A microscopy reporter for cGAMP reveals rare cGAS activation following DNA damage, and a lack of correlation with micronuclear cGAS enrichment
Bibliographic record
Abstract
Summary Cyclic GMP-AMP (cGAMP) synthase (cGAS) is the primary intracellular responder to pathogen DNA. Upon DNA-binding, cGAS generates cGAMP, which binds to STING, ultimately driving inflammatory signalling. Although normally silenced on self-DNA, cGAS can be activated during genotoxic stress. A universal by-product of these conditions are micronuclei, which accumulate cGAS, and which are therefore thought to be major cGAS activators. However, due to the inability to visualise cGAS activation in single cells, this hypothesis remains largely untested. Here we solve this question with an improved intracellular cGAMP reporter, which is compatible with microscopy, flow-cytometry and plate reader setups. Surprisingly, cGAS activation in response to multiple types of genotoxic stress is limited to a subfraction of cells and does not correlate with cGAS enrichment in micronuclei. Overall, our findings suggest a revised model of innate immune signalling in response to genotoxic stress, and introduce a novel and flexible tool with which to examine this model in future.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".