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Unusual chemical and enzymatic stability of polysialic acid containing <i>N</i> ‐glycolylneuraminic acid

2012· article· en· W3175131860 on OpenAlexaff
Leela Davies, Oliver M.T. Pearce, Matthew B. Tessier, Siavash Assar, Victoria Smutova, Alexey V. Pshezhetsky, Robert J. Woods, Ajit Varki

Bibliographic record

VenueThe FASEB Journal · 2012
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGlycosylation and Glycoproteins Research
Canadian institutionsUniversité de MontréalCentre Hospitalier Universitaire Sainte-Justine
Fundersnot available
KeywordsPolysialic acidSialic acidEnzymeNeural cell adhesion moleculeChemistrySialidaseCarboxylic acidSalt bridgeBiochemistryCarboxylateN-Acetylneuraminic acidStereochemistryNeuraminidaseCellCell adhesionGene

Abstract

fetched live from OpenAlex

The sialic acid N ‐glycolylneuraminic acid (Neu5Gc) is present only at trace levels in the brains of all vertebrates tested to date, suggesting a detrimental effect of Neu5Gc. As a candidate mechanism for this potential toxicity, we hypothesized a reduced enzymatic breakdown of polysialic acid (PSA), a polymer of α2–8 linked N ‐acetylneuraminic acid (Neu5Ac) found on the neural cell adhesion molecule (NCAM) and critical in many neurodevelopmental processes. We demonstrate that cultured neuroblastoma cells are able to incorporate Neu5Gc into PSA. Chemically synthesized polymers containing Neu5Gc exhibit resistance to the mammalian sialidase NEU1, an effect abolished by replacing the N ‐glycolyl group with N ‐propyl. Additional enzymatic and acidic conditions are being evaluated. Molecular modeling predicts similar tertiary structures of α2–8 linked Neu5Ac and Neu5Gc, but the presence of a glycolyl group creates a potentially stabilizing hydrogen bond with the adjacent carboxylate. This intrinsic stability of α2–8 linked Neu5Gc in PSA provides a potential explanation for the evolutionarily conserved absence of Neu5Gc from the vertebrate brain.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.025
GPT teacher head0.283
Teacher spread0.258 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2012
Admission routes1
Has abstractyes

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