Lipopolysaccharide (LPS) plus hypoxia and reoxygenation (H/R) reduces electrical coupling between microvascular endothelial cells by dephosphorylating connexin40
Bibliographic record
Abstract
LPS or H/R decreases electrical coupling between mouse microvascular endothelial cells (hindlimb muscle origin) by targeting Cx40, PKA‐dependently. Since LPS can compromise microvascular blood flow, resulting in micro‐regional hypoxia and reoxygenation episodes, we examined the effect of combined LPS+H/R on coupling between these cells. To assess coupling, we measured the spread of electrical current injected into the cell monolayer and computed the monolayer intercellular resistance (inverse measure of coupling). In wild type cells, but not in Cx40 null cells, LPS (10μg/ml, 1h)+ H(1h)/R(10–30 min) increased resistance by ~200%, well above the level observed for LPS or H/R alone (~100%). PKA activation and serine phosphorylation of Cx40 are required for baseline Cx40 gap junctional coupling. By immunoprecipitating Cx40, we found that LPS or H/R reduced Cx40 serine phosphorylation by ~40%, while LPS+H/R reduced it by ~70%. Based on preliminary data, this reduction was prevented by PKA activation, and mimicked in control cells by PKA inhibition. We propose that LPS+H/R reduces inter‐endothelial electrical coupling by PKA‐sensitive serine dephosphorylation of Cx40. (Supported by CIHR and HSFO.)
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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 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".