ARL1 and membrane traffic in Saccharomyces cerevisiae

To examine the functions of the Arf-like protein, Arl1p, in Saccharomyces cerevisiae, a null allele, arl1delta::HIS3, was constructed in two strains. In one background only, loss of ARL1 resulted in temperature-sensitive (ts) growth (suppressed on high-osmolarity media). Allelic variation at the SSD1 locus accounted for differences between strains. Strains lacking ARL1 exhibited several defects in membrane traffic. First, arl1delta strains secreted less protein as measured by TCA-precipitable radioactivity found in the media of [(35)S]-labelled cells. A portion of newly synthesized carboxypeptidase Y (CPY) was secreted rather than correctly targeted to the vacuole. Uptake of the fluid-phase marker, lucifer yellow, was reduced. All these phenotypes were exacerbated in an ssd1 background. The ts phenotype of the arl1deltassd1 strain was suppressed by YPT1, the yeast Rab1a homologue, suggesting that ARL1 and YPT1 have partially overlapping functions. These findings demonstrate that ARL1 encodes a regulator of membrane traffic.     

An Integrated Approach to High Integrity Software Verification

Using automated reasoning techniques, we tackle the niche activity of proving that a program is free from run-time exceptions. Such a property is particularly valuable in high integrity software, for example, safety- or security-critical applications. The context for our work is the SPARK Approach for the development of high integrity software. The SPARK Approach provides a significant degree of automation in proving exception freedom. Where this automation fails, however, the programmer is burdened with the task of interactively constructing a proof and possibly also having to supply auxiliary program annotations. We minimize this burden by increasing the automation, through an integration of proof planning and a program analysis oracle. We advocate a ‘cooperative’ integration, where proof-failure analysis directly constrains the search for auxiliary program annotations. The approach has been successfully tested on industrial data.     

Some Thermal Properties of a Copper–Tin Alloy

The thermal properties (heat capacity, thermal diffusivity, and electrical resistivity) of a Cu + 10 wt% Sn alloy in both solid and liquid phases have been reported. Using these values it was confirmed that the Lorenz relation is suitable for obtaining thermal conductivity from electrical resistivity in the liquid phase of this alloy. Also, the temperature differential (d/dT) obtained from such an approach was in excellent agreement with the thermal conductivity values calculated from thermal diffusivity.     

Shielded gradients. And the general solution to the near field problem of electromagnet design

The development of actively shielded gradients introduced the concept of surface distributed conductors for the production of electromagnetic fields. This represented the most significant step in electromagnetic coil design since the discovery of the electromagnetic field equations a century earlier. Further, the associated recognition of the Biot-Savart equation as the convolution of the current distribution function with the inverse square spatial dispersion, permits a solution of the general near field problem with implications for other scientific fields that have yet to be explored.     

Monaural and binaural story recall by schizophrenic subjects.

P. Green and other investigators have reported that schizophrenic Ss have poorer recall of stories presented to both ears than to the single best ear (binaural deficit) and poorer recall of stories presented to the left ear than to the right ear (monaural asymmetry) than do normal control Ss. These studies are plagued by potential methodological problems, including differences in overall accuracy, which artifactually affect the difference scores, and scoring methods that are vulnerable to systematic bias. In this study, scores of schizophrenic, bipolar, and normal control Ss on the Auditory Comprehension Test were compared. Scoring bias was avoided by the use of blind scoring and a revised scoring manual, and artifactual effects of accuracy were considered in interpreting the results. Contrary to previous findings, the groups did not differ on either monaural asymmetry or binaural deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term potentiation in vivo in layers II/III of rat barrel cortex

Long-term potentiation was studied in vivo in the rat barrel cortex. It was found that LTP lasting several hours could be induced in layer II/III by tetanic stimuli applied in layer IV. The probability of inducing LTP at a given site was high (86%) provided that the electrodes were not displaced too far horizontally. LTP was not observed if the stimulating electrode was located on the far side of the neighbouring barrel-column from the recording electrode. The strongest LTP was induced by stimulating layer IV septal locations or the edge of the barrel and recording in the near half of the neighbouring barrel. However, examples were found of LTP from layer IV to II/III within the same barrel, within the same septum and from barrel to adjacent septum. The probability of inducing LTP on a particular occasion was greatly increased by iontophoresis of bicuculline at the recording site during the tetanus (from 20 to 55% judged by a change in peak amplitude). The average increase in the peak amplitude was 29 +/- 3.2% for protocol 1 (urethane anesthesia, monopolar stimulation) and 23 +/- 7% for protocol 2 (barbiturate anesthesia, bipolar stimulation). The probability of inducing LTP was greater if the first tetanus was accompanied by BMI application (67%) than for any subsequent attempts (39%). These results suggest it should be possible to study the effect of LTP on sensory processing in defined positions within the barrel field.     

Characterisation of erythrocyte shapes and sizes by NMR diffusion-diffraction of water: correlations with electron micrographs

Irradiation of the mammalian foetus produces a broad spectrum of congenital abnormalities, growth retardations, developmental delays, and functional deficits, depending upon the dose and the specific gestational phase of irradiation. The developing brain is particularly susceptible to production of deleterious effects, with decreased brain size, behavioural alterations, and mental retardation having been documented. Supplementing the limited human data, rodent models have been extensively used to investigate the specific processes by which relatively low doses, with correspondingly minor cellular damage to the developing neocortex, can produce dramatic postnatal consequences in brain structure and function. The effects of a variety of physical (dose, linear energy transfer, dose rate, fractionation) and biological (species, strain, gestational age, time course post-irradiation) parameters have been examined in an attempt to provide much needed information on such critical aspects as dose response, threshold doses for effect, and extrapolation to human risk estimates. Various acute cellular responses (e.g. appearance of pyknotic cells and macrophages) observed in the developing neocortex 0-24 h after in utero irradiation can be associated with postnatal effects. Moreover, it is possible to correlate thinning of specific layers of the cerebral cortex with specific behavioural aberrations, allowing prediction of brain structural changes from functional alterations, and vice versa. Thus, it is possible to speculate as to the mechanisms and targets for extremely sensitive, radiation-induced cellular damage in the developing foetal brain, that will interfere with the orderly and precisely programmed development of the mammalian brain, leading finally to postnatal expression as delays in growth and development, perturbations in behaviour, and alterations in brain structure.     

Effect of the non-NMDA receptor antagonist GYKI 52466 on the microdialysate and tissue concentrations of amino acids following transient forebrain ischaemia

The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate glutamate concentration in the striatum may be related to the neuroprotection provided by GYKI 52466 in this region.