structure influences this brain tropism is not clear, but the transmissible nature of prion diseases has allowed for the development of ex vivo brain slice models of disease. To date, work has been done in cerebellar cultures, but prion diseases are known to differentially affect many other brain regions. We have adapted this approach to a coronally sliced whole brain organotypic culture and demonstrate distinct profiles of cytotoxicity and neuronal loss upon exposure to four mouse-adapted scrapie strains. We were able to induce infection both diffusely through submersion of slice cultures in infectious media and locally through contact with prion-coated stainless-steel wires. Moreover, we observed consistent strain-specific regional differences in prion deposition by 8 weeks of infection, recapitulating what is seen in vivo. We predict that coronal whole brain organotypic slice cultures can be a powerful tool for elucidating strain-specific mechanisms of prion spread and pathology.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".