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Record W3106103044 · doi:10.1111/jth.15171

Multimerin 1 supports platelet function in vivo and binds to specific GPAGPOGPX motifs in fibrillar collagens that enhance platelet adhesion

2020· article· en· W3106103044 on OpenAlexafffund
Alexander Leatherdale, D’Andra Parker, Subia Tasneem, Yiming Wang, Dominique Bihan, Arkadiusz Bonna, Samir W. Hamaia, Peter L. Gross, Heyu Ni, Bradley W. Doble, David Lillicrap, Richard W. Farndale, Catherine P.M. Hayward

Bibliographic record

VenueJournal of Thrombosis and Haemostasis · 2020
Typearticle
Languageen
FieldMedicine
TopicPlatelet Disorders and Treatments
Canadian institutionsHamilton Regional Laboratory Medicine ProgramThrombosis and Atherosclerosis Research InstituteSt. Michael's HospitalCanadian Blood ServicesUniversity of TorontoQueen's UniversityMcMaster University
FundersCanadian Institutes of Health ResearchBritish Heart FoundationWellcome TrustHeart and Stroke Foundation of Canada
KeywordsPlateletIn vivoPlatelet adhesionPlatelet adhesivenessAdhesionFunction (biology)ChemistryCell biologyPlatelet aggregationImmunologyBiology

Abstract

fetched live from OpenAlex

Background Multimerin 1 (human: MMRN1, mouse: Mmrn1) is a homopolymeric, adhesive, platelet and endothelial protein that binds to von Willebrand factor and enhances platelet adhesion to fibrillar collagen ex vivo. Objectives To examine the impact of Mmrn1 deficiency on platelet adhesive function, and the molecular motifs in fibrillar collagen that bind MMRN1 to enhance platelet adhesion. Methods Mmrn1‐deficient mice were generated and assessed for altered platelet adhesive function. Collagen Toolkit peptides, and other triple‐helical collagen peptides, were used to identify multimerin 1 binding motifs and their contribution to platelet adhesion. Results MMRN1 bound to conserved GPAGPOGPX sequences in collagens I, II, and III (including GPAGPOGPI, GPAGPOGPV, and GPAGPOGPQ) that enhanced activated human platelet adhesion to collagen synergistically with other triple‐helical collagen peptides ( P < .05). Mmrn1 −/− and Mmrn1 +/− mice were viable and fertile, with complete and partial platelet Mmrn1 deficiency, respectively. Relative to wild‐type mice, Mmrn1 −/− and Mmrn1 +/− mice did not have overt bleeding, increased median bleeding times, or increased wound blood loss ( P ≥ .07); however, they both showed significantly impaired platelet adhesion and thrombus formation in the ferric chloride injury model ( P ≤ .0003). Mmrn1 −/− platelets had impaired adhesion to GPAGPOGPX peptides and fibrillar collagen ( P ≤ .03) and formed smaller aggregates than wild‐type platelets when captured onto collagen, triple‐helical collagen mimetic peptides, von Willebrand factor, or fibrinogen ( P ≤ .008), despite preserved, low shear, and high shear aggregation responses. Conclusions Multimerin 1 supports platelet adhesion and thrombus formation and binds to highly conserved, GPAGPOGPX motifs in fibrillar collagens that synergistically enhance platelet adhesion.

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 score0.006

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)0.0020.000

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 head0.050
GPT teacher head0.300
Teacher spread0.250 · 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

Citations39
Published2020
Admission routes2
Has abstractyes

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