ALS-associated mutant SOD1<Superscript>G93A</Superscript> causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes

Background  

Amyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease that causes motor neuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause for the familial form of this disease. Transgenic mice expressing mutant SOD1 develop age-dependent motor neuron degeneration, skeletal muscle weakness, paralysis and death similar to humans. The mechanism whereby mutant SOD1 induces motor neuron degeneration is not understood but widespread mitochondrial vacuolation has been observed during early phases of motor neuron degeneration. How this vacuolation develops is not clear, but could involve autophagic vacuolation, mitochondrial permeability transition (MPT) or uncharacterized mechanisms. To determine which of these possibilities are true, we examined the vacuolar patterns in detail in transgenic mice expressing mutant SOD1^G93A.     

Exchange interaction and Jahn—Teller correlations in novel tetranuclear supramolecular Cu(II) grid complexes: an ESR study

Novel tetranuclear Cu(II) complexes in which four Cu(II) ions are arranged in a square planar fashion by four bis(bipyridyl)pyrimidine ligands were investigated by X and Q band ESR in the temperature range 4.2-300 K. The ESR spectra of this grid-like structure were well simulated as rising from triplet species. Analysis of their intensities allowed the spectra to be assigned to the first excited triplet state, and revealed intramolecular antiferromagnetic coupling of the Cu(II) spins. The isotropic exchange interaction J was determined as ?47 K and reducing to about ?5 K on functionalizing the bridging pyrimidine ring at the 2-position by methyl or phenyl. For comparison an ESR investigation was also carried out on the mononuclear analogue Cu(II)—(terpyridine)₂ complexes with substituted terpyridine ligands at the 5′ and 5″ position. Depending on the substitutent, the spectra exhibit a static or dynamic Jahn—Teller effect at room temperature. The temperature dependence of their g-values is examined by a modified Silver—Getz model which includes cooperative Jahn—Teller interactions. There is evidence that both an anisotropic spin exchange contribution to D = 0.0159 cm^?1 and a coupled (static) Jahn—Teller effect are responsible for efficient coupling between the four Cu(II) ions in the grid complexes with non-substituted pyrimidine bridges.     

ACTIVATION KINETICS OF PHOTOSYNTHETIC OXYGEN EVOLUTION UNDER 20–40 NANOSECOND LASER FLASHES

Abstract— Chlorella samples, incubated for varying periods in darkness, were exposed to a series of 20–40 nsec flashes, spaced 15 sec apart, from a Q-switched ruby laser. A stationary Teflon-covered platinum electrode measured the microjet of oxygen produced by each flash. After a dark preincubation exceeding 3 min, at 23°C, little or no oxygen is evolved until the third flash in a sequence. The yields from subsequent flashes increase monotonically until a constant value is reached. If low levels of background light are supplied, or if the interval between series of flashes is decreased, oxygen is evolved on the second or even the first flash. Very similar results were obtained from analogous experiments with tailless 28 μsec flashes from a xenon flashtube. In particular, very little oxygen was evolved from the second flash following a long dark period whatever the spacing between flashes. This means that there are no systematic differences between the effects of saturating 20 nsec and 28 μsec light flashes on the activation processes during the first few flashes following a long dark period. No oscillations of flash yield with successive flashes were observed because of the long interval between flashes. These results are consistent with the idea that the reaction center of Photosystem II must undergo a dark process lasting considerably longer than 28 μsec before it can absorb a second photon.     

A simple model for a two-stage chemical reaction with diffusion

We analyse the evolution of a two-stage chemical reaction betweentwo neighbouring plumes of reactants. Under the assumption thatthe plumes are approximately Gaussian we derive a system ofordinary differential equations for the total amount, the centroidand the variance of each reactant. We compare the solution ofthese equations with full numerical simulation of the reaction.Excellent agreement is obtained, with solution of the near-Gaussianmodel requiring considerably less computational effort thanthe full simulations. Of key importance is the yield of thereaction, and we discuss this feature in particular.     

Imaging cytoplasmic cAMP in mouse brainstem neurons

Background  

cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca²⁺ levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before.