PDE6s are heterogeneously distributed in native endothelium of mesenteric arteries from mice
Bibliographic record
Abstract
Cyclic nucleotides (cGMP, cAMP) being key components of cellular pathways, their local levels are the core of important regulatory mechanisms. Although endothelium is the foremost vascular producer of NO, regulatory mechanisms of the NO/cGMP remain to be determined in endothelial cells. Polarity of native endothelial cells also suggests potential cyclic nucleotides microdomains. cGMP‐specific phosphodiesterases, PDE5 and PDE9, have previously been identified in endothelial cells. However, both active isoforms of retina‐restricted PDE6 (α & β) appear to be expressed in native endothelial cells as well. In opposition to PDE5 which is homogeneously distributed in endothelial cells, both PDE6s appear to be localized at the nuclear membrane interface as evidenced by confocal microscopy. However, α isoform is sparsely distributed while β forms a continuous perinuclear ring. Interestingly, PDE6s could not be detected in cultured endothelial cell lines. Dynamic mathematical modeling revealed that the experimental intracellular distributions of PDE6s and PDE5 have a significant impact on local cGMP levels, especially in the perinuclear region where cGMP levels are reduced significantly in response to a pulse of NO. Combined experimental and modeling results suggest that PDE6 might have a significant impact on cGMP‐dependent endothelial function in native arteries. Supported by FRSQ, NSERC and HSFC.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".