Abstract 021: Extended Proliferation Capacity of Cardiomyocytes is Insufficient to Complete Cardiac Regeneration in Mice with a Mutation of Cardiac Myosin Binding Protein C
Bibliographic record
Abstract
Introduction: Adult mammalian cardiac regeneration rate is inadequate to compensate for the loss of myocardium following injury. One-day old (P1) mice fully regenerate myocardium after ventricular apex resection by division of cardiomyocytes (CMs). This regeneration ability is lost by P7. While CMs of a P1 mouse are mostly mononuclear, CMs withdraw from cell cycle and become mostly binuclear in the first post-natal week. CMs in mice with a mutation of a sarcomeric cardiac myosin-binding protein C (MyBP-C t/t ) have an extended proliferating capacity. In MyBP-C t/t mice, there are more CMs per ventricle and a significant number of CMs remain mononuclear compared to WT. Hypothesis: The loss of regeneration potential during the first post-natal week in WT mice is a result of rigid sarcomeric structure of maturing CMs, and a mutation of sarcomeric MyBP-C would extend the regenerative capacity of CMs beyond P1. Methods: We performed apical resections on P10 MyBP-C t/t and WT mice with sham-operated controls (n=61 of 118 survived surgery). For the resection surgery, neonates were anesthetized on ice, causing transient sedation, apnea and asystole. We assessed cardiac regeneration over two weeks by measuring cell cycle activity: Ki67 and pH3 expressions, and BrdU incorporation. Results: All cell cycle activity markers in MyBP-C t/t CMs were significantly higher than in WT. At 7 days-post resection (dpr) the number of BrdU-positive CM nuclei per 40X field was (mean±SD): 1.8±1.2 in MyBP-C t/t resections (n=4), 0.7±0.3 in MyBP-C t/t shams (n=5), 0.3±0.3 in WT resections (n=3), and 0.2±0.2 in WT shams (n=3). However, an increase in cell cycle activity in MyBP-C t/t resected hearts was not significant compared to MyBP-C t/t sham controls. Interestingly, using VonKossa silver staining, we observed pronounced dystrophic calcifications due to CM necrosis in MyBP-C t/t resected hearts only. The calcifications filled the resected area and were positive for cardiac troponin and proliferation markers as early as 3dpr, suggesting that proliferating CMs underwent necrosis and aborted regeneration. Conclusion: An extended proliferation capacity of MyBP-C t/t CMs beyond the first post-natal week is insufficient for complete cardiac regeneration following apical resection.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".