Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones

Background: Fasciola hepatica is of worldwide significance, impacting on the health, welfare and productivity of livestock and regarded by WHO as a re-emerging zoonosis. Triclabendazole (TCBZ), the drug of choice for controlling acute fasciolosis in livestock, is also the drug used to treat human infections. However TCBZ-resistance is now considered a major threat to the effective control of F. hepatica. It has yet to be demonstrated whether F. hepatica undergoes a genetic clonal expansion in the snail intermediate host, Galba truncatula, and to what extent amplification of genotypes within the snail facilitates accumulation of drug resistant parasites. Little is known about genotypic and phenotypic variation within and between F. hepatica isolates. Results: Six clonal isolates of F. hepatica (3× triclabendazole-resistant, TCBZ-R and 3× triclabendazole-susceptible, TCBZ-S) were generated. Snails infected with one miracidium started to shed cercariae 42–56 days post-infection and shed repeatedly up to a maximum of 11 times. A maximum of 884 cercariae were shed by one clonally-infected snail (FhLivS1) at a single time point, with > 3000 clonal metacercariae shed over its lifetime. Following experimental infection all 12 sheep were FEC positive at the time of TCBZ treatment. Sheep infected with one of three putative TCBZ-S clones and treated with TCBZ had no parasites in the liver at post-mortem, whilst sheep each infected with putative TCBZ-R isolates had 35–165 adult fluke at post-mortem, despite TCBZ treatment. All six untreated control animals had between 15–127 parasites. A single multi-locus genotype was reported for every fluke from each of the six clonal isolates. Adult F. hepatica showed considerable variation in weight, ranging from 20–280 mg, with variation in weight evident within and amongst clonal isolates. Conclusions: A genetic clonal expansion occurs within G. truncatula, highlighting the potential for amplification of drug resistant genotypes of F. hepatica. Variation in the weight of parasites within and between clonal isolates and when comparing isolates that are either susceptible or resistant to TCBZ represent inherent variation in liver fluke and cannot be attributed to their resistance or susceptibility traits

Population-level manipulations of field vole densities induce subsequent changes in plant quality but no impacts on vole demography

Grazing-induced changes in plant quality have been suggested to drive the negative delayed density-dependence exhibited by many herbivore species, but little field evidence exists to support this hypothesis. We tested a key premise of the hypothesis that reciprocal feedback between vole grazing pressure and the induction of anti-herbivore silicon defences in grasses drives observed population cycles in a large-scale field experiment in northern England. We repeatedly reduced population densities of field voles (Microtus agrestis) on replicated 1-ha grassland plots at Kielder Forest, northern England, over a period of one year. Subsequently, we tested for the impact of past density on vole life history traits in spring, and whether these effects were driven by induced silicon defences in the voles’ major over-winter food, the grass Deschampsia caespitosa. After several months of density manipulation, leaf silicon concentrations diverged and averaged 22% lower on sites where vole density had been reduced, but this difference did not persist beyond the period of the density manipulations. There were no significant effects of our density manipulations on vole body mass, spring population growth rate, or mean date for the onset of spring reproduction the following year. These findings show that grazing by field voles does induce increased silicon defences in grasses at a landscape-scale. However, at the vole densities encountered, levels of plant damage appear to be below those needed to induce changes in silicon levels large and persistent enough to affect vole performance, confirming the threshold effects we have previously observed in lab-based studies. Our findings do not support the plant quality hypothesis for observed vole population cycles in northern England, at least over the range of vole densities that now prevail here

Initial Validation of the Suicide Competency Assessment Form among Behavioral Health Staff in the National Health Services (NHS) Trust. Archives of Suicide Research

Objective: The Suicide Competency Assessment Form (SCAF) provides a framework for suicide prevention skills training. This study assessed SCAF psychometric properties in a sample of behavioral health staff. Method: A cross-sectional survey of National Health Services (NHS) staff from varying disciplines (N=170) was conducted. Results: The SCAF yielded a one-factor structure with high internal consistency. Nursing assistants reported lower SCAF scores compared to other professionals. SCAF scores demonstrated positive associations with prior suicide prevention training, job enthusiasm, and several suicide/self-injury prevention outcome expectations (i.e., optimism working with self-harming patients and perceived ability to help self-harming patients). SCAF scores further demonstrated incremental validity in the form of multivariate model associations with suicide/self-injury prevention outcome expectations. Improved job satisfaction mediated the pathway from SCAF scores to perceived ability to help self-harming patients. Conclusion: The SCAF can be utilized in suicide prevention training and clinical supervision

Exploring supply management status, internal collaboration and operating performance

An important internal link in the supply chain is between supply managers and their internal customers. These individuals must collaborate to determine purchase specifications, develop sourcing strategies, ensure supplier performance, and maintain effective supplier relationships. Using power and social networking as the theoretical lenses, we develop and test a conceptual model examining the supply management function’s status, supply manager’s networking behavior, collaboration with the internal customer, and operating performance (lower cost, better quality, faster delivery, and consistent delivery). We also examine the mediating effect of collaboration and networking behavior on the positive effect of status and operating performance. Data gathered in an online survey of supply management professionals are examined using path analysis. Results show that without including the mediators, supply management status is directly related to all four operating performance measures. It is also positively related to collaboration with the internal customer and networking behavior. Contrary to expectations, the supply manager’s networking behavior is not related to collaboration with the internal customer. Collaboration is positively related to all four operating performance measures. However, the supply manager’s networking behavior is only related to one operating performance measure, better quality. Mediation analysis shows that supply management status has a direct effect on faster delivery performance beyond what is explained by collaboration and the supply manager’s networking behavior. The findings suggest that organizations should look for ways to elevate the status of the supply management function to improve internal collaboration and operating performance.Keywords: status, operating performance, supply management, networking, collaboration, internal custome

Mutation detection in cholestatic patients using microarray resequencing of ATP8B1 and ABCB11

© 2013 McKay KE et al. Background: Neonatal cholestasis is a common presentation of childhood liver diseases and can be a feature of various conditions including disorders of bile acid biogenesis and transport, various inborn errors of metabolism and perinatal infections. Some inherited metabolic diseases can be easily screened using biochemical assays, however many can only be accurately diagnosed by DNA sequencing. Fluorescent capillary Sanger sequencing (FS) is the gold standard method used by clinical laboratories for genetic diagnosis of many inherited conditions; however, it does have limitations. Recently microarray resequencing (MR) has been introduced into research and clinical practice as an alternative method for genetic diagnosis of heterogeneous conditions. In this report we compared the accuracy of mutation detection for MR with FS in a group of patients with 'low-normal' gamma glutamyl transpeptidase (gGT) cholestasis without known molecular diagnoses. Methods: 29 patient DNA samples were tested for mutations in the ATP8B1 and ABCB11 genes using both FS and MR. Other known causes of "low gGT cholestasis such as ARC syndrome and bile acid biosynthesis disorders were excluded. Results: Mutations were identified in 13/29 samples. In 3/29 samples FS and MR gave discordant results: MR had a false positive rate of 3.4% and a false negative rate of 7%. Conclusions: The major advantage of MR over FS is that multiple genes can be screened in one experiment, allowing rapid and cost-effective diagnoses. However, we have demonstrated that MR technology is limited in sensitivity. We therefore recommend that MR be used as an initial evaluation, with FS deployed when genetic and clinical or histopathological findings are discordant

A combination of mutations in AKR1D1 and SKIV2L in a family with severe infantile liver disease.

Infantile cholestatic diseases can be caused by mutations in a number of genes involved in different hepatocyte molecular pathways. Whilst some of the essential pathways have a well understood function, such as bile biosynthesis and transport, the role of the others is not known. Here we report the findings of a clinical, biochemical and molecular study of a family with three patients affected with a severe infantile cholestatic disease. A novel homozygous frameshift germline mutation (c.587delG) in the AKR1D1 gene; which encodes the enzyme Δ 4-3-oxosteroid 5β-reductase that is required for synthesis of primary bile acids and is crucial for establishment of normal bile flow, was found in all 3 patients. Although the initial bile acid analysis was inconclusive, subsequent testing confirmed the diagnosis of a bile acid biogenesis disorder. An additional novel homozygous frameshift mutation (c.3391delC) was detected in SKIV2L in one of the patients. SKIV2L encodes a homologue of a yeast ski2 protein proposed to be involved in RNA processing and mutations in SKIV2L were recently described in patients with Tricohepatoenteric syndrome (THES). A combination of autozygosity mapping and whole-exome-sequencing allowed the identification of causal mutations in this family with a complex liver phenotype. Although the initial 2 affected cousins died in the first year of life, accurate diagnosis and management of the youngest patient led to successful treatment of the liver disease and disease-free survival.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Silicon-induced root nodulation and synthesis of essential amino acids in a legume is associated with higher herbivore abundance

Ecologists have become increasingly aware that silicon uptake by plants, especially the Poaceae, can have beneficial effects on both plant growth and herbivore defence. The effects of silicon on other plant functional groups, such as nitrogen-fixing legumes, have been less well studied. Silicon could, however, indirectly promote herbivore performance in this group if reported increases in N2 fixation caused improvements in host plant quality for herbivores. We tested how silicon supplementation in the legume (Medicago sativa) affected plant growth rates, root nodulation and foliage quality (silicon content and amino acid profiles) for an insect herbivore (Acyrthosiphon pisum). Plants supplemented with silicon (Si+) grew three times as quickly as those without supplementation (Si−), almost entirely in shoot mass. While root growth was unaffected by silicon uptake, root nodules containing nitrogen-fixing bacteria were 44% more abundant on Si+ plants. Aphid abundance was twice as high on Si+ plants compared to Si− plants and was positively correlated with silicon-stimulated plant growth. Si+ plants accumulated more than twice as much silicon as Si− plants, but did not have higher silicon concentrations because of dilution effects linked to the rapid growth of Si+ plants. Si+ plants showed a 65% increase in synthesis of essential foliar amino acids, probably due to increased levels of root nodulation. These results suggest that increased silicon supply makes M. sativa more susceptible to A. pisum, mainly because of increased plant growth and resource availability (i.e. essential amino acids). While silicon augmentation of the Poaceae frequently improves herbivore defence, the current study illustrates that this cannot be assumed for other plant families where the beneficial effects of silicon on plant growth and nutrition may promote herbivore performance in some instances

Non-Additive Effects of Genotypic Diversity Increase Floral Abundance and Abundance of Floral Visitors

Background: In the emerging field of community and ecosystem genetics, genetic variation and diversity in dominant plant species have been shown to play fundamental roles in maintaining biodiversity and ecosystem function. However, the importance of intraspecific genetic variation and diversity to floral abundance and pollinator visitation has received little attention. Methodology/Principal Findings: Using an experimental common garden that manipulated genotypic diversity (the number of distinct genotypes per plot) of Solidago altissima, we document that genotypic diversity of a dominant plant can indirectly influence flower visitor abundance. Across two years, we found that 1) plant genotype explained 45 % and 92 % of the variation in flower visitor abundance in 2007 and 2008, respectively; and 2) plant genotypic diversity had a positive and non-additive effect on floral abundance and the abundance of flower visitors, as plots established with multiple genotypes produced 25 % more flowers and received 45 % more flower visits than would be expected under an additive model. Conclusions/Significance: These results provide evidence that declines in genotypic diversity may be an important but little considered factor for understanding plant-pollinator dynamics, with implications for the global decline in pollinators due t