Oxytocin and parturition: a role for increased myometrial calcium and calcium sensitization?
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Preterm birth is associated with the majority of all death and chronic disability related to pregnancy, birth and the neonatal period. The costs to families and to the health care system are enormous. Current approaches to prevent or arrest preterm labour have been unsuccessful. This failure is largely based on our poor understanding of the regulation of the timing and maintenance of parturition. Oxytocin (OT) is the most potent known uterine stimulant. It is produced in the hypothalamus and secreted into the maternal bloodstream. However, OT also is produced within the uterine decidua in late gestation and the concentrations increase around the time of labour onset. The receptor for OT (OTR) is a G-protein coupled receptor linked through G alpha(q/11) to phospholipase C (PLC). Activation of PLC causes increased inositol trisphosphate (IP3) and diacyl glycerol (DAG). IP3 activates specific receptors in the sarcoplasmic reticulum to release Ca2+ into the cytosol. This may induce further influx of Ca2+ from the extracellular space and the increased Ca2+, after binding to calmodulin, activates myosin light chain kinase to phosphorylate myosin light chains (MLC) and cause contraction of the myocyte. DAG activates protein kinase C (PKC), several isoforms of which have been implicated in uterine contraction, but the substrates for this enzyme in the uterine myocyte are essentially unknown. Oxytocin may also cause "Ca2+-sensitization," a process whereby there is a greater contractile force generated from a given increase in cytosolic Ca2+, although the contribution of this process to myometrial contraction remains an area of debate. This phenomenon occurs mainly due to inhibition of myosin light chain phosphatase (MLCP), the enzyme that reverses the phosphorylation of MLC. There are several important potential mediators of this MLCP-inhibitory pathway in the myometrium, including the small monomeric G-protein RhoA, its downstream kinase Rho-associated kinase (ROK). and the 17-kDa PKC-potentiated inhibitor of protein phosphatase 1c (CPI-17). The roles in the myometrium of other recently identified MLCP interacting molecules also requires further investigation. These Ca2+-sensitization pathways could be important in the mechanisms underlying pre-term or term labour. An increased understanding of the complexities of the multitude of regulatory mechanisms for uterine contractility may lead to new pharmacologic agents for the prevention or reversal of uterine contractions. This, in turn, is necessary to facilitate the development of novel and effective strategies to reduce the incidence of preterm birth.
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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 | 0.001 | 0.001 |
| 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) | 0.000 | 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 it