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Record W4292651823 · doi:10.1073/pnas.2121251119

The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages

2022· article· en· W4292651823 on OpenAlexafffund
Phoenix Toboz, Mehdi Amiri, Negar Tabatabaei, Catherine R. Dufour, Seung Hyeon Kim, Carine Fillebeen, Charles Ayemoba, Arkady Khoutorsky, Manfred Nairz, Lijian Shao, Kostandin V. Pajcini, Ki-Wook Kim, Vincent Giguère, Regiana L. Oliveira, Marco Constante, Manuela M. Santos, Carlos R. Morales, Kostas Pantopoulos, Nahum Sonenberg, Sandra Pinho, Soroush Tahmasebi

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2022
Typearticle
Languageen
FieldMedicine
TopicErythrocyte Function and Pathophysiology
Canadian institutionsUniversité de MontréalJewish General HospitalMcGill University
FundersNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteCanadian Institutes of Health ResearchGovernment of CanadaChicago Community Trust
KeywordsProtein biosynthesisSerineLysosomeIntegrated stress responseBiochemistryMetabolismHemolysisMessenger RNABiologyAmino acidTranslation (biology)KinaseHypoxia (environmental)Cell biologyChemistryEnzymeImmunologyOxygenGene

Abstract

fetched live from OpenAlex

GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importance of liver macrophages as the primary cell type mediating these effects. During different stress conditions, such as hemolysis, amino acid deficiency or hypoxia, GCN2 knockout ( GCN2 −/− ) mice displayed resistance to anemia compared with wild-type ( GCN2 +/+ ) mice. GCN2 −/− liver macrophages exhibited defective erythrophagocytosis and lysosome maturation. Molecular analysis of GCN2 −/− cells demonstrated that the ATF4-NRF2 pathway is a critical downstream mediator of GCN2 in regulating red blood cell clearance and iron recycling.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.324
Threshold uncertainty score0.311

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.026
GPT teacher head0.270
Teacher spread0.244 · 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 teacher head, 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

Citations20
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicErythrocyte Function and PathophysiologyFrench-language works237,207