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Urban areas are inherently noisy, and this noise can disrupt biological processes as diverse as communication, migration, and reproduction. We investigated how exposure to urban noise affects sleep, a process critical to optimal biological functioning, in Australian magpies (Cracticus tibicen). Eight magpies experimentally exposed to noise in captivity for 24-h spent more time awake, and less time in non-rapid eye movement (non-REM) and REM sleep at night than under quiet conditions. Sleep was also fragmented, with more frequent interruptions by wakefulness, shorter sleep episode durations, and less intense non-REM sleep. REM sleep was particularly sensitive to urban noise. Following exposure to noise, magpies recovered lost sleep by engaging in more, and more intense, non-REM sleep. In contrast, REM sleep showed no rebound. This might indicate a long-term cost to REM sleep loss mediated by noise, or contest hypotheses regarding the functional value of this state. Overall, urban noise has extensive, disruptive impacts on sleep composition, architecture, and intensity in magpies. Future work should consider whether noise-induced sleep restriction and fragmentation have long-term consequences.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.