Effectiveness of Novel Borane−Phosphine Complexes in Inhibiting Cell Death Depends on the Source of Superoxide Production Induced by Blockade of Mitochondrial Electron Transport
Bibliographic record
Abstract
Central neurons undergo cell death after axotomy. One of the signaling pathways for this process is oxidative modification of one or more critical sulfhydryls in association with superoxide generation within mitochondria. Agents that reduce oxidized sulfhydryls are neuroprotective of axotomized retinal ganglion cells, and we hypothesized that this occurs via reversal of the effects of mitochondrial-produced superoxide. To study this, we measured the ability of the novel borane-phosphine complex drugs bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) and (3-propionic acid methyl ester)diphenylphosphine borane complex (PB2) to inhibit the death of neuron-like RGC-5 cells induced by perturbation of the mitochondrial electron transport chain. We found that borane-phosphine complexes prevent neuronal cell death from superoxide produced by the redox-cycling agent menadione and the complex III inhibitor antimycin A, which produce superoxide towards the cytoplasm and matrix, but not the complex I inhibitor rotenone, which produces superoxide in the matrix alone. The ability of these disulfide reductants to prevent cell death may be predicted by the topology of superoxide production with respect to the mitochondrial matrix and extramitochondrial space.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".