Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration

The AMPA receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNF alpha) have both been implicated in motor neurone vulnerability in Amyotrophic Lateral Sclerosis/Motor Neurone Disease. TNF alpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNF alpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/ml, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using Fura-2 AM microfluorimetry we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggests that TNF alpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in ALS

The influence of ribosome modulation factor on the survival of stationary-phase Escherichia coli during acid stress

Ribosome modulation factor (RMF) was shown to have an influence on the survival of Escherichia coli under acid stress during stationary phase, since the viability of cultures of a mutant strain lacking functional RMF decreased more rapidly than that of the parent strain at pH 3. Loss of ribosomes was observed in both strains when exposed to low pH, although this occurred at a higher rate in the RMF-deficient mutant strain, which also suffered from higher levels of rRNA degradation. It was concluded that the action of RMF in limiting the damage to rRNA contributed to the protection of E coli under acid stress. Expression of the rmf gene was lower during stationary phase after growth in acidified media compared to media containing no added acid, and the increased rmf expression associated with transition from exponential phase to stationary phase was much reduced in acidified media. It was demonstrated that RMF was not involved in the stationary-phase acid-tolerance response in E coli by which growth under acidic conditions confers protection against subsequent acid shock. This response was sufficient to overcome the increased vulnerability of the RMF-deficient mutant strain to acid stress at pH values between 6.5 and 5.5.

Continuous sky view factor maps from high resolution urban digital elevation models

This paper presents a new method to calculate sky view factors (SVFs) from high resolution urban digital elevation models using a shadow casting algorithm. By utilizing weighted annuli to derive SVF from hemispherical images, the distance light source positions can be predefined and uniformly spread over the whole hemisphere, whereas another method applies a random set of light source positions with a cosine-weighted distribution of sun altitude angles. The 2 methods have similar results based on a large number of SVF images. However, when comparing variations at pixel level between an image generated using the new method presented in this paper with the image from the random method, anisotropic patterns occur. The absolute mean difference between the 2 methods is 0.002 ranging up to 0.040. The maximum difference can be as much as 0.122. Since SVF is a geometrically derived parameter, the anisotropic errors created by the random method must be considered as significant.

A doubling of the sun's coronal magnetic field during the last 100 years

The solar wind is an extended ionized gas of very high electrical conductivity, and therefore drags some magnetic flux out of the Sun to fill the heliosphere with a weak interplanetary magnetic field(1,2). Magnetic reconnection-the merging of oppositely directed magnetic fields-between the interplanetary field and the Earth's magnetic field allows energy from the solar wind to enter the near-Earth environment. The Sun's properties, such as its luminosity, are related to its magnetic field, although the connections are still not well understood(3,4). Moreover, changes in the heliospheric magnetic field have been linked with changes in total cloud cover over the Earth, which may influence global climate(5), Here we show that measurements of the near-Earth interplanetary magnetic field reveal that the total magnetic flux leaving the Sun has risen by a factor of 1.4 since 1964: surrogate measurements of the interplanetary magnetic field indicate that the increase since 1901 has been by a factor of 2,3, This increase may be related to chaotic changes in the dynamo that generates the solar magnetic field. We do not yet know quantitatively how such changes will influence the global environment.