The development of a radio receptor assay for gamma aminobutyric acid and its application in the study of neurological diseases.

The methodology of a radioreceptor assay for the inhibitory neurotransmitter, GABA, is described in detail. This is a filtration assay which utilises the binding of tritiated muscimol to synaptic membranes prepared from pig brain. The assay is modified from previously described techniques, and these modifications, along with the technical difficulties encountered in the development of the assay, are described in detail. In its final form the assay provides an accurate and reproducible technique which may be used to measure GABA concentrations in extracellular fluids such as cerebrospinal fluid and plasma. Studies are described in which the assay has been used for this purpose in studying patients with neurological disease. CSF and blood were obtained from patients undergoing diagnostic lumbar puncture, and the methods of collection and storage of CSF were standardised in order to avoid artefactual changes in GABA concentrations. These methods are described in detail. Thirty-four patients who were subsequently found to be free from structural neurological disease were used as a control population, and CSF GABA concentrations in these patients were analysed according to their age and sex. In patients with neurological disease attention was focussed primarily on those with extrapyramidal disorders, and low CSF GABA concentrations were found in patients with Huntington's disease. Patients with Alzheimer's disease also had significantly lower CSF GABA than controls. The clinical value of CSF GABA estimation in these disorders and in the other diseases studied is considered. It is concluded from these studies that CSF GABA estimation is unlikely to become a useful diagnostic tool in clinical practice, but may in the future be a useful guide to those neurological disorders in which drugs which enhance GABA neurotransmission may be of benefit

Plant speciation in the Namib Desert: potential origin of a widespread derivative species from a narrow endemic

Parapatric (or ‘budding’) speciation is increasingly recognised as an important phenomenon in plant evolution but its role in extreme (e.g. desert) environments is poorly documented. To test this speciation model in a hypothesised sister pair, the Southwest – North African disjunct Senecio flavus and its putative progenitor, the Namibian Desert endemic S. englerianus. Phylogenetic inferences were combined with niche divergence tests, morphometrics, and experimental-genetic approaches. We also evaluated the potential role of an African Dry Corridor (ADC) in promoting the hypothesised northward expansion of S. flavus (from Namibia), using palaeodistribution models. Belonging to an isolated (potential ‘relict’) clade, the two morphologically distinct species showed pronounced niche divergence in Namibia and signs of digenic-epistatic hybrid incompatibility (based on F2 pollen fertility). The presence of ‘connate-fluked’ pappus hairs in S. flavus, likely increasing dispersal ability, is controlled by a single gene locus. Our results provide evidence for a possible (and rare) example of ‘budding’ speciation in which a wider-ranged derivative (S. flavus) originated at the periphery of a smaller-ranged progenitor (S. englerianus) in the Namib Desert region. The Southwest – North African disjunction of S. flavus could have been established by dispersal across intermediate ADC areas during periods of (Late) Pleistocene aridification.</p