Melanoma biology and new targeted therapy

Melanoma is a cancer that arises from melanocytes, specialized pigmented cells that are found predominantly in the skin. The incidence of melanoma is rising steadily in western populations--the number of cases worldwide has doubled in the past 20 years. In its early stages malignant melanoma can be cured by surgical resection, but once it has progressed to the metastatic stage it is extremely difficult to treat and does not respond to current therapies. Recent discoveries in cell signalling have provided greater understanding of the biology that underlies melanoma, and these advances are being exploited to provide targeted drugs and new therapeutic approaches.     

The effects of forest fragmentation on the population ecology and natural history of a funnel-web spider

Habitat fragmentation strongly affects the abundance, distribution, body size and population genetics of invertebrates. Urban growth in Brazil has led to severe fragmentation, especially in the Atlantic Forest and savannas. The effects of this fragmentation on the common funnel-web spider Aglaoctenus lagotis were examined in two forest fragments within the interior savanna: a smaller fragment within an urban environment and a larger fragment within a rural environment. The reproductive period occurred in October, coinciding with the beginning of the rainy season, when the species was aggregated in the two forest fragments. The smaller fragment contained a larger population, and the spiders had a larger average prosoma size and web area. The presence of a larger population in a smaller area within the urban centre may reflect a limited dispersal ability, reduced predator abundance or low interspecific competition. The larger prosoma length and web area in the smaller habitat fragment suggest greater resource availability and a higher probability of capturing prey in the urban environment. In both areas, a larger number of capture threads was positively correlated with the presence of inquiline spiders in the webs. The genetic data indicate close similarity between and within the two areas, indicating that the species has low genetic variability or that the areas studied, consistent with their proximity, have separated only recently. Most savannas and forests in midwestern Brazil have recently undergone severe fragmentation, and further studies of this nature are needed.     

The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene

Amyloid beta-protein (AP) is a peptide of relative molecular mass (Mr) 42,000 found in the senile plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles of patients with Alzheimer's disease and Down's syndrome (trisomy 21). Recent molecular genetic evidence has indicated that AP is encoded as part of a larger protein by a gene on chromosome 21 (refs 5-7). The defect in the inherited autosomal dominant form of Alzheimer's disease, familial Alzheimer's disease (FAD), has been mapped to the same approximate region of chromosome 21 by genetic linkage to anonymous DNA markers, raising the possibility that this gene product, which could be important in the pathogenesis of Alzheimer's disease, is also the site of the inherited defect in FAD (ref. 5). We have determined the pattern of segregation of the AP gene in FAD pedigrees using restriction fragment length polymorphisms. The detection of several recombination events with FAD suggests that the AP gene is not the site of the inherited defect underlying this disorder.     

Marine iguanas die from trace oil pollution

An oil tanker ran aground on the Galapagos island of San Cristóbal on 17 January 2001, spilling roughly three million litres of diesel and bunker oil. The slick started to spread westwards and was dispersed by strong currents, so only a few marine animals were killed immediately as a result. Here we draw on the long-term data sets gathered before the spill to show that a population of marine iguanas (Amblyrhychus cristatus) on Sante Fe island suffered a massive 62% mortality in the year after the accident, due to a small amount of residual oil contamination in the sea. Another population on the more remote island of Genovesa was unaffected.     

Functional analysis of an archaebacterial voltage-dependent K+ channel

All living organisms use ion channels to regulate the transport of ions across cellular membranes. Certain ion channels are classed as voltage-dependent because they have a voltage-sensing structure that induces their pores to open in response to changes in the cell membrane voltage. Until recently, the voltage-dependent K+, Ca2+ and Na+ channels were regarded as a unique development of eukaryotic cells, adapted to accomplish specialized electrical signalling, as exemplified in neurons. Here we present the functional characterization of a voltage-dependent K+ (K(V)) channel from a hyperthermophilic archaebacterium from an oceanic thermal vent. This channel possesses all the functional attributes of classical neuronal K(V) channels. The conservation of function reflects structural conservation in the voltage sensor as revealed by specific, high-affinity interactions with tarantula venom toxins, which evolved to inhibit eukaryotic K(V) channels.     

Evolutionary origins of vertebrate appendicular muscle

The evolution of terrestrial tetrapod species heralded a transition in locomotor strategies. While most fish species use the undulating contractions of the axial musculature to generate propulsive force, tetrapods also rely on the appendicular muscles of the limbs to generate movement. Despite the fossil record generating an understanding of the way in which the appendicular skeleton has evolved to provide the scaffold for tetrapod limb musculature, there is, by contrast, almost no information as to how this musculature arose. Here we examine fin muscle formation within two extant classes of fish. We find that in the teleost, zebrafish, fin muscles arise from migratory mesenchymal precursor cells that possess molecular and morphogenetic identity with the limb muscle precursors of tetrapod species. Chondrichthyan dogfish embryos, however, use the primitive mechanism of direct epithelial somitic extensions to derive the muscles of the fin. We conclude that the genetic mechanism controlling formation of tetrapod limb muscles evolved before the Sarcopterygian radiation.     

Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. FAD Collaborative Study Group

Alzheimer's disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of the general uniformity of the disease phenotype. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21. But two other studies, one of predominantly multiplex kindreds with a late age-of-onset, the other of a cadre of kindreds with a unique Volga German ethnic origin, found absence of linkage at least to D21S1/S11. So far it has not been possible to discern whether these conflicting reports reflect aetiological heterogeneity, differences in methods of pedigree selection, effects of confounding variables in the analysis (for example, diagnostic errors, assortative matings), or true non-replication. To resolve this issue, we have now examined the inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedigrees with familial Alzheimer's disease. Our data suggest that Alzheimer's disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.