Hypoxia and adrenergic function: HIF1a, a potential regulatory switch
Bibliographic record
Abstract
Stress hormones epinephrine (epi) and cortisol, initiate behavioral and physiological changes for coping with and overcoming stress. Knowledge of molecular events whereby stress controls epi may permit early intervention in stress‐related disorders. Immobilization stress (IMMO) in rats controls epi released from the adrenal medulla, the source of circulating epi, in part through biosynthesis by phenylethanolamine N‐methyltransferase (PNMT). IMMO stress regulates PNMT through transcriptional activators, Egr‐1 and Sp1. Hypoxia (5% O 2 ) also activates PNMT via Egr‐1 and Sp1 and HIF1a, a factor controlling genes under hypoxic stress. A hypoxia response element exists in the proximal PNMT promoter but HIF1a seems to mediate PNMT promoter transcriptional activity indirectly by stimulating Egr‐1 and Sp1. If Egr‐1 and Sp1 elements in the promoter are mutated or Egr‐1or Sp1 siRNA is present in PC12 cells harboring a PNMT promoter‐luciferase construct, promoter stimulation by hypoxia or HIF1a is prevented. Selective inhibitors of cAMP and PLC as well as PKA, PKC, PI 3 K, ERK1/2 and p38 block hypoxia stimulated promoter activity and the rise in Egr‐1 and Sp1. Currently HIF1a siRNA effects on hypoxic induction of the PNMT promoter and Egr‐1 and Sp1 are being investigated. Under stress HIF1a may act as a transcriptional switch elevating Egr‐1 and Sp1, and thereby PNMT expression. Emerald Foundation, Sobel and Keller Fund, McLean Hospital
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".