Trans-biome diversity in Australian grass-specialist lizards (Diplodactylidae: Strophurus).

Comparisons of biodiversity patterns within lineages that occur across major climate gradients and biomes, can provide insights into the relative roles that lineage history, landscape and climatic variation, and environmental change have played in shaping regional biotas. In Australia, while there has been extensive research into the origins and patterns of diversity in the Australian Arid Zone (AAZ), how diversity is distributed across this biome and the Australian Monsoonal Tropics (AMT) to the north, has been less studied. We compared the timing and patterns of diversification across this broad aridity gradient in a clade of lizards (Strophurus: phasmid geckos) that only occur in association with a unique Australian radiation of sclerophyllous grasses (Triodia: spinifex). Our results indicate that overall genetic diversity is much higher, older and more finely geographically structured within the AMT, including distantly related clades endemic to the sandstone escarpments of the Kimberley and Arnhem Plateau. Niche modelling analyses also suggest that the distribution of taxa in the AMT is more strongly correlated with variation in topographic relief than in the AAZ. The two broad patterns that we recovered - (i) lineage endemism increases as latitude decreases, and (ii) endemism is tightly correlated to rocky regions - parallel and corroborate other recent studies of habitat generalists and specialised saxicoline lineages occurring across these same regions. Early Miocene diversification estimates also suggest that, soon after Triodia grasses colonised Australia and began to diversify in the Miocene, phasmid geckos with Gondwanan ancestry shifted into these grasses, and have subsequently remained closely associated with this unique vegetation type.

C5a receptor antagonists.

The anaphylatoxin C5a is an extremely potent proinflammatory peptide produced during activation of the complement system. The structure of C5a includes a core region (N-terminal residues 1-63) consisting of four, antiparallel alpha-helices held together by three disulfide linkages and a structured C-terminal tail (residues 64-74). The C5a receptor belongs to the large class of seven transmembrane, G-protein-linked receptors. C5a appears to interact with its receptor at two sites: the C5a core binds to the receptor s N-terminal extracellular domain while C5a s tail binds the receptor near Arg206, near the membrane surface of transmembrane helix V. C5a receptors are concentrated on blood granulocytes (neutrophils, eosinophils, and basophils) and tissue inflammatory cells (macrophages, mast cells, microglia); thus the main effects of C5a are manifest as inflammation. Additionally, C5a receptors are also present, albeit in lower concentrations, on non-myeloid cells, e.g. endothelial and smooth muscle cells where they may further influence inflammatory reactions such as blood cell emigration and tissue edema. C5a has been implicated in myriad disorders, both acute and chronic; therefore a C5a receptor antagonist is predicted to have utility as a therapeutic agent. Unfortunately, few specific C5a receptor antagonists have been reported, and only two have demonstrated activity in vivo. Furthermore, those reported are peptidic and hence have limited application therapeutically. The current state of C5a receptor antagonists is discussed as well as the potential for their use against various human disorders. A model of C5a receptor dimerization is presented to account for the high potency of the disulfide antagonist C5aRAD.