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Record W4387538480 · doi:10.1101/2023.10.10.561758

mTOR inhibits autophagy to facilitate cell swelling and rapid wound repair

2023· preprint· en· W4387538480 on OpenAlexafffund
Gordana Scepanovic, Rodrigo Fernández‐González

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsHospital for Sick ChildrenTed Rogers Centre for Heart ResearchUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsAutophagymTORC1Wound healingCell biologyPI3K/AKT/mTOR pathwayEmbryonic stem cellCell growthCellBiologyChemistryCancer researchSignal transductionApoptosisImmunologyBiochemistry

Abstract

fetched live from OpenAlex

SUMMARY Embryonic wounds repair rapidly, with no inflammation or scarring. Embryonic wound healing is driven by collective cell movements facilitated by the swelling of the cells adjacent to the wound. The mechanistic target of rapamycin complex 1 (mTORC1) is often associated with cell growth. We found that disrupting mTORC1 signalling prevented cell swelling and slowed down wound repair. Catabolic processes, such as autophagy, can inhibit cell growth. Using five-dimensional time-lapse microscopy, as well as pharmacological and genetic manipulations, we demonstrated that the number of autophagosomes decreased during wound repair, suggesting that autophagy must be tightly regulated for rapid wound healing. Quantitative image analysis showed that mTOR inhibition increased autophagy, and that activating autophagy prevented cell swelling and slowed down embryonic wound closure. Finally, reducing autophagy in embryos in which mTORC1 signalling was disrupted rescued rapid wound repair. Together, our results show that mTORC1 activation upon wounding negatively regulates autophagy, allowing cells to increase their volumes to facilitate rapid wound healing.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.037
GPT teacher head0.246
Teacher spread0.209 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations2
Published2023
Admission routes2
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicAutophagy in Disease and Therapy→French-language works237,207→