The emergence of resistance to the benzimidazole anthlemintics in parasitic nematodes of livestock is characterised by multiple independent hard and soft selective sweeps

Anthelmintic resistance is a major problem for the control of parasitic nematodes of livestock and of growing concern for human parasite control. However, there is little understanding of how resistance arises and spreads or of the “genetic signature” of selection for this group of important pathogens. We have investigated these questions in the system for which anthelmintic resistance is most advanced; benzimidazole resistance in the sheep parasites Haemonchus contortus and Teladorsagia circumcincta. Population genetic analysis with neutral microsatellite markers reveals that T. circumcincta has higher genetic diversity but lower genetic differentiation between farms than H. contortus in the UK. We propose that this is due to epidemiological differences between the two parasites resulting in greater seasonal bottlenecking of H. contortus. There is a remarkably high level of resistance haplotype diversity in both parasites compared with drug resistance studies in other eukaryotic systems. Our analysis suggests a minimum of four independent origins of resistance mutations on just seven farms for H. contortus, and even more for T. circumincta. Both hard and soft selective sweeps have occurred with striking differences between individual farms. The sweeps are generally softer for T. circumcincta than H. contortus, consistent with its higher level of genetic diversity and consequent greater availability of new mutations. We propose a model in which multiple independent resistance mutations recurrently arise and spread by migration to explain the widespread occurrence of resistance in these parasites. Finally, in spite of the complex haplotypic diversity, we show that selection can be detected at the target locus using simple measures of genetic diversity and departures from neutrality. This work has important implications for the application of genome-wide approaches to identify new anthelmintic resistance loci and the likelihood of anthelmintic resistance emerging as selection pressure is increased in human soil-transmitted nematodes by community wide treatment programs

Incidental Finding of Sickle Cell Trait From an Everyday Diabetes Test: Should General Health Care Providers and testing centres report, retest, or refer?

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.The HbA1c test is increasingly widely used as a diagnostic and screening test for diabetes mellitus type 2 (T2DM) but the presence of haemoglobin variants, such as sickle haemoglobin, can interfere with results in some analytical systems. These interferences are occasionally reported by laboratories, leading unprepared patients to suspect they may be sickle cell carriers and seek confirmation through a sickle cell test. Incidental findings of Hb variants, and the reporting thereof, present multiple ethical challenges to laboratories, medical practitioners, patients and their family members, but there appear to be no international or national guidelines on how to deal with the reporting of these findings. This paper explores issues such as whether informed consent is necessary, how the results should be communicated, how the patient may be affected by knowing their carrier status, the timing of communications, complications caused by partial results, and being a ‘healthy carrier’ at the same time as potentially experiencing symptoms

Efficient generation of transgenic pigs using equine infectious anaemia virus (EIAV) derived vector

AbstractTraditional methods of transgene delivery in livestock are inefficient. Recently, human immunodeficiency virus (HIV-1) based lentiviral vectors have been shown to offer an efficient transgene delivery system. We now extend this method by demonstrating efficient generation of transgenic pigs using an equine infectious anaemia virus derived vector. We used this vector to deliver a green fluorescent protein expressing transgene; 31% of injected/transferred eggs resulted in a transgenic founder animal and 95% of founder animals displayed green fluorescence. This compares favourably with results using HIV-1 based vectors, and is substantially more efficient than the standard pronuclear microinjection method, indicating that lentiviral transgene delivery may be a general tool with which to efficiently generate transgenic mammals

Estimating population size, density and dynamics of Pre-Pottery Neolithic villages in the central and southern Levant: an analysis of Beidha, southern Jordan

The Pre-Pottery Neolithic (PPN) of the central and southern Levant played an integral role in the Neolithic Demographic Transition (NDT) from mobile hunter-gatherer to village-based, agro-pastoralist societies. An understanding of population dynamics is essential for reconstructing the trajectories of these early village societies. However, few investigations have produced absolute estimates of population parameters for these villages and those which have base estimates on a limited methodological framework. This research examines the methodological and theoretical basis for existing estimates, and explores a range of methodologies in order to derive more empirically-robust demographic data. Results reveal that commonly utilized methodologies and population density coefficients employed for estimating PPN village populations require re-evaluation. This article presents the application of methodologies to the PPNB site of Beidha in southern Jordan

Introgression of Ivermectin Resistance Genes into a Susceptible Haemonchus contortus Strain by Multiple Backcrossing

Anthelmintic drug resistance in livestock parasites is already widespread and in recent years there has been an increasing level of anthelmintic drug selection pressure applied to parasitic nematode populations in humans leading to concerns regarding the emergence of resistance. However, most parasitic nematodes, particularly those of humans, are difficult experimental subjects making mechanistic studies of drug resistance extremely difficult. The small ruminant parasitic nematode Haemonchus contortus is a more amenable model system to study many aspects of parasite biology and investigate the basic mechanisms and genetics of anthelmintic drug resistance. Here we report the successful introgression of ivermectin resistance genes from two independent ivermectin resistant strains, MHco4(WRS) and MHco10(CAVR), into the susceptible genome reference strain MHco3(ISE) using a backcrossing approach. A panel of microsatellite markers were used to monitor the procedure. We demonstrated that after four rounds of backcrossing, worms that were phenotypically resistant to ivermectin had a similar genetic background to the susceptible reference strain based on the bulk genotyping with 18 microsatellite loci and individual genotyping with a sub-panel of 9 microsatellite loci. In addition, a single marker, Hcms8a20, showed evidence of genetic linkage to an ivermectin resistance-conferring locus providing a starting point for more detailed studies of this genomic region to identify the causal mutation(s). This work presents a novel genetic approach to study anthelmintic resistance and provides a “proof-of-concept” of the use of forward genetics in an important model strongylid parasite of relevance to human hookworms. The resulting strains provide valuable resources for candidate gene studies, whole genome approaches and for further genetic analysis to identify ivermectin resistance loci

Using the Elaboration Likelihood Model, multimedia and modern culture to promote academic honesty

Many students act as if academic honesty is an arcane nicety that does not apply in the world outside academia. At the same time, academic dishonesty, including plagiarism, is recognised as a chronic problem. This paper reports on a project that was undertaken to combat these problems. The project adopted a positive rather than punitive approach and used multimedia resources, examples from popular culture and the Elaboration Likelihood Model (ELM) (Petty & Cacioppo 2000) to foster student engagement with academic honesty within a classroom setting and the adoption of its practices with assessable tasks. As academic honesty, or rather its negation through dishonesty, continues to occur, an innovative approach was required. The ELM is a model of how individuals process information, but it has not been used often as a framework for introducing new teaching and learning resources within educational institutions. The evaluation of the resulting resources by academic staff and students suggests that whilst this approach of using resources inspired by the ELM will not alone eradicate academic dishonesty, it will contribute to an understanding and acceptance by students of the need to pursue academic honesty. Furthermore, the resources have created sufficient momentum to see them adopted in subjects in other degree courses as well as emerge as a foundation for other similarly styled projects at the home institution

Working from the centre: supporting unit and course coordinators to implement academic integrity policies, resources and scholarship

A key area of concern in higher education is academic integrity, which involves the adherence by students to standards of honesty, originality, and attribution. The literature indicates that plagiarism is widespread in Australian higher education institutions and that plagiarism, collusion and cheating are increasing. To maintain institutional credibility it is necessary to advance academic rigour and integrity as well as deal with breaches of academic integrity, especially by reducing instances of plagiarism. The current project is one of four academic integrity priority projects commissioned by the OLT in 2012. The aim of this project was to develop a national academic integrity resource for those with policy responsibilities and who are also at the front-line of teaching in the classroom, namely, unit/course coordinators. In accord with the funded proposal, the project outcomes and outputs: Include pedagogical resources, which support the development of academic integrity in students, for educators in a wide variety of academic fields of study, across undergraduate and postgraduate study, and across different types of institutions, Support unit/course coordinators to drive curriculum renewal in a manner that reinforces the scaffolded development of academic skills and academic integrity, and their own professional development, and Include resources and materials to help busy unit/course coordinators contribute to the scholarship of academic integrity

Simulating the Commercial Implementation of Gene-Editing for Influenza A Virus Resistance in Pigs: An Economic and Genetic Analysis

The development of swine Influenza A Virus resistance along with genetic technologies could complement current control measures to help to improve animal welfare standards and the economic efficiency of pig production. We have created a simulation model to assess the genetic and economic implications of various gene-editing methods that could be implemented in a commercial, multi-tiered swine breeding system. Our results demonstrate the length of the gene-editing program was negatively associated with genetic progress in commercial pigs and that the time required to reach fixation of resistance alleles was reduced if the efficiency of gene-editing is greater. The simulations included the resistance conferred in a digenic model, the inclusion of genetic mosaicism in progeny, and the effects of selection accuracy. In all scenarios, the level of mosaicism had a greater effect on the time required to reach resistance allele fixation and the genetic progress of the herd than gene-editing efficiency and zygote survival. The economic analysis highlights that selection accuracy will not affect the duration of gene-editing and the investment required compared to the effects of gene-editing-associated mosaicism and the swine Influenza A Virus control strategy on farms. These modelling results provide novel insights into the economic and genetic implications of targeting two genes in a commercial pig gene-editing program and the effects of selection accuracy and mosaicism