Publications by authors named "Aaron Ingham"

32 Publications

Bias, dispersion, and accuracy of genomic predictions for feedlot and carcase traits in Australian Angus steers.

Genet Sel Evol 2021 Sep 26;53(1):77. Epub 2021 Sep 26.

CSIRO, Agriculture and Food, Queensland Bioscience Precinct, 306 Carmody Rd., St Lucia, Brisbane, QLD, 4067, Australia.

Background: Improving feedlot performance, carcase weight and quality is a primary goal of the beef industry worldwide. Here, we used data from 3408 Australian Angus steers from seven years of birth (YOB) cohorts (2011-2017) with a minimal level of sire linkage and that were genotyped for 45,152 SNPs. Phenotypic records included two feedlot and five carcase traits, namely average daily gain (ADG), average daily dry matter intake (DMI), carcase weight (CWT), carcase eye muscle area (EMA), carcase Meat Standard Australia marbling score (MBL), carcase ossification score (OSS) and carcase subcutaneous rib fat depth (RIB). Using a 7-way cross-validation based on YOB cohorts, we tested the quality of genomic predictions using the linear regression (LR) method compared to the traditional method (Pearson's correlation between the genomic estimated breeding value (GEBV) and its associated adjusted phenotype divided by the square root of heritability); explored the factors, such as heritability, validation cohort, and phenotype that affect estimates of accuracy, bias, and dispersion calculated with the LR method; and suggested a novel interpretation for translating differences in accuracy into phenotypic differences, based on GEBV quartiles (Q1Q4).

Results: Heritability (h) estimates were generally moderate to high (from 0.29 for ADG to 0.53 for CWT). We found a strong correlation (0.73, P-value < 0.001) between accuracies using the traditional method and those using the LR method, although the LR method was less affected by random variation within and across years and showed a better ability to discriminate between extreme GEBV quartiles. We confirmed that bias of GEBV was not significantly affected by h, validation cohort or trait. Similarly, validation cohort was not a significant source of variation for any of the GEBV quality metrics. Finally, we observed that the phenotypic differences were larger for higher accuracies.

Conclusions: Our estimates of h and GEBV quality metrics suggest a potential for accurate genomic selection of Australian Angus for feedlot performance and carcase traits. In addition, the Q1Q4 measure presented here easily translates into possible gains of genomic selection in terms of phenotypic differences and thus provides a more tangible output for commercial beef cattle producers.
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http://dx.doi.org/10.1186/s12711-021-00673-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474816PMC
September 2021

ImmuneDEX: a strategy for the genetic improvement of immune competence in Australian Angus cattle.

J Anim Sci 2021 Mar;99(3)

CSIRO Agriculture & Food, Queensland Bioscience Precinct, St. Lucia, Brisbane, QLD, Australia.

In animal breeding and genetics, the ability to cope with disease, here defined as immune competence (IC), with minimal detriment to growth and fertility is a desired objective which addresses both animal production and welfare considerations. However, defining and objectively measuring IC phenotypes using testing methods which are practical to apply on-farm has been challenging. Based on previously described protocols, we measured both cell-mediated immune response (Cell-IR) and antibody-mediated immune response (Ab-IR) and combined these measures to determine an animal's IC. Using a population of 2,853 Australian Angus steers and heifers, we compared 2 alternative methods to combine both metrics into a single phenotype to be used as a tool for the genetic improvement of IC. The first method, named ZMEAN, is obtained by taking the average of the individual metrics after subjecting each to a Z-score standardization. The second, ImmuneDEX (IDEX), is a weighted average that considers the correlation between Cell-IR and Ab-IR, as well as the difference in ranking of individuals by each metric, and uses these as weights in the averaging. Both simulation and real data were used to understand the behavior of ZMEAN and IDEX. To further ascertain the relationship between IDEX and other traits of economic importance, we evaluated a range of traits related to growth, feedlot performance, and carcass characteristics. We report estimates of heritability of 0.31 ± 0.06 for Cell-IR, 0.42 ± 0.06 for Ab-IR, 0.42 ± 0.06 for ZMEAN and 0.370 ± 0.06 for IDEX, as well as a unity genetic correlation (rg) between ZMEAN and IDEX. While a moderately positive rg was estimated between Cell-IR and Ab-IR (rg = 0.33 ± 0.12), strongly positive estimates were obtained between IDEX and Cell-IR (rg = 0.80 ± 0.05) and between IDEX and Ab-IR (rg = 0.85 ± 0.04). We obtained a moderately negative rg between IC traits and growth including an rg = -0.38 ± 0.14 between IDEX and weaning weight, and negligible with carcass fat measurements, including an rg = -0.03 ± 0.12 between IDEX and marbling. Given that breeding with a sole focus on production might inadvertently increase susceptibility to disease and associated antibiotic use, our analyses suggest that ImmuneDEX will provide a basis to breed animals that are both highly productive and with an enhanced ability to resist disease.
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http://dx.doi.org/10.1093/jas/skaa384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936916PMC
March 2021

Associations between immune competence phenotype and feedlot health and productivity in Angus cattle.

J Anim Sci 2021 Feb;99(2)

F.D. McMaster Laboratory, Agriculture and Food, CSIRO, Armidale, NSW, Australia.

Genetic strategies aimed at improving general immune competence (IC) have the potential to reduce the incidence and severity of disease in beef production systems, with resulting benefits of improved animal health and welfare and reduced reliance on antibiotics to prevent and treat disease. Implementation of such strategies first requires that methodologies be developed to phenotype animals for IC and demonstration that these phenotypes are associated with health outcomes. We have developed a methodology to identify IC phenotypes in beef steers during the yard weaning period, which is both practical to apply on-farm and does not restrict the future sale of tested animals. In the current study, a total of 838 Angus steers, previously IC phenotyped at weaning, were categorized as low (n = 98), average (n = 653), or high (n = 88) for the IC phenotype. Detailed health and productivity data were collected on all steers during feedlot finishing, and associations between IC phenotype, health outcomes, and productivity were investigated. A favorable association between IC phenotype and number of mortalities during feedlot finishing was observed with higher mortalities recorded in low IC steers (6.1%) as compared with average (1.2%, P < 0.001) or high (0%, P = 0.018) IC steers. Disease incidence was numerically highest in low IC steers (15.3 cases/100 animals) and similar in average IC steers (10.1 cases/100 animals) and high IC steers (10.2 cases/100 animals); however, differences between groups were not significant. No significant influence of IC phenotype on average daily gain was observed, suggesting that selection for improved IC is unlikely to incur a significant penalty to production. The potential economic benefits of selecting for IC in the feedlot production environment were calculated. Health-associated costs were calculated as the sum of lost production costs, lost capital investment costs, and disease treatment costs. Based on these calculations, health-associated costs were estimated at AUS$103/head in low IC steers, AUS$25/head in average IC steers, and AUS$4/head in high IC steers, respectively. These findings suggest that selection for IC has the potential to reduce mortalities during feedlot finishing and, as a consequence, improve the health and welfare of cattle in the feedlot production environment and reduce health-associated costs incurred by feedlot operators.
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http://dx.doi.org/10.1093/jas/skab016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901007PMC
February 2021

Immune competence traits assessed during the stress of weaning are heritable and favorably genetically correlated with temperament traits in Angus cattle1.

J Anim Sci 2019 Oct;97(10):4053-4065

CSIRO, Agriculture and Food, F.D. McMaster Laboratory, Armidale, NSW, Australia.

Selection for production traits with little or no emphasis on health-related traits has the potential to increase susceptibility to disease in food-producing animals. A possible genetic strategy to mitigate such effects is to include both production and health traits in the breeding objective when selecting animals. For this to occur, reliable methodologies are required to assess beneficial health traits, such as the immune capacity of animals. We describe here a methodology to assess the immune competence of beef cattle which is both practical to apply on farm and does not restrict the future sale of tested animals. The methodology also accommodates variation in prior vaccination history of cohorts of animals being tested. In the present study, the immune competence phenotype of 1,100 Angus calves was assessed during yard weaning. Genetic parameters associated with immune competence traits were estimated and associations between immune competence, temperament, and stress-coping ability traits were investigated. Results suggested that immune competence traits, related to an animal's ability to mount both antibody and cell-mediated immune responses, are moderately heritable (h2 = 0.32 ± 0.09 and 0.27 ± 0.08, respectively) and favorably genetically correlated with the temperament trait, flight time (r = 0.63 ± 0.31 and 0.60 ± 0.29 with antibody and cell-mediated immune responses, respectively). Development of methodologies to assess the immune competence phenotype of beef cattle is a critical first step in the establishment of genetic selection strategies aimed at improving the general disease resistance of beef herds. Strategies aimed at reducing the incidence of disease in beef cattle are expected to significantly improve animal health and welfare, reduce reliance on the use of antibiotics to treat disease, and reduce disease-associated costs incurred by producers.
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http://dx.doi.org/10.1093/jas/skz260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776280PMC
October 2019

Quantification of differences in resistance to gastrointestinal nematode infections in sheep using a multivariate blood parameter.

Vet Parasitol 2019 Jun 20;270:31-39. Epub 2019 May 20.

CSIRO Agriculture and Food, St Lucia, Queensland, 4067, Australia. Electronic address:

Breeding for resistance to gastrointestinal nematodes (GIN) in sheep relies largely on the use of worm egg counts (WEC) to identify animals that are able to resist infection. As an alternative to such measures of parasite load we aimed to develop a method to identify animals showing resistance to GIN infection based on the impact of the infection on blood parameters. We hypothesized that blood parameters may provide a measure of infection level with a blood-feeding parasite through perturbation of red blood cell parameters due to feeding behaviour of the parasite, and white blood cell parameters through the mounting of an immune response in the host animal. We measured a set of blood parameters in 390 sheep that had been exposed to an artificial regime of repeated challenges with Trichostrongylus colubriformis followed by Haemonchus contortus. A simple analysis revealed strong relationships between single blood parameters and WECs with correlation coefficients -0.54 to -0.60. We then used more complex multi-variate methods based on supervised classifier models (including Bayesian Network) as well as regression models (Lasso and Elastic Net) to study the relationships between WECs and blood parameters, and derived algorithms describing the relationships. The ability of these algorithms to classify sheep GIN resistance status was tested using the WEC and blood parameters collected from a different group of 418 sheep that had acquired natural infections of H. contortus from pasture. We identified the most resistant and most susceptible animals (10% percentiles) of this group based on WECs, and then compared the identities of these animals to the identities of animals that were predicted to be most resistant and most susceptible by our algorithms. The models showed varying abilities to predict susceptible and resistant sheep, with up to 65% of the most susceptible animals and 30% of the most resistant animals identified by the Elastic Net model algorithms. The prediction algorithms derived from female sheep data performed better than those for male sheep in some cases, with the predicted animals accounting for up to 50-60% of the actual resistant and susceptible female animals. Heritability values were calculated for blood parameters and the aggregate trait descriptions defined by the novel prediction algorithms. The aggregate trait descriptions were moderately heritable and may therefore be suitable for use in genetic selection strategies. The present study indicates that multivariate models based on blood parameter data showed some ability to predict the resistance status of sheep to infection with H. contortus.
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http://dx.doi.org/10.1016/j.vetpar.2019.05.007DOI Listing
June 2019

Transcriptome analysis unraveled potential mechanisms of resistance to Haemonchus contortus infection in Merino sheep populations bred for parasite resistance.

Vet Res 2019 Jan 24;50(1). Epub 2019 Jan 24.

United States Department of Agriculture, Agriculture Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD, USA.

Haemonchus contortus is one of the most pathogenic gastrointestinal nematodes in small ruminants. To understand molecular mechanisms underlying host resistance to this parasite, we used RNA-sequencing technology to compare the transcriptomic response of the abomasal tissue, the site of the host-parasite interaction, of Merino sheep bred to be either genetically resistant or susceptible to H. contortus infection. Two different selection flocks, the Haemonchus selection flock (HSF) and the Trichostrongylus selection flock (TSF), and each contains a resistant and susceptible line, were studied. The TSF flock was seemingly more responsive to both primary and repeated infections than HSF. A total of 127 and 726 genes displayed a significant difference in abundance between resistant and susceptible animals in response to a primary infection in HSF and TSF, respectively. Among them, 38 genes were significantly affected by infection in both flocks. Gene ontology (GO) enrichment of the differentially expressed genes identified in this study predicted the likely involvement of extracellular exosomes in the immune response to H. contortus infection. While the resistant lines in HSF and TSF relied on different mechanisms for the development of host resistance, adhesion and diapedesis of both agranulocytes and granulocytes, coagulation and complement cascades, and multiple pathways related to tissue repair likely played critical roles in the process. Our results offered a quantitative snapshot of changes in the host transcriptome induced by H. contortus infection and provided novel insights into molecular mechanisms of host resistance.
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http://dx.doi.org/10.1186/s13567-019-0622-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345051PMC
January 2019

A comparison of transcriptomic patterns measured in the skin of Chinese fine and coarse wool sheep breeds.

Sci Rep 2017 10 30;7(1):14301. Epub 2017 Oct 30.

CSIRO Agriculture and Food, Queensland Bioscience Precinct, 306 Carmody Rd, 4067, Queensland, Australia.

We characterised wool traits, and skin gene expression profiles of fine wool Super Merino (SM) and coarse wool Small Tail Han (STH) sheep. SM sheep had a significantly higher total density of wool follicles, heavier fleeces, finer fibre diameter, and increased crimp frequency, staple length and wool grease (lanolin) production. We found 435 genes were expressed at significantly different levels in the skin of the two breeds (127 genes more highly in SM and 308 genes more highly in STH sheep). Classification of the genes more highly expressed in SM sheep revealed numerous lipid metabolic genes as well as genes encoding keratins, keratin-associated proteins, and wool follicle stem cell markers. In contrast, mammalian epidermal development complex genes and other genes associated with skin cornification and muscle function were more highly expressed in STH sheep. Genes identified in this study may be further evaluated for inclusion in breeding programs, or as targets for therapeutic or genetic interventions, aimed at altering wool quality or yield. Expression of the lipid metabolic genes in the skin of sheep may be used as a novel trait with the potential to alter the content or properties of lanolin or the fleece.
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http://dx.doi.org/10.1038/s41598-017-14772-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662721PMC
October 2017

Cloning and tissue distribution of novel splice variants of the ovine ghrelin gene.

BMC Vet Res 2014 Sep 6;10:211. Epub 2014 Sep 6.

Background: The ghrelin axis is involved in the regulation of metabolism, energy balance, and the immune, cardiovascular and reproductive systems. The manipulation of this axis has potential for improving economically valuable traits in production animals, and polymorphisms in the ghrelin (GHRL) and ghrelin receptor (GHSR) genes have been associated with growth and carcass traits. Here we investigate the structure and expression of the ghrelin gene (GHRL) in sheep, Ovis aries.

Results: We identify two ghrelin mRNA isoforms, which we have designated Δex2 preproghrelin and Δex2,3 preproghrelin. Expression of Δex2,3 preproghrelin is likely to be restricted to ruminants, and would encode truncated ghrelin and a novel C-terminal peptide. Both Δex2 preproghrelin and canonical preproghrelin mRNA isoforms were expressed in a range of tissues. Expression of the Δex2,3 preproghrelin isoform, however, was restricted to white blood cells (WBC; where the wild-type preproghrelin isoform is not co-expressed), and gastrointestinal tissues. Expression of Δex2 preproghrelin and Δex2,3 preproghrelin mRNA was elevated in white blood cells in response to parasitic worm (helminth) infection in genetically susceptible sheep, but not in resistant sheep.

Conclusions: The restricted expression of the novel preproghrelin variants and their distinct WBC expression pattern during parasite infection may indicate a novel link between the ghrelin axis and metabolic and immune function in ruminants.
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http://dx.doi.org/10.1186/s12917-014-0211-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172912PMC
September 2014

Phenobarbital induction and chemical synergism demonstrate the role of UDP-glucuronosyltransferases in detoxification of naphthalophos by Haemonchus contortus larvae.

Antimicrob Agents Chemother 2014 Dec 6;58(12):7475-83. Epub 2014 Oct 6.

CSIRO Agriculture Flagship, St. Lucia, Queensland, Australia.

We used an enzyme induction approach to study the role of detoxification enzymes in the interaction of the anthelmintic compound naphthalophos with Haemonchus contortus larvae. Larvae were treated with the barbiturate phenobarbital, which is known to induce the activity of a number of detoxification enzymes in mammals and insects, including cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UDPGTs), and glutathione (GSH) S-transferases (GSTs). Cotreatment of larvae with phenobarbital and naphthalophos resulted in a significant increase in the naphthalophos 50% inhibitory concentration (IC50) compared to treatment of larvae with the anthelmintic alone (up to a 28-fold increase). The phenobarbital-induced drug tolerance was reversed by cotreatment with the UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, probenecid, and sulfinpyrazone. Isobologram analysis of the interaction of 5-nitrouracil with naphthalophos in phenobarbital-treated larvae clearly showed the presence of strong synergism. The UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, and probenecid also showed synergistic effects with non-phenobarbital-treated worms (synergism ratio up to 3.2-fold). This study indicates that H. contortus larvae possess one or more UDPGT enzymes able to detoxify naphthalophos. In highlighting the protective role of this enzyme group, this study reveals the potential for UDPGT enzymes to act as a resistance mechanism that may develop under drug selection pressure in field isolates of this species. In addition, the data indicate the potential for a chemotherapeutic approach utilizing inhibitors of UDPGT enzymes as synergists to increase the activity of naphthalophos against parasitic worms and to combat detoxification-mediated drug resistance if it arises in the field.
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http://dx.doi.org/10.1128/AAC.03333-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249576PMC
December 2014

A one shot blood phenotype can identify sheep that resist Haemonchus contortus challenge.

Vet Parasitol 2014 Oct 27;205(3-4):595-605. Epub 2014 Aug 27.

Queensland Bioscience Precinct, CSIRO Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. Electronic address:

Gastrointestinal nematodes remain a major limitation to the productivity of livestock systems. Selective breeding to produce populations that have an enhanced ability to resist infection is a viable and ongoing option to reduce this impact. The development of new phenotypes that facilitate this process is therefore of great interest. For this reason we explored relationships between haematological parameters and the ability of sheep to resist nematode infection. A multivariate analytical approach was used to define algorithms based on the blood parameters that can be used to rank the ability of sheep to resist nematode infection in a single blood sample and can be applied independent of infection status. The algorithms were shown to classify susceptible sheep with a 100% accuracy and resistant sheep with 80% accuracy. Further development of this platform approach may be an important advance for small ruminant production systems worldwide and might also be applied to other diseases of livestock or even environmental stressors such as heat.
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http://dx.doi.org/10.1016/j.vetpar.2014.08.009DOI Listing
October 2014

Sensory rewiring in an echolocator: genome-wide modification of retinogenic and auditory genes in the bat Myotis davidii.

G3 (Bethesda) 2014 Aug 4;4(10):1825-35. Epub 2014 Aug 4.

Computational and Systems Biology, CSIRO Agriculture Flagship, Queensland Bioscience Precinct, Brisbane, Queensland, Australia.

Bats comprise 20% of all mammalian species and display a number of characteristics, including true flight, echolocation, and a heightened ability to resist viral load that uniquely position this group for comparative genomic studies. Here we searched for evidence of genomic variation consistent with sensory rewiring through bat evolution. We focused on two species with divergent sensory preferences. Myotis davidii is a bat species that echolocates and possesses dim- but not daylight-adapted vision whereas the black flying fox (Pteropus alecto) has highly developed day vision but does not echolocate. Using the naked mole rat as a reference, we found five functional genes (CYP1A2, RBP3, GUCY2F, CRYBB1, and GRK7) encoding visual proteins that have degenerated into pseudogenes in M. davidii but not P. alecto. In a second approach genome-wide codon usage bias (CUB) was compared between the two bat species. This CUB ranking systematically enriched for vision-related (CLN8, RD3, IKZF1, LAMC3, CRX, SOX8, VAX2, HPS1, RHO, PRPH2, and SOX9) and hearing-related (TPRN, TMIE, SLC52A3, OTOF, WFS1, SOD1, TBX18, MAP1A, OTOS, GPX1, and USH1G) machinery in M. davidii but not P. alecto. All vision and hearing genes selectively enriched in M. davidii for which orthologs could be identified also were more biased in the echolocating M. lucifugus than the nonecholocating P. vampyrus. We suggest that the existence of codon bias in vision- and hearing-related genes in a species that has evolved echolocation implies CUB is part of evolution's toolkit to rewire sensory systems. We propose that the two genetic changes (pseudogene formation and CUB) collectively paint a picture of that incorporates a combination of destruction and gain-of-function. Together, they help explain how natural selection has reduced physiological costs associated with the development of a smaller eye poorly adapted to day vision but that also contribute to enhanced dim light vision and the hearing adaptations consonant with echolocation.
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http://dx.doi.org/10.1534/g3.114.011262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199690PMC
August 2014

The sheep genome illuminates biology of the rumen and lipid metabolism.

Science 2014 Jun;344(6188):1168-1173

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.
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http://dx.doi.org/10.1126/science.1252806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157056PMC
June 2014

RNF14 is a regulator of mitochondrial and immune function in muscle.

BMC Syst Biol 2014 Jan 29;8:10. Epub 2014 Jan 29.

CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St, Lucia, Queensland, Australia.

Background: Muscle development and remodelling, mitochondrial physiology and inflammation are thought to be inter-related and to have implications for metabolism in both health and disease. However, our understanding of their molecular control is incomplete.

Results: In this study we have confirmed that the ring finger 14 protein (RNF14), a poorly understood transcriptional regulator, influences the expression of both mitochondrial and immune-related genes. The prediction was based on a combination of network connectivity and differential connectivity in cattle (a non-model organism) and mice data sets, with a focus on skeletal muscle. They assigned similar probability to mammalian RNF14 playing a regulatory role in mitochondrial and immune gene expression. To try and resolve this apparent ambiguity we performed a genome-wide microarray expression analysis on mouse C2C12 myoblasts transiently transfected with two Rnf14 transcript variants that encode 2 naturally occurring but different RNF14 protein isoforms. The effect of both constructs was significantly different to the control samples (untransfected cells and cells transfected with an empty vector). Cluster analyses revealed that transfection with the two Rnf14 constructs yielded discrete expression signatures from each other, but in both cases a substantial set of genes annotated as encoding proteins related to immune function were perturbed. These included cytokines and interferon regulatory factors. Additionally, transfection of the longer transcript variant 1 coordinately increased the expression of 12 (of the total 13) mitochondrial proteins encoded by the mitochondrial genome, 3 of which were significant in isolated pair-wise comparisons (Mt-coxII, Mt-nd2 and mt-nd4l). This apparent additional mitochondrial function may be attributable to the RWD protein domain that is present only in the longer RNF14 isoform.

Conclusions: RNF14 influences the expression of both mitochondrial and immune related genes in a skeletal muscle context, and has likely implications for the inter-relationship between bioenergetic status and inflammation.
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http://dx.doi.org/10.1186/1752-0509-8-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906743PMC
January 2014

Understanding parasitic infection in sheep to design more efficient animal selection strategies.

Vet J 2013 Aug 13;197(2):143-52. Epub 2013 May 13.

Commonwealth Scientific and Industrial Research Organisation, Animal, Food and Health Science, F.D. McMaster Laboratory, Armidale, NSW 2350, Australia.

Modern livestock breeding practices provide new opportunities for producing animals that are adapted to their production environment and are free of disease. Using current knowledge of biology and by seeking 'the desired outcome' animal selection strategies can be designed that deliver more precisely defined results so maximising genetic gain and minimising risk. This review briefly describes the evolution of genetic selection in livestock and considers some of the positive and negative aspects of selection practices over time. The selection of sheep to withstand gastro-intestinal nematode parasitism is used as an example to explain how developments in selection strategy have improved genetic progress for complex traits. Re-evaluation of the understanding of the outcomes of selection for parasite resistance is used here to examine whether a more sophisticated approach is desirable, and to propose a number of additional phenotype measurement strategies that could complement and improve the quality of information used for animal selection. Finally some ideas are presented for creating a situation where a designed, highly defined breeding objective might be used to increase precision and reduce risk. This may become possible via research to adapt or develop tools for more sophisticated phenotypic evaluation, to discover biological processes integral to desired breed changes, and to define desired animal types which match economic and societal expectations.
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http://dx.doi.org/10.1016/j.tvjl.2013.03.029DOI Listing
August 2013

Trichostrongylus colubriformis larvae induce necrosis and release of IL33 from intestinal epithelial cells in vitro: implications for gastrointestinal nematode vaccine design.

Int J Parasitol 2012 17;42(3):295-304. Epub 2012 Feb 17.

F.D. McMaster Laboratory, CSIRO Livestock Industries, Armidale, NSW, Australia.

Gastrointestinal nematodes represent a major production problem for ruminant livestock. Enhancing immunity to gastrointestinal nematodes through vaccination is desirable but mechanistic understanding of initial host responses that facilitate gastrointestinal nematode protective immunity is limited. We hypothesise that gastrointestinal nematode invasion induces mucosal epithelium damage and alarmin (e.g. IL33) release, thereby contributing to initiation of protective gastrointestinal nematode immunity. To test this, an in vitro air-liquid interface human HT-29 epithelial cell-Trichostrongylus colubriformis co-culture system was developed. Exsheathed L3 T. colubriformis exhibited both sinusoidal and burrowing motions in the co-culture system. Burrowing parasites, but not ivermectin-paralysed larvae, induced necrotic death of epithelial cells (annexin V(+)/propidium iodide(+)/caspase 3/7(-)). Microscopy confirmed that larvae consumed labelled necrotic epithelial cell contents. Trichostrongylus colubriformis larvae and their post-exsheathment antigens (excretory/secretory products) significantly induced IL33 mRNA expression in the epithelial cells. Immunoblot confirmed that IL33 was released from epithelial cells due to the damage caused by motile larvae. Exposure of HT-29 cells to alum or Sigma proprietary adjuvants induced significant epithelial cell IL33 mRNA expression without inducing cellular necrosis. Hence, the intracellular contents were not released externally where they might exert alarmin activity and this may limit their ability to trigger a protective anti-gastrointestinal nematode response. We conclude that T. colubriformis motion at the infection site induces intestinal epithelial cell necrosis which facilitates the release of intracellular contents, including IL33, and may be fundamental to the initiation of an appropriate host response to gastrointestinal nematodes. Our co-culture model is useful for studying initial epithelial cell-parasite interactions without conducting expensive animal trials.
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http://dx.doi.org/10.1016/j.ijpara.2012.01.007DOI Listing
July 2012

The RIPK2 gene: a positional candidate for tick burden supported by genetic associations in cattle and immunological response of knockout mouse.

Immunogenetics 2012 May;64(5):379-88

CSIRO Livestock Industries, Queensland Bioscience Precinct, ST Lucia, QLD, Australia.

Ticks and tick-borne diseases have a detrimental impact on livestock production causing estimated losses of around $200 million per year in Australia alone. Host resistance to ticks is heritable, within-breed heritability estimates being around 0.35, and with large differences between breeds. Previously a QTL for tick burden was detected on BTA14 at ~72 Mb distal to the centromere, near the gene receptor-interacting serine-threonine kinase 2 (RIPK2). To identify polymorphisms in this region, we sequenced all exons of the RIPK2 gene, identifying 46 single nucleotide polymorphism (SNP). Using SNP from RIPK2 as well as SNP from the bovine genome sequence, we genotyped two samples, one of 1,122 taurine dairy cattle and one of 761 zebu and zebu composite beef cattle. We confirmed that SNP and haplotypes from this region, including from RIPK2, were associated with tick burden in both dairy and beef cattle. To determine whether RIPK2 influences response to tick salivary gland extract (SGE), an immunisation experiment with tick SGE in a RIPK2 knockout (RIPK2 −/−) mouse strain was conducted. There was a significant (P < 0.05) reduction in IgG production in the RIPK2 −/− mouse in response to the SGE compared to its background strain C57BL/ 6 as well as the outbred CD1 mouse strain. In addition, antibodies generated by RIPK2 −/− mice recognised a different set of antigens within SGE when compared to parental-derived antibodies. In summary, the SNP association with tick burden at BTA14 was confirmed and quantitative and qualitative differences in antibody production were observed between RIPK2 −/− and wild-type mice.
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http://dx.doi.org/10.1007/s00251-012-0601-9DOI Listing
May 2012

Proteomic analysis of the abomasal mucosal response following infection by the nematode, Haemonchus contortus, in genetically resistant and susceptible sheep.

J Proteomics 2012 Apr 25;75(7):2141-52. Epub 2012 Jan 25.

CSIRO Livestock Industries, St. Lucia, Brisbane, Queensland 4067, Australia.

Sheep have a variable ability to resist gastrointestinal nematode infection, but the key factors mediating this response are poorly defined. Here we report the first large-scale application of quantitative proteomic technologies to define proteins that are differentially abundant between sheep selectively bred to have an enhanced (resistant) or reduced (susceptible) ability to eliminate nematodes. Samples were collected from the abomasal mucosa three days after experimental challenge with the nematode, Haemonchus contortus. This timing reflects the initial interaction of host and parasite, and the tissue represents the immediate interface. We identified and quantified more than 4400 unique proteins, of which 158 proteins showed >1.5 fold difference between the resistant and susceptible sheep. Trefoil factor 2, a member of RAS oncogene family (RAP1A) and ring finger protein 126 were amongst the proteins found to be highly abundant in the abomasal surface of resistant sheep, whereas adenosine deaminase and the gastrokine-3 like precursor were found at higher levels in susceptible sheep. Construction of gut proteome interaction networks identified mitochondrial function and energetic partitioning as important components of an effective nematode eliminating response. The differentially abundant proteins may be useful targets for phenotypic tests that aim to identify sheep with an enhanced ability to resist nematode infection.
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http://dx.doi.org/10.1016/j.jprot.2012.01.016DOI Listing
April 2012

Divergent ghrelin expression patterns in sheep genetically resistant or susceptible to gastrointestinal nematodes.

Vet Parasitol 2011 Sep 11;181(2-4):194-202. Epub 2011 May 11.

CSIRO Livestock Industries, St. Lucia, Queensland, Australia.

Gastrointestinal nematodes are a major problem for pastoral ruminant production systems. This problem could be reduced by the application of breeding strategies that select for nematode resistant sheep, but no suitable molecular markers are available. Research selection flocks containing lines that are resistant (R) or susceptible (S) to gastrointestinal nematodes provide an excellent resource for discovering selectable markers, and for studying the underlying mechanisms of an effective anti-nematode response. In this study we have used a combination of quantitative real time PCR assays and ELISA to determine if nematode challenge impacts on the expression of the satiety-regulating hormone ghrelin. The expression responses were then compared between the selection flock R and S lines. The results show that the basal levels of ghrelin in plasma were greater than 2-fold higher in nematode naïve S line sheep. Three days after a primary nematode challenge divergent ghrelin expression patterns were observed between the selection lines, with levels increasing in R sheep while decreasing in S sheep. After a secondary challenge this trend was repeated, but following a third challenge ghrelin expression levels rose in both R and S sheep, by which time the S animals had acquired an effective immune response to the nematodes, as measured by a significant reduction in faecal egg output. Importantly, this phenomenon was observed in gene expression studies in gut tissues and also in ELISA measurements of ghrelin peptide levels in plasma. A regression analysis showed that ghrelin transcript expression in the gut accounted for >40% of the variation in faecal egg count measured following Haemonchus or Trichostrongylus infection. We therefore hypothesise that the direction of ghrelin expression (up or down) immediately following nematode exposure may play an important role in regulating the differing anti-nematode responses that occur in the R and S lines. Such differences identify ghrelin as a previously unrecognized factor influencing the acquisition of immunity to nematodes.
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http://dx.doi.org/10.1016/j.vetpar.2011.05.007DOI Listing
September 2011

The interplay between evolution, regulation and tissue specificity in the Human Hereditary Diseasome.

BMC Genomics 2010 Dec 2;11 Suppl 4:S23. Epub 2010 Dec 2.

CSIRO Livestock Industries, Queensland Bioscience Precinct, St. Lucia, Queensland, Australia.

Background: Human disease genes can be distinguished from essential (embryonically lethal) and non-disease genes using gene attributes. Such attributes include gene age, tissue specificity of expression, regulatory capacity, sequence length, rate of sequence variation and capacity for interaction. The resulting information has been used to inform data mining approaches seeking to identify novel disease genes. Given the dynamic nature of this field and the rapid rise in relevant information, we have chosen to perform a single integrated mining approach to explore relationships among gene attributes and thereby characterise evolutionary trends associated with disease genes.

Results: All against all cross comparison of 2,522 disease gene attributes revealed significant relationships existed between the age, disease-association and expression pattern of genes and the tissues within which they are expressed. We found that the over-representation of disease genes among old genes holds for tissue-specific genes, but the correlation between age and disease association vanished when conditioning on tissue-specificity. Of the 32 tissues studied, the genes expressed in pancreas are on average older than the genes expressed in any other tissue, while the testis expressed the lowest proportion of old genes. Following a focussed analysis on the impact of regulatory apparatus on evolution of disease genes, we show that regulators, comprising transcription factors and post-translation modified proteins, are over-represented among ancient disease genes. In addition, we show that the proportion of regulator genes is affected by gene age among disease genes and by tissue-specificity among non-disease genes. Finally, using 55,606 true positive gene interaction data, we find that old disease genes interacts with other old disease genes and interacting new genes interacts with genes originating from higher phylostrata.

Conclusion: This study supports the non-random nature of the human diseasome. We have identified a variety of distinct features and correlations to other molecular attributes that can be used to distinguish the set of disease causing genes. This was achieved by harnessing the power of mining large scale datasets from OMIM and other databases. Ultimately such knowledge may contribute to the identification of novel human disease genes and an enhanced understanding of human biology.
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http://dx.doi.org/10.1186/1471-2164-11-S4-S23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005915PMC
December 2010

A genomics-informed, SNP association study reveals FBLN1 and FABP4 as contributing to resistance to fleece rot in Australian Merino sheep.

BMC Vet Res 2010 May 26;6:27. Epub 2010 May 26.

CSIRO Livestock Industries, 306 Carmody Rd, St Lucia, QLD 4067, Australia.

Background: Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly Lucilia cuprina are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals. This microarray platform was used to profile the gene expression changes between skin samples of six resistant and six susceptible animals taken immediately before, during and after FR induction. Mixed-model equations were employed to normalize the data and 155 genes were found to be differentially expressed (DE). Ten DE genes were selected for validation using real-time PCR on independent skin samples. The genomic regions of a further 5 DE genes were surveyed to identify single nucleotide polymorphisms (SNP) that were genotyped across three populations for their associations with fleece rot resistance.

Results: The majority of the DE genes originated from the fleece rot subtracted libraries and over-representing gene ontology terms included defense response to bacterium and epidermis development, indicating a role of these processes in modulating the sheep's response to fleece rot. We focused on genes that contribute to the physical barrier function of skin, including keratins, collagens, fibulin and lipid proteins, to identify SNPs that were associated to fleece rot scores.

Conclusions: We identified FBLN1 (fibulin) and FABP4 (fatty acid binding protein 4) as key factors in sheep's resistance to fleece rot. Validation of these markers in other populations could lead to vital tests for marker assisted selection that will ultimately increase the natural fleece rot resistance of Merino sheep.
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http://dx.doi.org/10.1186/1746-6148-6-27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886023PMC
May 2010

Gene expression profiles of BMP4, FGF10 and cognate inhibitors, in the skin of foetal Merino sheep, at the time of secondary follicle branching.

Exp Dermatol 2009 Oct 7;18(10):877-9. Epub 2009 Mar 7.

The high concentration of secondary branched follicles is a distinctive feature of the Merino sheep. These follicles initiate from 100 days of gestation. Here, we report a transition in abundance of the BMP4 and FGF10 morphogens occurring at this time. At 103 days of gestation, FGF10 gene expression dropped steadily from maximal levels, in a trend that continued until day 143. Conversely, from day 105, BMP4 transcript levels rapidly increased to maximal levels that were maintained until 131 days, before declining. This profile closely matches reported changes in branched follicle numbers, which peak in density at day 134. SPRY4, a known regulator of FGF10, increased to maximal levels concomitant with the fall in FGF10, suggesting a relationship. Levels of the BMP4 inhibitor NOG matched the initial rise of BMP4, with a fivefold spike at 108 days; but consistent with the rise in BMP4, this high level was not sustained.
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http://dx.doi.org/10.1111/j.1600-0625.2008.00837.xDOI Listing
October 2009

The genome sequence of taurine cattle: a window to ruminant biology and evolution.

Science 2009 Apr;324(5926):522-8

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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http://dx.doi.org/10.1126/science.1169588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200PMC
April 2009

Selective induction of the Notch ligand Jagged-1 in macrophages by soluble egg antigen from Schistosoma mansoni involves ERK signalling.

Immunology 2009 Jul 14;127(3):326-37. Epub 2008 Nov 14.

Institute for Molecular Bioscience, University of Queensland, Qld, Australia.

Soluble egg antigen (SEA) from the helminth Schistosoma mansoni promotes T helper type 2 (Th2) responses by modulating antigen-presenting cell function. The Jagged/Notch pathway has recently been implicated in driving Th2 development. We show here that SEA rapidly up-regulated mRNA and protein expression of the Notch ligand Jagged-1 in both murine bone marrow-derived macrophages (BMMs) and human monocyte-derived macrophages (HMDMs). Another potential Th2-promoting factor, interleukin (IL)-33, was not transcriptionally induced by SEA in BMMs. Up-regulation of Jagged-1 mRNA by SEA was also apparent in conventional dendritic cells (DCs), although the effect was less striking than in BMMs. Conversely, SEA-pulsed DCs, but not BMMs, promoted IL-4 production upon T-cell activation, suggesting that Jagged-1 induction alone is insufficient for instructing Th2 development. A comparison of the responses initiated in BMMs by SEA and the bacterial endotoxin lipopolysaccharide (LPS) revealed common activation of extracellular signal-regulated kinase-1/2 (ERK-1/2) and p38 phosphorylation, as well as induction of Jagged-1 mRNA. However, only LPS triggered IkappaB degradation, phosphorylation of c-Jun N-terminal kinase (Jnk) and signal transducer and activator of transcription 1 (Stat1) Tyr701, and IL-33 and IL-12p40 mRNA up-regulation. Inducible gene expression was modified by the presence of the macrophage growth factor colony-stimulating factor (CSF)-1, which inhibited Jagged-1 induction by SEA and LPS, but enhanced LPS-induced IL-12p40 expression. Unlike LPS, SEA robustly activated signalling in HEK293 cells expressing either Toll-like receptor 2 (TLR2) or TLR4/MD2. Pharmacological inhibition of the ERK-1/2 pathway impaired SEA- and LPS-inducible Jagged-1 expression in BMMs. Taken together, our data suggest that Jagged-1 is an ERK-dependent target of TLR signalling that has a macrophage-specific function in the response to SEA.
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http://dx.doi.org/10.1111/j.1365-2567.2008.02979.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712101PMC
July 2009

Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes.

BioData Min 2008 Sep 19;1(1). Epub 2008 Sep 19.

Computational and Systems Biology, CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, St, Lucia, Brisbane, Queensland 4067, Australia.

Background: The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association.

Methods: We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported.

Results: Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes.

Conclusion: We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing genes. Our guilt-by-association algorithm should be useful for the discovery of additional modifiers of genetic diseases, and more generally, for the ability to associate genes of unknown function to clusters of genes with defined functions allowing for novel biological inference that can be subsequently validated.
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http://dx.doi.org/10.1186/1756-0381-1-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556670PMC
September 2008

Gastrointestinal nematode challenge induces some conserved gene expression changes in the gut mucosa of genetically resistant sheep.

Int J Parasitol 2008 Mar 7;38(3-4):431-42. Epub 2007 Aug 7.

CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, St. Lucia, Qld 4067, Australia.

Sheep have a varying ability to resist infection with gastrointestinal nematodes. This ability is due in part to genetic differences that exist between individuals. In order to define these differences we have used real-time PCR to quantify gene expression responses in the gut mucosal surface of genetically resistant and susceptible sheep, following a nematode challenge. Expression profiles were determined in response to two different nematode species, Haemonchus contortus and Trichostrongylus colubriformis, and in divergent sheep originating from two different genetic backgrounds. Results show that the response generated differs between resistant and susceptible animals and is further impacted by the origin of the sheep and nematode species used for challenge. However, some conserved features of a response mounted by a resistant or a susceptible animal were identified. Genes found to be more abundantly expressed in resistant animals include markers of an early inflammatory response, several Toll-like receptors (TLR2, 4, 9) and free radical producing genes (DUOX1 and NOS2A). Conversely, genes differentiating susceptible animals indicate a prolonged response and development of a chronic inflammatory state, characterised by elevated expression of members of the NF-kappabeta signalling pathway (IKBKB and NFKBIA) together with delayed expression of regulatory markers such as IL2RA (CD25), IL10 and TGFbeta2. While multiple nematode response pathways were identified, the identification of conserved aspects of the response which associate with resistance provides evidence that alternative nematode control strategies, such as breeding for resistant animals, may be feasible.
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http://dx.doi.org/10.1016/j.ijpara.2007.07.012DOI Listing
March 2008

Recombinant production of antimicrobial peptides in heterologous microbial systems.

Biotechnol Appl Biochem 2007 May;47(Pt 1):1-9

CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, St Lucia, Queensland 4067, Australia.

The emergence and rapid horizontal spread of antibiotic-resistant traits in bacteria of human and veterinary clinical significance has been a driving force in the search for new classes of antibiotics. Recent studies have shown that AMPs (antimicrobial peptides) potentially have a role in addressing this problem. These AMPs are produced naturally by a diverse array of organisms, including bacteria, plants, insects, fish and mammals. Given this diversity, researchers trying to perform comparative studies on AMPs are likely to encounter difficulties in obtaining workable quantities of peptide. Such studies are required for optimization of antimicrobial activity, product stability, mode of delivery and industrial-scale production, and are vital if these peptides are ever to be brought to the market. Recombinant expression of AMPs is one hope for producing suitable amounts of diverse peptides. Here we review the literature regarding microbial heterologous expression systems for the production of recombinant AMPs.
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http://dx.doi.org/10.1042/BA20060207DOI Listing
May 2007

Simultaneous identification of differential gene expression and connectivity in inflammation, adipogenesis and cancer.

Bioinformatics 2006 Oct 24;22(19):2396-404. Epub 2006 Jul 24.

CSIRO Livestock Industries, Queensland Bioscience Precinct 306 Carmody Road, Brisbane, Queensland 4067, Australia.

Motivation: Biological differences between classes are reflected in transcriptional changes which in turn affect the levels by which essential genes are individually expressed and collectively connected. The purpose of this communication is to introduce an analytical procedure to simultaneously identify genes that are differentially expressed (DE) as well as differentially connected (DC) in two or more classes of interest.

Results: Our procedure is based on a two-step approach: First, mixed-model equations are applied to obtain the normalized expression levels of each gene in each class treatment. These normalized expressions form the basis to compute a measure of (possible) DE as well as the correlation structure existing among genes. Second, a two-component mixture of bi-variate distributions is fitted to identify the component that encapsulates those genes that are DE and/or DC. We demonstrate our approach using three distinct datasets including a human systemic inflammation oligonucleotide data; a spotted cDNA data dealing with bovine in vitro adipogenesis and SAGE database on cancerous and normal tissue samples.
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http://dx.doi.org/10.1093/bioinformatics/btl392DOI Listing
October 2006

Lessons from an estivating frog: sparing muscle protein despite starvation and disuse.

Am J Physiol Regul Integr Comp Physiol 2006 Mar 20;290(3):R836-43. Epub 2005 Oct 20.

Commonwealth Scientific and Industrial Research Organization Livestock Industries, 306 Carmody Rd., St. Lucia, Brisbane, Queensland 4072, Australia.

Long (6- to 9-mo) bouts of estivation in green-striped burrowing frogs lead to 28% atrophy of cruralis oxidative fibers (P < 0.05) and some impairment of in vitro gastrocnemius endurance (P < 0.05) but no significant deficit in maximal twitch force production. These data suggest the preferential atrophy of oxidative fibers at a rate slower than, but comparable to, laboratory disuse models. We tested the hypothesis that the frog limits atrophy by modulating oxidative stress. We assayed various proteins at the transcript level and verified these results for antioxidant enzymes at the biochemical level. Transcript data for NADH ubiquinone oxidoreductase subunit 1 (71% downregulated, P < 0.05) and ATP synthase (67% downregulated, P < 0.05) are consistent with mitochondrial quiescence and reduced oxidant production. Meanwhile, uncoupling protein type 2 transcription (P = 0.31), which is thought to reduce mitochondrial leakage of reactive oxygen species, was maintained. Total antioxidant defense of water-soluble (22.3 +/- 1.7 and 23.8 +/- 1.5 microM/microg total protein in control and estivator, respectively, P = 0.53) and membrane-bound proteins (31.5 +/- 1.9 and 42.1 +/- 7.3 microM/microg total protein in control and estivator, respectively, P = 0.18) was maintained, equivalent to a bolstering of defense relative to oxygen insult. This probably decelerates muscle atrophy by preventing accumulation of oxidative damage in static protein reserves. Transcripts of the mitochondrially encoded antioxidant superoxide dismutase type 2 (67% downregulated, P < 0.05) paralleled mitochondrial activity, whereas nuclear-encoded catalase and glutathione peroxidase were maintained at control values (P = 0.42 and P = 0.231), suggesting a dissonance between mitochondrial and nuclear antioxidant expression. Pyruvate dehydrogenase kinase 4 transcription was fourfold lower in estivators (P = 0.11), implying that, in contrast to mammalian hibernators, this enzyme does not drive the combustion of lipids that helps spare hypometabolic muscle.
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http://dx.doi.org/10.1152/ajpregu.00380.2005DOI Listing
March 2006

Identification and expression of Toll-like receptors 1-10 in selected bovine and ovine tissues.

Vet Immunol Immunopathol 2006 Jan 10;109(1-2):23-30. Epub 2005 Aug 10.

CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, St. Lucia, Qld 4067, Australia.

Members of the Toll-like receptor (TLR) family are vital to immune function through the sensing of pathogenic agents and initiation of an appropriate immune response. More specifically, tissue and cell specific TLR expression patterns have been correlated with the ability to respond to various pathogenic challenges. Bovine sequence exists for 4 of the 10 human TLR Reference Sequences and no ovine TLR sequence has been reported. The main goal of this study was to determine if homologues of human TLRs 1-10 exist within the cattle and sheep. Subsequent to this, quantitative real time PCR assays were to be developed to produce transcript expression profiles in cattle skin and sheep gut-associated lymphoid tissue, as these epithelial tissues are the primary sites of host/pathogen interactions for numerous pathogens. Our findings show that homologues of human TLRs 1-10 do indeed exist within both cattle and sheep, with respective bovine and ovine homologues sharing at least 95% nucleotide sequence identity and 83-90% identity to the corresponding human Reference Sequences. Conservation of the amino acid sequence between homologous ruminant and human TLRs ranged between 84 and 97%. Quantitative real time PCR (qPCR) assays confirmed expression of all 10 TLRs within ovine jejunum, Peyer's patch and mesenteric lymph nodes. While in bovine skin all TLRs apart from TLR6 were detected. The most abundant TLR transcripts within the ovine jejunum were TLRs 3, 5 and 6, while TLRs 6, 7 and 10 were abundant in both ovine Peyer's patch and mesenteric lymph node. In bovine skin TLRs 2 and 7 were most abundant. In all tissues tested TLR4 expression was at the lower limit of detection.
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http://dx.doi.org/10.1016/j.vetimm.2005.06.014DOI Listing
January 2006

Highly conserved alpha-toxin sequences of avian isolates of Clostridium perfringens.

J Clin Microbiol 2004 Mar;42(3):1345-7

Commonwealth Scientific and Industrial Research Organisation, Livestock Industries, Australian Animal Health Laboratory, Geelong 3220, Australia.

Clostridium perfringens causes necrotic enteritis in chickens, and alpha-toxin has been suggested to be a key virulence determinant. Analysis of the alpha-toxin of 25 chicken-derived C. perfringens strains demonstrated high homology to mammal-derived strains rather than to the only avian-derived C. perfringens alpha-toxin sequence reported previously.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC356866PMC
http://dx.doi.org/10.1128/JCM.42.3.1345-1347.2003DOI Listing
March 2004
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