Highly virulent Aerococcus viridans activates the RIPK3 signaling pathway, inducing necroptosis and inflammation in bovine mammary epithelial cells and murine mammary tissue
Bibliographic record
Abstract
Aerococcus viridans (A. viridans), a conditionally pathogenic bacterium widely present in the environment, has been increasingly detected in bovine mastitis; however, its pathogenic mechanisms remain unclear. Necroptosis is a form of programmed cell death associated with bovine mastitis. The objective was to elucidate molecular mechanisms underlying induction of acute infection by virulent A. viridans, in two infection models, in vitro (bovine mammary epithelial cells) and in vivo (murine mammary gland). Compared to an avirulent strain, virulent A. viridans induced significantly higher levels of late apoptotic/necrotic bMECs, accompanied by increased LDH release and markedly elevated secretions of IL-1β, TNF-α and IL-6. Furthermore, the highly virulent strain activated RIPK3 and phosphorylation of MLKL, whereas the avirulent strain failed to activate this pathway. In addition, the highly virulent strain also induced severe mammary tissue damage and inflammatory cell infiltration in vivo, with extensive acinar destruction and high expression of p-RIPK3 and p-MLKL in mammary tissues, consistent with in vitro findings. In both infection models, a specific RIPK3 inhibitor (GSK872) markedly alleviated inflammation and tissue injury, reduced cytokine release and downregulated RIPK3-MLKL signaling induced by the highly virulent strain. We concluded that the molecular mechanism by which a highly virulent strain of A. viridans induces mastitis was activation of an RIPK3-dependent necroptosis pathway, providing a theoretical basis for development of novel therapeutic strategies.
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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".