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Function of PHR1 in Candida albicans cell wall assembly

2011· dissertation· en· W23636710 on OpenAlexfundno aff
Satjana Pattanasak

Bibliographic record

VenueJAMA Psychiatry · 2011
Typedissertation
Languageen
FieldMedicine
TopicAntifungal resistance and susceptibility
Canadian institutionsnot available
FundersNational Institute on Alcohol Abuse and AlcoholismCanadian Institutes of Health ResearchNational Institute of General Medical SciencesNational Institute on Drug AbuseGeorgetown University
KeywordsCandida albicansCell wallVirulenceMicrobiologyBiologyCorpus albicansYeastGeneCellBiochemistry

Abstract

fetched live from OpenAlex

Thesis (Ph.D.)--Georgetown University, 2011.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. Candida albicans is usually present as a commensal of the mucosal surfaces of the gastrointestinal and urogenital tracts but it is a major cause of hospital-acquired infection in immunocompromised individuals. Candida spp. are the fourth most common cause of bloodstream infection. Moreover, the mortality rate of systemic candidiasis is very high due to the difficulty in diagnosis and treatment. Candida albicans is a polymorphic fungus that can change its morphology ranging from hyphae to yeast. The ability to switch between these morphologies is believed to be involved in the pathogenesis and virulence of this organism. The Candida albicans PHR1 (pH-regulated) gene is an alkali-expressed gene that encodes a 548 amino acid residue GPI-anchored cell surface glycoprotein. The deletion of PHR1 in C. albicans resulted in pH-conditional defects of cell morphology and virulence. The enzyme encoded by PHR1 is required for proper cross-linking of beta-1,3-glucans and beta-1,6-glucans in the cell wall. Both this enzyme and the cell wall itself are absent in host cells, which makes it an interesting target for new antifungal drug development.; We developed methods to study protein-protein interactions which combined protein cross-linking, Triton℗ʼX-114 extraction, ion exchange chromatography, 2 dimensional SDS-PAGE and mass spectrometry of an epitope tagged Phr1p that proved successful in analyzing interactions of membrane bound Phr1p. Therefore, these procedures might be useful for studying other membrane proteins. The results showed that the Phr1p forms a complex about double the size of Phr1p and mass spectrometry indicated that Phr1p was the only major component of this complex. Together this suggests that Phr1p forms a dimer. The dimer was enriched in the detergent-rich phase after Triton℗ʼX-114 extraction and phase separation, an observation consistent with the dimer retaining a hydrophobic GPI-anchor moiety. Western Blotting results showed about 25-60% of Phr1p was in a dimeric form which may indicate that the function of the dimeric form of Phr1p is distinct from that of the monomeric form.

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 score0.005
Threshold uncertainty score0.018

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 science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.003

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 head0.264
Teacher spread0.253 · 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".

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Citations0
Published2011
Admission routes1
Has abstractyes

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