Hif-1α paralogs play a role in the hypoxic ventilatory response of larval and adult zebrafish (<i>Danio rerio</i>)
Bibliographic record
Abstract
Hypoxia inducible factor (Hif) 1α, an extensively studied transcription factor, is involved in the regulation of many biological processes in hypoxia including the hypoxic ventilatory response. In zebrafish, there are two paralogs of Hif-1α (Hif-1A and Hif-1B), but little is known about the specific roles or potential sub-functionalization of the paralogs in response to hypoxia. Using knockout lines of Hif-1α paralogs, we examined their involvement in the hypoxic ventilatory response, measured as ventilation frequency (fV) in larval and adult zebrafish (Danio rerio). In wild-type zebrafish, fV increased across developmental time [4 days post fertilization (dpf), 7 dpf, 10 dpf and 15 dpf] in response to hypoxia (55 mmHg). In contrast, the Hif-1B knockout fish did not exhibit an increase in hypoxic fV at 4 dpf. Similar to wild-types, as larvae of all knockout lines developed, the magnitude of fV increased but to a lesser degree than in the wild-type larvae, until 15 dpf at which point there was no difference among the genotypes. In adult zebrafish, only in Hif-1B knockout fish was there an attenuation in fV during sustained exposure to 30 mmHg for 1 h but no effect when exposed for a shorter duration to progressive hypoxia. The mechanism of action of Hif-1α, in part, may be through its downstream target, nitric oxide synthase (NOS), and its product, nitric oxide (NO). Overall, the effect of each Hif-1α paralog on the hypoxic ventilatory response of zebrafish varies over development and is dependent on the type of hypoxic stress.
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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".