Single fibre action potentials in skeletal muscle related to recording distances

Single muscle fibre action potentials (SFAPs) are considered to be functions of a bioelectrical source and electrical conductivity parameters of the medium. In most model studies SFAPs are computed as a convolution of the bioelectrical source with a transfer function. Calculated peak-to-peak amplitudes of SFAPs decrease with increasing recording distances. In this paper an experimental validation of model results is presented. Experiments were carried out on the m. extensor digitorum longus (EDL) of the rat. Using a method including fluorescent labelling of the active fibre, the distance between the active fibre and the recording electrode was derived. With another method, the decline of the peak-to-peak amplitude of SFAPs detected along a multi-electrode was obtained. With both experimental methods, in general peak-to-peak amplitudes of SFAPs decreased with increasing recording distances, as was found in model results with present volume conduction theory. However, this behaviour was not found in all experiments. The rate of decline of the peak-to-peak amplitudes with recording distance was always less than in models

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes