Identifying potential PARIS homologs in D. melanogaster
Bibliographic record
Abstract
Mitochondrial destruction leads to the formation of reactive oxygen species, increases cellular stress, causes apoptotic cell death, and involves a cascade of proteins including PARKIN, PINK1, and Mitofusin2. Mitochondrial biogenesis pathways depend upon the activity of the protein PGC-1α. These two processes are coordinated by the activity of a transcriptional repressor, Parkin interacting substrate (PARIS). The PARIS protein is degraded through the activity of the PARKIN protein, which in turn eliminates the transcriptional repression that PARIS imposes upon a downstream target, PGC-1α. Genes in this pathway have been implicated in Parkinson's disease, and there is a strong relationship between mitochondrial dysfunction and pre-mature neuron death. The identification of a PARIS homolog in Drosophila melanogaster would increase our understanding of the roles that PARIS and interacting genes play in higher organisms. We identified three potential PARIS homologs in D. melanogaster, one of which encodes a protein with similar domains to the Homo sapiens PARIS protein, CG15436. The Drosophila eye is formed from neuronal precursors, making it an ideal system to assay the effects of altered gene expression on neuronal tissue formation. The eye-specific expression of RNAi constructs for these genes revealed that both CG15269 and Crol caused neurodegenerative phenotypes, whereas CG15436 produced a phenotype similar to srl-EY. Crol-RNAi expression reduced mean lifespan when expressed in dopaminergic neurons, whereas CG15436-RNAi significantly increased lifespan. CG15436 was PARIS-like in both structure and function, and we characterized the effects of decreased gene expression in both the neuron-rich D. melanogaster eye and in dopaminergic neurons.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 | 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".