Spontaneous DNA Extracellular Trap Formation and Th2-biased Immune Responses in Cystic Fibrosis-like Airways of Mice with Lung-specific Nedd4-2 Ubiquitin Ligase Deletion
Bibliographic record
Abstract
Extracellular DNA exerts major pathological effects in cystic fibrosis (CF) airways. However, the cause for increased DNA and the contribution of neutrophil extracellular traps (NETs) in cystic fibrosis (CF) airways is uncertain. Additionally, suitable mouse models to study CF lung disease are lacking. We investigated the inflammatory profile and the presence of NETs in a novel mouse model with cystic fibrosis-like lung disease (Nedd4L lung-specific knockout; NL-KO). Our studies show that NL-KO mice have a Th2-biased background inflammation, spontaneous leukocyte infiltration and NET formation in their airways. Overall, inflammatory changes in NL-KO mouse airways occur age-dependently and spontaneously in the absence of detectable infection. Furthermore, NL-KO mice challenged with LPS and P. aeruginosa have an exacerbated inflammatory profile and impaired bacterial clearance, respectively. In conclusion, we show the relevance of NL-KO mouse model to study inflammation, infection, and the role of NETs in CF-like lung disease.
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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) | 0.002 | 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".