The Unfolded Protein Response in Health and Disease
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 endoplasmic reticulum (ER) is the principal cellular organelle in which correct folding and maturation of transmembrane, secretory, and ER-resident proteins occur. Research over the past decade has demonstrated that mutations in proteins or agents/conditions that disrupt protein folding adversely affect ER homeostasis, leading to ER stress. This in turn initiates the unfolded protein response (UPR), an integrated intracellular signalling pathway that responds to ER stress by increasing the expression of ER-resident molecular chaperones, attenuating global protein translation and degrading unfolded proteins. Failure to relieve prolonged or acute ER stress causes the cell to undergo apoptotic cell death. Recent groundbreaking studies have provided compelling evidence that ER stress and UPR activation contribute to the development and progression of human disease, including neurodegenerative disorders, diabetes, obesity, cancer, and cardiovascular disease. Furthermore, the ability of the UPR to modulate oxidative stress, inflammation, and apoptosis provides important cellular clues as to how this evolutionarily conserved cellular-stress pathway maintains and responds to both normal physiologic and pathologic processes. In this Forum issue, many aspects of the UPR are reviewed in the context of how ER stress and UPR activation influence human disease. This current information provides a solid foundation for future investigations aimed at targeting the UPR in an attempt to reduce the risk of human disease.
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 | 0.001 | 0.001 |
| 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) | 0.000 | 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