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Record W3005048641 · doi:10.1128/mbio.03202-19

Reducing Aspergillus fumigatus Virulence through Targeted Dysregulation of the Conidiation Pathway

2020· article· en· W3005048641 on OpenAlexafffund
James I. P. Stewart, Vinicius M. Fava, Joshua D. Kerkaert, Adithya S. Subramanian, Fabrice N. Gravelat, Mélanie Lehoux, P. Lynne Howell, Robert A. Cramer, Donald C. Sheppard

Bibliographic record

VenuemBio · 2020
Typearticle
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsInstitute of Infection and ImmunityHospital for Sick ChildrenUniversity of TorontoMcGill University Health Centre
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchNational Institute of Allergy and Infectious DiseasesNatural Sciences and Engineering Research Council of CanadaCystic Fibrosis CanadaCanada Research ChairsGovernment of CanadaBurroughs Wellcome Fund
KeywordsConidiationAspergillus fumigatusVirulenceBiologyMicrobiologyDownregulation and upregulationGliotoxinVirulence factorCell biologyGeneBiochemistry

Abstract

fetched live from OpenAlex

The mold Aspergillus fumigatus reproduces by the production of airborne spores (conidia), a process termed conidiation. In immunocompromised individuals, inhaled A. fumigatus conidia can germinate and form filaments that penetrate and damage lung tissues; however, conidiation does not occur during invasive infection. In this study, we demonstrate that forced activation of conidiation in filaments of A. fumigatus can arrest their growth and impair the ability of this fungus to cause disease in both an insect and a mouse model of invasive infection. Activation of conidiation was linked to profound changes in A. fumigatus metabolism, including a shift away from the synthesis of polysaccharides required for cell wall structure and virulence in favor of carbohydrates used for energy storage and stress resistance. Collectively, these findings suggest that activation of the conidiation pathway may be a promising approach for the development of new agents to prevent or treat A. fumigatus infection.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.492
Threshold uncertainty score0.208

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.027
GPT teacher head0.252
Teacher spread0.225 · 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 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

Citations29
Published2020
Admission routes2
Has abstractyes

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