Cockroach Allergen Proteinases Regulate Proteinase‐Activated Receptor‐1 (PAR1) Signalling
Bibliographic record
Abstract
Objective To assess potential pro‐fibrotic PAR1 MAPKinase signaling by cockroach allergen‐derived trypsin‐like proteinases. Methods Cockroach allergen‐derived trypsin‐like enzymes, known to cause lung inflammation, were identified with serine proteinase activity‐based probes (ABP). Enzymes were purified (ion‐exchange chromatography) and analyzed for their ABP reactivity & substrate‐inhibitor kinetic profiles. Each enzyme was evaluated for causing calcium (Fluo‐4) and MAPKinase signaling (western blot) in PAR1‐expressing KNRK cells. Additionally, the cleavage‐internalization of fluorescently‐tagged PAR1 constructs was monitored as an index of receptor activation. Results Cockroach allergen contained three ABP‐labeled 20–26 kDa MW proteinases with distinct enzyme kinetics. The allergen‐derived enzymes activated PAR1 MAPK and calcium signaling, but with distinct concentration‐effect kinetics. PAR1 cleavageinternalization caused by the allergen proteinases was similar to that caused by trypsin, but NOT thrombin. Conclusions Cockroach allergen contains three different trypsin‐like proteinases that can activate “biased” PAR1 pro‐fibrogenic MAPKinase (but not Ca++) signaling pathways. We suggest that the allergen proteinases can act as pro‐fibrotic factors in the setting of airway allergic inflammation and asthma. Support: CIHR, NIH USA and Lung Assn. of AB & NWT
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".