Mitochondrial integrity is impaired in MELAS patients (LB164)
Bibliographic record
Abstract
Mitochondrial diseases are disorders that can be caused by either mitochondrial or nuclear DNA mutations. One of the most prominently studied mitochondrial diseases is mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS), caused by a mutation in the tRNA‐leucine gene within mtDNA. While the symptoms of this disease have been studied, the molecular manifestations of this mutation remain to be clearly understood. Since alterations in organelle function underlie the pathophysiology of various mitochondrial diseases, we explored mitochondrial morphology, cytochrome c oxidase activity, reactive oxygen species (ROS) production and mitochondrial membrane potential in patient (n=3) and control fibroblast cell lines (n=3). Cells transfected with Mito ds‐Red and visualized using confocal microscopy revealed an increase in mitochondrial fragmentation in cells from MELAS patients, compared to control, coincident with reduced cytochrome c oxidase activity, higher ROS production and a greater membrane potential. The increase in organelle fragmentation observed in MELAS cells led us to investigate the proteins which regulate mitochondrial fission (Fis1 and Drp1) and fusion (Opa1). Our data suggest that the increase in organelle fragmentation was due to a tendency for a higher expression of Fis1 in MELAS cells, suggesting that mtDNA mutations have consequences for the expression of nuclear‐encoded fission proteins, resulting in altered organelle morphology. Future work will investigate the use of fission protein inhibitors to ameliorate mitochondrial function in MELAS cells. Grant Funding Source : Supported by Mitacs and Panacea Global
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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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".