Maintenance of transmitter release from neuromuscular junctions with different patterns of usage ‘in vivo’

The basic mechanisms underlying chemically-mediated neurotransmission at synapses are well established. Synaptic vesicles release their contents of neurotransmitter by exocytosis, and are then recycled and refilled before re-priming for re-release. It is less clear, however, what determines the differences in the quantitative aspects of this process at synapses with different in vivo activity patterns, and the extent to which they can be adapted to changing patterns of usage. The neuromuscular junction is particularly suited to investigations of these issues, due to the presence of distinctive muscle fibre types, with well-differentiated physiological roles and hence, activity patterns. The relative accessibility of NMJs means that chronic recording and manipulation of in vivo activity patterns of single motor neurones are possible. Several laboratories around the world now examining how transmitter release at NMJs is adapted to maintain (or not) release under these identified activity patterns. This review will cover the current state of knowledge and briefly highlight areas where more research is required. For example, current knowledge is largely derived from invertebrate preparations, indicating a need for more detailed comparisons at mammalian NMJs with different activity patterns. Finally, it is not yet clear in any species whether adaptations observed with imposed activity can be driven to complete transformation, with appropriate stimulus regimes.     

The induction of chromosomal damage in rat hepatocytes and lymphocytes II. Alkylation damage and repair of rat-liver DNA after diethylnitrosamine,dimethylnitrosamine and ethyl methanesulphonate in relation to clastogenic effects

Rat-liver DNA alkylation by diethylnitrosamine (DEN), dimethylnitrosamine (DMN) and ethyl methanesulphonate (EMS) was studied in an attempt to relate chromosome-damaging effects of these agents (the formation of micronuclei in hepatocytes; see preceding paper) to specific alkylation patterns. No correlation was observed between the induction of micronuclei and liver DNA N-alkylation, measured as 3- and 7-alkyl-purines. O⁶-Alkylguanine is probably not involved in micronucleus induction because it is lost from DNA too rapidly to explain the much more persistent clastogenic effects. In contrast, both the initial amounts of alkylphosphotriesters and the persistencies of these products roughly paralleled the respective effects on micronucleus induction. The possible involvement of alkylphosphotriesters or other O-alkylation products of comparable stabilities is discussed. Results with DMN suggest that part of the primary DNA methylation damage is converted into a secondary (DNA) lesion and that both the primary and secondary lesion(s) contribute to the process of micronucleus formation.     

The Importance of Hydrodynamics for Protected and Endangered Biodiversity of Lowland Rivers

This paper examines the relationship between protected and endangered riverine species (target species) and hydrodynamics in river-floodplain ecosystems, combining ecological and policy-legal aspects of biodiversity conservation in river management. The importance of different hydrodynamic conditions along a lateral gradient was quantified for various taxonomic groups. Our results show that (i) target species require ecotopes along the entire hydrodynamic gradient; (ii) different parts of the hydrodynamic gradient are important to different species, belonging to different taxonomic groups; (iii) in particular low-dynamic parts are important for many species and (iv) species differ in their specificity for hydrodynamic conditions. Many species of higher plants, fish and butterflies have a narrow range for hydrodynamics and many species of birds and mammals use ecotopes along the entire gradient. Even when focussing only on target species, the entire natural hydrodynamic gradient is important. This means that the riverine species assemblage as a whole can benefit from measures focussing on target species only. River reconstruction and management should aim at re-establishing the entire hydrodynamic gradient, increasing the spatial heterogeneity of hydrodynamic conditions.     

A Mesoscale Model of DNA and Its Renaturation

A mesoscale model of DNA is presented (3SPN.1), extending the scheme previously developed by our group. Each nucleotide is mapped onto three interaction sites. Solvent is accounted for implicitly through a medium-effective dielectric constant and electrostatic interactions are treated at the level of Debye-Hückel theory. The force field includes a weak, solvent-induced attraction, which helps mediate the renaturation of DNA. Model parameterization is accomplished through replica exchange molecular dynamics simulations of short oligonucleotide sequences over a range of composition and chain length. The model describes the melting temperature of DNA as a function of composition as well as ionic strength, and is consistent with heat capacity profiles from experiments. The dependence of persistence length on ionic strength is also captured by the force field. The proposed model is used to examine the renaturation of DNA. It is found that a typical renaturation event occurs through a nucleation step, whereby an interplay between repulsive electrostatic interactions and colloidal-like attractions allows the system to undergo a series of rearrangements before complete molecular reassociation occurs.