The Glutamate and Chloride Permeation Pathways Are Colocalized in Individual Neuronal Glutamate Transporter Subunits

Glutamate transporters have a homotrimeric subunit structure with a large central water-filled cavity that extends partially into the plane of the lipid bilayer (Yernool et al., 2004). In addition to uptake of glutamate, the transporters also mediate a chloride conductance that is increased in the presence of substrate. Whether the chloride channel is located in the central pore of the trimer or within the individual subunits has been controversial. We find that coexpression of wild-type neuronal glutamate transporter EAAT3 subunits with subunits mutated at R447, a residue governing substrate selectivity (Bendahan et al., 2000), results in transport activity consistent with two distinct noninteracting populations of transporters, in agreement with previous work suggesting that each subunit operates independently to transport substrate (Awes et al., 2004; Grewer et al., 2005; Koch and Larsson, 2005). In wild-type homotrimeric transporters, the glutamate concentration dependence of the anion conductance and the kinetics of glutamate flux were isolated and measured, and the anion channel activation was fitted to analytical expressions corresponding to (1) a central pore gated by binding to one or more subunits and (2) a channel pore in each subunit. The data indicate that glutamate-binding sites, transport pathways, and chloride channels reside in individual subunits in a trimer and function independently

Considerations for developing models of multiphase flow in deformable porous media.

This document summarizes research and planning for the development of a numerical simulation capability for nonisothermal multiphase, multicomponent transport in heterogeneous deformable porous materials. Particular attention is given to describing a mathematical formulation for flow in deformable media and for numerical techniques for dealing with phase transitions. A development plan is formulated to provide a computational capability motivated by current and future needs in geosystems management for energy security

High Spatial Resolution Thermal-Infrared Spectroscopy with ALES: Resolved Spectra of the Benchmark Brown Dwarf Binary HD 130948BC

We present 2.9-4.1 micron integral field spectroscopy of the L4+L4 brown dwarf binary HD 130948BC, obtained with the Arizona Lenslets for Exoplanet Spectroscopy (ALES) mode of the Large Binocular Telescope Interferometer (LBTI). The HD 130948 system is a hierarchical triple system, in which the G2V primary is joined by two co-orbiting brown dwarfs. By combining the age of the system with the dynamical masses and luminosities of the substellar companions, we can test evolutionary models of cool brown dwarfs and extra-solar giant planets. Previous near-infrared studies suggest a disagreement between HD 130948BC luminosities and those derived from evolutionary models. We obtained spatially-resolved, low-resolution (R~20) L-band spectra of HD 130948B and C to extend the wavelength coverage into the thermal infrared. Jointly using JHK photometry and ALES L-band spectra for HD 130948BC, we derive atmospheric parameters that are consistent with parameters derived from evolutionary models. We leverage the consistency of these atmospheric quantities to favor a younger age (0.50 \pm 0.07 Gyr) of the system compared to the older age (0.79 \pm 0.22 Gyr) determined with gyrochronology in order to address the luminosity discrepancy.Comment: 17 pages, 9 figures, Accepted to Ap

Effects of a Carbohydrate and Protein Recovery Beverage on Performance in Trained Weightlifters

INTRODUCTION: Previous investigations have examined nutrient timing with untrained subject and less is known about effects in trained subjects. OBJECTIVES: The purpose of this study was to examine the effects of a carbohydrate and protein supplement (CHO+PROT) on performance measures in trained weightlifters. METHODS: 10 trained weightlifters (30.8±5.1 years, 177.4 ±4.0 cm, 94.3 ± 12.4 kg, training age = 5.3 ± 2.9 years) completed a 12 week training program utilizing block periodization. Using a double blind placebo design, jump height, scaled peak power measured in vertical jumps and peak force and rate of force development measured in isometric mid-thigh pulls were compared between groups using a series of 2x4 (group x time) repeated measures ANOVA’s. RESULTS: No significant differences (p \u3e 0.05) were observed between treatment and placebo groups in respect to measures of jump height and peak power with weighted and unweighted jumps. Likewise, no statistical differences (p \u3e 0.05) were observed for peak force or rate of force development with isometric mid-thigh pulls. CONCLUSION: These findings indicate that a CHO+PROT supplement provided no additional performance benefits compared to a placebo within a 12 week block periodization protocol in trained weightlifters

FPGA-Based Tracklet Approach to Level-1 Track Finding at CMS for the HL-LHC

During the High Luminosity LHC, the CMS detector will need charged particle tracking at the hardware trigger level to maintain a manageable trigger rate and achieve its physics goals. The tracklet approach is a track-finding algorithm based on a road-search algorithm that has been implemented on commercially available FPGA technology. The tracklet algorithm has achieved high performance in track-finding and completes tracking within 3.4 $\mu$s on a Xilinx Virtex-7 FPGA. An overview of the algorithm and its implementation on an FPGA is given, results are shown from a demonstrator test stand and system performance studies are presented.Comment: Submitted to proceedings of Connecting The Dots/Intelligent Trackers 2017, Orsay, Franc

Insulin Responsiveness in Metabolic Syndrome after Eight Weeks of Cycle Training

Introduction Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Methods Eighteen nondiabetic, sedentary subjects, 11 with the metabolic syndrome, participated in 8 wk of increasing intensity stationary cycle training. Results Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (V˙O2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. The activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of type 2x fibers decreased with a concomitant increase in type 2a mixed fibers in the control subjects, but in metabolic syndrome, type 2x fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups, and GLUT4 expression increased in the metabolic syndrome subjects. The excess phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. Conclusions In the absence of weight loss, the cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis and increased the expression of insulin receptors and GLUT4 in muscle but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337, and this is not ameliorated by 8 wk of endurance exercise training

Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine

Objective Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques. Methods and results Swine were rendered diabetic through streptozotocin injection and hyperlipidemic through a high fat diet. Arterial remodeling and local endothelial shear stress (ESS) were assessed using intravascular ultrasound, coronary angiography and computational fluid dynamics at weeks 23 and 30. Coronary arteries were harvested and 142 arterial subsegments were analyzed using histomorphologic staining, immunostaining and real time PCR. Heparanase staining and activity was increased in arterial segments with low ESS, in lesions with thin cap fibroatheroma (TCFA) morphology and in lesions with severely degraded internal elastic laminae. In addition, heparanase staining co-localized with staining for CD45 and MMP-2 within atherosclerotic plaques. Dual staining with gelatinase zymography and heparanase immunohistochemical staining demonstrated co-localization of matrix metalloprotease activity with heparanase staining. A heparanase enzymatic activity assay demonstrated increased activity in TCFA lesions, subsegments with low ESS and in macrophages treated with oxidized LDL or angiotensin II. Conclusions Taken together, our results support a critical role for heparanase in the development of vulnerable plaques and suggest a novel therapeutic target for the treatment of atherosclerosis.Novartis (Firm)Boston Scientific CorporationNational Institutes of Health (U.S.) (Grant R01 GM49039

Hormone and Adpokine Alterations across Eleven Weeks of Training in Division I Collegiate Throwers: an Exploratory Study

Conceptually, it is important to understand the underlying physiological mechanisms of any training program model. This understanding aids the coach/sport scientist in making better choices in manipulating variables in formulating the training model. These underlying mechanisms can be associated with training variable manipulation and fatigue management aspects as well as the overall health of the athlete. Hormone and cytokine concentrations can be linked to alterations resulting from the manipulation of training variables and to subsequent alterations in performance (Haff et al., 2008; Ishigaki et al., 2005; Jurimae et al., 2010; Stone et al., 2007). For example, alterations in the testosterone: cortisol ratio (T:C) has been associated with alterations in training volume as well as physiological aspects such as lean body mass (LBM), fat content and strength/power performance (Haff et al., 2008; Häkkinen, 1989; Stone et al., 2007). Although cytokine production is part of the adaptive process, markedly increased/excessive cytokine production has been related poor fatigue management and over training (Angeli et al., 2004; Jurimae et al., 2010; Smith, 2000). The present study followed NCAA division 1 (D-1) collegiate throwers over a period of an 11 week fall semester preparation-phase block form of periodized training. Volume and intensity alterations and their effects on physiological variables (e.g. neuromuscular, hormonal, cytokine) are a key component in understanding the effects of a training process. Alterations in these physiological variables were tracked over time in Division-1 collegiate throwers