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 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 | 0.000 | 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 | 0.000 |
| 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".