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Record W2023683779 · doi:10.4161/tisb.23699

How do your contacts (or their absence) shape your fate?

2013· article· en· W2023683779 on OpenAlex

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueTissue Barriers · 2013
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicTGF-β signaling in diseases
Canadian institutionsUniversity of TorontoSt. Michael's Hospital
FundersCanadian Institutes of Health Research
KeywordsMyofibroblastCell biologyReprogrammingMyocardinCrosstalkBiologyTransforming growth factorEpithelial–mesenchymal transitionTranscription factorFibrosisTransforming growth factor betaActinCytokineCytoskeletonSerum response factorImmunologyDownregulation and upregulationCellGeneticsMedicinePathologyGene

Abstract

fetched live from OpenAlex

Tissue accumulation of contractile myofibroblasts is a key feature of a multitude of fibrotic diseases. Myofibroblast generation either from epithelial or mesenchymal precursors involves the activation of a myogenic program, hallmarked by the expression of α-smooth muscle actin (SMA). Recent research suggests that this robust phenotypic reprogramming requires two critical inputs: the fibrogenic cytokine transforming growth factor-β1 (TGFβ) and an injury (or absence) of intercellular junctions. This two-hit paradigm of epithelial-myofibroblast transition (EMyT) postulates that the injured (contact-deprived) epithelium is locally and selectively sensitive (topically susceptible) to the transforming effect of TGFβ, while the intact areas are quite resistant to the phenotype-changing effect of this cytokine. Searching for molecular mechanisms underlying the synergy between contact injury and TGFβ, we found that an interplay among three multifunctional transcriptional (co)activators, the junction component β-catenin, the TGFβ receptor target Smad3, and the actin cytoskeleton-regulated myocardin-related transcription factor (MRTF) controls the magnitude and timing of SMA expression.(1) Moreover, this regulation is realized not only at the transcriptional level. Notably, these factors form a pretranscriptional circuit, in which they impact each other's activity and stability. Based on this recent paper we ponder about the mechanisms of cellular plasticity in the context of EMyT. We propose that topical susceptibility to TGFβ, triggered by cell contact-modulated pretranscriptional and transcriptional control is realized through the crosstalk of a few master regulators, whose coordinated action tailors SMA expression and contributes to the major decision of whether injury leads to healing or fibrosis.

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 categoriesInsufficient 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 score0.291
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
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.019
GPT teacher head0.262
Teacher spread0.243 · 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