Altered calcineurin‐NFAT signaling in the hearts of NFATc2 null mice
Bibliographic record
Abstract
The Ca 2+ ‐ dependent phosphatase, calcineurin, and its downstream transcriptional effectors, nuclear factor of activated T‐cells (NFAT), are major intracellular modulators of cardiac hypertrophy. Transcription factor NFATc2 has recently been identified as the major NFAT isoform responsible for calcineurin‐mediated cardiac hypertrophy. We thus investigated the role of each NFAT isoform (c1–c4), the NFATc2 binding partner GATA‐4, and NFAT/GATA‐4 kinases in regulating the cardiac phenotype by assessing their expression at the transcript and protein levels in NFATc2 −/− mice. Cardiac mRNA and protein expressions of other members of the NFAT family were similar in wild type and NFATc2−/− mice, suggesting that individual NFAT isoforms are independently regulated. Expression of cytoplasmic GATA‐4 was unchanged whereas nuclear GATA‐4 was higher in hearts from NFATc2 −/− mice, indicating increased nuclear transit of this transcription factor in the absence of NFATc2. In support of this, the expression of MAPK, responsible for GATA‐4 DNA binding ability, remained unchanged whereas GSK3‐β, which promotes GATA‐4 nuclear export, was lower in NFATc2 −/− hearts. Taken together, our data identify molecular partners that may compensate for the lack of NFATc2, thereby providing further insight towards understanding calcineurin‐mediated cardiomyopathy. Supported by CIHR, NSERC and CRC to RNM.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".