Primary cilium restricts TGF-β/SMAD signaling induced RIBEs in the co-culture model.
Why this work is in the frame
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Bibliographic record
Abstract
Transforming growth factor β (TGF-β) is the predominant cytokine responding to ionizing radiation and participates in radiation induced bystander effects (RIBEs). Primary cilia (PC) coordinates with multiple signaling pathways, exhibit specialized functions in TGF-β signal transduction. Our previous studies using a medium transfer model revealed that PC modulates RIBEs by restricting TGF-β signaling. To further investigate PC's mechanistic role in RIBEs, proton microbeam radiation (MR) and partial radiation (PR) were used to arrange the co-culture bystander system. Key methodologies included siRNA-mediated PC formation modulation, inhibition of DNA damage response kinases ataxia telangiectasia-mutated gene (ATM), Ataxia telangiectasia and Rad3-related protein (ATR) or DNA-dependent protein kinase (DNApk), and quantitative analysis of γH2AX foci, cell proliferation, and reactive oxygen/nitrogen species (ROS/NO). The results showed that, firstly, PC inhibition in both PR and MR models significantly increased γH2AX foci formation and protein levels within 12 h while suppressing cell proliferation, which were reversed by TGF-β signaling inhibition. Secondly, although inhibition of ATM, ATR, or DNApk reduced γH2AX foci but resulted in decrease of proliferation rate. Scavenging ROS/NO similarly attenuated DNA damage but enhanced cell survival. Third, SMAD2/3 complex inhibition in PC-deficient bystander cells downregulated ATM/ATR expression and reduced intracellular NO/ROS levels. These results demonstrate that TGF-β1 drives RIBEs-associated DNA damage through canonical p-SMAD2/3 signaling, which amplifies ROS/NO production and hyperactivates ATM, ATR or DNApk. Crucially, PC acts as a regulatory role in DNA damages of RIBEs progression.
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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 it