A calcium‐independent PKC isoform mediates cerebral vasoconstriction through actin cytoskeleton reorganization (841.2)
Bibliographic record
Abstract
The role of PKC in force production and vasoconstriction in resistance arterioles is hypothesized to be through several mechanisms including: increased calcium influx, calcium sensitization, and thin filament regulation. PKC involvement in these pathways was proposed based on pharmacological experiments without direct biochemical measurement of the phosphoproteins. We studied the effect of phorbol dibutyrate (PDBu, 1 microM) on rat middle cerebral artery in a pressure myography setup. A slow profound constriction was obtained as a result of PDBu treatment. The constriction was associated with increased myosin light chain (LC20) phosphorylation that was similar to that evoked by a maximal dose of 5‐HT producing a smaller constriction. PDBu constrictions were abolished by GF109302X, but neither with a calcium‐dependent PKC inhibitor, nor with calcium‐free Krebs’, though the latter reduced LC20 phosphorylation. There was no evidence of increased phosphorylation of caldesmon and calponin, ruling out a role for thin filament regulation. G‐actin content was greatly reduced in both regular and calcium‐free Krebs’ solution together with an increase in paxillin phosphorylation in both conditions implicating actin cytoskeleton reorganization as a potential mechanism contributing to force generation independent of LC20 phosphorylation following PKC activation. Grant Funding Source : Supported by CIHR MOP‐97988
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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) | 0.000 | 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) | 0.003 | 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".