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Record W4308620347 · doi:10.1016/j.isci.2022.105546

PERIOD 2 regulates low-dose radioprotection via PER2/pGSK3β/β-catenin/Per2 loop

2022· article· en· W4308620347 on OpenAlexfundno aff
Aris T. Alexandrou, Yixin Duan, Shanxiu Xu, Clifford G. Tepper, Ming Fan, Jason Tang, Jonathan Berg, Wassim A. Basheer, Tyler Valicenti, Paul F. Wilson, Matthew A. Coleman, Andrew Vaughan, Loning Fu, David J. Grdina, Jefferey Murley, Aijun Wang, Gayle E. Woloschak, Jian Jian Li

Bibliographic record

VenueiScience · 2022
Typearticle
Languageen
FieldNeuroscience
TopicCircadian rhythm and melatonin
Canadian institutionsnot available
FundersUniversity of Texas MD Anderson Cancer CenterOffice of ScienceNational Cancer InstituteNational Institutes of HealthUniversity of TorontoU.S. Department of Energy
KeywordsPER2HaematopoiesisCell biologyPeriod (music)Progenitor cellBiologyStem cellRadiosensitivityDNA damageCircadian rhythmCircadian clockCancer researchInternal medicineEndocrinologyMedicineCLOCKDNAGeneticsRadiation therapy

Abstract

fetched live from OpenAlex

During evolution, humans are acclimatized to the stresses of natural radiation and circadian rhythmicity. Radiosensitivity of mammalian cells varies in the circadian period and adaptive radioprotection can be induced by pre-exposure to low-level radiation (LDR). It is unclear, however, if clock proteins participate in signaling LDR radioprotection. Herein, we demonstrate that radiosensitivity is increased in mice with the deficient Period 2 gene (Per2def) due to impaired DNA repair and mitochondrial function in progenitor bone marrow hematopoietic stem cells and monocytes. Per2 induction and radioprotection are also identified in LDR-treated Per2wt mouse cells and in human skin (HK18) and breast (MCF-10A) epithelial cells. LDR-boosted PER2 interacts with pGSK3β(S9) which activates β-catenin and the LEF/TCF mediated gene transcription including Per2 and genes involved in DNA repair and mitochondrial functions. This study demonstrates that PER2 plays an active role in LDR adaptive radioprotection via PER2/pGSK3β/β-catenin/Per2 loop, a potential target for protecting normal cells from radiation injury.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScience and technology studies, Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.030
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0020.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.017
GPT teacher head0.235
Teacher spread0.218 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations10
Published2022
Admission routes1
Has abstractyes

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