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The Molecular Tool‐Kit of Viral Hemorrhagic Fevers

2015· article· en· W1194094708 on OpenAlexaff
Erica Ollmann Saphire, Zachary A. Bornholdt, Marnie L. Fusco, Dafna M. Abelson, Takao Hashiguchi, Jeffrey Lee, Yoshihiro Kawaoka, John M. Dye, James E. Crowe

Bibliographic record

VenueThe FASEB Journal · 2015
Typearticle
Languageen
FieldMedicine
TopicViral Infections and Outbreaks Research
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsVP40EbolavirusCell biologyViral life cycleRandom hexamerViral proteinBiologyVirusEndosomeEpitopeVirologyTSG101Viral matrix proteinEbola virusGeneAntibodyMolecular biologyViral replicationGenetics

Abstract

fetched live from OpenAlex

Ebola and Marburg viruses cause hemorrhagic fever with up to 90% lethality, and their genomes encode just seven genes. The few gene products encoded, their “tool‐kit”, are leveraged into a greater array of functions, by remodeling or rearranging of the 3D protein structures. The surface glycoprotein adopts a massive, heavily glycosylated form on the viral surface, but is remodeled into a minimal receptor‐binding core once inside the endosome. As a result, binding of many potential antibodies is lost as their epitopes are stripped form the virus. Crystal structures of potently neutralizing antibodies, however, reveal how one remains bound and reaches into the cryptic receptor‐binding site. Others likely neutralize by locking the GP structure in place. Additional protein transformation takes place at the other end of the virus life cycle, assembly and budding of nascent virions. Through multiple crystal structures, biochemistry and cellular microscopy, we illustrated that the matrix protein VP40 rearranges into different structures, each with a distinct function required for the ebolavirus life cycle. A butterfly‐shaped VP40 dimer trafficks to the cellular membrane. A distinct, linear hexamer structure is critical for assembly and release of the virion. A third structure of VP40, an RNA‐binding ring, regulates viral transcription inside infected cells.

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 score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.002

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 head0.033
GPT teacher head0.313
Teacher spread0.281 · 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

Citations0
Published2015
Admission routes1
Has abstractyes

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