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Granzyme B is important in the progression of atherosclerosis

2008· article· en· W2261384280 on OpenAlexaff
Rani P. Cruz, Wendy A. Boivin, Hongyan Zhao, Jonathan C. Choy, Bruce M. McManus, David J. Granville

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtease and Inhibitor Mechanisms
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsElastinGranzyme BInflammationApolipoprotein EGamma-ray burstImmune systemPathologyMedicineChemistryImmunologyT cellDisease

Abstract

fetched live from OpenAlex

Granzyme B (GrB) is a serine protease expressed in certain T‐cells, NK cells, mast cells and macrophages. We have shown GrB expression in human atherosclerotic plaques and its levels correspond to disease severity. Hypothesis: During chronic hyperlipidemia and inflammation, GrB contributes to elastin degradation, medial thinning and reduced elasticity. Methods: To study the role of GrB in a chronic inflammatory, hyperlipidemic environment, ApoE−/− x GrB−/− double knockout (ApoE/GrB‐DKO) mice were created, fed a high fat diet for 30 wks and sacrificed. Tissues were stained with H&E, ORO and Movat's pentachrome. GrB co‐localization to elastin was assessed using confocal microscopy. Results: ApoE−/− mice developed xanthomatosis and atherosclerotic lesions by 30 weeks. The absence of the GrB gene in the ApoE/GrB‐DKO mice abolished cutaneous xanthomatosis in addition to both the frequency and size of atherosclerotic lesions. The absence of GrB was associated with a marked reduction of elastin degradation in both the skin and blood vessels. Using confocal microscopy, we observed GrB strongly co‐localized to the shoulder regions of plaques in addition to the medial elastin fibres. Conclusion: GrB plays a key role in atherosclerotic plaque formation. Lipid accumulation on elastin fibres promotes the recruitment of GrB resulting in a slow, chronic degradation of elastin.

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 score0.002
Threshold uncertainty score0.005

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.020
GPT teacher head0.252
Teacher spread0.232 · 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
Published2008
Admission routes1
Has abstractyes

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