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Record W4205325712 · doi:10.1038/s41467-022-27974-w

In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins

2022· article· en· W4205325712 on OpenAlexaff
Jérôme Montnach, Laila Ananda Blömer, Ludivine Lopez, Luiza Filipis, Hervé Meudal, Aude Lafoux, Sébastien Nicolas, Duong Chu, Cécile Caumes, Rémy Béroud, Chris Jopling, Frank Bosmans, Corinne Huchet, Céline Landon, Marco Canepari, Michel De Waard

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicNicotinic Acetylcholine Receptors Study
Canadian institutionsQueen's University
FundersFondation LeducqNational Institutes of HealthNational Institute of Neurological Disorders and StrokeConseil Régional des Pays de la LoireAFM-TéléthonAgence Nationale de la Recherche
KeywordsIn vivoSodium channelIon channelHEK 293 cellsChemistryBiophysicsPeptideEx vivoVoltage-gated ion channelCell biologyBiologyBiochemistrySodiumReceptorGenetics

Abstract

fetched live from OpenAlex

Abstract Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins targeting ion channels have the potential to control excitable cell activities with low invasiveness and high spatiotemporal precision. As proof-of-concept, we develop HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium (Na V ) channels and validate its activity in vitro in HEK293 cells, ex vivo in brain slices and in vivo on mice neuromuscular junctions. We find that HwTxIV-Nvoc enables precise spatiotemporal control of neuronal Na V channel function under all conditions tested. By creating multiple photoactivatable toxins, we demonstrate the broad applicability of this toxin-photoactivation technology.

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 score0.268
Threshold uncertainty score0.571

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 science0.0010.001
Research integrity0.0000.001
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 head0.013
GPT teacher head0.289
Teacher spread0.276 · 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

Citations41
Published2022
Admission routes1
Has abstractyes

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