Radiation-induced cell signaling: inside-out and outside-in
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
Exposure of tumor cells to clinically relevant doses of ionizing radiation causes DNA damage as well as mitochondria-dependent generation of reactive oxygen species. DNA damage causes activation of ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3-related protein, which induce cell cycle checkpoints and also modulate the activation of prosurvival and proapoptotic signaling pathways, such as extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase 1/2, respectively. Radiation causes a rapid reactive oxygen species-dependent activation of ERBB family and other tyrosine kinases, leading to activation of RAS proteins and multiple protective downstream signaling pathways (e.g., AKT and ERK1/2), which alter transcription factor function and the apoptotic threshold of cells. The initial radiation-induced activation of ERK1/2 can promote the cleavage and release of paracrine ligands, which cause a temporally delayed reactivation of receptors and intracellular signaling pathways in irradiated and unirradiated bystander cells. Hence, signals from within the cell can promote activation of membrane-associated receptors, which signal back into the cytosol: signaling from inside the cell outward to receptors and then inward again via kinase pathways. However, cytosolic signaling can also cause release of membrane-associated paracrine factors, and thus, paracrine signals from outside of the cell can promote activation of growth factor receptors: signaling from the outside inward. The ultimate consequence of these signaling events after multiple exposures may be to reprogram the irradiated and affected bystander cells in terms of their expression levels of growth-regulatory and cell survival proteins, resulting in altered mitogenic rates and thresholds at which genotoxic stresses cause cell death. Inhibition of signaling in one and/or multiple survival pathways enhances radiosensitivity. Prolonged inhibition of any one of these pathways, however, gives rise to lineages of cells, which have become resistant to the inhibitor drug, by evolutionary selection for the clonal outgrowth of cells with point mutations in the specific targeted protein that make the target protein drug resistant or by the reprogramming of multiple signaling processes within all cells, to maintain viability. Thus, tumor cells are dynamic with respect to their reliance on specific cell signaling pathways to exist and rapidly adapt to repeated toxic challenges in an attempt to maintain tumor cell survival.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.001 |
| 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