MyosinA is a druggable target in the widespread protozoan parasite Toxoplasma gondii.

Toxoplasma gondii is a widespread apicomplexan parasite that can cause severe disease in its human hosts. The ability of T. gondii and other apicomplexan parasites to invade into, egress from, and move between cells of the hosts they infect is critical to parasite virulence and disease progression.

Optimal experimental designs for estimating genetic and non-genetic effects underlying infectious disease transmission.

Background: The spread of infectious diseases in populations is controlled by the susceptibility (propensity to acquire infection), infectivity (propensity to transmit infection), and recoverability (propensity to recover/die) of individuals. Estimating genetic risk factors for these three underlying host epidemiological traits can help reduce disease spread through genetic control strategies. Previous studies have identified important 'disease resistance single nucleotide polymorphisms (SNPs)', but how these affect the underlying traits is an unresolved question.

The nedd-8 activating enzyme gene underlies genetic resistance to infectious pancreatic necrosis virus in Atlantic salmon.

Genetic resistance to infectious pancreatic necrosis virus (IPNV) in Atlantic salmon is a rare example of a trait where a single locus (QTL) explains almost all of the genetic variation. Genetic marker tests based on this QTL on salmon chromosome 26 have been widely applied in selective breeding to markedly reduce the incidence of the disease. In the current study, whole genome sequencing and functional annotation approaches were applied to characterise genes and variants in the QTL region.

Estimating individuals' genetic and non-genetic effects underlying infectious disease transmission from temporal epidemic data.

Individuals differ widely in their contribution to the spread of infection within and across populations. Three key epidemiological host traits affect infectious disease spread: susceptibility (propensity to acquire infection), infectivity (propensity to transmit infection to others) and recoverability (propensity to recover quickly). Interventions aiming to reduce disease spread may target improvement in any one of these traits, but the necessary statistical methods for obtaining risk estimates are lacking.

Escaping from Flatland: Antimalarial Activity of sp-Rich Bridged Pyrrolidine Derivatives.

We utilized synthetic photochemistry to generate novel sp-rich scaffolds and report the design, synthesis, and biological testing of a diverse series of amides based on the 1-(amino-methyl)-2-benzyl-2-aza-bicyclo[2.1.1]hexane scaffold.

Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies.

Purpose: Anti-drug antibodies can impair the efficacy of therapeutic proteins and, in some circumstances, induce adverse health effects. Immunogenicity can be promoted by aggregation; here we examined the ability of recombinant mouse heat shock protein 70 (rmHSP70) - a common host cell impurity - to modulate the immune responses to aggregates of two therapeutic mAbs in mice.

Methods: Heat and shaking stress methods were used to generate aggregates in the sub-micron size range from two human mAbs, and immunogenicity assessed by intraperitoneal exposure in BALB/c mice.

Balancing selection at a premature stop mutation in the myostatin gene underlies a recessive leg weakness syndrome in pigs.

Balancing selection provides a plausible explanation for the maintenance of deleterious alleles at moderate frequency in livestock, including lethal recessives exhibiting heterozygous advantage in carriers. In the current study, a leg weakness syndrome causing mortality of piglets in a commercial line showed monogenic recessive inheritance, and a region on chromosome 15 associated with the syndrome was identified by homozygosity mapping. Whole genome resequencing of cases and controls identified a mutation causing a premature stop codon within exon 3 of the porcine Myostatin (MSTN) gene, similar to those causing a double-muscling phenotype observed in several mammalian species.

Arginine to Glutamine Variant in Olfactomedin Like 3 () Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed.

Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and have subsequently been found in this breed in Europe and the USA.

Dissecting the Genomic Architecture of Resistance to Parasitism in the Chicken.

Coccidiosis in poultry, caused by protozoan parasites of the genus , is an intestinal disease with substantial economic impact. With the use of anticoccidial drugs under public and political pressure, and the comparatively higher cost of live-attenuated vaccines, an attractive complementary strategy for control is to breed chickens with increased resistance to parasitism. Prior infection with leads to complete immunity against challenge with homologous strains, but only partial resistance to challenge with antigenically diverse heterologous strains.

Phenotypic and genetic variation in the response of chickens to Eimeria tenella induced coccidiosis.

Background: Coccidiosis is a major contributor to losses in poultry production. With emerging constraints on the use of in-feed prophylactic anticoccidial drugs and the relatively high costs of effective vaccines, there are commercial incentives to breed chickens with greater resistance to this important production disease. To identify phenotypic biomarkers that are associated with the production impacts of coccidiosis, and to assess their covariance and heritability, 942 Cobb500 commercial broilers were subjected to a defined challenge with Eimeria tenella (Houghton).

Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle.

Background: The significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics.

Methods: The present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches.

Reliability of a New Medicine Ball Throw Power Test.

The purpose of this study was to examine the reliability of a new upper body medicine ball push-press (MBP-P) test. Twenty-three strength trained volunteers performed a series of supine MBP-P throws using loads representing 5% and10% of their 5RM bench press (5 repetitions at each load). Throws were performed on a force platform (2000 Hz), with medicine ball kinematic data collected using a high-speed motion capture (500 Hz).

Quantitative genetic analysis of the bTB diagnostic single intradermal comparative cervical test (SICCT).

Background: Bovine tuberculosis (bTB) is a disease of significant economic importance and is a persistent animal health problem with implications for public health worldwide. Control of bTB in the UK has relied on diagnosis through the single intradermal comparative cervical test (SICCT). However, limitations in the sensitivity of this test hinder successful eradication and the control of bTB remains a major challenge.

A simulation model to investigate interactions between first season grazing calves and Ostertagia ostertagi.

A dynamic, deterministic model was developed to investigate the consequences of parasitism with Ostertagia ostertagi, the most prevalent and economically important gastrointestinal parasite of cattle in temperate regions. Interactions between host and parasite were considered to predict the level of parasitism and performance of an infected calf. Key model inputs included calf intrinsic growth rate, feed quality and mode and level of infection.

Which is the best phenotypic trait for use in a targeted selective treatment strategy for growing lambs in temperate climates?

Targeted selective treatment (TST) requires the ability to identify the animals for which anthelmintic treatment will result in the greatest benefit to the entire flock. Various phenotypic traits have previously been suggested as determinant criteria for TST; however, the weight gain benefit and impact on anthelmintic efficacy for each determinant criterion is expected to be dependent upon the level of nematode challenge and the timing of anthelmintic treatment. A mathematical model was used to simulate a population of 10,000 parasitologically naïve Scottish Blackface lambs (with heritable variation in host-parasite interactions) grazing on medium-quality pasture (grazing density=30 lambs/ha, crude protein=140g/kg DM, metabolisable energy=10MJ/kg DM) with an initial larval contamination of 1000, 3000 or 5000 Teladorsagia circumcincta L3/kg DM.

Genetic and genomic basis of antibody response to porcine reproductive and respiratory syndrome (PRRS) in gilts and sows.

Background: Our recent research showed that antibody response to porcine reproductive and respiratory syndrome (PRRS), measured as sample-to-positive (S/P) ratio, is highly heritable and has a high genetic correlation with reproductive performance during a PRRS outbreak. Two major quantitative trait loci (QTL) on Sus scrofa chromosome 7 (SSC7; QTLMHC and QTL130) accounted for ~40 % of the genetic variance for S/P. Objectives of this study were to estimate genetic parameters for PRRS S/P in gilts during acclimation, identify regions associated with S/P, and evaluate the accuracy of genomic prediction of S/P across populations with different prevalences of PRRS and using different single nucleotide polymorphism (SNP) sets.

Gene expression comparison of resistant and susceptible Atlantic salmon fry challenged with Infectious Pancreatic Necrosis virus reveals a marked contrast in immune response.

Background: Infectious Pancreatic Necrosis (IPN) is a highly contagious birnavirus disease of farmed salmonid fish, which often causes high levels of morbidity and mortality. A large host genetic component to resistance has been previously described for Atlantic salmon (Salmo salar L.), which mediates high mortality rates in some families and zero mortality in others.

Variations in T Cell Transcription Factor Sequence and Expression Associated with Resistance to the Sheep Nematode Teladorsagia circumcincta.

This study used selected lambs that varied in their resistance to the gastrointestinal parasite Teladorsagia circumcincta. Infection over 12 weeks identified susceptible (high adult worm count, AWC; high fecal egg count, FEC; low body weight, BW; low IgA) and resistant sheep (no/low AWC and FEC, high BW and high IgA). Resistance is mediated largely by a Th2 response and IgA and IgE antibodies, and is a heritable characteristic.

Genome-wide association reveals QTL for growth, bone and in vivo carcass traits as assessed by computed tomography in Scottish Blackface lambs.

Background: Improving meat quality including taste and tenderness is critical to the protection and development of markets for sheep meat. Phenotypic selection for such measures of meat quality is constrained by the fact that these parameters can only be measured post-slaughter. Carcass composition has an impact on meat quality and can be measured on live animals using advanced imaging technologies such as X-ray computed tomography (CT).

Genomics and disease resistance studies in livestock.

This paper considers the application of genetic and genomic techniques to disease resistance, the interpretation of data arising from such studies and the utilisation of the research outcomes to breed animals for enhanced resistance. Resistance and tolerance are defined and contrasted, factors affecting the analysis and interpretation of field data presented, and appropriate experimental designs discussed. These general principles are then applied to two detailed case studies, infectious pancreatic necrosis in Atlantic salmon and bovine tuberculosis in dairy cattle, and the lessons learnt are considered in detail.

Exploring the utility of cross-laboratory RAD-sequencing datasets for phylogenetic analysis.

Background: Restriction site-Associated DNA sequencing (RAD-Seq) is widely applied to generate genome-wide sequence and genetic marker datasets. RAD-Seq has been extensively utilised, both at the population level and across species, for example in the construction of phylogenetic trees. However, the consistency of RAD-Seq data generated in different laboratories, and the potential use of cross-species orthologous RAD loci in the estimation of genetic relationships, have not been widely investigated.

Hui and Walter's latent-class model extended to estimate diagnostic test properties from surveillance data: a latent model for latent data.

Diagnostic test sensitivity and specificity are probabilistic estimates with far reaching implications for disease control, management and genetic studies. In the absence of 'gold standard' tests, traditional Bayesian latent class models may be used to assess diagnostic test accuracies through the comparison of two or more tests performed on the same groups of individuals. The aim of this study was to extend such models to estimate diagnostic test parameters and true cohort-specific prevalence, using disease surveillance data.

The genetic architecture of growth and fillet traits in farmed Atlantic salmon (Salmo salar).

Background: Performance and quality traits such as harvest weight, fillet weight and flesh color are of economic importance to the Atlantic salmon aquaculture industry. The genetic factors underlying these traits are of scientific and commercial interest. However, such traits are typically polygenic in nature, with the number and size of QTL likely to vary between studies and populations.

Genomic prediction for tuberculosis resistance in dairy cattle.

Background: The increasing prevalence of bovine tuberculosis (bTB) in the UK and the limitations of the currently available diagnostic and control methods require the development of complementary approaches to assist in the sustainable control of the disease. One potential approach is the identification of animals that are genetically more resistant to bTB, to enable breeding of animals with enhanced resistance. This paper focuses on prediction of resistance to bTB.