Potentiation of triclabendazole sulphoxide-induced tegumental disruption by methimazole in a triclabendazole-resistant isolate of Fasciola hepatica

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The flavin monooxygenase system (FMO) was inhibited using methimazole (MTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The FMO system was inhibited by a 2-h pre-incubation in methimazole (100 mu M), then incubated for a further 22 h in NCTC medium containing either MTZ; MTZ+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nM); MTZ+NADPH+TCBZ (15 mu g/ml); or MTZ+NADPH+triclabendazole sulphoxide (TCBZ.SO) (15 mu g/ml). Changes to fluke ultrastructure following drug treatment and metabolic inhibition were assessed using transmission electron microscopy. After treatment with either TCBZ or TCBZ.SO on their own, there was greater disruption to the TCBZ-susceptible than triclabedazole-resistant isolate. However, co-incubation with MTZ+TCBZ, but more particularly MTZ+TCBZ.SO, led to more severe changes to the TCBZ-resistant isolate than with each drug on its own, with severe swelling of the basal infolds and mucopolysaccharide masses in the syncytium, accompanied by a reduction in numbers of secretory bodies. The synthesis and production of secretory bodies in the tegumental cells was severely affected as well. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action. The results support the concept of altered drug metabolism in TCBZ-resistant flukes, and this process may play a role in the development of drug resistance.

Assessment of fighting ability in animal contests

Selection should favour accurate information gathering regarding the likely costs and benefits of continued conflict. Here we consider how variation in the abilities of contestants to assess resource-holding potential (RHP) influences fights. This has been examined in various game theory models. However, discriminating between assessment strategies has proven difficult and has resulted in confusion. To add clarity, we group existing models into three main types that differ in the information about RHP that contestants are presumed to gather: (1) pure self-assessment, (2) cumulative assessment and (3) mutual assessment. Within this framework we outline methods advocated to discriminate successfully between the three main assessment models. We discuss support for each model, before highlighting a number of conflicting and inconclusive studies, leading us to consider alternative approaches to investigate assessment. Furthermore, we examine support for newly emerging concepts such as 'varying degrees of assessment', 'switching assessment' strategies and the possibility of contestants adopting different assessment strategies within a fight involving distinctive roles. We suggest future studies will benefit by judicious use of a battery of techniques to determine how animals settle contests. Finally, we highlight difficulties with current game theory models, and raise concerns regarding the use of certain behavioural criteria to accept or reject a model, particularly since this may conflict with evidence for a given assessment strategy. Furthermore, the failure of existing models to account for newly emerging concepts points to limitations of their use and leads us to challenge game theoreticians to develop upon them. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Coalitional Games and Contracts Based on Individual Deviations

We study what coalitions form and how the members of each coalition split the coalition value in coalitional games in which only individual deviations are allowed. In this context we employ three stability notions: individual, contractual, and compensational stability. These notions differ in terms of the underlying contractual assumptions. We characterize the coalitional games in which individually stable outcomes exist by means of the top-partition property. Furthermore, we show that any coalition structure of maximum social worth is both contractually and compensationally stable.

Predicting intentions to purchase organic food: The role of affective and moral attitudes in the Theory of Planned Behaviour

This study examined the usefulness of integrating measures of affective and moral attitudes into the Theory of Planned Behaviour (TPB)-model in predicting purchase intentions or organic foods. Moral attitude was operationalised Lis positive self-rewarding feelings of doing the right thing. Questionnaire data were gathered in three countries: Italy (N = 202), Finland (N = 270) and UK (N = 200) in March 2004. Questions focussed on intentions to purchase organic apples and organic ready-to-cook pizza instead of their conventional alternatives. Data were analysed using Structural Equation Modelling by simultaneous multi-group analysis of the three Countries. Along with attitudes, moral attitude and subjective norms explained considerable shares of variances in intentions. The relative influences of these variables varied between the Countries, such that in the UK and Italy moral attitude rather than subjective norms had stronger explanatory power. In Finland it was other way around. Inclusion of moral attitude improved the model fit and predictive ability of the model, although only marginally in Finland. Thus the results partially Support the usefulness of incorporating moral measures as well as affective items for attitude into the framework of TPB. (c) 2007 Elsevier Ltd. All rights reserved.

Clinical significance of sperm DNA damage in assisted reproduction outcome

Background: Sperm DNA damage shows great promise as a biomarker of infertility. The study aim is to determine the usefulness of DNA fragmentation (DF), including modified bases (MB), to predict assisted reproduction treatment (ART) outcomes. Methods: DF in 360 couples (230 IVF and 130 ICSI) was measured by the alkaline Comet assay in semen and in sperm following density gradient centrifugation (DGC) and compared with fertilization rate (FR), embryo cumulative scores (ECS1) for the total number of embryos/treatment, embryos transferred (ECS2), clinical pregnancy (CP) and spontaneous pregnancy loss. MB were also measured using formamidopyrimidine DNA glycosylase to convert them into strand breaks. Results: In IVF, FR and ECS decreased as DF increased in both semen and DGC sperm, and couples who failed to achieve a CP had higher DF than successful couples (+12.2 semen, P = 0.004; +9.9 DGC sperm, P = 0.010). When MB were added to existing strand breaks, total DF was markedly higher (+17.1 semen, P = 0.009 and +13.8 DGC sperm, P = 0.045). DF was not associated with FR, ECS or CP in either semen or DGC sperm following ISCI. In contrast, by including MB, there was significantly more DNA damage (+16.8 semen, P = 0.008 and +15.5 DGC sperm, P = 0.024) in the group who did not achieve CP. Conclusion: SDF can predict ART outcome for IVF. Converting MB into further DNA strand breaks increased the test sensitivity, giving negative correlations between DF and CP for ICSI as well as IVF. © 2010 The Author.

Targeted genome-wide investigation identifies novel SNP's associated with diabetic nephropathy

Loci contributing to complex disease have been identified by focusing on genome-wide scans utilising non-synonymous single nucleotide polymorphisms (nsSNPs). We employed Illumina’s HNS12 BeadChip (13,917 high-value SNPs) which was specifically designed to capture nsSNPs and ideally complements more dense genome-wide association studies that fail to consider many of these putatively functional variants. The HNS12 panel also includes 870 tag SNPs covering the major histocompatibility region. All individuals genotyped in this study were Caucasians with (cases) and without (controls) diabetic nephropathy. About 449 individuals with type 2 diabetes (203 cases, 246 controls) were genotyped in the initial study. 1,467 individuals with type 1 diabetes (718 cases, 749 controls) were genotyped in the follow up study. 11,152 SNPs were successfully analysed and ranked for association with diabetic nephropathy based on significance (P) values. The top ranked 32 SNPs were subsequently genotyped using MassARRAY iPLEX™ and TaqMan technologies to investigate association of these polymorphisms with nephropathy in individuals with type 1 diabetes. The top ranked nsSNP, rs1543547 (P = 10-5), is located in RAET1L, a major histocompatibility class I-related gene at 6q25.1. Of particular interest, multiple nsSNPs within the top ranked (0.2%) SNPs are within several plausible candidate genes for nephropathy on 3q21.3 and 6p21.3.

European hare (Lepus europaeus) invasion ecology: Implication for the conservation of the endemic Irish hare (Lepus timidus hibernicus)

European hare Lepus europaeus populations have undergone recent declines but the species has successfully naturalised in many countries outside its native range. It was introduced to Ireland during the mid-late nineteenth century for field sport and is now well established in Northern Ireland. The native Irish hare Lepus timidus hibernicus is an endemic subspecies of mountain hare L. timidus and has attracted major conservation concern following a long-term population decline during the twentieth century and is one of the highest priority species for conservation action in Ireland. Little is known about the European hare in Ireland or whether it poses a significant threat to the native mountain hare subspecies by compromising its ecological security or genetic integrity. We review the invasion ecology of the European hare and examine evidence for interspecific competition with the mountain hare for habitat space and food resources, interspecific hybridisation, disease and parasite transmission and possible impacts of climate change. We also examine the impact that introduced hares can have on native non-lagomorph species. We conclude that the European hare is an emerging and significant threat to the conservation status of the native Irish hare. Invasive mammal species have been successfully eradicated from Ireland before and immediate action is often the only opportunity for cost-effective eradication. An urgent call is issued for further research whilst the need for a European hare invasive Species Action Plan (iSAP) and Eradication strategy are discussed.

Interactions between invasive and native crustaceans: differential functional responses of intraguild predators towards juvenile hetero-specifics

Intraguild predation (IGP) between invasive and native species can lead to species exclusions or co-existence, dependent on the direction and strength of the interaction. Recently, derivation of 'functional responses' has been identified as a means of comparing the community impacts of invasive and native species. Here, we employ a novel use of this functional response methodology to evaluate any IGP asymmetries between the invasive Ponto-Caspian amphipod Echinogammarus ischnus and the North American native Gammarus fasciatus. The direction and magnitude of intraguild predation of adult males on hetero-specific adult females has previously been shown to reverse across a water conductivity gradient. This partially explains field patterns, but does not predict the co-existence of the two species observed in many habitats and locations. Here, we compared intraguild predation by both species on each other's juveniles in high- and low- conductivity water. G. fasciatus has a higher type II functional response towards E. ischnus juveniles compared to the reciprocal interaction. Conductivity did not influence the predation rate on juveniles of either E. ischnus or G. fasciatus. Thus, the male/female IGP advantage to the native G. fasciatus in low conductivity water is compounded by a juvenile IGP asymmetry, which also counteracts the male/female IGP advantage to E. ischnus in high conductivity waters, helping to explain field patterns of exclusion and co-existence. Thus, complex asymmetries in mutual IGP associated with inherent species differences, environmental modulation, and life-history effects can help us understand and predict the population and community level outcomes of species invasions.

Phylloseptin-1 (PSN-1) from Phyllomedusa sauvagei skin secretion: a novel broad-spectrum antimicrobial peptide with antibiofilm activity

Amphibian skin secretions have proven to be rich sources of antimicrobial peptides that are proposed to be fundamental components of the innate immune system. As amphibian skin is a multi-functional organ playing, among other things, a crucial role in respiration, it has been deemed that a core biological role for such peptides is control of microbial flora on this surface. To date, however, antimicrobial efficacy has been universally determined by means of establishing minimum inhibitory concentrations (MICs) using planktonic organisms rather than those within a biofilm such as would occur on this exposed surface. Here we describe the identification and structural characterisation of a novel 19 amino acid residue antimicrobial peptide of the phylloseptin family, named PSN-1, from the skin secretion of the waxy monkey frog, Phyllomedusa sauvagei. PSN-1 displayed broad-spectrum activity against a range of planktonic organisms with a high potency (MIC 5 µM) against Staphylococcus aureus. In a specific bioassay with the same organism grown as a biofilm, the minimal biofilm eradication concentration (MBEC) was found to be of the same high potency (5 µM). The present data would suggest that evaluation of actions and potency of amphibian skin secretion antimicrobial peptides might best be achieved by evaluating MBEC rather than MIC using planktonic organisms and that data arising from such studies may have more biological relevance in reflecting the purpose for which they have evolved through natural selection.

A general framework for measuring inconsistency through minimal inconsistent sets

Hunter and Konieczny explored the relationships between measures of inconsistency for a belief base and the minimal inconsistent subsets of that belief base in several of their papers. In particular, an inconsistency value termed MIVC, defined from minimal inconsistent subsets, can be considered as a Shapley Inconsistency Value. Moreover, it can be axiomatized completely in terms of five simple axioms. MinInc, one of the five axioms, states that each minimal inconsistent set has the same amount of conflict. However, it conflicts with the intuition illustrated by the lottery paradox, which states that as the size of a minimal inconsistent belief base increases, the degree of inconsistency of that belief base becomes smaller. To address this, we present two kinds of revised inconsistency measures for a belief base from its minimal inconsistent subsets. Each of these measures considers the size of each minimal inconsistent subset as well as the number of minimal inconsistent subsets of a belief base. More specifically, we first present a vectorial measure to capture the inconsistency for a belief base, which is more discriminative than MIVC. Then we present a family of weighted inconsistency measures based on the vectorial inconsistency measure, which allow us to capture the inconsistency for a belief base in terms of a single numerical value as usual. We also show that each of the two kinds of revised inconsistency measures can be considered as a particular Shapley Inconsistency Value, and can be axiomatically characterized by the corresponding revised axioms presented in this paper.