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Record W3009846583 · doi:10.1101/gad.332643.119

The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice

2020· article· en· W3009846583 on OpenAlex
Birgit Ritschka, Tania Knauer-Meyer, Daniel Sampaio Gonçalves, Alba Mas, Jean‐Luc Plassat, Matej Durik, Hugues Jacobs, Elisa Pedone, Umberto Di Vicino, Maria Pia Cosma, William M. Keyes

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueGenes & Development · 2020
Typearticle
Languageen
FieldMedicine
TopicTelomeres, Telomerase, and Senescence
Canadian institutionsnot available
FundersInstitute of GeneticsFondation ARC pour la Recherche sur le CancerMinisterio de Ciencia e InnovaciónUniversité de StrasbourgGeneralitat de CatalunyaAgence Nationale de la RechercheCentre de Regulació GenòmicaFondation Schlumberger pour l’Education et la RechercheCentres de Recerca de Catalunya
KeywordsSenescenceBiologyRegeneration (biology)Cell biologyLiver regenerationCellular senescenceGene expressionCancer researchGenePhenotypeGenetics

Abstract

fetched live from OpenAlex

Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16 Ink4a , and p19 Arf become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration.

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.

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 categoriesnone
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 score0.389
Threshold uncertainty score0.701

Codex and Gemma teacher scores by category

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

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 head0.026
GPT teacher head0.259
Teacher spread0.233 · 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