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Record W4393139342 · doi:10.1016/j.jbc.2024.106038

Abstract 2225 Assessing Compound Efficacy in Huntington's Disease Pathology using pEGFP-Q74 Transfected HeLa Cells

2024· article· en· W4393139342 on OpenAlexfundno aff
Jillian Berko, S.A. Krueger

Bibliographic record

VenueJournal of Biological Chemistry · 2024
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsHeLaTransfectionHuntington's diseaseMolecular biologyDiseaseCellBiologyCancer researchCell culturePathologyMedicineGenetics

Abstract

fetched live from OpenAlex

Huntington's disease (HD) is a rare neurodegenerative disease impacting approximately 2.7 individuals out of 100,000 worldwide. However, it presents an appealing focus for nucleic acid-targeting therapies. This is due to its origin in an expanded DNA repeat, which, when transcribed, produces harmful repeat RNA. Thus, we hypothesized that a compound that binds to the disease-causing DNA and inhibits transcription to prevent the formation of toxic RNA could be promising as a HD therapeutic. By preventing the formation of toxic RNA, the downstream translation that forms homopolymeric proteins could be knocked down, potentially diminishing protein aggregates that often cause HD symptoms and disease progression. This investigation focuses on a specific compound functioning as a groove binder. In this study we tested the compound of interest in Hela Cells transfected with the pEGFP-Q74 plasmid. A fluorescence microscope was used to determine if the amount of protein aggregates increased or decreased in the presence of our compound in a normal length repeat as compared to the disease length. Thus, this work contributes to understanding the efficacy of this compound as a treatment for HD.

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 score0.002
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)0.0020.000

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 head0.060
GPT teacher head0.321
Teacher spread0.261 · 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
Published2024
Admission routes1
Has abstractyes

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