Region-Specific Quantification of 2-Hydroxyglutarate Enantiomers in Murine Brain during Mitochondrial Complex I Deficiency
Bibliographic record
Abstract
The Ndufs4 –/– mouse is a model of mitochondrial Complex I deficiency that contributes to altered production of the tricarboxylic acid cycle metabolites. We hypothesized that l -2-hydroxyglutarate ( l -2-HG) levels would be elevated in the pathologically affected regions of the Ndufs4 –/– mouse brain in parallel with metabolic acidosis. We employed a stable isotope dilution method for the concurrent quantification of l -lactate and the distinct 2-HG enantiomers in isolated mouse brain regions. While lactate levels were elevated, as expected in the Ndufs4 –/– brain, the levels of l -2-HG and the enantiomer d -2-HG were markedly reduced in a region-specific manner, and this decrease was also reproduced in the Ndufs4 –/– serum. The specific and reproducible decreases in 2-HG quantified in Complex I deficiency may have utility as a unique disease biomarker. Quantitative analysis of the mitochondrial proteome of the Ndufs4 –/– mouse brainstem indicated an increased abundance of l -2-HG dehydrogenase, suggesting that 2-HG enantiomers are metabolized in the Ndufs4 –/– mouse yielding FADH 2 to alleviate the bioenergetic deficit.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".