CLIX: a search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure.

A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza-virus hemagglutinin and of proposing a number of potential new ligands to this protein.     

Assessing Habitat Use by Snapper (Chrysophrys auratus) from Baited Underwater Video Data in a Coastal Marine Park

Baited Underwater Video (BUV) systems have become increasingly popular for assessing marine biodiversity. These systems provide video footage from which biologists can identify the individual fish species present. Here we explore the relevance of spatial dependence and marine park boundaries while estimating the distribution and habitat associations of the commercially and recreationally important snapper species Chrysophrys auratus in Moreton Bay Marine Park during a period when new Marine National Parks zoned as no-take or “green” areas (i.e., areas with no legal fishing) were introduced. BUV studies typically enforce a minimum distance among BUV sites, and then assume that observations from different sites are independent conditional on the measured covariates. In this study, we additionally incorporated the spatial dependence among BUV sites into the modelling framework. This modelling approach allowed us to test whether or not the incorporation of highly correlated environmental covariates or the geographic placement of BUV sites produced spatial dependence, which if unaccounted for could lead to model bias. We fitted Bayesian logistic models with and without spatial random effects to determine if the Marine National Park boundaries and available environmental covariates had an effect on snapper presence and habitat preference. Adding the spatial dependence component had little effect on the resulting model parameter estimates that emphasized positive association for particular coastal habitat types by snapper. Strong positive relationships between the presence of snapper and rock habitat, particularly rocky substrate composed of indurated freshwater sediments known as coffee rock, and kelp habitat reinforce the consideration of habitat availability in marine reserve design and the design of any associated monitoring programs.     

Modulation of Locomotion and Reproduction by FLP Neuropeptides in the Nematode Caenorhabditis elegans

Neuropeptides function in animals to modulate most, if not all, complex behaviors. In invertebrates, neuropeptides can function as the primary neurotransmitter of a neuron, but more generally they co-localize with a small molecule neurotransmitter, as is commonly seen in vertebrates. Because a single neuron can express multiple neuropeptides and because neuropeptides can bind to multiple G protein-coupled receptors, neuropeptide actions increase the complexity by which the neural connectome can be activated or inhibited. Humans are estimated to have 90 plus neuropeptide genes; by contrast, nematodes, a relatively simple organism, have a slightly larger complement of neuropeptide genes. For instance, the nematode Caenorhabditis elegans has over 100 neuropeptide-encoding genes, of which at least 31 genes encode peptides of the FMRFamide family. To understand the function of this large FMRFamide peptide family, we isolated knockouts of different FMRFamide-encoding genes and generated transgenic animals in which the peptides are overexpressed. We assayed these animals on two basic behaviors: locomotion and reproduction. Modulating levels of different neuropeptides have strong as well as subtle effects on these behaviors. These data suggest that neuropeptides play critical roles in C. elegans to fine tune neural circuits controlling locomotion and reproduction.     

The RAD6 DNA repair pathway in Saccharomyces cerevisiae: What does it do,and how does it do it?

The RAD6 pathway of budding yeast, Saccharomyces cerevisiae, is responsible for a substantial fraction of this organism's resistance to DNA damage, and also for induced mutagenesis. The pathway appears to incorporate two different recovery processes, both regulated by RAD6. The error-prone recovery prcess accounts for only a small amount of RAD6-dependent resistance, but probably all induced mutagenesis. The underlying mechanism, for error-prone recovery is very likely to be translesion synthesis. The error-free recovery process accounts for most of RAD6-dependent resistace, but its mechanism is less clear; it may entail error-free bypass by template switching and/or DNA gap filling by recombination. RAD6 regulates these activities by ubiquitinateins, and the roles they play in error-free and error-prone recovery, have not yet been established.