Gentamicin B1 is not a minor gentamicin component with major nonsense mutation suppression activity
Bibliographic record
Abstract
Abstract Nonsense mutations are single base substitutions that introduce a premature termination codon (PTC) preventing the formation of full-length protein. They are the causative mutations in about 10% of patients in a large number of rare genetic diseases. High concentrations of the antibiotic gentamicin can induce the incorporation of an amino acid at a PTC and formation of full-length protein, a process called PTC readthrough. Gentamicin is composed of several related aminoglycosides. We recently reported ( doi/10.1073/pnas.1620982114 ) that the major gentamicin components that are responsible for its antibacterial activity showed weak to no PTC readthrough activity but that the minor component gentamicin B1 was a potent readthrough inducer. We have now determined that gentamicin B1 acquired from the sole supplier at the time the study was carried out was not gentamicin B1 but instead the closely related aminoglycoside G418. Gentamicin B1 recently became available from a second commercial source. Here, we provide nuclear magnetic resonance (NMR) assignment data for the two commercial compounds and verify only the second is indeed gentamicin B1. We show that gentamicin B1 lacks PTC readthrough activity in HDQ-P1 and DMS-114 cells homozygous for the TP53 R213X nonsense mutation, as well as in a cell-free translation assay.
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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) | 0.002 | 0.001 |
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".