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Record W4401512697 · doi:10.1016/j.cell.2024.07.026

High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases

2024· article· en· W4401512697 on OpenAlexaff
Xiaoxiao Jia, Jeremy Chase Crawford, Deborah Gebregzabher, Ebony A. Monson, Robert C. Mettelman, Yanmin Wan, Yanqin Ren, Janet Chou, Tanya Novak, Hayley A. McQuilten, Michele V. Clarke, Annabell Bachem, Isabelle J. H. Foo, Svenja Fritzlar, Julio Carrera Montoya, Alice M. Trenerry, Shuai Nie, Michael G. Leeming, Thi H. O. Nguyen, Łukasz Kedzierski, Dene R. Littler, Andrew J. Kueh, Tina Cardamone, Chinn Yi Wong, Luca Hensen, Aira F. Cabug, Mona Agrawal, Tim Flerlage, David F. Boyd, Lee-Ann Van de Velde, Jennifer R. Habel, Liyen Loh, Hui‐Fern Koay, Carolien E. van de Sandt, Igor E. Konstantinov, Stuart P. Berzins, Katie L. Flanagan, Linda M. Wakim, Marco J. Herold, Amanda Green, Heather S. Smallwood, Jamie Rossjohn, Ryan S. Thwaites, Christopher Chiu, Nichollas E. Scott, Jason M. Mackenzie, Sammy Bedoui, Patrick C. Reading, Sarah L. Londrigan, Karla J. Helbig, Adrienne G. Randolph, Paul G. Thomas, Jianqing Xu, Zhongfang Wang, Brendon Y. Chua, Katherine Kedzierska

Bibliographic record

VenueCell · 2024
Typearticle
Languageen
FieldMedicine
TopicInfluenza Virus Research Studies
Canadian institutionsInstitute of Infection and Immunity
FundersArkansas Children's HospitalCenters for Disease Control and PreventionAmerican Lebanese Syrian Associated CharitiesNational Institutes of HealthU.S. Department of Health and Human ServicesTexas Children's HospitalChildren's Mercy HospitalNational Health and Medical Research CouncilUniversity of California, San FranciscoChildren's Healthcare of AtlantaBoston Children's HospitalNational Institute of Allergy and Infectious DiseasesMayo Clinic
KeywordsBiologyRespiratory systemExpression (computer science)Computational biologyVirologyImmunologyCell biology

Abstract

fetched live from OpenAlex

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah−/− mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease.

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)0.000
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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.025
Threshold uncertainty score0.519

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 head0.056
GPT teacher head0.345
Teacher spread0.290 · 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

Citations22
Published2024
Admission routes1
Has abstractyes

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