Reduced Models of the Circadian Oscillators in <i>Neurospora crassa</i> and <i>Drosophila melanogaster</i> Illustrate Mechanistic Similarities
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Bibliographic record
Abstract
We have developed a reduced model representing feedback loops of transcriptional regulation underlying circadian rhythms in Neurospora crassa. The model contains two delay differential equations that describe the dynamics of two core gene products, FRQ and WCC. In a negative feedback loop, FRQ protein represses frq transcription by binding the white-collar complex (WCC), which consists of the WC-1 and WC-2 proteins. In a positive feedback loop, WCC indirectly enhances its own formation. The model simulates circadian oscillations, light entrainment, and a phase-response curve (PRC) similar to experimental PRCs. The Neurospora model is virtually identical to a model describing Drosophila circadian rhythm generation, illustrating that rhythm generation in these divergent organisms shares important mechanistic elements. Significant dynamic differences were found when the parameter spaces of both models were explored to analyze changes in oscillations and bifurcations to steady states. Stochastic fluctuations in molecule numbers were simulated with the Gillespie algorithm. Circadian oscillations and entrainment to light were simulated with <80 molecules of FRQ and WCC present on average. Simulations suggest that in both Neurospora and Drosophila, only the negative feedback loop is essential for circadian oscillations. Similar models may aid understanding of circadian mechanisms in mammals and other organisms.
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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 | 0.001 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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