The bacterial serine protease inhibitor ecotin inhibits neutrophil elastase enzymatic activity in cystic fibrosis sputa
Bibliographic record
Abstract
Cystic Fibrosis (CF) airway disease is characterized by impaired mucociliary clearance, chronic, polymicrobial infections and robust, neutrophil-dominated inflammation. Pulmonary disease is the leading cause of morbidity and mortality in people with CF and is due to progressive airflow obstruction and ultimately respiratory failure. One of the earliest abnormalities in CF airway disease is the recruitment of neutrophils to the lungs. Neutrophil activation leads to the release of their intracellular content, including neutrophil elastase (NE), that damages lung tissues in CF. Our goal is to characterize a known bacterial NE inhibitor, ecotin, in the CF airway environment. Our results indicate that ecotins cloned from four Gram-negative bacterial species ( Campylobacter rectus , Campylobacter showae , Escherichia coli and Pseudomonas aeruginosa) inhibit NE activity in CF sputum samples in a dose-dependent manner. Although we observed differences in the NE-inhibitory activity of the tested ecotins with the Campylobacter homologs being the most effective in NE inhibition in CF sputa, none of the ecotins impaired the ability of human neutrophils to kill major CF respiratory pathogens, P. aeruginosa or S. aureus , in vitro . Overall, we demonstrate that bacterial ecotins inhibit NE activity in CF sputa without compromising bacterial killing by neutrophils.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".