Subcellular, biochemical and biophysical alterations in two glial cell models of ARSACS
Bibliographic record
Abstract
Abstract Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a developmental and degenerative disorder caused by loss-of-function mutations in the gene that codifies for the sacsin chaperone. Sacsin was initially described as a neuronal protein but is found in various cell types, including astroglial, microglial, kidney, and skin cell lines. We and others have shown that virtually all cell and animal models of ARSACS show disruption of intermediate filament (IF) cytoskeleton and organelle distribution. This article extends previous observations from our lab on the C6 astroglial-like model and describes the development and characterization of a new human microglial cell model based on HMC3 cells. HMC3 cells knocked out for sacsin show similar alterations to C6 astroglial-like cells: aberrant distribution of IF network and organelles, downregulation of developmental transcription factors STAT3 and Smad1, and alterations in autophagy machinery and markers of intracellular stress, resulting in morphological changes. Our results extend previous observations suggesting a possible role for glial cells in ARSACS and provide new tools to understand the glial-specific mechanisms involved in this pathology.
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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 | 0.001 | 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".