Signal Transduction and Gene Regulation in the Endothelium
Bibliographic record
Abstract
Extracellular signals act on G-protein-coupled receptors (GPCRs) to regulate homeostasis and adapt to stress. This involves rapid intracellular post-translational responses and long-lasting gene-expression changes that ultimately determine cellular phenotype and fate changes. The lipid mediator sphingosine 1-phosphate (S1P) and its receptors (S1PRs) are examples of well-studied GPCR signaling axis essential for vascular development, homeostasis, and diseases. The biochemical cascades involved in rapid S1P signaling are well understood. However, gene-expression regulation by S1PRs are less understood. In this review, we focus our attention to how S1PRs regulate nuclear chromatin changes and gene transcription to modulate vascular and lymphatic endothelial phenotypic changes during embryonic development and adult homeostasis. Because S1PR-targeted drugs approved for use in the treatment of autoimmune diseases cause substantial vascular-related adverse events, these findings are critical not only for general understanding of stimulus-evoked gene regulation in the vascular endothelium, but also for therapeutic development of drugs for autoimmune and perhaps vascular diseases.
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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) | 0.001 | 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".