Sexual dichotomy in calcium buffering capacity may be dependent on the severity of endoplasmic reticulum stress in the skeletal muscle of the vitamin D3 deficient transgenic G93A mouse model of amyotrophic lateral sclerosis
Bibliographic record
Abstract
Background We previously demonstrated that dietary vitamin D 3 (D 3 ) restriction hastened the decline in functional capacity following disease onset in the G93A mouse model of amyotrophic lateral sclerosis (ALS). ALS is a progressive neuromuscular disease characterized by the degeneration and death of motor neurons. Objective In this pilot study, we analyzed the quadriceps of G93A mice following dietary D 3 restriction at 2.5% the adequate intake for vitamin D receptor and markers of intracellular calcium trafficking (calbindin d28k, calretinin), endoplasmic reticulum (ER) stress (SERCA2, CHOP) and apoptosis (bax/bcl2 ratio, caspase 12 cleaved/pro ratio). Methods Beginning at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D 3 /g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D 3 /g feed; 10 M, 9 F) D 3 . At age 113 d, the quadriceps were analyzed for protein content. Differences were considered significant at P ≤ 0.10. Results In females, DEF had 30% lower calbindin d28k (P = 0.075), 69% higher cleaved/pro caspase 12 ratio (P = 0.100), and 103% higher bax/bcl2 ratio (P = 0.057) vs. AI. DEF males had 67% higher CHOP (P = 0.048) vs. AI. Conclusion Dietary D 3 at 2.5% the AI reduces calcium buffering capacity and increases prolonged ER stress‐induced apoptosis in female, but not in male, G93A mice. We hypothesize a reciprocal interaction between ER stress and calcium buffering. (Supported by NSERC and Faculty of Health, York University) Grant Funding Source : NSERC and Faculty of Health, York University
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".