PDE6s generate cGMP microdomains in native endothelial cells
Bibliographic record
Abstract
Cyclic GMP (cGMP) is a key messenger for cellular functions including ion channel regulation and gene expression. Nucleotides microdomains have a significant impact on cellular function. Phosphodiesterases (PDEs) play a prime role in the regulation of these functions through hydrolysis of cGMP and thus regulation of cGMP levels. Endothelial PDEs were studied for their impact on local cGMP levels. PDE5 and PDE9 are cGMP‐specific PDEs expressed in endothelial cells. Interestingly, the retina‐confined PDE6 have also been found in freshly isolated native endothelial cells by qPCR and immunostaining. Although PDE5 and PDE6γ are homogeneously distributed, PDE6α and PDE6β are mainly found in the perinuclear region. While PDE6β forms a continuous ring, PDE6α are distributed in clusters within the same region. Mathematical modeling revealed the dissimilar role of PDE5 and PDE6s in the spatial regulation of local cGMP following a bolus of NO. The presence of PDE6s near the nucleus suggests a potential role in the regulation of transcription factors. Therefore, endothelial PDEs and more specifically PDE6, might play a significant role in the control of cGMP‐mediated cellular functions through the fine‐tuning of cGMP microdomains. Supported by FRQS, HSFC and NSERC.
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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 | 0.000 | 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".