Microtubule-Connexin-43 regulation suppresses arrhythmias and fibrosis in Duchenne muscular dystrophy mice
Bibliographic record
Abstract
ABSTRACT Dilated cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD) patients due to advancements in skeletal muscle therapies yet limited presence of cardiac treatments. The phosphorylation status of gap junction protein Connexin-43 (Cx43) drives Cx43 remodeling and the development of arrhythmias and fibrosis. Based on evidence that Colchicine drug treatment improves Cx43 phosphorylation and remodeling, we compared the microtubule cytoskeleton in DMD mice (mdx) versus mdx mice genetically altered to be Cx43-phosphorylation-deficient (mdxS3A). Reciprocally, we analyzed the microtubule cytoskeleton in mdx mice genetically altered to be Cx43-phospho-mimicking (mdxS3E). We found a link between the phospho-status of Connexin-43 and regulation of microtubule organization, in which phospho-dead Cx43 (S3A) inhibits improvements seen with Colchicine treatment in mdx mice, and phospho-mimic S3E promotes microtubule reorganization in mdx mice. A reduction in arrhythmias and fibrosis suggests an unsuspecting Cx43-microtubule link for translational corrective activities for DMD cardiomyopathy.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 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 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".