D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation
Bibliographic record
Abstract
Non-enzymatic glycation of proteins by reducing saccharides for instance D-glucose is an important post-translational modification regulating protein function. Already two centuries ago, D-glucose (Glc) was identified in the urine of diabetic patients. Recently, abnormally high level of D-ribose (Rib) in the urine of type 2 diabetics has been discovered, which is highly active in protein glycation, resulting in the production of advanced glycation end products (AGEs). Accumulation of AGEs leads to altered cellular function, for example AGE accumulation in the nervous system impairs cognitive ability, yet the mechanisms mediating this process for Rib are unknown. Here we found that treatment with Rib accelerated AGE formation in U251 and U87MG astrocytoma cells and in mouse brain, inducing upregulation of receptor for AGEs (RAGE). Astrocytoma cells with elevated levels of RAGE displayed enhanced activity of the proinflammatory nuclear transcription factor kappaB and increased expression of tumor necrosis factor alpha and glial fibrillary acidic protein. Moreover, injection of Rib induced astrocyte activation in mouse hippocampus and impaired spatial learning and memory abilities. These results indicate that mouse spatial cognitive impairment caused by Rib-derived AGEs is correlated with activation of an astrocyte-mediated, RAGE-dependent inflammatory response. This study may provide insights into the mechanism of Rib-involved cognitive impairments and diabetic encephalopathy.
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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 | 0.000 | 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) | 0.000 | 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".