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Record W2946652522 · doi:10.1016/j.celrep.2019.04.090

c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells

2019· article· en· W2946652522 on OpenAlexafffund
Eric A. Shikatani, Rickvinder Besla, Sherine Ensan, Aditi Upadhye, Nadiya Khyzha, Angela Li, Takuo Emoto, Felix Chiu, Norbert Degousée, J. Moreau, Heather M. Perry, Danya Thayaparan, Henry S. Cheng, Shaun Pacheco, David Smyth, Hossein Noyan, Caleb C. J. Zavitz, Carla M. T. Bauer, Ingo Hilgendorf, Peter Libby, Filip K. Świrski, Jennifer L. Gommerman, Jason E. Fish, Martin R. Stämpfli, Myron I. Cybulsky, Barry B. Rubin, Christopher J. Paige, Timothy P. Bender, Coleen A. McNamara, Mansoor Husain, Clinton S. Robbins

Bibliographic record

VenueCell Reports · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAtherosclerosis and Cardiovascular Diseases
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health NetworkMcMaster UniversityUniversity of Toronto
FundersCanadian Institutes of Health ResearchCanada First Research Excellence Fund
KeywordsMYBAntibodyBiologyInflammationTranscription factorB cellBone marrowCellCholesterolImmunologyCell biologyCancer researchEndocrinologyBiochemistryGene

Abstract

fetched live from OpenAlex

Mechanisms that govern transcriptional regulation of inflammation in atherosclerosis remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as an important mediator of atherosclerotic disease in mice. Atherosclerosis-prone animals fed a diet high in cholesterol exhibit increased levels of c-Myb in the bone marrow. Use of mice that either harbor a c-Myb hypomorphic allele or where c-Myb has been preferentially deleted in B cell lineages revealed that c-Myb potentiates atherosclerosis directly through its effects on B lymphocytes. Reduced c-Myb activity prevents the expansion of atherogenic B2 cells yet associates with increased numbers of IgM-producing antibody-secreting cells (IgM-ASCs) and elevated levels of atheroprotective oxidized low-density lipoprotein (OxLDL)-specific IgM antibodies. Transcriptional profiling revealed that c-Myb has a limited effect on B cell function but is integral in maintaining B cell progenitor populations in the bone marrow. Thus, targeted disruption of c-Myb beneficially modulates the complex biology of B cells in cardiovascular disease.

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 score0.003

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.010
GPT teacher head0.218
Teacher spread0.208 · 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

Citations5
Published2019
Admission routes2
Has abstractyes

Explore more

Same venueCell ReportsSame topicAtherosclerosis and Cardiovascular DiseasesFrench-language works237,207