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Record W4400726016 · doi:10.1126/scitranslmed.adk4802

Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming

2024· article· en· W4400726016 on OpenAlexaff
Tian Y. Du, Steven R. Hall, Felicity Chung, Sergey Kurdyukov, Edouard Crittenden, Karishma Patel, Charlotte A. Dawson, Adam Westhorpe, Keirah E. Bartlett, Sean A. Rasmussen, Cesar L. Moreno, Christopher E. Denes, Laura-Oana Albulescu, Amy E. Marriott, Joel P. Mackay, Mark C. Wilkinson, José Marı́a Gutiérrez, Nicholas R. Casewell, G. Gregory Neely

Bibliographic record

VenueScience Translational Medicine · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicVenomous Animal Envenomation and Studies
Canadian institutionsQueen Elizabeth II Health Sciences Centre
FundersWellcome Trust
KeywordsCobraAntidoteNajaVenomMedicineToxicologyPharmacologyBiologyToxicityInternal medicineComputer scienceBiochemistry

Abstract

fetched live from OpenAlex

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including EXT1 , B4GALT7 , EXT2 , EXTL3 , XYLT2 , NDST1 , and SLC35B2 , which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration–approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.084
Threshold uncertainty score0.366

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 head0.015
GPT teacher head0.321
Teacher spread0.306 · 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

Citations17
Published2024
Admission routes1
Has abstractyes

Explore more

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