Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep.

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single-cell sequencing indicates that they are not only enriched but also differentially expressed and contribute to clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy by introducing a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.

Parotid Acinic Cell Carcinoma as a Presentation of Birt-Hogg-Dube Syndrome.

Birt-Hogg-Dube syndrome (BHD) is a rare autosomal dominant disease classically associated with fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cancers. Information about its manifestation aside from the ones listed prior is limited. There have been several reports of BHD associated with parotid oncocytomas and rare benign epithelial tumors. Here, we report the first known case of BHD in association with parotid acinic cell carcinoma, a rare low-grade malignant tumor of salivary glands.

Neuron-specific knockouts indicate the importance of network communication to Drosophila rhythmicity.

Animal circadian rhythms persist in constant darkness and are driven by intracellular transcription-translation feedback loops. Although these cellular oscillators communicate, isolated mammalian cellular clocks continue to tick away in darkness without intercellular communication. To investigate these issues in Drosophila, we assayed behavior as well as molecular rhythms within individual brain clock neurons while blocking communication within the ca. 150 neuron clock network. We also generated CRISPR-mediated neuron-specific circadian clock knockouts. The results point to two key clock neuron groups: loss of the clock within both regions but neither one alone has a strong behavioral phenotype in darkness; communication between these regions also contributes to circadian period determination. Under these dark conditions, the clock within one region persists without network communication. The clock within the famous PDF-expressing s-LNv neurons however was strongly dependent on network communication, likely because clock gene expression within these vulnerable sLNvs depends on neuronal firing or light.