Patient safety without borders: measuring the global burden of adverse events
Bibliographic record
Abstract
<h3>Summary</h3> PIWI-interacting (pi)RNA pathways control transposable elements (TEs) and endogenous genes in animal gonads, playing important roles in gamete formation. Here, we report a mechanism by which endogenous protein-coding regions, that normally provide their sequences for translation, serve as origins of non-coding piRNA biogenesis in <i>Drosophila melanogaster</i> testes. The products, namely endo-piRNAs, formed silencing complexes with Aubergine (Aub) in germ cells. Proximity proteome combined to functional analyses revealed a testis-specialized chaperone, Cyclophilin 40 (Cyp40), selectively increases endo-piRNA occupancy inside Aub-RISCs aside from other TE-related piRNAs. Moreover, Argonaute 2 (Ago2) activities were found critical for endo-piRNA production. We provide evidence that Ago2-bound short interfering (si)RNAs and micro(mi)RNAs specify precursors and direct endo-piRNA biogenesis. Consistently, Aub and Ago2 cooperate in spermatid differentiation and regulate endogenous genes via endo-piRNA-directed mRNA cleavage. Collectively, our data highlight that Drosophila testes employ a unique strategy to expand the diversity of germline piRNAs supporting late spermatogenesis. <h3>Headlines</h3> Endogenous protein-coding regions derive non-coding endo-piRNAs endo-piRNA and TE-piRNA are produced via distinct mechanisms siRNA and miRNA activities direct secondary piRNA biogenesis endo-piRNA pathway controls chromatin and sperm formation
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".