Acetylcholine Deficiency in Caenorhabditis elegans Induced by Hyperthermia Can Be Compensated by ACh-esterase Inhibition or Activation of GAR-3 mAChRs
Bibliographic record
Abstract
The nervous system is a target of hyperthermic failure of animal behavior. Caenorhabditis elegans can be used as an excellent model organism to investigate mechanisms underlying thermotolerance of nervous system. Inhibition of ACh-esterase by neostigmine produces rise in thermotolerance of C. elegans swimming induced by mechanical stimulus at constant temperature 36 °C. Protection of C. elegans behavior against heat stress by neostigmine indicates that hyperthermia induces ACh deficiency in the C. elegans nervous system which is one of the causes of hyperthermic failure of behavior. Activation of mAChRs by pilocarpine or oxotremorine M elevates behavior thermotolerance similarly with neostigmine while inhibition of these receptors by atropine has opposite effect. These results suggest that ACh protects C. elegans behavior against hyperthermia by binding with mAChRs. It is known that three G-protein coupled ACh receptors of C. elegans (GAR-1, GAR-2 and GAR-3) have sequence homology with five known subtypes of mammalian mAChRs. To identify mAChRs responsible for regulation of behavior response to hyperthermia we investigated effects of loss-of-function mutations in gar-1, gar-2 and gar-3 genes on the sensitivity of behavior thermotolerance to neostigmine and pilocarpine. Among them only loss-of-function gar-3 mutation caused insensitivity of C. elegans behavior thermotolerance to neostigmine and pilocarpine. Thus it is GAR-3 mAChR that mediates rise in behavior thermotolerance produced by ACh-esterase inhibitor neostigmine or agonists of mammalian mAChRs.
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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) | 0.000 | 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 | 0.000 |
| 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 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".