Episodic ataxia type 2(EA-2) is a rare, autosomal dominant disorder characterised by recurrent episodes of ataxia and dysarthria,due to mutations in the CACNA1A gene on chromosome 19 encoding voltage-dependent Ca2+ channels. The aim of the present study was to explore whether axonal membrane properties, assessed using nerve excitability techniques, were abnormal in patients with EA-2 . Nerve excitability techniques were applied to the median nerve of three individuals from three generations of a single family, all of whom had typical features of EA-2. This family was found to have a novel mutation at codon 1451 of the Ca2+ channel alpha 1A subunit. Nerve excitability testing demonstrated significant abnormalities,with all patients outside the normal 95 % confidence limits in having a high rheobase and reduced early hyperpolarizing threshold electrotonus. On average there were also significant reductions in refractoriness,late sub excitability and early depolarizing threshold electrotonus. Mathematical modelling indicated that a similar pattern of abnormalities may result from a reduced voltage dependence of slow K+ channels (KCNQ channels). There are significant and distinctive changes in peripheral nerve excitability in EA-2 patients,which are presumably induced indirectly. These findings raise the possibility that excitability testing may prove a convenient screening test for patients with this suspected channelopathy.
Purpose The purpose of this research was to isolate humic substances and humin from an estuarine sediment core using a novel sequential extraction procedure to characterise the isolates, to determine their compositions and to understand how the organic matter (OM) changes with time. Materials and methods The sediments were exhaustively extracted using the following media: 0.1 M NaOH; 0.1 M NaOH + 6 M urea; and dimethylsulphoxide (DMSO) + H2SO4 (94:6 v/v). Pyrolysis gas chromatography mass spectroscopy (pyGC/MS), and nuclear magnetic resonance (NMR) spectroscopy were the analytical tools that gave the most significant data for the characterisation of the organic isolates. Results and discussion The results indicate subtle molecular compositional differences in relation to the alkaline and alkaline-urea isolates. The humic acids (HAs) and fulvic acids (FAs) are readily solvated in aqueous alkaline media compared to the aqueous insoluble hydrophobic humin (HU) components. In addition to aliphatic hydrocarbons, peptide materials make considerable contributions to the component structures of the isolates. Aryl and O-aryl C units characteristic of lignin, and of cutan structures from plants, indicate contributions from terrestrial OM to the organic components in the HU, especially from the base of the core. The evidence suggests that components of terrestrial plant materials and of microbial biomass are preferentially preserved with time and make the major contributions to the OM retained over long time scales. The data acquired provide detailed information about the origins, compositions, nature and the associations of the OM in the estuarine sediment core. Such information provides a greater understanding of the role of these organic components in the carbon (C) sink. Conclusions Humic acids and FAs are mineralised with time whereas HU is highly recalcitrant and represents a long-term sink for organic C. Humin is a separate organic entity and does not conform to the definitions of a humic substance. Terrestrial OM is preserved over long time scales in the environment. Protein makes significant contributions to all the organic isolates and its preservation suggests encapsulation in hydrophobic domains, or interactions with clay minerals.