Limited Hydrolysis of Polysialic Acid by Human Neuraminidase Enzymes
Bibliographic record
Abstract
Regulation of sialic acids by human neuraminidase (hNEU) enzymes is important to many biological processes. Defining hNEU substrate tolerance can help to elucidate the roles of these enzymes in regulating sialosides in human health and disease. Polysialic acid (polySia) is a polyanion of α(2→8) linked sialic acids with roles in nervous, reproductive, and immune systems and is dysregulated in some malignancies and mental disorders. The unique chemical properties of this polymer, which include an enhanced susceptibility to acid-catalyzed hydrolysis, have hampered its study. Herein we describe the first systematic study of hNEU isoenzyme activity towards polysialic acid in vitro. The experimental design allowed us to study the impact of several factors that may influence polysialic acid degradation including pH, polymer size, and the relative ionic strength of the surrounding media. We report that short chains of polysialic acid (degree of polymerization, DP 3-8) were substrates of NEU3 and NEU4 at acidic pH, but not at neutral pH. No hNEU-catalyzed hydrolysis of longer polymers (DP 10-20) was detected. These findings suggest a neuraminidase-independent mechanism for polysialic acid turnover such as internalization and degradation in endosomes and lysosomes.
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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".