A fruitful fly forward : the role of the fly in drug discovery for neurodegeneration

AD, Alzheimer’s disease; APP, amyloid precursor protein; BBB, blood brain barrier; GFP, green fluorescent protein; HTS, high-throughput screening; HD, Huntington’s disease; LB, Lewy bodies; PD, Parkinson’s disease; PolyQ, Polyglutamine; RNAi, RNA interference; SNCA, α-synuclein gene; UAS, Upstream Activating Sequence.peer-reviewe

In defense of the progressive stack: A strategy for prioritizing marginalized voices during in-class discussion

Progressive stacking is a strategy for prioritizing in-class contributions that allows marginalized students to speak before non-marginalized students. I argue that this strategy is both pedagogically and ethically defensible. Pedagogically, it provides benefits to all students (e.g., expanded in-class discourse) while providing special benefits (e.g., increased self-efficacy) to marginalized students, helping to address historic educational inequalities. Ethically, I argue that neither marginalized nor non-marginalized students are wronged by such a policy. First, I present a strategy for self-disclosure that reduces the risk of inadvertent, unwanted disclosure while respecting marginalized student autonomy in a manner analogous to accommodations provided under the Americans with Disabilities Act. Second, I argue that non-marginalized students are not wronged because such students are not silenced during discussion and because non-marginalized students benefit from the prioritization of marginalized voices

Spatial organization of visuomotor reflexes in Drosophila

In most animals, the visual system plays a central role in locomotor guidance. Here, we examined the functional organization of visuomotor reflexes in the fruit fly, Drosophila, using an electronic flight simulator. Flies exhibit powerful avoidance responses to visual expansion centered laterally. The amplitude of these expansion responses is three times larger than those generated by image rotation. Avoidance of a laterally positioned focus of expansion emerges from an inversion of the optomotor response when motion is restricted to the rear visual hemisphere. Furthermore, motion restricted to rear quarter-fields elicits turning responses that are independent of the direction of image motion about the animal's yaw axis. The spatial heterogeneity of visuomotor responses explains a seemingly peculiar behavior in which flies robustly fixate the contracting pole of a translating flow field

Aberrant lysosomal carbohydrate storage accompanies endocytic defects and neurodegeneration in Drosophila benchwarmer

Lysosomal storage is the most common cause of neurodegenerative brain disease in preadulthood. However, the underlying cellular mechanisms that lead to neuronal dysfunction are unknown. Here, we report that loss of Drosophila benchwarmer (bnch), a predicted lysosomal sugar carrier, leads to carbohydrate storage in yolk spheres during oogenesis and results in widespread accumulation of enlarged lysosomal and late endosomal inclusions. At the bnch larval neuromuscular junction, we observe similar inclusions and find defects in synaptic vesicle recycling at the level of endocytosis. In addition, loss of bnch slows endosome-to-lysosome trafficking in larval garland cells. In adult bnch flies, we observe age-dependent synaptic dysfunction and neuronal degeneration. Finally, we find that loss of bnch strongly enhances tau neurotoxicity in a dose-dependent manner. We hypothesize that, in bnch, defective lysosomal carbohydrate efflux leads to endocytic defects with functional consequences in synaptic strength, neuronal viability, and tau neurotoxicity