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Record W2963304872 · doi:10.1038/s41467-019-11140-w

Active thrombin produced by the intestinal epithelium controls mucosal biofilms

2019· article· en· W2963304872 on OpenAlexafffund
Jean‐Paul Motta, Alexandre Denadai‐Souza, David Sagnat, Laura Guiraud, Anissa Edir, Chrystelle Bonnart, Mireille Sebbag, Perrine Rousset, Ariane Lapeyre, Carine Séguy, Noa Mathurine-Thomas, Heather J. Galipeau, Delphine Bonnet, Laurent Alric, André G. Buret, John L. Wallace, Antoine Dufour, Elena F. Verdú, Morley D. Hollenberg, Éric Oswald, Matteo Sérino, Céline Deraison, Nathalie Vergnolle

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAntimicrobial Peptides and Activities
Canadian institutionsUniversity of CalgaryMcMaster University
FundersCanadian Institutes of Health ResearchRégion Occitanie Pyrénées-MéditerranéeCrohn's and Colitis CanadaAgence Nationale de la RechercheEquipexCentre National de la Recherche ScientifiqueAlberta Innovates - Health Solutions
KeywordsThrombinEpitheliumMucusMicrobiologyIntestinal mucosaBiologyBiofilmCell biologyIntestinal epitheliumMucinBacteriaImmunologyBiochemistryMedicineInternal medicine

Abstract

fetched live from OpenAlex

Proteolytic homeostasis is important at mucosal surfaces, but its actors and their precise role in physiology are poorly understood. Here we report that healthy human and mouse colon epithelia are a major source of active thrombin. We show that mucosal thrombin is directly regulated by the presence of commensal microbiota. Specific inhibition of luminal thrombin activity causes macroscopic and microscopic damage as well as transcriptomic alterations of genes involved in host-microbiota interactions. Further, luminal thrombin inhibition impairs the spatial segregation of microbiota biofilms, allowing bacteria to invade the mucus layer and to translocate across the epithelium. Thrombin cleaves the biofilm matrix of reconstituted mucosa-associated human microbiota. Our results indicate that thrombin constrains biofilms at the intestinal mucosa. Further work is needed to test whether thrombin plays similar roles in other mucosal surfaces, given that lung, bladder and skin epithelia also express thrombin.

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 score0.002

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 integrity0.0000.001
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 head0.011
GPT teacher head0.257
Teacher spread0.247 · 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

Citations62
Published2019
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicAntimicrobial Peptides and ActivitiesFrench-language works237,207