An atlas of Caenorhabditis elegans chemoreceptor expression

One goal of modern day neuroscience is the establishment of molecular maps that assign unique features to individual neuron types. Such maps provide important starting points for neuron classification, for functional analysis, and for developmental studies aimed at defining the molecular mechanisms of neuron identity acquisition and neuron identity diversification. In this resource paper, we describe a nervous system-wide map of the potential expression sites of 244 members of the largest gene family in the C. elegans genome, rhodopsin-like (class A) G-protein-coupled receptor (GPCR) chemoreceptors, using classic gfp reporter gene technology. We cover representatives of all sequence families of chemoreceptor GPCRs, some of which were previously entirely uncharacterized. Most reporters are expressed in a very restricted number of cells, often just in single cells. We assign GPCR reporter expression to all but two of the 37 sensory neuron classes of the sex-shared, core nervous system. Some sensory neurons express a very small number of receptors, while others, particularly nociceptive neurons, coexpress several dozen GPCR reporter genes. GPCR reporters are also expressed in a wide range of inter- and motorneurons, as well as non-neuronal cells, suggesting that GPCRs may constitute receptors not just for environmental signals, but also for internal cues. We observe only one notable, frequent association of coexpression patterns, namely in one nociceptive amphid (ASH) and two nociceptive phasmid sensory neurons (PHA, PHB). We identified GPCRs with sexually dimorphic expression and several GPCR reporters that are expressed in a left/right asymmetric manner. We identified a substantial degree of GPCR expression plasticity; particularly in the context of the environmentally-induced dauer diapause stage when one third of all tested GPCRs alter the cellular specificity of their expression within and outside the nervous system. Intriguingly, in a number of cases, the dauer-specific alterations of GPCR reporter expression in specific neuron classes are maintained during postdauer life and in some case new patterns are induced post-dauer, demonstrating that GPCR gene expression may serve as traits of life history. Taken together, our resource provides an entry point for functional studies and also offers a host of molecular markers for studying molecular patterning and plasticity of the nervous system

Histone arginine methylation in cocaine action in the nucleus accumbens

Repeated cocaine exposure regulates transcriptional regulation within the nucleus accumbens (NAc), and epigenetic mechanisms - such as histone acetylation and methylation on Lys residues - have been linked to these lasting actions of cocaine. In contrast to Lys methylation, the role of histone Arg (R) methylation remains underexplored in addiction models. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, including self-administration, and in the NAc of cocaine-addicted humans. Such PRMT6 down-regulation occurs selectively in NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2-MSNs), with opposite regulation occurring in D1-MSNs, and serves to protect against cocaine-induced addictive-like behavioral abnormalities. Using ChIP-seq, we identified Src kinase signaling inhibitor 1 (Srcin1; also referred to as p140Cap) as a key gene target for reduced H3R2me2a binding, and found that consequent Srcin1 induction in the NAc decreases Src signaling, cocaine reward, and the motiv ation to self-administer cocaine. Taken together, these findings suggest that suppression of Src signaling in NAc D2-MSNs, via PRMT6 and H3R2me2a down-regulation, functions as a homeostatic brake to restrain cocaine action, and provide novel candidates for the development of treatments for cocaine addiction. Keywords: histone arginine (R) methylation; drug addiction; medium spiny neurons; ChIP-seq; Sr

Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior

Tidal dynamics in the Gulf of Maine and New England Shelf : an application of FVCOM

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): C12010, doi:10.1029/2011JC007054.The unstructured-grid, Finite-Volume Community Ocean Model (FVCOM) was used to simulate the tides in the Gulf of Maine (GoM) and New England Shelf (NES) for homogeneous and summer stratified conditions. FVCOM captures the near-resonant nature of the semidiurnal tide and energy flux in the GoM and the complex dynamics governing the tide in the NES. Stratification has limited impact on tidal elevation, but can significantly modify the tidal current profile. Internal tides are energetic in the stratified regions over steep bottom topography, but their contribution to the total tidal energy flux is only significant over the northeast flank of Georges Bank. The model suggests that the tidal flushing-induced eddy east of Monomoy Island is the dynamic basis for the locally observed phase lead of the M2 tide. The southward propagating tidal wave east of Cape Cod encounters the northeastward propagating tidal wave from the NES south of Nantucket Island, forming a zone of minimum sea level along a southeast-oriented line from Nantucket Island. These two waves are characterized by linear dynamics in which bottom friction and advection are negligible in the momentum balance, but their superposition leads to a strong nonlinear current interaction and large bottom stress in the zone of lowest sea elevation.This research is supported by the U.S. GLOBEC Northwest Atlantic/Georges Bank Program NSF (OCE-0234545, 0227679, 0606928, 0726851 and 0814505) to Changsheng Chen and Qixchun Xu and NSF grant (OCE-02-27679) and the WHOI Smith Chair to Robert Beardsley and Richard Limeburner. The tidal model-data comparison on Nantucket Sound/Shoals is partially the result of research sponsored by the MIT Sea Grant College Program, under NOAA grant NA06OAR4170019, MIT SG project 2006-R/RC-102, 2006-R/RC-103, 2006-R/RC-102, 2006-R/RC-107, 2008-R/RC-107), 2010-R/RC-116 and the NOAA NERACOOS Program for the UMASS team. C. Chen’s contribution is also supported by Shanghai Ocean University International Cooperation Program (A-2302-11-0003), the Program of Science and Technology Commission of Shanghai Municipality (09320503700), the Leading Academic Discipline Project of Shanghai Municipal Education Commission (project J50702), and Zhi jiang Scholar and 111 project funds of the State Key Laboratory for Estuarine and Coastal Research, East China Normal University (ECNU).2012-06-1

Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons

Repeated cocaine administration increases the dendritic arborization of nucleus accumbens neurons, but the underlying signaling events remain unknown. Here, we show that repeated cocaine negatively regulates the active form of Rac1, a small GTPase that controls actin remodeling in other systems. We show further, using viral-mediated gene transfer, that overexpression of a dominant negative mutant of Rac1, or local knockout of Rac1 from floxed Rac1 mice, is sufficient to increase the density of immature dendritic spines on nucleus accumbens neurons, whereas overexpression of a constitutively active Rac1 mutant, or light activation of a photoactivatible form of Rac1, blocks the ability of repeated cocaine to produce this effect. Downregulation of Rac1 activity in nucleus accumbens likewise promotes behavioral responses to cocaine, with Rac1 activation producing the opposite effect. These findings establish an important role for Rac1 signaling in mediating structural and behavioral plasticity to cocaine

Determination of Frequency-Dependent Shear Modulus of Viscoelastic Layer via a Constrained Sandwich Beam

Viscoelastic material can significantly reduce the vibration energy and radiated noise of a structure, so it is widely used in lightweight sandwich structures. The accurate and efficient determination of the frequency-dependent complex modulus of viscoelastic material is the basis for the correct analysis of the vibro-acoustic behavior of sandwich structures. Based on the behavior of a sandwich beam whose core is a viscoelastic layer, a combined theoretical and experimental study is proposed to characterize the properties of the viscoelastic layer constituting the core. In this method, the viscoelastic layer is bonded between two constraining layers. Then, a genetic algorithm is used to fit the analytical solution of the frequency¬ response function of the free–free constrained beam to the measured result, and then the frequency-dependent complex modulus is estimated for the viscoelastic layer. Moreover, by varying the length of the beams, it is possible to characterize the frequency-dependent complex modulus of the viscoelastic material over a wide frequency range. Finally, the characterized frequency-dependent complex modulus is imported into a finite element model to compute the complex natural frequencies of a sandwich beam, and a comparison of the simulated and measured results displays that the errors in the real parts are within 2.33% and the errors in the imaginary parts are within 3.31%. It is confirmed that the proposed method is feasible, accurate, and reliable. This provides essential technical support for improving the acoustic vibration characteristics of sandwich panels by introducing viscoelastic materials

Forecasting the crowd: An effective and efficient neural network for citywide crowd information prediction at a fine spatio-temporal scale

Modelling and forecasting citywide crowd information (e.g., crowd volume of a region, the inflow of crowds into a region, outflow of crowds from a region) at a fine spatio-temporal scale is crucial for urban and transport planning, city management, public safety, and traffic management. However, this is a challenging task due to its complex spatial and temporal dependences. This paper proposes an effective and efficient model to reduce the training time cost while maintaining predictive accuracy in forecasting citywide crowd information at a fine spatio-temporal scale. Our model integrates Gated Recurrent Unit (GRU), convolutional neural network (CNN), and k-nearest neighbors (k-NN) to jointly capture the spatial and temporal dependences between two regions in a city. The evaluation with two different datasets in two different cities shows that compared to the state-of-the-art baselines, our model has better predictive accuracy (reducing the mean absolute errors MAEs by 20.99% on average) and a lower training time cost (reducing the time cost to only 26.16% on average of that of the baselines). Our model also has better abilities in making accurate predictions with low time cost under the influences of large-scale special events (when massive crowds of people are gathering in a short time) and for regions with high and irregular crowd changes. In summary, our model is an effective, efficient, and reliable method for forecasting citywide crowd information at a fine spatio-temporal scale, and has a high potential for many applications, such as city management, public safety, and transportation