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ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity.
It has been postulated that synaptic potentiation during waking is offset by a homoeostatic reduction in net synaptic strength during sleep. However, molecular mechanisms to support such a process are lacking. Here we demonstrate that deficiencies in the RNA-editing gene Adar increase sleep due to synaptic dysfunction in glutamatergic neurons in Drosophila. Specifically, the vesicular glutamate transporter is upregulated, leading to over-activation of NMDA receptors, and the reserve pool of glutamatergic synaptic vesicles is selectively expanded in Adar mutants. Collectively these changes lead to sustained neurotransmitter release under conditions that would otherwise result in synaptic depression. We propose that a shift in the balance from synaptic depression towards synaptic potentiation in sleep-promoting neurons underlies the increased sleep pressure of Adar-deficient animals. Our findings provide a plausible molecular mechanism linking sleep and synaptic plasticity
Structural Analysis and Deletion Mutagenesis Define Regions of QUIVER/SLEEPLESS that Are Responsible for Interactions with Shaker-Type Potassium Channels and Nicotinic Acetylcholine Receptors.
Ly6 proteins are endogenous prototoxins found in most animals. They show striking structural and functional parallels to snake α-neurotoxins, including regulation of ion channels and cholinergic signaling. However, the structural contributions of Ly6 proteins to regulation of effector molecules is poorly understood. This question is particularly relevant to the Ly6 protein QUIVER/SLEEPLESS (QVR/SSS), which has previously been shown to suppress excitability and synaptic transmission by upregulating potassium (K) channels and downregulating nicotinic acetylcholine receptors (nAChRs) in wake-promoting neurons to facilitate sleep in Drosophila. Using deletion mutagenesis, co-immunoprecipitations, ion flux assays, surface labeling and confocal microscopy, we demonstrate that only loop 2 is required for many of the previously described properties of SSS in transfected cells, including interactions with K channels and nAChRs. Collectively our data suggest that QVR/SSS, and by extension perhaps other Ly6 proteins, target effector molecules using limited protein motifs. Mapping these motifs may be useful in rational design of drugs that mimic or suppress Ly6-effector interactions to modulate nervous system function
Efficient Methods to Assimilate Satellite Retrievals Based on Information Content
One of the outstanding problems in data assimilation has been and continues to be how best to utilize satellite data while balancing the tradeoff between accuracy and computational cost. A number of weather prediction centers have recently achieved remarkable success in improving their forecast skill by changing the method by which satellite data are assimilated into the forecast model from the traditional approach of assimilating retrievals to the direct assimilation of radiances in a variational framework. The operational implementation of such a substantial change in methodology involves a great number of technical details, e.g., pertaining to quality control procedures, systematic error correction techniques, and tuning of the statistical parameters in the analysis algorithm. Although there are clear theoretical advantages to the direct radiance assimilation approach, it is not obvious at all to what extent the improvements that have been obtained so far can be attributed to the change in methodology, or to various technical aspects of the implementation. The issue is of interest because retrieval assimilation retains many practical and logistical advantages which may become even more significant in the near future when increasingly high-volume data sources become available. The central question we address here is: how much improvement can we expect from assimilating radiances rather than retrievals, all other things being equal? We compare the two approaches in a simplified one-dimensional theoretical framework, in which problems related to quality control and systematic error correction are conveniently absent. By assuming a perfect radiative transfer model and perfect knowledge of radiance and background error covariances, we are able to formulate a nonlinear local error analysis for each assimilation method. Direct radiance assimilation is optimal in this idealized context, while the traditional method of assimilating retrievals is suboptimal because it ignores the cross-covariances between background errors and retrieval errors. We show that interactive retrieval assimilation (where the same background used for assimilation is also used in the retrieval step) is equivalent to direct assimilation of radiances with suboptimal analysis weights. We illustrate and extend these theoretical arguments with several one-dimensional assimilation experiments, where we estimate vertical atmospheric profiles using simulated data from both the High-resolution InfraRed Sounder 2 (HIRS2) and the future Atmospheric InfraRed Sounder (AIRS)
A linear method for the retrieval of sun-induced chlorophyll fluorescence from GOME-2 and SCIAMACHY data
Global retrievals of near-infrared sun-induced chlorophyll fluorescence (SIF)
have been achieved in the last few years by means of a number of space-borne
atmospheric spectrometers. Here, we present a new retrieval method for medium
spectral resolution instruments such as the Global Ozone Monitoring
Experiment-2 (GOME-2) and the SCanning Imaging Absorption SpectroMeter for
Atmospheric CHartographY (SCIAMACHY). Building upon the previous work by
Guanter et al. (2013) and Joiner et al. (2013), our approach provides a
solution for the selection of the number of free parameters. In particular, a
backward elimination algorithm is applied to optimize the number of
coefficients to fit, which reduces also the retrieval noise and selects the
number of state vector elements automatically. A sensitivity analysis with
simulated spectra has been utilized to evaluate the performance of our
retrieval approach. The method has also been applied to estimate SIF at 740 nm
from real spectra from GOME-2 and for the first time, from SCIAMACHY. We find
a good correspondence of the absolute SIF values and the spatial patterns from
the two sensors, which suggests the robustness of the proposed retrieval
method. In addition, we compare our results to existing SIF data sets, examine
uncertainties and use our GOME-2 retrievals to show empirically the relatively
low sensitivity of the SIF retrieval to cloud contamination
Neurodegeneration: Paying It Off with Sleep
SummaryA new study in fruit flies suggests modulation of neural activity links sleep and Alzheimer’s disease. Both sleep loss and amyloid beta increase neural excitability, which reinforces the accumulation of amyloid beta and shortens lifespan
Potential of the TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor for the monitoring of terrestrial chlorophyll fluorescence
Global monitoring of sun-induced chlorophyll fluorescence (SIF) is improving our knowledge about the photosynthetic functioning of terrestrial ecosystems. The feasibility of SIF retrievals from spaceborne atmospheric spectrometers has been demonstrated by a number of studies in the last years. In this work, we investigate the potential of the upcoming TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor satellite mission for SIF retrieval. TROPOMI will sample the 675–775 nm spectral window with a spectral resolution of 0.5 nm and a pixel size of 7 km × 7 km. We use an extensive set of simulated TROPOMI data in order to assess the uncertainty of single SIF retrievals and subsequent spatio-temporal composites. Our results illustrate the enormous improvement in SIF monitoring achievable with TROPOMI with respect to comparable spectrometers currently in-flight, such as the Global Ozone Monitoring Experiment-2 (GOME-2) instrument. We find that TROPOMI can reduce global uncertainties in SIF mapping by more than a factor of 2 with respect to GOME-2, which comes together with an approximately 5-fold improvement in spatial sampling. Finally, we discuss the potential of TROPOMI to map other important vegetation parameters at a global scale with moderate spatial resolution and short revisit time. Those include leaf photosynthetic pigments and proxies for canopy structure, which will complement SIF retrievals for a self-contained description of vegetation condition and functioning
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