Molecular Mechanics of Smooth Muscle Contractile Proteins in Airway Hyperresponsiveness and Asthma
Bibliographic record
Abstract
Airway hyperresponsiveness (AH) is a hallmark of asthma. The dynamics of the airway smooth muscle (SM) contraction, rather than its force-generating capacity, have been postulated to be key features of AH. Two mechanisms were proposed whereby an increased velocity of shortening (Vmax) of the airway SM leads to excessive bronchoconstriction. The first mechanism involves a greater Vmax during the initial portion of contraction, whereas the second mechanism implicates a greater Vmax after muscle stretches, such as after each tidal breath. This review focuses on the components of the contractile apparatus that have so far been reported to enhance the mechanics of the myosin molecular motor, thus leading to a greater Vmax. A greater activation of myosin, via increased phosphorylation of its regulatory light chain (LC20) by myosin light chain kinase, correlates with an increased Vmax in models of AH and in human asthmatic bronchial SM cells. However, poor correlations between these two parameters have also been reported in other models. A greater expression of the fast SM myosin heavy chain isoform [(+)insert or SM-B] also correlates with the greater Vmax measured in models of AH and in human asthmatic bronchial SM cells. However, the (+)insert isoform can only explain a twofold increase in Vmax, as extrapolated from its velocity of actin filament propulsion in the in vitro motility assay. Further considerations are given to the combination of these two factors with other components of the contractile machinery, thereby leading to the enhancement of airway SM function.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".