Reduced neurosteroid potentiation of GABAA receptors in epilepsy and depolarized hippocampal neurons

OBJECTIVE: Neurosteroids regulate neuronal excitability by potentiating γ-aminobutyric acid type-A receptors (GABARs). In animal models of temporal lobe epilepsy, the neurosteroid sensitivity of GABARs is diminished and GABAR subunit composition is altered. We tested whether similar changes occur in patients with epilepsy and if depolarization-induced increases in neuronal activity can replicate this effect. METHODS: We determined GABAR α4 subunit expression in cortical tissue resected from pediatric epilepsy patients. Modulation of human GABARs by allopregnanolone and Ro15-4513 was measured in Xenopus oocytes using whole-cell patch clamp. To extend the findings obtained using tissue from epilepsy patients, we evaluated GABAR expression and modulation by allopregnanolone and Ro15-4513 in cultured rat hippocampal neurons exposed to high extracellular potassium (HK) to increase neuronal activity. RESULTS: Expression of α4 subunits was increased in pediatric cortical epilepsy specimens encompassing multiple pathologies. The potentiation of GABA-evoked currents by the neurosteroid allopregnanolone was decreased in Xenopus oocytes expressing GABARs isolated from epilepsy patients. Furthermore, receptors isolated from epilepsy but not control tissue were sensitive to potentiation by Ro15-4513, indicating higher expression of α INTERPRETATION: These findings suggest that seizure activity-induced upregulation of

Parched elastohydrodynamic lubrication: Instrumentation and procedure

A counter rotating bearing rig was designed and constructed to study transient elastohydrodynamic lubrication phenomena. New instrumentation is described and test procedures are documented. Ball and race speed measurement systems and the capacitance (film thickness) measurement system were upgraded. Methods for measuring bearing torque and race temperatures were implemented

Liver and extrahepatic contributions to postheparin serum lipase activity of the rat

The influence of the amount of heparin injected on the contributions of liver and of extrahepatic tissues to the lipase activity of postheparin serum of the rat was studied. It was found that when high doses of heparin (20 I.U./100 g bodyweight) were injected, the liver contributes for 63% to the total triacylglycerol lipase activity of postheparin serum. At low heparin levels (0.4 I.U./100 g bodyweight) the lipase activity in the postheparin serum is almost solely derived from the extrahepatic tissues. The activity of the liver enzyme in the postheparin serum was found to increase very fast after heparin injection. 2 min after heparin injection a maximum activity of the liver enzyme in the serum was found. Subsequently the liver en

Siderophore production and the evolution of investment in a public good:An adaptive dynamics approach to kin selection

International audienc

Effects of Internal Configuration on Afterburner Shell Temperatures

A brief investigation was conducted in the altitude wind tunnel to determine the extent to which the afterburner shell cooling problem could be alleviated by internal configuration changes. Data were obtained with and without a cooling liner installed and for variations in the radial fuel distribution and in the radial distribution in flame-seat area. Consideration is given to the effects on both shell temperature and afterburner performance. In the range of fuel-air ratio investigated, the use of a cooling liner resulted in substantial reductions in shell temperature with no penalty in performance. Appreciable reductions in afterburner shell temperature were made possible by control of the radial fuel distribution; however, the effects on performance are uncertain and may depend on other variables not investigated. No direct relation was found between shell temperature and the clearance between the flame holder and the shell; however, some cooling effect may possibly be achieved by varying the clearance

Precise Determination of |V{us}| from Lattice Calculations of Pseudoscalar Decay Constants

Combining the ratio of experimental kaon and pion decay widths, Gamma(K to mu antineutrino{mu} (gamma)) / Gamma(pi to mu \antineutrino (gamma)), with a recent lattice gauge theory calculation of f{K}/f{pi} provides a precise value for the CKM quark mixing matrix element |V{us}|=0.2236(30) or if 3 generation unitarity is assumed |V{us}|=0.2238(30). Comparison with other determinations of that fundamental parameter, implications, and an outlook for future improvements are given

A major QTL corresponding to the Rk locus for resistance to root-knot nematodes in cowpea (Vigna unguiculata L. Walp.).

Key messageGenome resolution of a major QTL associated with the Rk locus in cowpea for resistance to root-knot nematodes has significance for plant breeding programs and R gene characterization. Cowpea (Vigna unguiculata L. Walp.) is a susceptible host of root-knot nematodes (Meloidogyne spp.) (RKN), major plant-parasitic pests in global agriculture. To date, breeding for host resistance in cowpea has relied on phenotypic selection which requires time-consuming and expensive controlled infection assays. To facilitate marker-based selection, we aimed to identify and map quantitative trait loci (QTL) conferring the resistance trait. One recombinant inbred line (RIL) and two F2:3 populations, each derived from a cross between a susceptible and a resistant parent, were genotyped with genome-wide single nucleotide polymorphism (SNP) markers. The populations were screened in the field for root-galling symptoms and/or under growth-chamber conditions for nematode reproduction levels using M. incognita and M. javanica biotypes. One major QTL was mapped consistently on linkage group VuLG11 of each population. By genotyping additional cowpea lines and near-isogenic lines derived from conventional backcrossing, we confirmed that the detected QTL co-localized with the genome region associated with the Rk locus for RKN resistance that has been used in conventional breeding for many decades. This chromosomal location defined with flanking markers will be a valuable target in marker-assisted breeding and for positional cloning of genes controlling RKN resistance

Lubricated Bearing Lifetimes of a Multiply Alkylated Cyclopentane and a Linear Perfluoropolyether Fluid in Oscillatory Motion at Elevated Temperatures in Ultrahigh Vacuum

Bearing life tests in vacuum with three space liquid lubricants, two multiply alkylated cyclopentanes (MACs) and a linear perfluoropolyether (PFPE) were performed. Test conditions included: an 89 N axial load (mean Hertzian stress 0.66 GPa), vacuum level below 7x10(exp -4) Pa, and a +/-30deg dither angle. Dither rate was 75 cycles per minute. Higher (110 to 122 C) and lower temperature tests (75 C) were performed. For the higher temperature tests, the PFPE, Fomblin (Ausimont SpA) Z25 outperformed Pennzane (Shell Global Solutions) X-2000 by more than an order of magnitude. Lubricant evaporation played a key role in these high temperature results. At 75 C, the order was reversed with both Pennzane X-1000 and X-2000 outperforming Fomblin Z25 by more than an order of magnitude. Most Pennzane tests were suspended without failure. The primary failure mechanism in these lower temperature tests was lubricant consumption in the tribocontacts