Exploration of the Neuronal Subtype Specificity of an Ethanol Responsive Gene: Glycogen Synthase Kinase 3 Beta (Gsk3b)

Exploration of the Neuronal Subtype Specificity of an Ethanol Responsive Gene: Glycogen Synthase Kinase 3 Beta (Gsk3b) Dalton Huey, Depts. of Bioinformatics, Biology & Chemistry, A. van der Vaart, G. M. Harris, and M. F. Miles, with Dr. Sarah Golding, Dept. of Biology Previous work done in our laboratory revealed that Glycogen Synthase Kinase 3 Beta (Gsk3b) functions as a hub gene in a network of genes regulated by acute ethanol in the medial prefrontal cortex (mPFC) across a mouse genetic panel. Adult mice treated with acute ethanol showed increased phosphorylation of GSK3B on the Ser9 residue in prefrontal cortex. Subsequent viral-mediated overexpression of Gsk3bin mouse mPFC caused an increase in ethanol consumption and pharmacological inhibition of GSK3B decreased ethanol consumption. However, it is unknown what neuron subtypes are driving this change in behavior. Here, we provide evidence that deletion of Gsk3bin Camk2a+ glutamatergic neurons of the mPFC results in a decrease in ethanol consumption in both continuous and intermittent access drinking paradigms. Furthermore, we have recently designed and validated a plasmid for Cre-dependent overexpression of Gsk3b, along with a Cre-dependent reporter as a control. These plasmids are planned for use in conjunction with different Cre drivers for viral-mediated expression in any cell type. Dissection of the neural circuitry of this ethanol responsive pathway can lead to a better assessment of Gsk3bas a potential target for the treatment of alcohol use disorders. Work supported by grants R01A027581 and P50AA022537 to MFM.https://scholarscompass.vcu.edu/uresposters/1313/thumbnail.jp

Free vibrations of thin-walled semicircular graphite-epoxy composite frames

A detailed study is made of the effects of variations in lamination and material parameters of thin walled composite frames on their vibrational characteristics. The structures considered are semicircular thin walled frames with I and J sections. The flanges and webs of the frames are modelled by using 2-D shell and plate finite elements. A mixed formulation is used with the fundamental unknowns consisting of both the generalized displacements and stress resultants in the frames. The frequencies and modes predicted by the 2-D finite element model are compared with those obtained from experiments, as well as with the predictions of a 1-D thin walled beam finite element model. A detailed study is made of the sensitivity of the vibrational response to variations in the fiber orientation, material properties of the individual layers, and boundary conditions

A perfect storm: An archaeological management crisis in the Mississippi River Delta

Engineered projects resulting in unintended consequences, coastal erosion, subsidence, and sea-level rise are rapidly destroying archaeological sites in the Mississippi River Delta (MRD). The processes of site obliteration are intensifying and accelerating due to anthropogenic transformation of the environment, including cumulative engineered alterations of the landscape and climate change. Combined with increased inundation and erosion from storm surges, hundreds of terrestrial sites formerly located on natural levees, barrier islands, and other coastal landforms are progressively eroded, redeposited, deeply buried, and submerged. These include thousand-year-old earthen mounds and shell middens constructed by Native Americans, as well as centuries-old fishing communities along the coast. These irreplaceable cultural properties can provide crucial information on the unique history and ecology of the MRD. Ongoing studies include consulting with interested parties and implementing data sharing agreements. Re- searchers have formed a consortium of universities and state and federal agencies, and are partnering with culturally affiliated Native American tribes, descendant groups, and coastal communities. The consortium is developing a robust GIS-enabled risk matrix for analyzing threats and effects to endangered sites. It is using the risk matrix to select 30 sites for monitoring, assessment, aerial photogrammetry, and recording environmental data on water table fluctuations. Analysis of action-based scientific data on these imperiled and rapidly disappearing places is urgently needed and will provide the impetus and baseline for future studies. Otherwise, ongoing site destruction will erase any remaining opportunities for learning about Louisiana’s deep history and diverse cultural heritage

Book Review: Pottery Works: Potteries of New York State\u27s Capital District and Upper Hudson Region by Warren F. Broderick and William Bouck

Book Review: Pottery Works: Potteries of New York State\u27s Capital District and Upper Hudson Region by Warren F. Broderick and William Bouck 1995, Dickinson University Press, Canbury, NJ, 285 pages, $59.50

Marketing Montana Christmas Trees

Paper published as Bulletin 2 in the UM Bulletin Forestry Series.https://scholarworks.umt.edu/umforestrybulletin/1000/thumbnail.jp

Gravitational Lensing Statistics as a Probe of Dark Energy

By using the comoving distance, we derive an analytic expression for the optical depth of gravitational lensing, which depends on the redshift to the source and the cosmological model characterized by the cosmic mass density parameter $\Omega_m$, the dark energy density parameter $\Omega_x$ and its equation of state $\omega_x = p_x/\rho_x$. It is shown that, the larger the dark energy density is and the more negative its pressure is, the higher the gravitational lensing probability is. This fact can provide an independent constraint for dark energy.Comment: 9 pages, 2 figure

Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1.

Obesity produces a chronic inflammatory state involving the NFκB pathway, resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1. In this study, we report that these kinases attenuate β-adrenergic signaling in white adipose tissue. Treatment of 3T3-L1 adipocytes with specific inhibitors of these kinases restored β-adrenergic signaling and lipolysis attenuated by TNFα and Poly (I:C). Conversely, overexpression of the kinases reduced induction of Ucp1, lipolysis, cAMP levels, and phosphorylation of hormone sensitive lipase in response to isoproterenol or forskolin. Noncanonical IKKs reduce catecholamine sensitivity by phosphorylating and activating the major adipocyte phosphodiesterase PDE3B. In vivo inhibition of these kinases by treatment of obese mice with the drug amlexanox reversed obesity-induced catecholamine resistance, and restored PKA signaling in response to injection of a β-3 adrenergic agonist. These studies suggest that by reducing production of cAMP in adipocytes, IKKε and TBK1 may contribute to the repression of energy expenditure during obesity. DOI: http://dx.doi.org/10.7554/eLife.01119.001

Optimal search strategies for hidden targets

What is the fastest way of finding a randomly hidden target? This question of general relevance is of vital importance for foraging animals. Experimental observations reveal that the search behaviour of foragers is generally intermittent: active search phases randomly alternate with phases of fast ballistic motion. In this letter, we study the efficiency of this type of two states search strategies, by calculating analytically the mean first passage time at the target. We model the perception mecanism involved in the active search phase by a diffusive process. In this framework, we show that the search strategy is optimal when the average duration of "motion phases" varies like the power either 3/5 or 2/3 of the average duration of "search phases", depending on the regime. This scaling accounts for experimental data over a wide range of species, which suggests that the kinetics of search trajectories is a determining factor optimized by foragers and that the perception activity is adequately described by a diffusion process.Comment: 4 pages, 5 figures. to appear in Phys. Rev. Let

The structures of secretory and dimeric immunoglobulin A

Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here, we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a β-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen-binding fragments (Fabs) and preserves steric accessibility to receptor-binding sites, likely influencing antigen binding and effector functions