Abstract 025: Oxidative-stress Mediates Apoptosis in a Human Model of Danon Disease and Heart Failure
Bibliographic record
Abstract
Emerging evidence has highlighted the importance of autophagy, an intracellular recycling pathway, in regulating cardiomyocyte bioenergetics, function, and survival. However, the mechanisms responsible for cellular dysfunction and death in cardiomyocytes with impaired autophagic flux remain unclear. Danon disease is a familial cardiomyopathy associated with impaired autophagy due to mutations in the gene encoding lysosomal associated membrane protein type 2 (LAMP-2). To investigate the pathogenesis of Danon disease, we created iPS cells from a patient with a mutation in LAMP-2 who expired from heart failure. Danon iPS-derived cardiomyocytes recapitulated key features of the disease in vitro, including impaired autophagic flux, increased cell size, abnormal calcium handling, and increased expression of natriuretic peptides. Danon cells were noted to have significant amounts of mitochondrial oxidative stress and apoptosis, both of which could be abrogated by treatment with the antioxidant N-acetylcysteine. These results implicate mitochondrial oxidative stress and apoptosis in the pathogenesis of Danon disease. They also provide the basis for the use of antioxidants for Danon disease and other autophagy-related human diseases such as heart failure, diabetes, cancer, and neurodegenerative disorders.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".