<i>Bax-inhibitor-1</i> loss of function phenotypes are suppressed by <i>Buffy</i> in <i>Drosophila</i>
Bibliographic record
Abstract
Background. Bax Inhibitor-1 (BI-1), an integral transmembrane protein, acts as a suppressor of Bax-induced apoptosis through regulation of endoplasmic reticulum (ER) stress-induced cell death. The gene is highly conserved being found in a diverse range of organisms that include yeast, Arabidopsis, Drosophila, mouse and humans. BI-1 is implicated in the regulation of calcium levels, reactive oxygen species, apoptosis, autophagy and ER stress signalling pathways. We inhibited the cytoprotective BI-1 in the dopa decarboxylase (Ddc) expressing neurons and in the developing eye of Drosophila melanogaster to investigate its neuroprotective functions. Methods. We assessed the longevity and locomotor ability of flies in response to altered BI-1 expression in the Ddc-Gal4-expressing neurons where we exploited two RNAi transgenic fly lines. A control that expressed the benign lacZ responding transgene was used to compare against the RNAi transgenic flies. In addition, we compared the effect of the loss of BI-1 expression in the developing eye, through biometric analysis of the number of ommatidia and extent of disruption of the ommatidial arrays. Finally, Buffy and α-synuclein were co-expressed to evaluate the potential for interactions. Results. The inhibition of BI-1 in these neurons resulted in a shortened lifespan and precocious loss of locomotor ability. The co-expression of Buffy, the sole anti-apoptotic Bcl-2 homologue in Drosophila, with BI-1-RNAi resulted in suppression of the reduced lifespan and impaired climbing ability. Expression of human α-synuclein in Drosophila dopaminergic neurons results in age-dependent loss in climbing ability. We exploited this neurotoxic system to investigate possible BI-1 neuroprotective function. The co-expression of α-synuclein with BI-1-RNAi results in decreased survival coupled with an impaired climbing ability. In supportive experiments, we employed the neuron-rich Drosophila compound eye to investigate subtle phenotypes that result from altered gene expression. The inhibition of BI-1 in the Drosophila developing eye under the direction of the GMR-Gal4 transgene results in reduced ommatidia number and increased disruption of the ommatidial array. Similarly, the co-expression of BI-1-RNAi with Buffy results in the suppression of the eye phenotypes. The expression of α-synuclein along with the inhibition of BI-1 results in reduction of ommatidia number and increased disruption of the ommatidial array. Conclusions. Inhibition of BI-1 in the dopaminergic neurons of Drosophila results in a shortened lifespan and premature loss in climbing ability, phenotypes that appear to be strongly associated with models of Parkinson disease in Drosophila. These are suppressed upon overexpression of Buffy and worsened by co-expression with α-synuclein. This suggests that BI-1 acts in neuroprotection and that its inhibition can be counteracted by the overexpression of the pro-survival Bcl-2 homologue, Buffy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".