PB0424 The Critical Role of Filamin a in the Platelet Shape Change Reaction
Bibliographic record
Abstract
responses lead to tissue damage and uncontrolled coagulation in a process called immunothrombosis.In nucleated cells, the activation of the immune receptor cGAS by Self-or microbial-DNA results in the production of cGAMP, that binds to and activates the adaptor protein STING to induce the production of type-I Interferon and other pro-inflammatory cytokines.Interestingly, STING activation has been reported to contribute to immunothrombosis during sepsis and COVID-19.Aims: However, it is currently unknown whether the proteins from the cGAS-STING pathway are expressed in platelets and their mother cells the megakaryocytes.To fill this gap, we characterized the presence and function of these proteins in both cell populations.Methods: To complete this study, we relied on platelets and bone marrow megakaryocytes isolated from wt and cGAS-/-mice.Results: Here, we reveal for the first time that the proteins from the cGAS-STING pathway are expressed and functional in mouse bone marrow megakaryocytes.As such, STING stimulation of megakaryocytes drives the production of CCL5 and of type-I Interferon, both critical regulators of hematopoiesis.We also report that mouse platelets express cGAS, which produces cGAMP upon DNA stimulation.Furthermore, we reveal that cGAS and STING stimulation of platelets potentiates the aggregation of platelets and the membrane translocation of P-selectin.Conclusion(s): Taken together, our data unveil a new and intriguing role for the cGAS-STING axis in megakaryocytes and platelets and suggest that activation of cGAS and STING could contribute to both immune responses and coagulation.Whether this pathway directly fuels immunothrombosis will however necessitate further studies.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.003 |
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".