Targeted expression of the non‐native Ca <sup>+2</sup> ‐buffering protein parvalbumin exacerbates the dystrophic phenotype in mdx mouse slow muscle fibers
Bibliographic record
Abstract
We set out to determine the impact of interfering with Ca +2 /CaMbased signaling in dystrophin‐deficient myofibers. We thus crossbred mdx mice with transgenic mice expressing the Ca +2 ‐ buffering protein parvalbumin (PV), driven by the fiber‐specific Troponin I slow promoter. This approach forced expression of this non‐native fast Ca +2 ‐regulatory protein in slow fibers. Consistent with impairments in the downstream Ca +2 /CaM‐regulated enzyme calcineurin (Cn), the nuclear localization of NFATc1 was reduced in fibers from mdx/PV mice. We also detected significant reductions in Cn activity in slow fiber‐rich soleus muscles of mdx/PV mice in the absence of any fiber type conversions. Examination of mdx/PV muscle fibers revealed significant reductions in utrophin A, a therapeutically relevant protein that can compensate for the lack of dystrophin in skeletal muscle. In accordance with lower levels of utrophin A, we noted a clear exacerbation of the dystrophic phenotype in mdx/PV slow fibers as exemplified by several pathological indices such as increased fiber size variability and number of centrally located nuclei. These results further establish Ca +2 /CaM‐based signaling as key to regulating expression of utrophin A in muscle. Moreover, they illustrate the therapeutic potential of targeting Ca +2 /CaM‐ based signaling intermediates as well as strategies aimed at promoting the slow oxidative myofiber program in muscle, as effective countermeasures for Duchenne muscular dystrophy.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".