Variants of 5‐lipoxygenase from human neutrophils impact on leukotriene biosynthesis in HEK293 cells
Bibliographic record
Abstract
5‐lipoxygenase (5‐LO) catalyzes the oxygenation of arachidonic acid and is an essential enzyme forleukotriene (LT) biosynthesis. Human neutrophils (PMN) are important producers of LTB 4 , a potent chemoattractant involved in the inflammatory response. In this study, we evaluated whether alternative forms of 5‐LO mRNA exist in human PMN and if they are implicated in the biosynthesis of LTB 4 . RT − PCR analysis of total mRNA from human PMN revealed several potential variants of 5‐LO mRNA. Molecular cloning and sequencing experiments showed that at least three isoforms are present in human PMN. One containing all 14 exons with the expected splicing sites (full 5‐LO) producing a known protein of 78 kDa. Another isoform retained intron 10 (alpha‐10) resulting in a shift of the open reading frame and produces a protein of expected molecular weight of 56 kDa. A third isoform lacked the first 96 nucleotides of exon 10 (delta‐p10) and produces a protein of expected molecular weight of 74 kDa. HEK293 cells transfected with the full 5‐LO produced LTB 4 and 5‐hydroxyeicosatetraenoic acid (5‐HETE) following ionophore stimulation; however, cells transfected with either alternative isoform produced no 5‐LO products. HEK293 cells transfected with the full 5‐LO and co‐transfected with the alpha‐10 or the delta‐p10 isoform produced 25±2% (mean±sem) and 49±7% (mean±sem) less 5‐LO products, respectively, compared to cells expressing only the full 5‐LO. These alternative isoforms of 5‐LO may represent a new mechanism for the regulation of LT biosynthesis in inflammatory cells. (Supported by the Canadian Institutes of Health Research and the Canada Research Chairs Program).
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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 | 0.001 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".