Oxygen and dexamethasone modulate αENaC translation in fetal lung epithelia via availability of eIF4F
Bibliographic record
Abstract
At birth, fetal distal lung epithelia (FDLE) must rapidly upregulate Na + transport, the rate limiting step of which is the amiloride‐sensitive epithelial Na + channel (ENaC). Although glucocorticoids (GC) mature the fetal lung it is unknown how GC interact with pO 2 at birth to induce lung fluid absorption. We found that dexamethasone (DEX)‐induced αENaC mRNA was efficiently translated into protein in primary cultures of FDLE only under postnatal (21%) O 2 (Otulakowski et al., AJRCMB;in press). Sucrose density gradient analyses of polysomes showed changes in αENaC mRNA distribution consistent with specific modulation of αENaC translation initiation; ie. DEX treatment of cells under fetal (3%) O 2 decreased association of αENaC mRNA with large polysomes, while shifting DEX‐treated cells to 21% O 2 restored association with large polysomes. αENaC mRNA possesses a long 5′UTR with a high GC content near the 5′‐cap, typical of mRNAs sensitive to limiting availability of eIF4F, the mRNA 5′‐cap binding complex composed of eIF4E and eIF4G. Western blots and m 7 GTP‐Sepharose pull‐down experiments showed DEX decreased formation of eIF4F and increased association of eIF4E with its inhibitor 4E‐BP in FDLE cultured at 3% O 2 , mediated by changes in 4E‐BP phosphorylation. Conversely, FDLE cultured at 21% O 2 expressed lower levels of 4E‐BP and maintained eIF4E‐eIF4G association in the presence of DEX. This suggests that the 7‐fold increase in pO 2 acts synergistically with GC to prepare the newborn lung to actively absorb fetal lung liquid. Supported by CIHR.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".