Bibliographic record
Abstract
Remyelination is the generation of new myelin sheaths after injury, and is accomplished by oligodendrocyte precursor cells (OPCs) that proliferate, migrate, and differentiate into myelin-forming oligodendrocytes. A number of lesion-associated factors have been identified that interfere with the remyelination response. Chondroitin sulfate proteoglycans (CSPGs) are a family of extracellular matrix molecules that provide structural rigidity to tissues and act as signalling molecules to neurons and glia in the developing nervous system. After injury, CSPGs become highly upregulated by astrocytes as part of the glial scar and restrict axonal regeneration. The role of injury-induced CSPG deposition on OPCs and remyelination is far less understood. In this thesis, I characterized a potent inhibitory phenotype of murine OPC adhesion and process outgrowth cultured on CSPGs in vitro. I explored the various mechanisms underlying this inhibitory response, including candidate receptors, downstream signalling molecules, and structural ligands on CSPGs through selective enzymatic degradation. I screened 245 orally available, Health Canada approved medicines for their ability to overcome OPC process outgrowth in the presence of CSPGs, and found a persistent inhibitory phenotype for all drugs tested. Lastly, I assessed the utility of a novel CSPG synthesis inhibitor, fluorosamine, and found that it reduced CSPG synthesis by astrocytes, resulting in a more permissive environment for OPC growth in vitro. Following experimental demyelination with lysolecithin in vivo, fluorosamine treatment reduced the deposition of CSPGs and enhanced OPC maturation and remyelination. Altering the inhibitory microenvironment after injury may be beneficial for promoting repair in a number of neurological diseases.
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.
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".