Amyloidogenesis: historical and modern observations point to heparan sulfate proteoglycans as a major culprit
Bibliographic record
Abstract
Amyloids are complex tissue deposits and each type is identified by one of 22 different proteins or peptides which become re-folded into non-native conformational intermediates and then assemble into fibrils of a highly regular structure. All amyloid deposits also contain apolipoprotein E (apoE) as well as the basement membrane (BM) components, serum amyloid P and heparan sulfate proteoglycans (HSPG), perlecan or agrin. These BM components likely contribute to the overall organization of amyloid fibrils and HSPG has been further implicated in the genesis of amyloid. A growing body of evidence, summarized in this review, suggests that heparan sulfate (HS) promotes fibrillogenesis by associating with the amyloid precursors and inducing the conformational change required for their assembly into fibrils. HS also remains associated with the nascent fibrils contributing to its stability. These activities of HS are likely mediated through specific binding sites on the precursor proteins which appear to have sequence characteristics that are unique to amyloid.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".