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Record W2282969363 · doi:10.14288/1.0167316

Cytoskeletal control of B cell receptor dynamics and signaling

2015· article· en· W2282969363 on OpenAlexaff
Spencer A. Freeman

Bibliographic record

VenuecIRcle (University of British Columbia) · 2015
Typearticle
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsCytoskeletonCell biologyDynamics (music)Signal transductionControl (management)CellChemistryBiologyComputer scienceComputational biologyGeneticsPhysicsArtificial intelligence

Abstract

fetched live from OpenAlex

The nucleation, polymerization, and depolymerization of actin filaments is spatially and temporally controlled in order to regulate cell motility, cell morphology, and protein organization within the plasma membrane. By limiting receptor diffusion, the submembrane actin cytoskeleton modulates the signaling output of receptors such as the B-cell antigen (Ag) receptor (BCR) that are activated by clustering. Restricting BCR mobility limits BCR-BCR collisions and the resultant ‘tonic’ signaling. Conversely, more dynamic actin filaments or F-actin clearance promotes BCR-BCR collisions and leads to a ‘primed’ state where the threshold for Ag-induced activation is reduced. In chapter 2, I show a mechanism of receptor cross-talk where microbial danger signals (TLR ligands) prime B cells for Ag-induced activation by enhancing actin dynamics. TLR signaling reduced BCR confinement, promoted BCR-BCR collisions and potentiated responses to low densities of membrane-associated Ags. The interaction of B-cells with antigen-presenting cells displaying membrane-Ags results in initial BCR signaling that promotes cell spreading and increases the probability of BCRs encountering Ag. This is coupled with increased BCR mobility and the formation of BCR microclusters that recruit and activate signaling enzymes. Cell spreading and BCR microcluster mobility require severing of cortical submembrane actin, a precursor to F-actin branching that drives cell spreading. In chapter 3, I show that BCR signaling increases actin dynamics and BCR microcluster formation by activating the actin-severing protein cofilin via a signaling pathway involving Rap GTPases.

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 score0.002
Threshold uncertainty score0.007

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.006
GPT teacher head0.160
Teacher spread0.154 · 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
Published2015
Admission routes1
Has abstractyes

Explore more

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