Abstract 463: Circadian <i>Clock</i> Disruption Promotes Cardiac Cell Death During Hypoxic Injury
Bibliographic record
Abstract
Circadian rhythms play a fundamental role in cell metabolism and tissue homeostasis as well as in the diurnal oscillation of physiological processes such as blood pressure. Zeitgebers influence the circadian rhythms by serving as molecular switches for re-setting the intrinsic cellular clock. Herein, we show that oxygen is a Zeitgeber for the circadian rhythm and regulator of clock gene expression in cardiac myocytes. We further show that clock gene regulation promotes survival of cardiac myocytes by a mechanism that bi-directionally influences mitochondrial clearance and autophagy. Cardiac myocytes exhibited phasic oscillations in clock gene expression under basal conditions which was disrupted during hypoxia. This was accompanied by a marked time dependent decline in clock gene transcription that was maximal at ZT+18 and coincided with a reciprocal increase in mitochondrial clearance. Loss of function mutations of clock that disrupted nuclear localization or DNA binding to BMAL-1 promoted wide-spread cell death. Hence, the findings of the present study provide a novel signaling axis that operationally links hypoxia regulated clock gene expression and mitochondrial turn-over to cell survival.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".