Sleep and wake have global effects on brain physiology, from molecular changes and neuronal activities to synaptic plasticity. Sleep-wake homeostasis is maintained by the generation of a sleep need that accumulates during waking and dissipates during sleep. Here we investigate the molecular basis of sleep need using quantitative phosphoproteomic analysis of the sleep-deprived and Sleepy mouse models of increased sleep need. Sleep deprivation induces cumulative phosphorylation of the brain proteome, which dissipates during sleep. Sleepy mice, owing to a gain-of-function mutation in the Sik3 gene , have a constitutively high sleep need despite increased sleep amount. The brain proteome of these mice exhibits hyperphosphorylation, similar to that seen in the brain of sleep-deprived mice. Comparison of the two models identifies 80 mostly synaptic sleep-need-index phosphoproteins (SNIPPs), in which phosphorylation states closely parallel changes of sleep need. SLEEPY, the mutant SIK3 protein, preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, the best known measurable index of sleep need, in both Sleepy mice and sleep-deprived wild-type mice. Our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and therefore SNIPP phosphorylation is a molecular signature of sleep need. Whereas waking encodes memories by potentiating synapses, sleep consolidates memories and restores synaptic homeostasis by globally downscaling excitatory synapses. Thus, the phosphorylation-dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep-wake homeostasis.
The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is currently acquiring integral-field spectroscopy for the largest sample of galaxies to date. By 2020, the MaNGA Survey—which is one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV)—will have observed a statistically representative sample of 104 galaxies in the local universe (z ≲ 0.15). In addition to a robust data-reduction pipeline (DRP), MaNGA has developed a data-analysis pipeline (DAP) that provides higher-level data products. To accompany the first public release of its code base and data products, we provide an overview of the MaNGA DAP, including its software design, workflow, measurement procedures and algorithms, performance, and output data model. In conjunction with our companion paper (Belfiore et al.), we also assess the DAP output provided for 4718 observations of 4648 unique galaxies in the recent SDSS Data Release 15 (DR15). These analysis products focus on measurements that are close to the data and require minimal model-based assumptions. Namely, we provide stellar kinematics (velocity and velocity dispersion), emission-line properties (kinematics, fluxes, and equivalent widths), and spectral indices (e.g., D4000 and the Lick indices). We find that the DAP provides robust measurements and errors for the vast majority (>99%) of analyzed spectra. We summarize assessments of the precision and accuracy of our measurements as a function of signal-to-noise. We also provide specific guidance to users regarding the limitations of the data. The MaNGA DAP software is publicly available and we encourage community involvement in its development.
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