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Record W2917964750 · doi:10.22215/etd/2019-13407

Investigation of metal toxicity leads to the identification of novel translation associated genes in yeast (Saccharomyces cerevisiae)

2019· dissertation· en· W2917964750 on OpenAlexaff
Houman Moteshareie

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsCarleton University
Fundersnot available
KeywordsTranslation (biology)GeneSaccharomyces cerevisiaeComputational biologyBiologyYeastGeneticsGene expressionTranslational regulationMetal toxicityMetalloidHeavy metalsChemistryMessenger RNAMetalEnvironmental chemistry

Abstract

fetched live from OpenAlex

Heavy metal and metalloid pollutants in our environment are among the most concerning types of contaminations. Major chronic diseases in humans such as renal and cardiovascular diseases, and neurological decline, are strongly associated with heavy metals and metalloids. Therefore, investigation and understanding the molecular mechanisms of cellular responses and detoxification processes that overcome the toxicity of these compounds in living organisms is very important. To date, several genes are identified to play central roles in cellular detoxification process. The expression of such genes can be influenced at both the transcriptional and/or translational levels by the heavy metals. As a fundamental step in the gene expression pathway, we focused on the regulation of translation initiation under stress imposed by heavy metals and metalloids. Although a wealth of information exists on the process of eukaryotic translation, a comprehensive understanding of regulation of translation initiation under stress conditions is lacking. The growing list of novel factors affecting this process further indicate the existence of other novel players, which are yet to be discovered. In the current study, we sought out to identify novel genes encoding regulatory factors known that affect yeast translation initiation during stress when general translation seems to be shut down. Utilizing systems biology techniques, we investigated the effect of specific gene deletions under heavy metal and metalloid conditions on the general process of translation and internal initiation of translation (an alternative mode of translation mediated by specific RNA structures). We explicitly investigated the role of four of identified potential translation regulating genes based on their activity in heavy metals and metalloids sensitivity. We also performed a high-throughput plasmid-based screening of a library of non-essential gene deletion strains (~4500), using the baker's yeast (Saccharomyces cerevisiae) as our model organism to identify novel genes that are involved in internal translation initiation. To this end, we identified dozens of potential novel genes that may be involved in internal translation initiation. We further investigated the role of five potential factors to support their newly identified activity.

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 score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.027
GPT teacher head0.267
Teacher spread0.240 · 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
Published2019
Admission routes1
Has abstractyes

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