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MNDA regulates a novel nuclear‐mitochondrial circuit critical for progression of apoptosis in human neutrophils

2010· article· en· W2276190539 on OpenAlexafffund
Nasser Fotouhi‐Ardakani, Driss El Kebir, Natacha Pierre‐Charles, Lili Wang, Stéphane P. Ahern, János G. Filep, Éric Milot

Bibliographic record

VenueThe FASEB Journal · 2010
Typearticle
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsUniversité de Montréal
FundersCanadian Institutes of Health ResearchLeukemia and Lymphoma Society of Canada
KeywordsBiologyApoptosisCell biologyMitochondrionMolecular biologyGenetics

Abstract

fetched live from OpenAlex

Delayed neutrophil apoptosis perpetuates inflammation and delays the resolution of inflammation. We investigated the role of the nuclear protein MNDA (myeloid nuclear differentiation antigen) in progression of apoptosis of human neutrophils. We found that during constitutive apoptosis, MNDA is cleaved by caspase‐3 and relocated from the nucleus to the cytoplasm. MNDA co‐immunoprecipitates with the anti‐apoptotic protein Mcl‐1, accelerates proteasomal degradation of Mcl‐1, thereby contributing to collapse of mitochondrial transmembrane potential. MNDA knockdown with short hairpin RNA attenuates Mcl‐1 turnover, preserve mitochondrial function and confers resistance to apoptosis in myeloid HL‐60 cells. Culture of neutrophils with inflammatory mediators, including LPS, bacterial DNA, PAF or the acute phase reactants modified C‐reactive protein and serum amyloid A, prevents MNDA cleavage and translocation parallel with suppression of neutrophil apoptosis. Our results identify MNDA as a central mediator of a novel nucleus‐mitochondrion circuit that regulates progression of neutrophil apoptosis. (Grant support: LLSC and CIHR).

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 score0.004

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 integrity0.0000.000
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 head0.024
GPT teacher head0.285
Teacher spread0.261 · 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

Citations0
Published2010
Admission routes2
Has abstractyes

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