Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
- Candidate categories
- Insufficient payload (model declined to judge)
- Consensus categories
- Insufficient payload (model declined to judge)
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: Bench or experimentalConsensus signal: none
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.588
- Threshold uncertainty score
- 0.999
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.026 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.231 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.
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.
The record
- Venue
- Cell
- Topic
- Immunodeficiency and Autoimmune Disorders
- Field
- Immunology and Microbiology
- Canadian institutions
- McGill UniversityMcGill Genome CentreMcGill University Health CentreOntario Genomics
- Funders
- National Human Genome Research InstituteCenter for Mendelian Genomics, University of WashingtonQatar National Research FundFederal Aviation AdministrationNational Institutes of HealthNew South Wales GovernmentFondation Bettencourt SchuellerInstitut National de la Recherche AgronomiqueFonds National de la Recherche LuxembourgFonds de Recherche du Québec - SantéFondation Meyer pour le Développement Culturel et ArtistiqueInstitut National de la Santé et de la Recherche MédicaleSidra MedicineInstitut des maladies génétiques ImagineNational Center for Research ResourcesNational Institute of Allergy and Infectious DiseasesAgence Nationale de la RechercheFisher Center for Alzheimer's Research FoundationAustralian GovernmentCompute CanadaNational Center for Advancing Translational SciencesCalgary FoundationDeutsche ForschungsgemeinschaftMcGill UniversityFondation du SouffleMeyer FoundationEuropean Molecular Biology OrganizationRockefeller UniversityEuropean CommissionSidactionImmune Deficiency FoundationJPB FoundationCanadian Institutes of Health ResearchInstitut CurieCenter for Clinical and Translational Science, University of Illinois at ChicagoHorizon 2020 Framework ProgrammeFondation pour la Recherche MédicaleFundación SénecaAgency for Science, Technology and ResearchYale UniversitySt. Giles FoundationNational Health and Medical Research CouncilSCOR Corporate Foundation for ScienceHonjo International Scholarship FoundationGlenn Foundation for Medical ResearchHoward Hughes Medical Institute
- Keywords
- BiologyImmunityIRF1ImmunologyVirologyImmune systemMicrobiologyTranscription factorGeneticsGene
- Has abstract in OpenAlex
- yes