A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The accumulation of protein adducts caused by carbonyl stress (CS) is a hallmark of cellular aging and other diseases, yet the detailed cellular effects of this universal phenomena are poorly understood. An understanding of the global effects of CS will provide insight into disease mechanisms and can guide the development of therapeutics and lifestyle changes to ameliorate their effects. To identify cellular functions important for the response to carbonyl stress, multiple genome-wide genetic screens were performed using two known inducers of CS. We found that different cellular functions were required for resistance to stress induced by methylglyoxal (MG) and glyoxal (GLY). Specifically, we demonstrate the importance of macromolecule catabolism processes for resistance to MG, confirming and extending known mechanisms of MG toxicity, including modification of DNA, RNA, and proteins. Combining our results with related studies that examined the effects of ROS allowed a comprehensive view of the diverse range of cellular functions affected by both oxidative and carbonyl stress. To understand how these diverse cellular functions interact, we performed a quantitative epistasis analysis by creating multimutant strains from those individual genes required for glyoxal resistance. This analysis allowed us to define novel glyoxal-dependent genetic interactions. In summary, using multiple genome-wide approaches provides an effective approach to dissect the poorly understood effects of glyoxal in vivo. These data, observations, and comprehensive dataset provide 1) a comprehensive view of carbonyl stress, 2) a resource for future studies in other cell types, and 3) a demonstration of how inexpensive cell-based assays can identify complex gene-environment toxicities.
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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 | 0.000 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it