Ecological meltdown in predator-free forest fragments.

The manner in which terrestrial ecosystems are regulated is controversial. The "top-down" school holds that predators limit herbivores and thereby prevent them from overexploiting vegetation. "Bottom-up" proponents stress the role of plant chemical defenses in limiting plant depredation by herbivores. A set of predator-free islands created by a hydroelectric impoundment in Venezuela allows a test of these competing world views. Limited area restricts the fauna of small (0.25 to 0.9 hectare) islands to predators of invertebrates (birds, lizards, anurans, and spiders), seed predators (rodents), and herbivores (howler monkeys, iguanas, and leaf-cutter ants). Predators of vertebrates are absent, and densities of rodents, howler monkeys, iguanas, and leaf-cutter ants are 10 to 100 times greater than on the nearby mainland, suggesting that predators normally limit their populations. The densities of seedlings and saplings of canopy trees are severely reduced on herbivore-affected islands, providing evidence of a trophic cascade unleashed in the absence of top-down regulation.

Modelling heating of liver tumours with heterogeneous magnetic microsphere deposition.

Ferromagnetic embolization hyperthermia (FEH) is a novel treatment for liver cancer. Magnetic microspheres are injected into the hepatic artery and cluster in the periphery of tumours and are heated with externally applied magnetic fields. In order to more accurately simulate FEH, we modelled a three-dimensional heterogeneous distribution of heat sources. We constructed a fractal model of the vasculature in the periphery of a tumour. We used this model to compute the spatial distribution of the microspheres that lodge in capillaries. We used the distribution model as input to a finite-element heat transfer model of the FEH treatment. The overall appearance of the vascular tree is subjectively similar to that of the disorganized vascular network which encapsulates tumours. The microspheres are distributed in the tumour periphery in similar patterns to experimental observations. We expect the vasculature and microsphere deposition models to also be of interest to researchers of any targeted cancer therapies such as localized intra-arterial chemotherapy and selective internal radiotherapy. Our results show that heterogeneous microsphere distributions give significantly different results to those for a homogeneous model and thus are preferable when accurate results are required.

Novel GCH1 variant in Dopa-responsive dystonia and Parkinson's disease.

BACKGROUND: GTP cyclohydrolase I (GCH1) mutations are the commonest cause of Dopa-responsive dystonia (DRD). Clinical phenotypes can be broad, even within a single family. METHODS: We present clinical, genetic and functional imaging data on a British kindred in which affected subjects display phenotypes ranging from DRD to Parkinson's disease (PD). Twelve family members were studied. Clinical examination, dopamine transporter (DAT) imaging, and molecular genetic analysis of GCH1 and the commonest known familial PD-related genes were performed. RESULTS: We have identified a novel missense variant, c.5A > G, p.(Glu2Gly), within the GCH1 gene in affected family members displaying a range of phenotypes. Two affected subjects carrying this variant had abnormal DAT imaging. These two with abnormal DAT imaging had a PD phenotype, while the remaining three subjects with the novel GCH1 variant had normal DAT imaging and a DRD phenotype. CONCLUSIONS: We propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. GCH1 genetic testing should be considered in patients with PD and a family history of DRD.

Brainstem control of activity and responsiveness in resting frog tadpoles: tonic inhibition.

The hatchling Xenopus laevis tadpole was used to study the brain neurons controlling responsiveness. Tadpoles have reduced motor activity and responsiveness when they hang at rest, attached by cement gland mucus. Afferent input from cement gland mechanosensory neurons has both a phasic role in stopping swimming and a tonic role in reducing responsiveness while tadpoles hang attached. Both these roles depend on GABA(A)-mediated inhibition. We provide evidence supporting the hypothesis that long-term reduced responsiveness in attached tadpoles results from tonic activity in the reticulospinal GABAergic pathway mediating the stopping response. Two groups of putative stopping pathway interneurons were recorded in the caudal and rostral hindbrain of immobilised tadpoles. Both groups showed a sustained increase in activity during simulated attachment. This attached activity was irregular and unstructured. We consider whether low-level firing in cement gland afferents (at approximately 1 Hz) during simulated attachment is sufficient to explain the low-level firing (at approximately 0.5 Hz) in reticulospinal neurons. We then ask if a small population of these neurons (approximately 20) could produce sufficient inhibition of spinal neurons to reduce the whole tadpole's responsiveness. We conclude that for most of their 1st day of life GABAergic brainstem neurons could produce inhibition continuously while the tadpole is at rest.