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Sex differences in the fetal programming of hypertension: role of adrenal phenylethanolamine N‐methyltransferase gene expression (680.21)

2014· article· en· W2240446002 on OpenAlexafffund
Sandhya Khurana, Julie Grandbois, Phong Nguyen, Heather Peltsch, Suet Y. Lo, Krishnan Venkataraman, T.C. Tai

Bibliographic record

VenueThe FASEB Journal · 2014
Typearticle
Languageen
FieldMedicine
TopicBirth, Development, and Health
Canadian institutionsLaurentian UniversityNOSM University
FundersCanadian Institutes of Health Research
KeywordsPhenylethanolamineEndocrinologyOffspringInternal medicineFetusPhenylethanolamine N-methyltransferaseBlood pressureDexamethasoneBiologyGene expressionDownregulation and upregulationHomeostasisPregnancyGeneMedicineTyrosine hydroxylaseGeneticsDopamine

Abstract

fetched live from OpenAlex

Prenatal exposure to high levels of glucocorticoids (GCs) predisposes to hypertension in later life. GCs regulate catecholamine biosynthesis and are critical for blood pressure homeostasis. This study examined whether prenatal exposure to elevated GCs influences the development of adult hypertension via alterations in phenylethanolamine N‐methyl transferase (PNMT), a gene that is linked to hypertension. Pregnant Wistar‐Kyoto dams were injected with 100 μg/kg/day of the synthetic GC dexamethasone (DEX) in their third trimester. Blood pressure and weights of the offspring were measured from week 3‐18, at which point the animals were sacrificed. Total RNA and protein were extracted from the adrenals, and the expression of PNMT and its regulatory transcription factors analyzed by qPCR and Western blot. Results reveal that in utero exposure to DEX promotes the development of hypertension in the offspring. A more pronounced increase in blood pressure was seen in males than females. The mRNA transcripts for PNMT, and its transcriptional regulators Egr‐1, Sp1, GR and AP‐2, were elevated in the adrenals of these animals compared to saline controls, with differences in both sexes. Preliminary Western data also shows upregulation of PNMT and the transcription factor Egr‐1. These results suggest that prenatal GC exposure increases adrenal PNMT gene expression via altered transcriptional regulatory mechanisms. Grant Funding Source : Supported by CIHR

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.032
GPT teacher head0.257
Teacher spread0.225 · 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 designObservational
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
Published2014
Admission routes2
Has abstractyes

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