The Deubiquitinase <scp>USP2</scp> Modulates Photic Entrainment of the Circadian Clock at the Level of the Suprachiasmatic Nucleus
Bibliographic record
Abstract
Ubiquitin-specific peptidase 2 (USP2) is a deubiquitinase (DUB) with a diversity of functions in physiology. One of these functions is the regulation of circadian rhythms, which are physiological rhythms with a period of ~24 h. Previous studies have indicated a role for USP2 in photic entrainment, the process by which circadian clocks synchronize to environmental light cues. Here, we investigated the implication of USP2 in this process, using Usp2 knockout (KO) mice. Using different light treatments and running wheel recordings, we established that USP2 controls entrainment of the clock to light cues at dusk. Further, we showed that Usp2 is expressed throughout the suprachiasmatic nucleus (SCN), the site of the central clock, and in the retina. This raised the question of where USP2 acts on circadian photoreception. We found that it is not within the retina, as retinas of Usp2 KO mice have an intact structure and unaltered photoreception through intrinsically photosensitive retinal ganglion cells. Moreover, KO of Usp2 within the retina does not alter clock entrainment to light. In contract, KO of Usp2 in the SCN causes a light entrainment phenotype similar to full-body KO mice, showing that the action of USP2 in modulating photic entrainment predominantly takes place in the SCN. Finally, within the SCN, we found that induction of clock gene Per1 and activation of MAPK/ERK pathway in response to light were blunted in Usp2 KO mice. Altogether, we established a key role for USP2 in regulating photic entrainment by modulating light-responsive pathways within the SCN.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".