TDP-43 is an RNA-binding protein linked to amyotrophic lateral sclerosis (ALS) that is known to regulate the splicing, transport, and storage of specific mRNAs into stress granules. Although TDP-43 has been shown to interact with translation factors, its role in protein synthesis remains unclear, and no in vivo translation targets have been reported to date. Here we provide evidence that TDP-43 associates with futsch mRNA in a complex and regulates its expression at the neuromuscular junction (NMJ) in Drosophila. In the context of TDP-43-induced proteinopathy, there is a significant reduction of futsch mRNA at the NMJ compared with motor neuron cell bodies where we find higher levels of transcript compared with controls. TDP-43 also leads to a significant reduction in Futsch protein expression at the NMJ. Polysome fractionations coupled with quantitative PCR experiments indicate that TDP-43 leads to a futsch mRNA shift from actively translating polysomes to nontranslating ribonuclear protein particles, suggesting that in addition to its effect on localization, TDP-43 also regulates the translation of futsch mRNA. We also show that futsch overexpression is neuroprotective by extending life span, reducing TDP-43 aggregation, and suppressing ALS-like locomotor dysfunction as well as NMJ abnormalities linked to microtubule and synaptic stabilization. Furthermore, the localization of MAP1B, the mammalian homolog of Futsch, is altered in ALS spinal cords in a manner similar to our observations in Drosophila motor neurons. Together, our results suggest a microtubule-dependent mechanism in motor neuron disease caused by TDP-43-dependent alterations in futsch mRNA localization and translation in vivo.

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The very high speed of collapse of cavitation bubbles is responsible for a number of phenomena of interest in science and engineering: Luminescence, sonochemistry, cavitation damage, ultrasonic cleaning, etc. Strongly forced bubbles may collapse with such violence that the relatively slow processes of diffusion of the heat of compression and of excess vapor to the bubble wall are obviated. This leads to an approximately adiabatic system with nearly constant mass during the final stages of extreme collapses, accompanied by the evolution of sharp thermal and compositional boundary layers on either side of the interface. It is shown that the boundary layers, which are involved in the determination of the interfacial temperature through the balance of sensible and latent heats, may profitably be described mathematically through integral equations. This complements well the boundary integral solution of the fluid dynamics, which has been the basis of much progress in the field.

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