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Regulation of 3‐methylindole metabolism by nuclear receptors

2012· article· en· W3176035604 on OpenAlexaff
Matthew Gray, E. James Squires

Bibliographic record

VenueThe FASEB Journal · 2012
Typearticle
Languageen
FieldAgricultural and Biological Sciences
TopicPharmacological Effects and Assays
Canadian institutionsUniversity of Guelph
Fundersnot available
KeywordsTransactivationPregnane X receptorConstitutive androstane receptorNuclear receptorMetabolismReceptorMetaboliteFarnesoid X receptorChemistryAgonistExcretionInternal medicineEndocrinologyGene expressionBiochemistryBiologyTranscription factorGeneMedicine

Abstract

fetched live from OpenAlex

Regulation of 3‐methylindole metabolism by nuclear receptors 3‐methylindole (3MI) is a known pneumotoxin that is found in naturally in fecal matter and is a major component of tobacco smoke; it is also a major component of boar taint, the accumulation of malodorous compounds in pigs that negatively impacts meat quality. We studied the effects transactivation of the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and farnesoid X receptor (FXR) on gene expression and the metabolism of 3MI in porcine hepatocytes. Real‐time PCR was used to determine the expression of key genes in agonist treated porcine hepatocytes, while the production of major 3MI metabolites over time was quantified by HPLC. FXR transactivation significantly (p<0.05) increased the expression of CYP2E1, which is crucial to 3MI metabolism, 1.29 (1.19,1.40) fold over the untreated controls. PXR transactivation increased CYP2A19 expression 1.24 (1.14, 1.36) and CYP2C49 expression 4.51 (3.64, 5.57) fold; both of these enzymes have been shown to play a role in 3MI metabolism in pigs. FXR transactivation stimulated the formation of 6‐hydroxy‐3‐methylindole, a metabolite crucial in the 3MI excretion pathway, by 1.86 fold over the untreated controls. CAR and PXR transactivation did not affect overall 3MI metabolism or the formation of major metabolites. FXR may thus play an important role in regulating the excretion of 3MI, thus helping prevent toxicity, as well as improving meat quality in boars.

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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
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)0.0020.001

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 head0.018
GPT teacher head0.235
Teacher spread0.216 · 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

Citations0
Published2012
Admission routes1
Has abstractyes

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