Neurofilament depletion improves microtubule dynamics via modulation of Stat3/stathmin signaling

In neurons, microtubules form a dense array within axons, and the stability and function of this microtubule network is modulated by neurofilaments. Accumulation of neurofilaments has been observed in several forms of neurodegenerative diseases, but the mechanisms how elevated neurofilament levels destabilize axons are unknown so far. Here, we show that increased neurofilament expression in motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed microtubule dynamics. The disease is caused by a point mutation in the tubulin-specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes instable which then results in destabilization of axonal microtubules and defects in axonal transport, in particular in motoneurons. Depletion of neurofilament increases the number and regrowth of microtubules in pmn mutant motoneurons and restores axon elongation. This effect is mediated by interaction of neurofilament with the stathmin complex. Accumulating neurofilaments associate with stathmin in axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout increases Stat3-stathmin interaction and stabilizes the microtubules in pmn mutant motoneurons. Consequently, counteracting enhanced neurofilament expression improves axonal maintenance and prolongs survival of pmn mutant mice. We propose that this mechanism could also be relevant for other neurodegenerative diseases in which neurofilament accumulation and loss of microtubules are prominent features

Effects of harvesting ponderosa pine on nongame bird populations /

no.21

Selection effects of air pollution on gene pools of Norway spruce, European silver fir and European beech

The effects of industrial pollution on allelic and genotypic structures of Norway spruce, European silver fir and European beech were investigated by means of isozyme analysis. In a mixed Norway spruce-silver fir forest stand in an area heavily polluted by sulphur dioxide and heavy metals in the region of Spiš (eastern Slovakia), pairs of neighbouring damaged and apparently healthy trees were selected in two replicates (44 and 69 pairs in a heavily and moderately damaged stand, respectively). Pairwise sampling of trees with contrasting vitality was applied to reduce potential effects of site heterogeneity on the vitality of sampled trees. No significant differences in allelic and genotypic frequencies were found between sets of healthy and declining trees. There were differences in the single-locus heterozygosities, but these were not consistent between the replicates. However, the set of damaged trees exhibited higher levels of genetic multiplicity and diversity, possibly due to the deleterious effect of rare alleles under the conditions of air pollution. Consequently, following the decline of pollutant-sensitive trees, the remaining stand will be depleted of a part of alleles with unknown adaptive value to future selection pressures. © 2001 Published by Elsevier Science Ltd. All rights reserved