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Record W2766196932 · doi:10.1039/c7mt00110j

The cytochrome<i>b</i><sub>5</sub>CybE is regulated by iron availability and is crucial for azole resistance in<i>A. fumigatus</i>

2017· article· en· W2766196932 on OpenAlexaff
Matthias Misslinger, Fabio Gsaller, Peter Hortschansky, Christoph Müller, Franz Bracher, Michael Bromley, Hubertus Haas

Bibliographic record

VenueMetallomics · 2017
Typearticle
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsCentre for Drug Research and Development
FundersAustrian Science FundDeutsche Forschungsgemeinschaft
KeywordsAzoleAspergillus fumigatusResistance (ecology)CytochromeChemistryMicrobiologyBiologyComputational biologyBiochemistryAntifungalEcology

Abstract

fetched live from OpenAlex

CybE in the fungal pathogen Aspergillus fumigatus. Deletion of the CybE encoding gene (cybE) caused a severe growth defect in two different A. fumigatus isolates, emphasising the importance of the CB5R system in this pathogen, while the non-essentiality of cybE indicates the partial redundancy of the CPR and CB5R systems. Interestingly, the growth defect caused by the cybE loss of function was even more drastic in A. fumigatus strain AfS77 compared to strain A1160P+ indicating a strain-dependent degree of compensation, which is supported by azole resistance studies. In agreement with CybE being important for the assistance of the ergosterol biosynthetic P450 Cyp51, deletion of cybE decreased resistance to the Cyp51-targeting antifungal voriconazole and caused accumulation of the ergosterol pathway intermediate eburicol. Northern analysis indicated that CybE deficiency leads to the compensatory transcriptional upregulation of Cyp51-encoding cyp51A and CPR-encoding cprA. Overexpression of cybE did not affect azole resistance suggesting that CybE activity is not rate limiting. Expression of cybE was found to be repressed during iron starvation by the iron-regulatory transcription factor HapX demonstrating iron dependence of CybE not only at the level of enzyme activity but also at the level of gene expression.

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 score0.003
Threshold uncertainty score0.006

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 head0.014
GPT teacher head0.272
Teacher spread0.257 · 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

Citations23
Published2017
Admission routes1
Has abstractyes

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