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A cross species CD200R1 immune checkpoint agonist with potent anti-inflammatory properties

2017· article· en· W2913291603 on OpenAlexaff
Jean Gariépy, Ismat Khatri, Reginald M. Gorczynski, Ashley Young, Lindsay Woo, Chung‐Wai Chow, Marzena Cydzik, Aaron Prodeus

Bibliographic record

VenueThe Journal of Immunology · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsSunnybrook HospitalSunnybrook Health Science CentreMcMaster University Medical CentreCentre for Social InnovationMcMaster UniversityUniversity of Toronto
Fundersnot available
KeywordsAptamerImmune systemAgonistCTL*Cell biologyChemistryBiologyImmunologyReceptorPharmacologyMolecular biologyGeneticsCD8

Abstract

fetched live from OpenAlex

Abstract Functional aptamers displaying agonistic or antagonistic properties are showing great promise in terms of modulating immune responses. Our group has recently developed pegylated DNA aptamers that can either block inflammatory responses (CD200R1agonist) or restore tumor-directed immune responses (PD-1 antagonist) in vivo. Here, we report the derivation and design of a cross species mouse/human CD200R1 DNA aptamer agonist that blocks inflammatory responses in mouse models of skin graft rejection and asthma. This DNA aptamer was discovered by performing NGS and comparing the resulting aptamer motifs derived from independently screening mouse and human CD200R1 as targets. Importantly, this m/hCD200R1 agonistic aptamer does not suppress cytotoxic T-lymphocyte (CTL) induction in 5 day allo-mixed lymphocyte cultures (MLCs) derived from CD200R1 knockout mice, indicating that its mode of action is directly linked to CD200R1 activation. This study suggests that one can derive agonistic DNA aptamers that can be verified as immunomodulators in mouse models with outcomes translatable to the treatment of human conditions.

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)0.0020.001

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 head0.016
GPT teacher head0.237
Teacher spread0.221 · 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
Published2017
Admission routes1
Has abstractyes

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