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Record W2045666417 · doi:10.1172/jci22954

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor

2005· article· en· W2045666417 on OpenAlexafffund
Joel Weaver, Agathe Tarze, Tia C. Moffat, Morgane Le Bras, Aurélien Deniaud, Catherine Brenner, Gary D. Bren, Mario Y. Morin, Barbara N. Phenix, Li Dong, Susan X. Jiang, Valerie L. Sim, Bogdan Zurakowski, Jessica Lallier, Heather Hardin, Peter J. Wettstein, Rolf P.G. van Heeswijk, Andre Douen, Romano T. Kroemer, Sheng‐Tao Hou, Steffany A. L. Bennett, David H. Lynch, Guido Kroemer, Andrew D. Badley

Bibliographic record

VenueJournal of Clinical Investigation · 2005
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsOttawa HospitalNational Research Council CanadaUniversity of Ottawa
FundersCanadian Institutes of Health ResearchAlzheimer SocietyNational Institutes of HealthSidactionNational Institute of Allergy and Infectious DiseasesAssociation pour la Recherche sur le CancerStyrelsen för Internationellt UtvecklingssamarbeteWellcome TrustHeart and Stroke Foundation of Canada
KeywordsAdenine nucleotide translocatorApoptosisRitonavirNelfinavirIn vivoProteaseBiologyProtease inhibitor (pharmacology)LopinavirPharmacologyMitochondrial permeability transition poreProgrammed cell deathCell biologyBiochemistryVirologyEnzymeVirusViral load

Abstract

fetched live from OpenAlex

Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the HIV protease inhibitor (PI) nelfinavir, boosted with ritonavir, in models of nonviral disease associated with excessive apoptosis. In mice with Fas-induced fatal hepatitis, Staphylococcal enterotoxin B-induced shock, and middle cerebral artery occlusion-induced stroke, we demonstrate that PIs significantly reduce apoptosis and improve histology, function, and/or behavioral recovery in each of these models. Further, we demonstrate that both in vitro and in vivo, PIs block apoptosis through the preservation of mitochondrial integrity and that in vitro PIs act to prevent pore function of the adenine nucleotide translocator (ANT) subunit of the mitochondrial permeability transition pore complex.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.038
GPT teacher head0.309
Teacher spread0.270 · 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 source (direct Gemma or distilled Codex), 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

Citations91
Published2005
Admission routes2
Has abstractyes

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