Energy homeostasis plays a significant role in food consumption and body weight regulation with fat intake being an area of particular interest due to its palatability and high energy density. Increasing evidence from humans and animal studies indicate the existence of a taste modality responsive to fat via its breakdown product fatty acids. These studies implicate multiple candidate receptors and ion channels for fatty acid taste detection, indicating a complex peripheral physiology that is currently not well understood. Additionally, a limited number of studies suggest a reduced ability to detect fatty acids is associated with obesity and a diet high in fat reduces an individual's ability to detect fatty acids. To support this, genetic variants within candidate fatty acid receptors are also associated with obesity reduced ability to detect fatty acids. Understanding oral peripheral fatty acid transduction mechanisms and the association with fat consumption may provide the basis of novel approaches to control development of obesity.

The capacity of our gut microbial communities to maintain a stable and balanced state, termed 'resilience', in spite of perturbations is vital to our achieving and maintaining optimal health. A loss of microbial resilience is observed in a number of diseases including obesity, diabetes and metabolic syndrome. There are large gaps in our understanding of why an individual's co-evolved microflora consortium fail to develop resilience thereby establishing a trajectory towards poor metabolic health. This review examines the connections between the developing gut microbiota and intestinal barrier function in the neonate, infant and during the first years of life. We propose that the effects of early life events on the gut microflora and permeability, whilst it is in a dynamic and vulnerable state, are fundamental in shaping the microbial consortia's resilience and that it is the maintenance of resilience that is pivotal for metabolic health throughout life. We review the literature supporting this concept suggesting new potential research directions aimed at developing a greater understanding of the longitudinal effects of the gut microflora on metabolic health and potential interventions to recalibrate the 'at risk' infant gut microflora in the direction of enhanced metabolic health.

A simple method of inferring the genotyping error rate of SNP arrays and similar high-throughput genotyping methods from Mendelian errors is described. Application to genotypes from small families using the Affymetrix GeneChip Human Mapping 50 k Array indicates an error rate of about 0.1%, and this rate can be reduced by increasing the quality criterion for calls, though at the cost of a reduced genotype call rate, which limits the benefit available. Simulated data are used to show that the number of SNPs on this array is sufficient for such a low error rate to have little impact on identical by descent-based inference for disease linkage in sib-pair studies.

The ecdysone receptor is a hormone-dependent transcription factor that plays a central role in regulating the expression of vast networks of genes during development and reproduction in the phylum Arthropoda. The functional receptor is a heterodimer of the two nuclear receptor proteins ecdysone receptor (EcR) and ultraspiracle protein. The receptor is the target of the environmentally friendly bisacylhydrazine insecticides, which are effective against Lepidoptera but not against Hemiptera or several other insect orders. Here we present evidence indicating that much of the selectivity of the bisacylhydrazine insecticides can be studied at the level of their binding to purified ecdysone receptor ligand-binding domain (LBD) heterodimers. We report the crystal structure of the ecdysone receptor LBD heterodimer of the hemipteran Bemisia tabaci (Bt, sweet potato whitefly) in complex with the ecdysone analogue ponasterone A. Although comparison with the corresponding known LBD structure from the lepidopteran Heliothis virescens (Hv) ecdysone receptor revealed the overall mode of ponasterone A binding to be very similar in the two cases, we observed that the BtEcR ecdysteroid-binding pocket is structured differently to that of HvEcR in those parts that are not in contact with ponasterone A. We suggest that these differences in the ligand-binding pocket may provide a molecular basis for the taxonomic order selectivity of bisacylhydrazine insecticides. The nuclear receptor (NR)1 family of proteins plays a crucial role in the regulation of transcription, and its members include the receptors for steroid hormones, vitamins, thyroid hormones, and bile acids (1). The human genome contains about 48 members of this family, and these have been studied extensively as therapeutic targets (2). The Arthropoda display a more limited suite of NRs (3) about 21 of which occur in Drosophila melanogaster. Among these is the receptor for the major arthropod steroid hormone, 20-hydroxyecdysone, which is involved in the regulation of insect molting, metamorphosis, and reproduction (4 -9). The receptor is absent from mammals and is thus potentially useful as a safe insecticide target. Indeed members of the bisacylhydrazine family exert their insecticidal activity by binding to the ecdysone receptor and exhibit remarkable taxonomic order selectivity (10, 11). These compounds act selectively on the Lepidoptera and certain Coleoptera (10) but are ineffective against insects of the hemipteran order and therefore cannot be used to control certain insect pests. A study (12) of two hemipteran insect predators (Geocoris punctipes and Orius insidiosus) showed that these beneficial (predatory) hemipterans are relatively insensitive to the bisacylhydrazine tebufenozide, whereas lepidopteran insect pests are susceptible. An improved understanding of variation in the structure of the ligand-binding pockets of ecdysone receptors and the basis of the specificity of these compounds at the atomic level of detail of their interaction with the receptor may aid ...