Cytosolic Aggregation of Cellular Prion Protein Confined to Pancreatic Beta‐Cells
Bibliographic record
Abstract
Cellular prion protein (PrPC) is expressed in several tissues including neurons and pancreatic islets. To investigate whether PrPC expression was altered during the development of diabetes, we examined the pancreas in diabetes‐prone BioBreeding (BBdp) rats as well as non‐obese diabetic mice using light, fluorescent and confocal microscopy. PrPC was abundantly expressed in the four major endocrine cells within islets in BBdp rats and NOD mice. Surprisingly, cytosolic PrPC inclusions were observed in a subpopulation of beta‐cells in rats only. Inclusions were present in the islets of several rat strains including Wistar Furth, Sprague Dawley and Komeda. PrPC expression in the cytosol was weak, with strong staining of the cell membrane and pronounced aggregation in a subset of rat beta‐cells, particularly in older BBdp animals. The frequency of beta‐cells with inclusions increased with age in BBdp but not in controls. Moreover, in Sprague Dawley rats chronically infused with glucose, cytosolic PrPC expression was suppressed whereas the number of beta‐cells with inclusions increased. There was no co‐localization of gamma‐tubulin (microtubule complex), ubiquitin and proteasomes (protein degradation) and HSP70 (protein folding) with the PrPC inclusions consistent with proper folding of the PrPC protein. Thus, PrPC could play a role in glucoregulation and/or diabetes pathogenesis. (Supported by CIHR, CDA and JDRF) AS and GSW contributed equally.
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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) | 0.001 | 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 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".