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Record W4309941554 · doi:10.1038/s41467-022-34262-0

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

2022· article· en· W4309941554 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicDrug-Induced Hepatotoxicity and Protection
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersNational Cancer InstituteInstituto de Salud Carlos IIIEuskal Herriko UnibertsitateaNational Institutes of HealthUniversidad de NavarraCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasBanco Bilbao Vizcaya ArgentariaIkerbasque, Basque Foundation for ScienceSilence TherapeuticsInstituto de Investigación Marqués de Valdecilla“la Caixa” FoundationMinisterio de Economía y CompetitividadSpanish Clinical Research NetworkNewcastle UniversityCancer Research UKMinisterio de Ciencia e InnovaciónMinisterio de Ciencia, Innovación y UniversidadesFundación Científica Asociación Española Contra el CáncerUniversidad de MálagaYork UniversityE-RareAgencia Estatal de InvestigaciónUniversitat de ValènciaMcGill University
KeywordsEndoplasmic reticulumAcetaminophenPharmacologyCyclin D1ChemistryMagnesiumCell biologyCyclinLiver injuryMedicineCancer researchBiochemistryBiologyCell cycleApoptosis

Abstract

fetched live from OpenAlex

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.

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.

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 categoriesMeta-epidemiology (narrow), Science and technology studies, Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.823
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0030.000
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0010.008
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 head0.161
GPT teacher head0.418
Teacher spread0.257 · 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