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Synapses are endowed with the flexibility to change through experience, but must be sufficiently stable to last a lifetime. This tension is illustrated at theDrosophilaneuromuscular junction (NMJ), where two motor inputs that differ in structural and functional properties coinnervate most muscles to coordinate locomotion. To stabilize NMJ activity, motor neurons augment neurotransmitter release following diminished postsynaptic glutamate receptor functionality, termed presynaptic homeostatic potentiation (PHP). How these distinct inputs contribute to PHP plasticity remains enigmatic. We have used a botulinum neurotoxin to selectively silence each input and resolve their roles in PHP, demonstrating that PHP is input specific: Chronic (genetic) PHP selectively targets the tonic MN-Ib, where active zone remodeling enhances Ca²⁺influx to promote increased glutamate release. In contrast, acute (pharmacological) PHP selectively increases vesicle pools to potentiate phasic MN-Is. Thus, distinct homeostatic modulations in active zone nanoarchitecture, vesicle pools, and Ca²⁺influx collaborate to enable input-specific PHP expression. 

Mutations of the Cullin-3 (Cul3) E3 ubiquitin ligase are associated with autism and schizophrenia, neurological disorders characterized by sleep disturbances and altered synaptic function. Cul3 engages dozens of adaptor proteins to recruit hundreds of substrates for ubiquitination, but the adaptors that impact sleep and synapses remain ill-defined. Here we implicate Insomniac (Inc), a conserved protein required for normal sleep and synaptic homeostasis inDrosophila, as a Cul3 adaptor. Inc binds Cul3 in vivo, and mutations within the N-terminal BTB domain of Inc that weaken Inc-Cul3 associations impair Inc activity, suggesting that Inc function requires binding to the Cul3 complex. Deletion of the conserved C-terminus of Inc does not alter Cul3 binding but abolishes Inc activity in the context of sleep and synaptic homeostasis, indicating that the Inc C-terminus has the properties of a substrate recruitment domain. Mutation of a conserved, disease-associated arginine in the Inc C-terminus also abolishes Inc function, suggesting that this residue is vital for recruiting Inc targets. Inc levels are negatively regulated by Cul3 in neurons, consistent with Inc degradation by autocatalytic ubiquitination, a hallmark of Cullin adaptors. These findings link Inc and Cul3 in vivo and support the notion that Inc-Cul3 complexes are essential for normal sleep and synaptic function. Furthermore, these results indicate that dysregulation of conserved substrates of Inc-Cul3 complexes may contribute to altered sleep and synaptic function in autism and schizophrenia associated withCul3mutations. 

Individuals and organizations are accumulating data at an unprecedented rate owing to the advent of inexpensive cloud computing. Data owners are increasingly turning to secure and privacy-preserving collaborative analytics to maximize the value of their records. In this paper, we will survey the state-of-the- art of this growing area. We will describe how researchers are bringing security and privacy-enhancing technologies, such as differential privacy, secure multiparty computation, and zero-knowledge proofs, into the query lifecycle. We also touch upon some of the challenges and opportunities associated with deploying these technologies in the field. 

Individuals and organizations are using databases to store personal information at an unprecedented rate. This creates a quandary for data providers. They are responsible for protecting the privacy of individuals described in their database. On the other hand, data providers are sometimes required to provide statistics about their data instead of sharing it wholesale with strong assurances that these answers are correct and complete such as in regulatory filings for the US SEC and other goverment organizations. We introduce a system,ZKSQL, that provides authenticated answers to ad-hoc SQL queries with zero-knowledge proofs. Its proofs show that the answers are correct and sound with respect to the database's contents and they do not divulge any information about its input records. This system constructs proofs over the steps in a query's evaluation and it accelerates this process with authenticated set operations. We validate the efficiency of this approach over a suite of TPC-H queries and our results show that ZKSQL achieves two orders of magnitude speedup over the baseline.