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Record W3160757640 · doi:10.1016/j.isci.2021.102457

Cholesterol-binding translocator protein TSPO regulates steatosis and bile acid synthesis in nonalcoholic fatty liver disease

2021· article· en· W3160757640 on OpenAlex
Yuchang Li, Liting Chen, Lu Li, Chantal M. Sottas, Stephanie Petrillo, Anthoula Lazaris, Peter Metrakos, Hangyu Wu, Yuji Ishida, Takeshi Saito, Lucy Golden‐Mason, Hugo R. Rosen, Jeremy J. Wolff, Cristina I. Silvescu, Samuel Garza, Garett Cheung, Tiffany Huang, Jinjiang Fan, Martine Culty, Bangyan L. Stiles, Kinji Asahina, Vassilios Papadopoulos

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

VenueiScience · 2021
Typearticle
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesUniversity of Southern CaliforniaCanadian Institutes of Health ResearchNational Institute of Allergy and Infectious DiseasesSchool of Pharmacy, University of Southern CaliforniaNational Institutes of HealthNational Institute on Alcohol Abuse and Alcoholism
KeywordsTranslocator proteinNonalcoholic fatty liver diseaseFarnesoid X receptorSteatosisChemistryEndoplasmic reticulumDownregulation and upregulationEndocrinologyUnfolded protein responseBiologyInternal medicineBiochemistryFatty liverMedicineNuclear receptorTranscription factorInflammation

Abstract

fetched live from OpenAlex

downregulated acetyl-CoA acetyltransferase 2 and increased free cholesterol (FC). FC accumulation induced endoplasmic reticulum stress via IRE1A and protein kinase RNA-like ER kinase/ATF4/CCAAT-enhancer-binding protein homologous protein pathways and autophagy. TSPO deficiency activated cellular adaptive antioxidant protection; this adaptation was lost upon excessive FC accumulation. A TSPO ligand 19-Atriol blocked cholesterol binding and recapitulated many of the alterations seen in TSPO-deficient cells. These data suggest that TSPO deficiency accelerated the progression of SS. In NASH, however, loss of TSPO ameliorated liver fibrosis through downregulation of bile acid synthesis by reducing CYP7A1 and CYP27A1 levels and increasing farnesoid X receptor expression. These studies indicate a dynamic and complex role for TSPO in the evolution of NAFLD.

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)0.000
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.152
Threshold uncertainty score0.488

Codex and Gemma teacher scores by category

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 integrity0.0000.000
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 head0.021
GPT teacher head0.257
Teacher spread0.236 · 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