Exploring the role of the unique N‐termini of PDE4D variants in regulating mural cell morphology, migration and cAMP signaling (1065.1)
Bibliographic record
Abstract
Mural cells act adaptively to regulate vascular tone. After vascular damage, adoption of a synthetic phenotype increases proliferative and migratory capacity and aids in repair. Exaggerated, maladaptive responses can promote intimal hyperplasia, atherosclerotic lesion progression and arterial (re)stenosis. cAMP acting on protein kinase A (PKA) or exchange protein activated by cAMP (EPAC) regulate mural cell migration and adhesion. A cAMP signalosome in the leading edge of migrating mural cells contains PKA and phosphodiesterase (PDE) 4D8 and regulates actin assembly and migration. PDE4D isoforms share a common catalytic domain and C‐terminus. PDE4 inhibitors are non‐selective with respect to the individual PDE4 variants and compete with cAMP binding at the active site. The unique N‐termini of PDE4D isoforms are hypothesized to mediate selective protein‐protein based tethering to distinct subcellular domains. We examined the subcellular targeting, function and binding partners of the unique N‐termini of mural PDE4D variants and their impact on cAMP signalling. We show that these N‐terminal regions are important in regulating mural cell morphology, migration and adhesion. Grant Funding Source : Supported by Canadian Institutes of Health Research
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".