Selective activation of hippocampal guanylyl cyclase by a novel NO mimetic nitrate ester
Bibliographic record
Abstract
Studies of the distribution of α1 and α2 subunits of soluble guanylyl cyclase (sGC) indicate that the α2 subunit is expressed in relatively high abundance in brain, and is the major alpha subunit present in the hippocampus. Furthermore, the α2 subunit interacts with a PDZ domain of PSD95, a scaffolding protein that couples the NMDA receptor to neuronal nitric oxide synthase. Thus a membrane-bound NO-sensitive sGC is present in the hippocampus, and has been suggested to be a component of a signal transduction complex important for modulation of synaptic transmission and plasticity. We recently completed a study in which a novel NO mimetic nitrate ester (GT1061) reversed cognitive deficits in a cholinergic depletion model of Alzheimer's disease [1]. Of interest was that comparison of sGC activation in broken cell preparations of aorta and hippocampus showed that GT1061 selectively increased enzyme activity in the hippocampus (16to 20-fold in hippocampus vs. 2to 3 fold in aorta), suggesting that the enhanced activation of hippocampal sGC by GT1061 could be due to selectivity of the drug for targeting the α2β1 isoform of sGC.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".