Stress at the synapse : signal transduction mechanisms of adrenal steroids at neuronal membranes

As the key neuron-to-neuron interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. However, the signal transduction mechanisms by which stress mediates its lasting effects on synapse transmission and on memory are not fully understood. A key component of the stress response is the increased secretion of adrenal steroids. Adrenal steroids (e.g., cortisol) bind to genomic mineralocorticoid and glucocorticoid receptors (gMRs and gGRs) in the cytosol. In addition, they may act through membrane receptors (mMRs and mGRs), and signal transduction through these receptors may allow for rapid modulation of synaptic transmission as well as modulation of membrane ion currents. mMRs increase synaptic and neuronal excitability; mechanisms include the facilitation of glutamate release through extracellular signal-regulated kinase signal transduction. In contrast, mGRs decrease synaptic and neuronal excitability by reducing calcium currents through N-methyl-D-aspartate receptors and voltage-gated calcium channels by way of protein kinase A- and G protein-dependent mechanisms. This body of functional data complements anatomical evidence localizing GRs to the postsynaptic membrane. Finally, accumulating data also suggest the possibility that mMRs and mGRs may show an inverted U-shaped dose response, whereby glutamatergic synaptic transmission is increased by low doses of corticosterone acting at mMRs and decreased by higher doses acting at mGRs. Thus, synaptic transmission is regulated by mMRs and mGRs, and part of the stress signaling response is a direct and bidirectional modulation of the synapse itself by adrenal steroids.

Minimising lateral impact derailment potential at level crossings through guard rails

Derailments due to lateral collisions between heavy road vehicles and passenger trains at level crossings (LCs) are serious safety issues. A variety of countermeasures in terms of traffic laws, communication technology and warning devices are used for minimising LC accidents; however, innovative civil infrastructure solution is rare. This paper presents a study of the efficacy of guard rail system (GRS) to minimise the derailment potential of trains laterally collided by heavy road vehicles at LCs. For this purpose, a three-dimensional dynamic model of a passenger train running on a ballasted track fitted with guard rail subject to lateral impact caused by a road truck is formulated. This model is capable of predicting the lateral collision-induced derailments with and without GRS. Based on dynamic simulations, derailment prevention mechanism of the GRS is illustrated. Sensitivities of key parameters of the GRS, such as the flange way width, the installation height and contact friction, to the efficacy of GRS are reported. It is shown that guard rails can enhance derailment safety against lateral impacts at LCs.