Additional file 3 of Copper ions, prion protein and Aβ modulate Ca levels in central nervous system myelin in an NMDA receptor-dependent manner
Bibliographic record
Abstract
Additional file 3. Fig. S3. Schematic diagram of the proposed signaling arrangement of myelinic NMDARs and their regulation by Cu ions and PrPc. Action potentials conducted along myelinated axons release glutamate into the periaxonal space (Micu et al, 2016) which, together with the obligatory co-agonist glycine or D-serine, activates myelinic NMDARs resulting in physiological Ca increases in myelin. This is under potent control of Cu ions likely exerting their effects via PrPc ①. Genetic ablation of PrPc increases the sensitivity of NMDARs to agonist leading to increased myelinic Ca entry ②. Acute reduction of Cu levels in the periaxonal space by chelators such as BCS or Aβ1–42 impairs the ability of PrPc to regulate NMDARs resulting in excessive receptor activation and Ca-mediated injury to the myelin sheath. Thus, Cu ions in concert with PrPc may be fundamental regulators of physiological glutamatergic signaling across the axo-myelinic synapse; disruption of this mechanism may represent the earliest steps of demyelinating pathology.
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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 | 0.002 | 0.024 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.935 | 0.310 |
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".