Bibliographic record
Abstract
Piezo1 in the Lung: At Last!The search for a mechanosensitive ion channel that accounts for flow-induced vasoactivity led to the recent identification of Piezo1, a homotrimeric membrane-spanning protein complex that responds directly to mechanical distortion of the plasma membrane.In mice with endothelium-specific Piezo1 knockout (Piezo1DEC), embryonic lethality occurs around embryonic day 9.5-11.5, the age that corresponds to the formation of the circulatory system, identifying this endothelial channel as a major determinant of vascular development (1).In Piezo1-transfected kidney cells, shear rates as low as 5-10 dyn/cm 2 (a range relevant to shear rates in lung microvessels) induced Piezo1-dependent endothelial Ca 21 increases, revealing the channel's shear-sensitive properties.Taken together, these and similar findings (2) have supported the hypothesis that endothelial Piezo1 plays a central role in the mechanotransduction of vascular shear (3).The story, however, becomes complicated when we consider Piezo1's role as a regulator of organ perfusion.The channel is permissive to nonspecific cation transport, allowing cellular entry of divalent ions such as Ca 21 , as well as monovalent ions such as Na 1 .Because Ca 21 -dependent nitric oxide (NO) production causes vasorelaxation (4), and cellular depolarization after Na 1 entry causes vasoconstriction (5), the net vascular outcome in terms of organ perfusion depends on the balance between these opposing effects of nonspecific ion entry.In a study by Rode and colleagues (5), increases of flow in isolated mesenteric arteries induced vasoconstriction, an effect that was absent in the arteries of Piezo1DEC mice, implicating Piezo1 in the effect.Endothelial cells isolated from the arteries displayed flow-induced, Piezo1-dependent membrane depolarization, consistent with the notion that flow induces an inward current through the channel.The authors showed that because of endothelial-smooth muscle coupling, the endothelial depolarization caused voltage-gated Ca 21 entry in smooth muscle, which therefore caused the vasoconstriction.They proposed the fascinating hypothesis that this Piezo1 mechanism optimizes exercise performance by redistributing blood flow away from vasoconstricted nonmuscle beds, such as the mesentery, to skeletal muscle.By contrast, Wang and colleagues, who also studied responses in isolated, precontracted mesenteric arteries, found the opposite, namely, that flow caused Piezo1-induced vasorelaxation, and that the effect was absent in arteries obtained from Piezo1DEC mice (6).Thus, unlike Rode and colleagues, Wang and colleagues implicated Ca 21 entry through endothelial Piezo1 as the critical mechanism underlying the vasorelaxation.Wang and colleagues showed that the vasodilatation results from a mechanistic sequence initiated by Ca 21 -induced release of endothelial ATP, which then signals through the P2Y2 receptor to cause Akt-induced endothelial NO synthase activation, and hence NO release.Interestingly, induced deletion of endothelial Piezo1 caused systemic hypertension and
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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) | 0.001 | 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 | 0.002 |
| 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".