The role of Rab27A in human eosinophil exocytosis (38.3)
Bibliographic record
Abstract
Abstract Eosinophils play an effector role in airway damage in asthma and related disorders, since their secreted granule-stored products can induce many of the clinical features of asthma. Degranulation of eosinophils requires the activity of several GTP-binding proteins, many of which remain unidentified. We hypothesized that Rab27A is one of these GTP-binding proteins because, in other cells, it interacts with effectors that regulate vesicle motility, docking and fusion. Humans with Rab27A-deficiency develop Griscelli syndrome which is characterized by immunodeficiency and partial albinism due to secretory defects in various cell types. We have established that Rab27A is expressed in human peripheral blood eosinophils as determined by RT-PCR and Western blotting. To asses Rab27A activation we developed a novel assay allowing the pulldown of the active, GTP-bound form. Rab27A was activated in several leukocyte populations upon cell stimulation with degranulatory stimuli. In human eosinophils, Rab27A was transiently activated by secretory-IgA stimulation. Rab27A activation followed a temporal pattern similar to that of degranulation, suggesting that Rab27A activation induces secretory granule movement and exocytosis. A clearer understanding of granulocyte exocytosis may contribute to novel therapeutic strategies in asthma, allergic inflammation and related conditions. Funding provided by the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".