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Bone marrow cell intrinsic defect drives autoimmunity in New Zealand Black chromosome 13 congenic mice

2008· article· en· W2254253892 on OpenAlexaffabout
Christina Loh, Evelyn Pau, Nan‐Hua Chang, Joan Wither

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsToronto Western HospitalUniversity of Toronto
Fundersnot available
KeywordsCongenicBone marrowPhenotypeBiologyChromatinAutoimmunityImmunologyAntibodyCellImmune systemSystemic lupus erythematosusMolecular biologyPathologyGeneticsMedicineDiseaseGene

Abstract

fetched live from OpenAlex

Introgression of a New Zealand Black (NZB) chromosome 13 interval onto a lupus‐resistant B6 background (denoted, c13) is sufficient to produce many of the hallmarks of lupus, including, high titre anti‐chromatin antibody (Ab) production, abnormal T cell activation, and renal disease. These phenotypes occurred in the presence of a dendritic cell (DC) expansion. In this follow‐up study, we sought to localize and characterize the immune defects leading to these pathogenic abnormalities; this was achieved by generating subcongenic mice and bone marrow (BM) reconstituted mice, respectively. Subcongenic mouse strains, c13(47–89 Mb), c13(73–114 Mb), and c13(81–114 Mb), all demonstrated low titre anti‐chromatin Ab production, abnormal T cell activation, and DC expansion. Lethally irradiated B6.Thy1aIgHa mice were reconstituted with BM cells from B6.Thy1aIgHa, c13, or a mixture of both. Only mice reconstituted with c13 BM cells developed the aforementioned phenotypes. Moreover, in mixed BM chimeras, these abnormalities were seen in both B6.Thy1aIgHa‐ and c13‐derived cells. Thus, this study shows that a BM cell‐intrinsic defect that is not cell‐autonomous is driving the c13 mouse phenotype. Furthermore, this defect can be localized within the overlapping 81–89 Mb subcongenic chromosome 13 interval. Source of research support: The Arthritis Society and Canadian Institutes of Health Research.

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 score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.013
GPT teacher head0.220
Teacher spread0.207 · 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 routes2
Has abstractyes

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