2-C-198 - The contribution of heterogeneous nuclear ribonucleoprotein A1 to oligodendrocyte biology using in vivo and in vitro models of multiple sclerosis
Bibliographic record
Abstract
Authors: Ali Jahanbazi Jahan-Abad¹, Hannah Salapa¹, Cole Libner¹, Amber Anees¹, Patricia Thibault¹, Michael Levin¹ ¹University of Saskatchewan Abstract: Oligodendrocyte (OL) dysfunction and demyelination are crucial pathological features of multiple sclerosis (MS), but their underlying mechanisms in MS remain elusive. Recently, our lab discovered the contribution of neuronal dysfunction of RNA binding proteins (RBPs) such as heterogeneous nuclear ribonucleoprotein A1 (A1) and stress granule (SG) formation to the pathogenesis of neurodegeneration in MS. Previous studies have shown that A1 is involved in the regulation of myelin-related gene expressions in OLs. However, the function of A1 in OL biology in MS remains to be explored. C57BL/6 female mice were immunized with MOG35-55 to induce experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Immunohistochemistry staining was used to examine A1 dysfunction and cytoplasmic aggregation of G3BP, a marker for SG formation, in spinal cord OLs at the peak of EAE. siRNA knockdown against A1 was performed in an OL cell line to investigate its effects OL health. We found that EAE animals exhibited significant increases in A1 mislocalization and SG formation in OLs in spinal cords of EAE mice as compared to the naïve group. Furthermore, we observed that A1 colocalized within SGs in OLs in EAE mice. siRNA knockdown of A1 in OL cells resulted in increased cytotoxicity, decreased the number of junctions around the cells, and enhanced apoptosis and necroptosis. These data indicate that A1 is indispensable for OL health and function, which might involve in the pathogenesis of demyelination and neurodegeneration in MS patients.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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".