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Record W3052655082 · doi:10.1016/j.isci.2020.101476

The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity

2020· article· en· W3052655082 on OpenAlexfundno aff
Laurence Lecordier, Sophie Uzureau, Gilles Vanwalleghem, Magali Deleu, Jean‐Marc Crowet, Paul Barry, Barry Moran, Paul Voorheis, Andra C. Dumitru, Yoshiki Yamaryo‐Botté, Marc Dieu, Patricia Tebabi, Benoît Vanhollebeke, Laurence Lins, Cyrille Y. Botté, David Alsteens, Yves F. Dufrêne, David Pérez‐Morga, Derek P. Nolan, Étienne Pays

Bibliographic record

VenueiScience · 2020
Typearticle
Languageen
FieldMedicine
TopicTrypanosoma species research and implications
Canadian institutionsnot available
FundersEuropean Regional Development FundCentre National de la Recherche ScientifiqueEuropean Research CouncilFonds De La Recherche Scientifique - FNRSUniversité Libre de BruxellesWellcome TrustAgence Nationale de la RechercheInstitut National de la Santé et de la Recherche MédicaleAlliance Française contre les Maladies ParasitairesScience Foundation IrelandInstitut national de la recherche scientifiqueFondation Innovations en Infectiologie
KeywordsInfectivityTrypanosoma bruceiParasite hostingTrypanosomaVirologyBiologyMicrobiologyChemistryBiochemistryComputer science

Abstract

fetched live from OpenAlex

Human innate immunity to Trypanosoma brucei involves the trypanosome C-terminal kinesin Tb KIFC1, which transports internalized trypanolytic factor apolipoprotein L1 (APOL1) within the parasite. We show that Tb KIFC1 preferentially associates with cholesterol-containing membranes and is indispensable for mammalian infectivity. Knockdown of Tb KIFC1 did not affect trypanosome growth in vitro but rendered the parasites unable to infect mice unless antibody synthesis was compromised. Surface clearance of Variant Surface Glycoprotein (VSG)-antibody complexes was far slower in these cells, which were more susceptible to capture by macrophages. This phenotype was not due to defects in VSG expression or trafficking but to decreased VSG mobility in a less fluid, stiffer surface membrane. This change can be attributed to increased cholesterol level in the surface membrane in Tb KIFC1 knockdown cells. Clearance of surface-bound antibodies by T. brucei is therefore essential for infectivity and depends on high membrane fluidity maintained by the cholesterol-trafficking activity of Tb KIFC1.

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 score0.004
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 communication0.0000.000
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 head0.048
GPT teacher head0.368
Teacher spread0.320 · 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

Citations11
Published2020
Admission routes1
Has abstractyes

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