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Record W4311681234 · doi:10.22215/etd/2022-15147

Knockout of DROSHA Increases the Sensitivity of HCT116 Cells to Apoptosis in Response to Actinomycin-D Treatment

2022· dissertation· en· W4311681234 on OpenAlexaff
Gavin Sharpe

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicroRNA in disease regulation
Canadian institutionsCarleton University
Fundersnot available
KeywordsDroshaApoptosisBiologyDNA fragmentationmicroRNADNA damageGeneMolecular biologyCell biologyCell cultureProgrammed cell deathCancer researchDNARNARNA interferenceGenetics

Abstract

fetched live from OpenAlex

MicroRNAs are short non-coding RNAs that function as sequence-directed posttranscriptional inhibitors of gene expression.The cellular response to ten drugs including actinomycin-D (ACT-D) was examined in a genetically modified HCT116 colon cancer cell line with a deletion in the gene encoding a critical miRNA processing enzyme called DROSHA.We found that the DROSHA-null subline was more susceptible than the parental cells expressing wild-type DROSHA to apoptosis induced by several drugs, most prominently ACT-D.This increase in susceptibility to apoptosis was characterized by increased DNA-fragmentation, increased caspase-3/7 activity, and loss of membrane integrity.The increased susceptibility to apoptosis was not associated with differences in DNA-synthesis, RNA-synthesis, protein-synthesis, metabolic activity, p53 response or the induction of replicative-senescence.Our results suggest that these cell lines are equally sensitive to the direct effects of ACT-D but these DROSHA-null cells are more sensitive to apoptosis induced by a subset of drugs exemplified by ACT-D.

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 score0.001
Threshold uncertainty score0.004

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)0.0010.000

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 head0.008
GPT teacher head0.272
Teacher spread0.264 · 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
Published2022
Admission routes1
Has abstractyes

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