Anisomycin Activates Utrophin Upregulation Through a p38 Signaling Pathway
Bibliographic record
Abstract
Duchenne muscular dystrophy is a recessive X-linked disease characterized by progressive muscle wasting; cardiac or respiratory failure causes death in most patients by the third decade. The disease is caused by mutations in the dystrophin gene that lead to a loss of functional dystrophin protein. Although there are currently few treatments for Duchenne muscular dystrophy, previous reports have shown that upregulating the dystrophin paralog utrophin in Duchenne muscular dystrophy mouse models is a promising therapeutic strategy. We conducted in silico mining of the Connectivity Map database for utrophin-inducing agents, identifying the p38-activating antibiotic anisomycin. Treatments of C2C12, undifferentiated murine myoblasts, and mdx primary myoblasts with anisomycin conferred increases in utrophin protein levels through p38 pathway activation. Anisomycin also induced utrophin protein levels in the diaphragm of mdx mice. Our study shows that repositioning small molecules such as anisomycin may prove to have Duchenne muscular dystrophy clinical utility.
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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 | 0.001 |
| 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".