Oceanographic and atmospheric phenomena influence the abundance of whale sharks at Ningaloo Reef, Western Australia

Seasonal observations of whale shark abundance recorded by ecotourist operators at Ningaloo Reef, Western Australia from 1999 to 2004 were compared with weekly regional and global oceanographic and atmospheric variables, including average sea surface temperatures, along-shelf wind shear, sea level and the Southern Oscillation Index (SOI). Estimates of these physical variables were derived from either ground-based data or from remote sensing instruments. A generalised linear mixed-effects modelling (GLMM) approach with random sampling and model simulation was used to determine the relationships between the number of whale sharks and all model variants of the environmental parameters, using information-theoretic weights of evidence to rank models. SOI and wind shear had the most support for explaining the deviance in weekly whale shark abundance at Ningaloo Reef during a season. The SOI and wind shear variables positively influenced whale shark abundance such that more sharks were sighted when the Southern Oscillation was stronger and along-shelf winds were increasingly prevalent. This may reflect changes in the strength of oceanographic processes such as the Leeuwin Current (in response to the Southern Oscillation) and wind/current driven upwelling which may affect the abundance of whale sharks transported to the region and/or the availability of their prey by driving productivity changes.     

On FitzHugh's nerve axon equations

Summary After discussing some general properties which we think desirable in a nerve axon model, we consider a system first proposed by FitzHugh. We show that, assuming the existence of travelling wave solutions, the speed of propagation is bounded above and below.     

Affinity maturation of a novel antagonistic human monoclonal antibody with a long VH CDR3 targeting the Class A GPCR formyl-peptide receptor 1

Therapeutic monoclonal antibodies targeting G-protein-coupled receptors (GPCRs) are desirable for intervention in a wide range of disease processes. The discovery of such antibodies is challenging due to a lack of stability of many GPCRs as purified proteins. We describe here the generation of Fpro0165, a human anti-formyl peptide receptor 1 (FPR1) antibody generated by variable domain engineering of an antibody derived by immunization of transgenic mice expressing human variable region genes. Antibody isolation and subsequent engineering of affinity, potency and species cross-reactivity using phage display were achieved using FPR1 expressed on HEK cells for immunization and selection, along with calcium release cellular assays for antibody screening. Fpro0165 shows full neutralization of formyl peptide-mediated activation of primary human neutrophils. A crystal structure of the Fpro0165 Fab shows a long, protruding V_H CDR3 of 24 amino acids and in silico docking with a homology model of FPR1 suggests that this long V_H CDR3 is critical to the predicted binding mode of the antibody. Antibody mutation studies identify the apex of the long V_H CDR3 as key to mediating the species cross-reactivity profile of the antibody. This study illustrates an approach for antibody discovery and affinity engineering to typically intractable membrane proteins such as GPCRs.     

Proposed follow up programme after curative resection for lower third oesophageal cancer

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy.