Transport systems specific for L-glutamate and L-aspartate play an important role in the termination of neurotransmitter signals at excitatory synapses. We describe here the structure and function of a 66-kDa glycoprotein that was purified from rat brain and identified as an L-glutamate/L-aspartate transporter (GLAST). A GLAST-specific cDNA clone was isolated from a rat brain cDNA library. The cDNA insert encodes a polypeptide with 543 amino acid residues (59,697 Da). The amino acid sequence of GLAST suggests a distinctive structure and membrane topology, with some conserved motifs also present in prokaryotic glutamate transporters. The transporter function has been verified by amino acid uptake studies in the Xenopus laevis oocyte system. GLAST is specific for L-glutamate and L-aspartate, shows strict dependence on Na ions, and is inhibited by DL-threo-3-hydroxy-aspartate. In situ hybridization reveals a strikingly high density of GLAST mRNA in the Purkinje cell layer of cerebellum, presumably in the Bergmann glia cells, and a less dense distribution throughout the cerebrum. These data suggest that GLAST may be involved in the regulation of neurotransmitter concentration in central nervous system.
For the Emden-Fowler equation in Ω ⊂ R , the connectivity of the trivial solution and the one-point blow-up singular limit is studied with respect to the parameter λ > 0. The connectivity is assured when the domain Ω is simply connected and the total mass tends to 8 π from below, which is a generalization for the case that Ω is a ball.
At the National Meteorological Center (NMC), a new analysis system is being extensively tested for possible use in the operational global data assimilation system. This analysis system is called the spectral statistical-interpolation (SSI) analysis system because the spectral coefficients used in the NMC spectral model are analyzed directly using the same basic equations as statistical (optimal) interpolation. Results from several months of parallel testing with the NMC spectral model have been very encouraging. Favorable features include smoother analysis increments, greatly reduced changes from initialization, and significant improvement of 1-5-day forecasts. Although the analysis is formulated as a variational problem, the objective function being minimized is formally the same one that forms the basis of all existing optimal interpolation schemes. This objective function is a combination of forecast and observation deviations from the desired analysis, weighted by the inverses of the corresponding forecast- and observation-error covariance matrices. There are two principal differences in how the SSI implements the minimization of this functional as compared to the current OI used at NMC. First, the analysis variables are spectral coefficients instead of gridpoint values. Second, all observations are used at once to solve a single global problem. No local approximations are made, and there is no special data selection. Because of these differences, it is straightforward to include unconventional data, such as radiances, in the analysis. Currently temperature, wind, surface pressure, mixing ratio, and Special Sensor Microwave/Imager (SSM/I)total precipitable water can be used as the observation variables. Soon to be added are the scatterometer surface winds. This paper provides a detailed description of the SSI and presents a few results.
Drug and Therapeutics Bulletin (DTB) has moved home. At the end of November 2006, ownership of DTB was transferred from Which? to the BMJ Group. Here, in the first article published under the new banner, we explain the move and its implications.,Fifty-one patients with amaurosis fugax were followed for a mean of 4.9 years from their first attack. Females predominated under the age of 50 years in contrast to men who presented in the older age group. Minor permanent visual sequelae occurred in only three patients, but cerebral vascular symptoms were present at some time in just under half the group. A range of abnormalities was identified on cerebral angiography and some of these correlated with certain clinical findings. Twenty patients were treated by surgery and permanent relief of significant improvement in symptoms occurred in 14. A group of patients who were at greater risk of cerebral vascular complications following angiography and surgery was identified. It is concluded that careful patient selection is necessary before surgery is recommended but that in a significant number of cases with relatively focal atheroma confined to one proximal internal carotid artery an excellent long term result following surgery may be expected.,Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.