Immunocompetence increases with larval body size in a phytophagous moth

Despite the obvious benefit of an immune system, its efficacy against pathogens and parasites may show great variation among individuals, populations and species. Understanding the causes of this variation is becoming a central theme in ecology. Many biotic and abiotic factors are known to influence immunocompetence (temperature, age, etc.). However, for a given age, size among individuals varies, probably as a result of accumulated resources. Thus, these variable resources could be allocated to immune defence and, consequently, body size may explain part of the variation in immune responsiveness. However, the influence of body size on immune defence is often overlooked. The present study investigates variations in haemocyte count and phenoloxidase activity in larvae of the phytophagous vine moth Eupoecilia ambiguella Hübner of the same age, although differing in body size. The measurements of immune function are made both when the insects are immunologically naïve and 24 h after a bacterial immune challenge. The base levels of these immune parameters do not covary with body size in naïve larvae. After the bacterial immune challenge, more haemocytes and phenoloxidase enzyme are mobilized, and the mobilization of these immune effectors is correlated positively with individual body size. Thus, larger larvae exhibit higher immunocompetence than smaller ones, suggesting that smaller larvae might be more vulnerable to infection. These results suggest that body size is probably an underestimated variable, which nevertheless modulates the insect immune system and should thus be considered as a covariate in insect immune system measurement. It is recommended therefore, that body size should be taken into account in ecological immunity studies with insects. © 2013 The Royal Entomological Society     

Solution- and solid-state NMR studies of GPCRs and their ligands

G protein-coupled receptors (GPCRs) represent one of the major targets of new drugs on the market given their roles as key membrane receptors in many cellular signalling pathways. Structure-based drug design has potential to be the most reliable method for novel drug discovery. Unfortunately, GPCR-ligand crystallisation for X-ray diffraction studies is very difficult to achieve. However, solution- and solid-state NMR approaches have been developed and have provided new insights, particularly focussing on the study of protein-ligand interactions which are vital for drug discovery. This review provides an introduction for new investigators of GPCRs/ligand interactions using NMR spectroscopy. The guidelines for choosing a system for efficient isotope labelling of GPCRs and their ligands for NMR studies will be presented, along with an overview of the different sample environments suitable for generation of high resolution structural information from NMR spectra.     

Cleaner wrasses Labroides dimidiatus are more cooperative in the presence of an audience

Humans may help others even in?situations where the recipient will not reciprocate [1-5]. In some cases, such behavior can be explained by the helpers increasing their image score, which will increase the probability that bystanders will help them in the future [5-7]. For other animals, the notion that many interactions take place in an environment containing an audience of eavesdropping bystanders has also been proposed to have important consequences for social behavior, including levels of cooperation [8]. However, experimental evidence is currently restricted to the demonstration that cleaner fish Labroides dimidiatus can learn to solve a foraging task [9]. The cleaners learned to feed against their preference on artificial clients if that allowed them to access additional artificial clients, which would translate into cooperatively eating ectoparasites rather than cheating by eating client mucus under natural conditions [10]. Here we show that cleaners immediately increase current levels of cooperation in the presence of?bystander client reef fish. Furthermore, we find that bystanders respond to any occurrence of cleaners cheating their current client with avoidance. In conclusion, the results demonstrate, for the first time, that image scoring by an audience indeed leads to increased levels of cooperation in a nonhuman animal.     

Characterization of the induction and cellular role of the BaeSR two-component envelope stress response of Escherichia coli

The bacterial cell envelope is the interface between a bacterium and its environment and is constantly exposed to environmental changes. The BaeSR two-component system regulates one of six envelope stress responses in Escherichia coli and is induced by spheroplasting, overexpression of the pilin subunit PapG, and exposure to indole. The known BaeR regulon is small, consisting of eight genes, mdtABCD-baeSR, acrD, and spy, two of which encode the BaeSR two-component system itself. In this study, we investigated the molecular nature of the BaeS-inducing cue and the cellular role of the BaeSR envelope stress response. We demonstrated that at least two flavonoids and sodium tungstate are novel inducers of the BaeSR response. Interestingly, flavonoids and sodium tungstate led to much stronger induction of the BaeSR response in an mdtA efflux pump mutant, while indole did not. These findings are consistent with the hypothesis that flavonoids and sodium tungstate are natural substrates of the MdtABC efflux pump. Indole has recently been implicated in cell-cell signaling and biofilm repression through a putative interaction with the LuxR homologue SdiA. Using genetic analyses, we found that induction of the BaeSR response by indole occurs via a pathway separate from the SdiA biofilm pathway. Further, we demonstrated that the BaeSR response does not influence biofilm formation, nor is it involved in indole-mediated inhibition of biofilm formation. We hypothesize that the main function of the Bae response is to upregulate efflux pump expression in response to specific envelope-damaging agents.     

The role of hepcidin and ferroportin in iron absorption

The field of iron metabolism is moving rapidly. There have been significant advances in our understanding of how proteins carry out the process of iron absorption. The three main tissues involved in iron exchange are the enterocyte which contributes new iron to the system, the hepatocyte which stores and releases iron and the macrophages which recycles iron from effete red blood cells to the plasma. This review examines recent evidence into the function of the iron transporters divalent metal transporter and ferroportin in enterocytes. Evidence is also provided from the author's laboratory which presents an alternative hypothesis into how hepcidin a key regulator molecule might interact with ferroportin in enterocytes. It is proposed that ferroportin operates differently in enterocytes compared with macrophages. Specifically in enterocytes ferroportin appears to function in the uptake stage of iron absorption.     

The relationship between dose of vitamin E and suppression of oxidative stress in humans

The oxidation hypothesis of atherogenesis has been the focus of much research over the past 2 decades. However, randomized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect. Implicit in these trials is that the dose of vitamin E tested effectively suppressed oxidative stress status but this was never determined. We defined the dose-dependent effects of vitamin E (RRR-alpha-tocopherol) to suppress plasma concentrations of F2-isoprostanes, a biomarker of free radical-mediated lipid peroxidation, in participants with polygenic hypercholesterolemia and enhanced oxidative stress, a population at risk for cardiovascular events. A time-course study was first performed in participants supplemented with 3200 IU/day of vitamin E for 20 weeks. A dose-ranging study was then performed in participants supplemented with 0, 100, 200, 400, 800, 1600, or 3200 IU/day of vitamin E for 16 weeks. In the time-course study, maximum suppression of plasma F2-isoprostane concentrations did not occur until 16 weeks of supplementation. In the dose-ranging study there was a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 IU (35+/-2%, p<0.035) and 3200 IU (49+/-10%, p<0.005). This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease.     

SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor,CP-470,711

SAR studies on the stereoisomers of CP-470,711 suggested that in vivo epimerization was taking place in rats. Further metabolism studies revealed that no epimerization was occurring in dogs, and that no epimerization was expected in humans. A mechanism for the in vivo epimerization is proposed involving an oxidation-reduction pathway of the secondary benzylic alcohol, in contrast to an acid/base-promoted epimerization of the same center during chemical synthesis.