<i>Cdyl</i> Deficiency Brakes Neuronal Excitability and Nociception through Promoting <i>Kcnb1</i> Transcription in Peripheral Sensory Neurons
Bibliographic record
Abstract
Abstract Epigenetic modifications are involved in the onset, development, and maintenance of pain; however, the precise epigenetic mechanism underlying pain regulation remains elusive. Here it is reported that the epigenetic factor chromodomain Y‐like (CDYL) is crucial for pain processing. Selective knockout of CDYL in sensory neurons results in decreased neuronal excitability and nociception. Moreover, CDYL facilitates histone 3 lysine 27 trimethylation (H3K27me3) deposition at the Kcnb1 intron region thus silencing voltage‐gated potassium channel (K v ) subfamily member K v 2.1 transcription. Loss function of CDYL enhances total K v and K v 2.1 current density in dorsal root ganglia and knockdown of K v 2.1 reverses the pain‐related phenotypes of Cdyl deficiency mice. Furthermore, focal administration of a novel potent CDYL antagonist blunts nociception and attenuates neuropathic pain. These findings reveal that CDYL is a critical regulator of pain sensation and shed light on the development of novel analgesics targeting epigenetic mechanisms.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".