<scp>LHON</scp>: A look into nuclear and environmental factors; What is “sufficient”?
Bibliographic record
Abstract
Purpose In Leber's Hereditary Optic Neuropathy ( LHON ) mutations of the mt DNA , are necessary but not sufficient for visual loss. We studied nuclear/environmental interactions in patients and in the Wallace LHON mouse model, to consider what is “sufficient”. The LHON mutation causes a modest decrease in ATP production, but a large increase in ROS production. Nuclear genetic and environmental factors may play upon these factors Methods We noted in the data of Kirkman et al (Brain 2009) that heavy smoking mitigated visual loss by delaying disease onset. We reproduced these peculiar results (Carelli et al, Brain 2013). We also studied the ND 6 mutant Wallace mouse model of LHON . 30 mice of 12 groups were sacrificed at 23 months including ND 6 mutant vs ND 6 wildtype and nicotinamide nucleotide transhydrogenase‐ NNT +/+ vs ‐/‐ ( NNT deletion), under different environments of air and smoke. 10 experiments compared the axonal nerve fiber spectrums. Results In our patient pedigrees, heavy smoking also mitigated visual loss, but we saw in this, the existence of two subtypes of LHON . Type I, with an abrupt and severe loss of vision in the teens, was characterized by severe losses of both structure and function. Type II occured decades later with a more insidious onset, with less structural than functional loss. Type II patients were more likely to smoke. In the mice, we found the predominant loss of small fibers in NNT −/− mice carrying the ND 6 mutation which were exposed to smoke. Conclusions Both nuclear modifiers and environmental factors in combination with LHON mutations can lead to vision loss. NNT is a transhydrogenase that couples hydride transfer from NAD (H) to NADP (+) and proton translocation across the inner mitochondrial membrane. NNT is potentially an important nuclear modifying gene for LHON .
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".