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Record W2414939366 · doi:10.1002/jlb.67.1.127

Interaction of various intracellular signaling mechanisms involved in mononuclear phagocyte toxicity toward neuronal cells

2000· article· en· W2414939366 on OpenAlexafffund
Andis Klegeris, Patrick L. McGeer

Bibliographic record

VenueJournal of Leukocyte Biology · 2000
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPhosphodiesterase function and regulation
Canadian institutionsUniversity of British Columbia
FundersAlzheimer SocietyArthritis Society
KeywordsNeurotoxicityBiologyMicrogliaPhospholipase A2IntracellularPharmacologyNeuroinflammationCell biologyPhagocyteBiochemistryImmunologyInflammationToxicityPhagocytosisEnzymeMedicineInternal medicine

Abstract

fetched live from OpenAlex

Microglia become activated in a wide range of neurodegenerative disorders, including Alzheimer's disease. Such activation may lead to autodestruction of neurons. It is demonstrated here that activation of both human microglia and monocytic THP-1 cells by a combination of lipopolysaccharide and interferon-gamma results in secretion of neurotoxins that kill human neuronal SH-SY5Y cells. This neurotoxicity can be partially blocked by inhibitors of cytosolic phospholipase A2, cGMP-selective phosphodiesterases, or protein kinase C. When combinations of these inhibitors, or combinations of an inhibitor plus nordihydroguaiaretic acid, or the nonsteroidal anti-inflammatory drug diclofenac were tried, additive reductions in neurotoxicity were observed. It is concluded that the stimulants activated multiple intracellular pathways, and that combination therapies inhibiting these pathways might be beneficial for treating neurodegenerative disorders.

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 score0.005

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 integrity0.0010.000
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 head0.014
GPT teacher head0.243
Teacher spread0.228 · 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

Citations68
Published2000
Admission routes2
Has abstractyes

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