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Hypoxia‐regulated phenylethanolamine N‐methyltransferase expression

2008· article· en· W2253948680 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.

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSynthesis and Biological Activity
Canadian institutionsNOSM UniversityLaurentian University
Fundersnot available
KeywordsPhenylethanolamineLuciferasePhenylethanolamine N-methyltransferaseTransfectionCycloheximideChemistryMolecular biologyMessenger RNAHypoxia-inducible factorsMethyltransferaseHypoxia (environmental)Protein biosynthesisBiologyEnzymeCell biologyBiochemistryDNATyrosine hydroxylaseGeneMethylationOxygen

Abstract

fetched live from OpenAlex

Hypoxia is being used to identify mechanisms for stress‐induction of the epinephrine synthetic enzyme, phenylethanolamine N‐methyltransferase (PNMT). When PC12 cells transfected with a PNMT promoter‐luciferase reporter gene construct are exposed to hypoxia (5% oxygen), luciferase activity rapidly rises (6 hr) and is sustained for 72 hr. Signaling pathway inhibitor pre‐treatment prior to oxygen reduction abrogates induction and identifies two major signaling pathways, cAMP and phospholipase C (PLC). Downstream hypoxia inducible factor‐1α (HIF‐1α) and PNMT activators Egr‐1 and Sp1 are elevated. HIF‐1α co‐transfection or HIF‐1α activation by CoCl 2 and desferoxamine stimulate the PNMT promoter. While HIF‐1α is constitutively expressed, inclusion of the RNA synthesis inhibitor actinomycin D and protein synthesis inhibitor cycloheximide inhibit their induction. Hypoxia elevates Egr‐1 and Sp1 mRNA, protein and protein‐DNA binding complex formation as well. Stimulation is rapid but transient for Egr‐1 while sustained for Sp1 (24 hr). Egr‐1 binding site mutation in the PNMT promoter prevents activation by hypoxia. However, hypoxia generates long and short forms of PNMT mRNA, which produce inactive and active enzyme respectively. Thus, hypoxic stress transcriptionally activates PNMT but post‐transcriptional controls limit expression of functional enzyme.

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 score0.013
Threshold uncertainty score0.284

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 head0.021
GPT teacher head0.230
Teacher spread0.208 · 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