Affinity Binding of Glycosaminoglycans with β<sub>2</sub>-Microglobulin
Bibliographic record
Abstract
BACKGROUND: A constant finding in beta (2)-microglobulin (beta 2m) amyloidosis is an increase in tissue heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) at sites of amyloid deposits. However, the binding characteristics of PGs with beta 2m have not been elucidated yet. METHODS: Using affinity retardation chromatography, beta 2m- and glycosaminoglycan (GAG)-anchored columns, an affinity between beta 2m and GAGs was analyzed. Five peptides which spanned the entire beta 2m amino acid sequence were prepared, and an affinity between these peptides and heparin (HP) was examined. Furthermore, the specific binding of biotinylated beta 2m peptide for AA amyloid deposits via GAGs was examined on tissue sections. RESULTS: Using beta 2m-anchored column, HP showed the smallest dissociation constant (K(d)), i.e. the strongest affinity, among the GAGs examined. At 0.4 M NaCl, the K(d)s of beta 2m relative to BSA-anchored columns for HP, HS, CS-A, CS-B, and CS-C were 94, 620, 130, 660 and 190 microM, respectively. Using GAG-anchored columns, at 0.15 M NaCl, pH 7.4, beta 2m also showed an affinity for HP, with the K(d) relative to a reference column being 370 microM. Under the latter conditions, no beta 2m affinity for CSA was demonstrated. Among the five peptides, peptide-1, which is composed of residues 1-24, showed the highest affinity for HP, the K(d) being 190 microM. Peptides analogous to peptide-1, in which each basic amino acid was individually replaced by alanine, showed a remarkable decrease in affinity for HP. The specific binding of biotinylated beta 2m peptide for AA amyloid deposits via HS and CS was confirmed in situ by pretreatment with heparitinase and chondroitinase ABC. CONCLUSION: The present data indicate that HP/HS is effective in the binding of the beta 2m monomer, and the anatomic localization of beta 2m amyloid precursor protein.
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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) | 0.001 | 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 | 0.001 |
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".