1‐Oleoyl‐2‐acetyl‐glycerol (OAG) dependent Ca2+ influx is inhibited by dominant negative TRPC6 in human microvascular endothelial cells
Bibliographic record
Abstract
Ca 2+ signaling in endothelial cells plays a key role in maintaining the barrier function between blood vessel and tissues. The canonical transient receptor potential (TRPC) ion channel are considered important in Ca 2+ signal generation, but their roles in human microvascular endothelial cells (HMVECs) remain elusive. We previously showed that VEGF, acting through DAG could increase cation entry into HMVECs through a store independent process consistent with TRPC6 activation. To assess the response of HMVECs expressing endogenous, overexpressed and dominant‐negative TRPC6 channels to OAG, a structural analog of DAG, VEGF and other agents, adenoviruses were generated that encoded the DN‐TRPC6 or WT TRPC6 cDNAs (courtesy of Wiloliam Cole, University of Calgary). Calcium concentration was assessed in 20μM Fura‐2AM‐loaded HMVEC. Fluorescence intensity of the dye at 340nm excitation to that at 380nm (R norm ) was measured. OAG (200uM) induced an increase in R norm ‐ indicating increased calcium ‐ in control transduced and WT TRPC6, but the OAG mediated increase in calcium was blocked by the dominant negative isoform of TRPC6 adenovirus. (p<0.05, Student Newman Keuls Post‐hoc ANOVA). In HMVEC cells, natively expressed TRPC6s are involved in DAG mediated calcium entry. DN‐TRPC6 may block this calcium entry either through inhibition of TRPC6 homodimers, or by blocking functional TRPC heterodimers. The effect of VEGF on DN‐TRPC6 HMVECs will also be presented.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".