The abstract is read at the publisher; the summary is JClub's.
A mechanistic ODE model of the canonical AhR pathway in murine bone-marrow-derived macrophages identifies a dominant regime where faster promoter binding governs Cyp1a1 and Ahrr dynamics across 3-methylcholanthrene, indolo[3,2-]carbazole, and bisphenol A.
- Why it matters: It is unclear which biochemical steps in the canonical AhR pathway drive distinct ligand-specific transcriptional responses, limiting mechanistic interpretation of immunomodulatory effects.
- What they did: The model was calibrated to time-resolved qPCR for Cyp1a1 and Ahrr mRNA in mouse bone-marrow-derived macrophages exposed to 3-methylcholanthrene, indolo[3,2-]carbazole, and bisphenol A, using global optimization under a heteroskedastic likelihood and comparing 528 candidate models with ligand-varying reaction rates.
- The result: Model selection supports promoter binding as the key differentiator, suggests indolo[3,2-]carbazole requires no ligand-specific parameter relative to 3-methylcholanthrene, and indicates promoter binding and transcriptional differences are better supported than upstream signaling events.
The findingWhy it mattersWhat they didThe result
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