Intracellular proteases and sarcomere disassembly in neonatal cardiomyocytes
Bibliographic record
Abstract
Mammals lose the capacity to regenerate their hearts shortly after birth. Although it is known that neonatal cardiomyocytes need to undergo sarcomere disassemble for cytokinesis, the mechanism of this is unclear. We studied this in neonatal rat ventricular myocytes (NRVM). We performed immunofluorescence studies of multiple sarcomeric proteins in proliferating NRVM using confocal microscopy and time lapse imaging. We also developed a fluorescence activated cell sorting (FACS)‐based method to separate NRVM in different cell cycle stages. During NRVM division α‐actinin, troponin I and titin were completely disassembled. Both Z‐disk and M‐band ends of titin disassemble simultaneously. Interestingly, sarcomere disassembly begins promptly at late prophase, at the same time when the nuclear envelope breaks down. Reassembly of the myofibril starts when the nuclear envelope re‐forms. Western blot from cells separated into G0G1, S and G2M phases revealed that α‐actinin, troponin I and myosin binding protein C were most prominently degraded in the G2M phase. Live cell imaging of NRVM expressing Halo‐ tagged matrix metalloproteinase‐2 revealed a strong signal inside nuclei which is released into the cytosol when the nuclear envelope breaks down. This study suggests that a protease regulated in a precisely timed manner may be involved in the disassembly of the sarcomere during mitosis.
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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) | 0.000 | 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) | 0.001 | 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 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".