Clustering of nicotinic acetylcholine receptors: from the neuromuscular junction to interneuronal synapses

Fast and accurate synaptic transmission requires high-density accumulation of neurotransmitter receptors in the postsynaptic membrane. During development of the neuromuscular junction, clustering of acetylcholine receptors (AChR) is one of the first signs of postsynaptic specialization and is induced by nerve-released agrin. Recent studies have revealed that different mechanisms regulate assembly vs stabilization of AChR clusters and of the postsynaptic apparatus. MuSK, a receptor tyrosine kinase and component of the agrin receptor, and rapsyn, an AChR-associated anchoring protein, play crucial roles in the postsynaptic assembly. Once formed, AChR clusters and the postsynaptic membrane are stabilized by components of the dystrophin/utrophin glycoprotein complex, some of which also direct aspects of synaptic maturation such as formation of postjunctional folds. Nicotinic receptors are also expressed across the peripheral and central nervous system (PNS/CNS). These receptors are localized not only at the pre- but also at the postsynaptic sites where they carry out major synaptic transmission. In neurons, they are found as clusters at synaptic or extrasynaptic sites, suggesting that different mechanisms might underlie this specific localization of nicotinic receptors. This review summarizes the current knowledge about formation and stabilization of the postsynaptic apparatus at the neuromuscular junction and extends this to explore the synaptic structures of interneuronal cholinergic synapse

Electronic density of states derived from thermodynamic critical field curves for underdoped La-Sr-Cu-O

Thermodynamic critical field curves have been measured for $La_{2-x}Sr_{x}CuO_{4+\delta}$ over the full range of carrier concentrations where superconductivity occurs in order to determine changes in the normal state density of states with carrier concentration. There is a substantial window in the $H-T$ plane where the measurements are possible because the samples are both thermodynamically reversible and the temperature is low enough that vortex fluctuations are not important. In this window, the data fit Hao-Clem rather well, so this model is used to determine $H_c$ and $\kappa_c$ for each temperature and carrier concentration. Using N(0) and the ratio of the energy gap to transition temperature, $\Delta (0)/k_BT_c$, as fitting parameters, the $H_c vs T$ curves give $\Delta (0)/k_BT_c \sim 2.0$ over the whole range of $x$. Values of N(0) remain rather constant in the optimum-doped and overdoped regime, but drops quickly toward zero in the underdoped regime.

Assessing the Geomorphic Evolution and Hydrographic Changes Induced by Winter Storms along the Louisiana Coast

The influence that cold front passages have on Louisiana coastal environments, including land loss and land building processes, has been the primary topic of this multidisciplinary research. This research has combined meteorological, remote sensing, and coastal expertise from the University of Wisconsin (UW) and Louisiana State University (LSU). Analyzed data sets include remotely sensed radiometric data (AVHRR on NOAA-12,13,14, Multispectral Atmospheric Mapping Sensor (MAMS) and MODIS Airborne Simulator (MAS) on NASA ER-2), U.S. Army Corps of Engineers (USACE) water level data, water quality data from the Coastal Studies Institute (CSI) at LSU, USACE river discharge data, National Weather Service (NWS) and CSI wind in sitzi measurements, geomorphic measurements from aerial photography (NASA ER-2 and Learjet), and CSI ground based sediment burial pipes (for monitoring topographic change along the Louisiana coast) and sediment cores. The work reported here-in is a continuation of an initial investigation into coastal Louisiana landform modification by cold front systems. That initial effort demonstrated the importance of cold front winds in the Atchafalaya Bay sediment plume distribution (Moeller et al.), documented the sediment transport and deposition process of the western Louisiana coast (Huh et al.) and developed tools (e.g. water types identification, suspended solids estimation) from multispectral radiometric data for application to the current study. This study has extended that work, developing a Geomorphic Impact Index (GI(sup 2)) for relating atmospheric forcing to coastal response and new tools to measure water motion and sediment transport

Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility

Advanced Polymer Technology for Containing and Immobilizing Strontium-90 in the Subsurface - 8361

Many Department of Energy (DOE) sites, including Idaho and Hanford, have heavy metals and/or radionuclides (e.g. strontium-90) present that are strongly adsorbed in the vadose zone, but which nevertheless are propagating toward the water table. A key challenge for immobilization of these contaminants is bringing the chosen amendment or remediation technology into contact with the contaminated porous medium, while ensuring that contaminated water and colloids do not escape. This is particularly challenging when the subsurface geology is complex and highly heterogeneous, as is the case at many DOE sites. The Idaho National Laboratory (INL) in collaboration with the University of Texas at Austin (UT) has conducted research sponsored through the DOE Office of Environmental Management (EM) Advanced Remediation Technologies Phase I program that successfully demonstrated application of a novel, pH-triggered advanced polymer for creating a physical barrier that prevents heavy metals and radionuclides in vadose zone soil and soil-pore water from migrating to the groundwater. The focus of this paper is on the column and sandbox experiments conducted by researchers at the Idaho National Laboratory in support of the Phase I program objectives. Proof of these concepts provides a technology basis for confining or isolating a volume of contaminated groundwater, to be implemented in future investigations at the Vadose Zone Research Park (VZRP) at INL

Development of a novel 3D culture system for screening features of a complex implantable device for CNS repair

Tubular scaffolds which incorporate a variety of micro- and nanotopographies have a wide application potential in tissue engineering especially for the repair of spinal cord injury (SCI). We aim to produce metabolically active differentiated tissues within such tubes, as it is crucially important to evaluate the biological performance of the three-dimensional (3D) scaffold and optimize the bioprocesses for tissue culture. Because of the complex 3D configuration and the presence of various topographies, it is rarely possible to observe and analyze cells within such scaffolds in situ. Thus, we aim to develop scaled down mini-chambers as simplified in vitro simulation systems, to bridge the gap between two-dimensional (2D) cell cultures on structured substrates and three-dimensional (3D) tissue culture. The mini-chambers were manipulated to systematically simulate and evaluate the influences of gravity, topography, fluid flow, and scaffold dimension on three exemplary cell models that play a role in CNS repair (i.e., cortical astrocytes, fibroblasts, and myelinating cultures) within a tubular scaffold created by rolling up a microstructured membrane. Since we use CNS myelinating cultures, we can confirm that the scaffold does not affect neural cell differentiation. It was found that heterogeneous cell distribution within the tubular constructs was caused by a combination of gravity, fluid flow, topography, and scaffold configuration, while cell survival was influenced by scaffold length, porosity, and thickness. This research demonstrates that the mini-chambers represent a viable, novel, scale down approach for the evaluation of complex 3D scaffolds as well as providing a microbioprocessing strategy for tissue engineering and the potential repair of SCI

Evaluation of cognitive function in adult rhesus monkeys using the finger maze test

In research on cognitive function, the use of experimental animals is essential for the study of human cognitive processes and mechanisms. Furthermore, non-human primates are necessary for understanding higher cognitive functions in humans. However, there are few cognitive function tests available for non-human primates, Thus, we modified a finger maze test for application to non-human primates. In this study, we assessed learning and memory in 12 adult rhesus monkeys using a finger maze test that was developed to assess cognitive functions in captive non-human primates. The monkeys were trained with moving rewards indicating the correct direction, which allowed the monkeys to obtain the reward. Following training, subjects completed a learning trial and a memory trial two months later. Although the time required for training varied among the monkeys, 11 out of 12 monkeys completed the training and achieved a high success rate in the learning trial as well as in the memory trial conducted 2 months later. This is the first study to apply the finger maze test to adult rhesus monkeys. The finger maze test enabled us to assess learning and memory in several adult rhesus monkeys simultaneously

Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage