ApoNETosis: discovery of a novel form of neutrophil death with concomitant apoptosis and NETosis
Bibliographic record
Abstract
Neutrophils are the most abundant leukocyte in the human body. They have a short lifespan (average of 7 hours to 5.4 days) and types of neutrophil death affect many inflammatory and autoimmune disease states. Neutrophils have classically been known to die by apoptosis. A novel form of neutrophil death leading to the release of extracellular traps (NETs) that is different from apoptosis was discovered in 1996 1 . In the past decade, mechanistic details of NET formation (NETosis) have been studied in greater detail 2 , 3 . NETosis has now been defined as a unique form of cell death that is completely independent from apoptosis 1 , 2 . We have recently reported that higher doses of ultraviolet (UV) induce both apoptosis and NETosis in the same neutrophil, in Cell Death Discovery 4 . In this novel form of neutrophil death, ApoNETosis, NETotic steps override certain key apoptotic steps (Fig. 1 ). ApoNETosis, apoptosis, NETosis, and other forms of neutrophil death have unique similarities and differences, and understanding molecular steps regulating ApoNETosis could help to explain certain pathobiological conditions. Fig. 1: The key steps of UV-induced apoptosis and ApoNETosis. The alternative text for this image may have been generated using AI. Full size image Low dose UV irradiation induces low levels of mitochondrial ROS, cytochrome c release, caspase cascade activation, and finally nuclear condensation and blebbing. On the other hand, high dose UV irradiation results in large amounts of mitochondrial ROS, cytochrome c release, and caspase cascade activation. However, p38 activation and transcriptional firing are also induced, resulting in MPO-coated NET formation and NET release.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".