Genetic characterization of clk genes
Bibliographic record
Abstract
L'auteur a accord une licence non exclusive permettant la Bibliothque et Archives Canada de reproduire, publier, archiver, sauvegarder, conserver, transmettre au public par tlcommunication ou par l'Internet, prter, distribuer et vendre des thses partout dans le monde, des fins commerciales ou autres, sur support microforme, papier, lectronique et/ou autres formats.L'auteur conserve la proprit du droit d'auteur et des droits moraux qui protge cette thse.Ni la thse ni des extraits substantiels de celle-ci ne doivent tre imprims ou autrement reproduits sans son autorisation.Conformment la loi canadienne sur la protection de la vie prive, quelques formulaires secondaires ont t enlevs de cette thse.Bien que ces formulaires aient inclus dans la pagination, il n'y aura aucun contenu manquant. I~' Summaryclk-1 encodes an enzyme involved in the biosynthesis of ubiquinone (UQ), a redox active lipid that is found in all cellular membranes, inc1uding in the mitochondrial respiratory chain.In the nematode Caenorhabditis elegans clk-1 mutants display slow and deregulated physiological rates, inc1uding slow embryonic and post-embryonic development, retarded germline development, slow behaviours, and an increased lifespan.clk-1 slow germline development phenotype was previously linked to clk-1 altered ROS metabolism and its effect on lipid oxidization and the let-60/ras pathway. 1 have taken a genetic suppressor approach to further investigate the causes of the slow germline development phenotype of the clk-1 mutants.Through this approach one mutant that suppresses the germline phenotype of clk-1 was identified.This suppressor, gsc-1(qm216), restored clk-1 germline development to slightly faster rates than wild type worms.This effect was specific to clk-1 and gsc-1 did not speed germline development rates in wild type worms.Furthermore, this effect appeared to be additive to lowering cholesterollevels but not to increasing cytoplasmic ROS levels.gsc-1 by itself appeared to have a deleterious effect on brood size and to increase lifespan.Neither of these effects were additive to the clk-1 phenotype and were therefore believed to affect similar mechanisms.The genetic mapping of gsc-1 precisely located the mutation to the center of chromosome II and linked it tightly to the lin-5 mutation.However, none of the transgenic lines managed to complement the gsc-1 mutation and its identity was not discovered.ln addition, to determine the role of reactive oxygen species (ROS) in the Clk phenotype, 1 have been analyzing all clk mutants (clk-1 to -10), by increasing ROS levels through the disruption of sod-l and sod-2 genes, and scoring Clk phenotypes. 1 found that, although several clk mutants appear to have altered ROS levels, the phenomenon does not apply to aU clk worms and does not correlate with lifespan.The disruption of either sod-1 or -2 affects growth and embryonic viability: sod-2 tends to exacerbate the mutant phenotypes, while sod-1 shows First, 1 would like to thank my supervisor, Dr. Siegfried Hekimi, for his valuable guidance and instruction, and for giving me a chance to work with worms. 1 owe special thanks to Dr.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".