Differences in susceptibility to nutrient‐induced cell death between primary and immortalized Leigh Syndrome French Canadian type (LSFC) patient fibroblasts
Bibliographic record
Abstract
LSFC is a monogenic metabolic disease resulting from a mutation in the leucine‐rich pentatricopeptide repeat‐containing (LRPPRC) gene. It is characterized by cytochrome c oxidase (COX) deficiency and episodes of lactic acidosis leading to death at an early age. Recently, we reported that primary (P) LSFC fibroblasts were more susceptible than controls to necrosis induced by nutrient overload (palmitate 1 mM and lactate 10 mM), an effect associated with a lower [ATP] (FASEB J 2011 25:722.15). In this study, we compared P and immortalized (I) LSFC and control fibroblasts. Under basal conditions, control P and I cells displayed similar characteristics regarding (i) LRPPRC localization (immunocytochemistry) and content (Western) as well as (ii) COX activity. Both these parameters showed the expected decrease in LSFC P and I cells. However, compared to P cells, I cells from both groups had higher citrate synthase activity (~25%) and lower [ATP] (~40%). Accordingly, during nutrient overload, I cells were more susceptible than P cells to both necrosis and apoptosis. While this was observed for control and LSFC cells, LSFC I cells remain more susceptible to necrosis compared to their control counterpart. Collectively, our results highlight differences between P and I cells that ought to be considered for data interpretation and study design. (Supported by: Association de l'acidose lactique and CIHR Emerging Team Grant)
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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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".