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Record W4381687098 · doi:10.1038/s41467-023-39272-0

Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling

2023· article· en· W4381687098 on OpenAlexaff
Cristiane N. Santos, Hye Sun Kuehn, Brigette Boast, SuJin Hwang, Douglas B. Kuhns, Jennifer Stoddard, Julie E. Niemela, Danielle Fink, Stefania Pittaluga, Mones Abu‐Asab, John Davies, Valarie A. Barr, Tomoki Kawai, Ottavia M. Delmonte, Marita Bosticardo, Mary Garofalo, Magda Carneiro‐Sampaio, Raz Somech, Mohammad Gharagozlou, Nima Parvaneh, Lawrence E. Samelson, Thomas A. Fleisher, Anne Puel, Luigi D. Notarangelo, Bertrand Boisson, Jean‐Laurent Casanova, Beáta Dérfalvi, Sergio D. Rosenzweig

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldMedicine
TopicCell Adhesion Molecules Research
Canadian institutionsDalhousie University
FundersHoward Hughes Medical InstituteNational Institute of Allergy and Infectious DiseasesFondation pour la Recherche MédicaleInstitut National de la Santé et de la Recherche MédicaleNational Center for Advancing Translational SciencesAgence Nationale de la RechercheGeorgia Clinical and Translational Science AllianceSt. Giles FoundationNIH Clinical CenterNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsBiologyAutoimmunityMutationCytokinePhenotypeMotilitySignal transductionInflammationGermlineCell biologyWiskott–Aldrich syndrome proteinGeneticsImmune systemImmunologyCancer researchGeneCellActin cytoskeletonCytoskeleton

Abstract

fetched live from OpenAlex

We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)-6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.793
Threshold uncertainty score0.685

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.002
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 head0.061
GPT teacher head0.390
Teacher spread0.329 · 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 designObservational
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

Citations19
Published2023
Admission routes1
Has abstractyes

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