Veterinary Biosciences - Research Publications
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ItemMeasuring Sheep Tails: A Preliminary Study Using Length (Mm), Vulva Cover Assessment, and Number of Tail Joints(MDPI, 2023-03)Docking sheep tails is a long-standing practice that, when done at the recommended length, reduces the risk of flystrike. The recommended length is to cover the vulva of ewes and to a similar length in males. This length is often equated to three coccygeal joints left intact, and there are many other ways the recommended length is described by researchers, industry, and government. This study compared the observer consistency and retest consistency using three different tail length measurement methods: vulva cover assessment, length (mm), and joint palpation. The tails of 51 yearling and 48 weaner Merino ewes were assessed by two observers. Length and vulva cover assessment methods provided the most reliable results, and joint palpation was the least reliable method of tail measurement. In the sample, tails that covered the vulva of yearlings and weaners measured 57.6 mm (n = 14) and 63.7 mm (n = 30) on average, respectively, and contained two coccygeal joints (more than two coccygeal vertebrae). Tails that did not cover the vulva of yearlings and weaners measured 41.3 mm (n = 36) and 52.8 mm (n = 17) on average, respectively, and had less than two coccygeal joints. The two most reliable methods enable valid comparison to the best practice recommendations.
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ItemA phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity(BMC, 2024-03-14)BACKGROUND: Infection with parasitic nematodes (helminths), particularly those of the order Strongylida (such as Haemonchus contortus), can cause significant and burdensome diseases in humans and animals. Widespread drug (anthelmintic) resistance in livestock parasites, the absence of vaccines against most of these nematodes, and a lack of new and effective chemical entities on the commercial market demands the discovery of new anthelmintics. In the present study, we searched the Global Health Priority Box (Medicines for Malaria Venture) for new candidates for anthelmintic development. METHODS: We employed a whole-organism, motility-based phenotypic screening assay to identify compounds from the Global Health Priority Box with activity against larvae of the model parasite H. contortus, and the free-living comparator nematode Caenorhabditis elegans. Hit compounds were further validated via dose-response assays, with lead candidates then assessed for nematocidal activity against H. contortus adult worms, and additionally, for cytotoxic and mitotoxic effects on human hepatoma (HepG2) cells. RESULTS: The primary screen against H. contortus and C. elegans revealed or reidentified 16 hit compounds; further validation established MMV1794206, otherwise known as 'flufenerim', as a significant inhibitor of H. contortus larval motility (half-maximal inhibitory concentration [IC50] = 18 μM) and development (IC50 = 1.2 μM), H. contortus adult female motility (100% after 12 h of incubation) and C. elegans larval motility (IC50 = 0.22 μM). Further testing on a mammalian cell line (human hepatoma HepG2 cells), however, identified flufenerim to be both cytotoxic (half-maximal cytotoxic concentration [CC50] < 0.7 μM) and mitotoxic (half-maximal mitotoxic concentration [MC50] < 0.7 μM). CONCLUSIONS: The in vitro efficacy of MMV1794206 against the most pathogenic stages of H. contortus, as well as the free-living C. elegans, suggests the potential for development as a broad-spectrum anthelmintic compound; however, the high toxicity towards mammalian cells presents a significant hindrance. Further work should seek to establish the protein-drug interactions of MMV1794206 in a nematode model, to unravel the mechanism of action, in addition to an advanced structure-activity relationship investigation to optimise anthelmintic activity and eliminate mammalian cell toxicity.
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ItemImmunoreactivity of canine, feline, and equine D-dimer with antibodies to human D-dimer(Wiley, 2024)BACKGROUND: Commercially available D-dimer assays use antibodies against human D-dimer, with limited sensitivity and specificity data in companion animals. OBJECTIVES: To evaluate the immunoreactivity of D-dimer in plasma of dogs, horses, and cats with commercially available antibodies to human D-dimer. ANIMALS: Plasma samples were collected from healthy dogs and horses, and from surplus feline plasma submitted for diagnostic purposes. METHODS: Descriptive research study. A cross-linked fibrin lysate was prepared from plasma samples, and SDS-PAGE and immunoblotting were performed with a variety of commercially available antibodies to human D-dimer. RESULTS: The selected antibodies demonstrated variable reactivity with D-dimer of each species. The monoclonal antibody DD44 bound canine D-dimer with good specificity and sensitivity, but this antibody did not react with feline or equine D-dimer. The polyclonal antibody D2D bound putative D-dimer in dogs, cats, and horses with good specificity, and higher sensitivity compared to human D-dimer. CONCLUSIONS AND CLINICAL IMPORTANCE: The variable performance of commercially available human D-dimer assays between species is, in part, because of inter-species variation in D-dimer immunoreactivity. The use of these assays should follow validation studies. Monoclonal antibody DD44 could be a focus for the development of a canine-specific assay.
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ItemNo Preview AvailableComparative structure activity and target exploration of 1,2-diphenylethynes in Haemonchus contortus and Caenorhabditis elegans(ELSEVIER SCI LTD, 2024-08)Infections and diseases caused by parasitic nematodes have a major adverse impact on the health and productivity of animals and humans worldwide. The control of these parasites often relies heavily on the treatment with commercially available chemical compounds (anthelmintics). However, the excessive or uncontrolled use of these compounds in livestock animals has led to major challenges linked to drug resistance in nematodes. Therefore, there is a need to develop new anthelmintics with novel mechanism(s) of action. Recently, we identified a small molecule, designated UMW-9729, with nematocidal activity against the free-living model organism Caenorhabditis elegans. Here, we evaluated UMW-9729's potential as an anthelmintic in a structure-activity relationship (SAR) study in C. elegans and the highly pathogenic, blood-feeding Haemonchus contortus (barber's pole worm), and explored the compound-target relationship using thermal proteome profiling (TPP). First, we synthesised and tested 25 analogues of UMW-9729 for their nematocidal activity in both H. contortus (larvae and adults) and C. elegans (young adults), establishing a preliminary nematocidal pharmacophore for both species. We identified several compounds with marked activity against either H. contortus or C. elegans which had greater efficacy than UMW-9729, and found a significant divergence in compound bioactivity between these two nematode species. We also identified a UMW-9729 analogue, designated 25, that moderately inhibited the motility of adult female H. contortus in vitro. Subsequently, we inferred three H. contortus proteins (HCON_00134350, HCON_00021470 and HCON_00099760) and five C. elegans proteins (F30A10.9, F15B9.8, B0361.6, DNC-4 and UNC-11) that interacted directly with UMW-9729; however, no conserved protein target was shared between the two nematode species. Future work aims to extend the SAR investigation in these and other parasitic nematode species, and validate individual proteins identified here as possible targets of UMW-9729. Overall, the present study evaluates this anthelmintic candidate and highlights some challenges associated with early anthelmintic investigation.
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ItemNo Preview AvailableEvidence for dopamine production and distribution of dopamine D2 receptors in the equine gastrointestinal mucosa and pancreas(PUBLIC LIBRARY SCIENCE, 2024-02-27)Insulin dysregulation in horses is characterised by hyperinsulinaemia and/or tissue insulin resistance and is associated with increased risk of laminitis. There is growing evidence in other species that dopamine attenuates insulin release from the pancreas; however, this has yet to be examined in horses. The present study aimed to identify whether there are cells capable of producing or responding to dopamine within the equine gastrointestinal mucosa and pancreas. Tissue samples were collected from the stomach, small and large intestines, and pancreas of six mature horses following euthanasia. Samples of stomach contents and faeces were also collected. Immunohistochemistry was performed to identify tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine production, and dopamine D2 receptors in tissue sections. Additional immunostaining for glucagon, insulin and chromogranin A was performed to identify α cells, β cells and enteroendocrine cells, respectively. Gastric parietal cells expressed both TH and D2 receptors, indicating that they are capable of both producing and responding to dopamine. Dopamine was quantified in stomach contents and faeces by high-performance liquid chromatography with electrochemical detection, with similar concentrations found at both sites. Dopamine D2 receptors were expressed in duodenal epithelial cells but not more distally. A subset of enteroendocrine cells, located sporadically along the gastrointestinal tract, were found to be immunopositive for the D2 receptor. In pancreatic islets, TH was present in α cells, while D2 receptors were strongly expressed in β cells and variably expressed in α cells. These findings are consistent with studies of other species; however, dynamic studies are required to further elucidate the role of dopamine in the modulation of insulin and glucagon secretion in horses. This descriptive study provides preliminary evidence for a potential role of dopamine to act as a paracrine messenger in the gastrointestinal mucosa and endocrine pancreas of horses.
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ItemLocation has a significant effect on body condition and blood parameters in the eastern longneck turtle (Chelodina longicollis)(CSIRO PUBLISHING, 2023)The aim of this investigation was to explore the effect point of capture has on relative weight (Wr), as well as haematology and biochemistry values, in wild eastern longneck turtles (Chelodina longicollis). This study group consisted of two sites of turtles residing in Duck Pond (DP) and Ivanhoe Wetland (IW) in the Darebin Parklands, in Alphington, Melbourne. From DP, 184 turtles were captured, and from IW, 37 turtles were captured. All turtles were weighed and measured, and a random subset of 20 turtles from each waterbody was selected for blood collection. Significant differences were found to exist for Wr, basophils, glucose, uric acid, triglycerides and bile acids between the two sites. Serum glucose levels tended to decrease as a turtle increased in mass, straight carapace length (SCL) and Wr. The results of this investigation highlight the need to take location into consideration when assessing blood parameters in reptiles.
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ItemMosquitoes provide a transmission route between possums and humans for Buruli ulcer in southeastern Australia(NATURE PORTFOLIO, 2024-02)Buruli ulcer, a chronic subcutaneous infection caused by Mycobacterium ulcerans, is increasing in prevalence in southeastern Australia. Possums are a local wildlife reservoir for M. ulcerans and, although mosquitoes have been implicated in transmission, it remains unclear how humans acquire infection. We conducted extensive field survey analyses of M. ulcerans prevalence among mosquitoes in the Mornington Peninsula region of southeastern Australia. PCR screening of trapped mosquitoes revealed a significant association between M. ulcerans and Aedes notoscriptus. Spatial scanning statistics revealed overlap between clusters of M. ulcerans-positive Ae. notoscriptus, M. ulcerans-positive possum excreta and Buruli ulcer cases, and metabarcoding analyses showed individual mosquitoes had fed on humans and possums. Bacterial genomic analysis confirmed shared single-nucleotide-polymorphism profiles for M. ulcerans detected in mosquitoes, possum excreta and humans. These findings indicate Ae. notoscriptus probably transmit M. ulcerans in southeastern Australia and highlight mosquito control as a Buruli ulcer prevention measure.
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ItemDevelopment and validation of a long-read metabarcoding platform for the detection of filarial worm pathogens of animals and humans(BMC, 2024-01-20)BACKGROUND: Filarial worms are important vector-borne pathogens of a large range of animal hosts, including humans, and are responsible for numerous debilitating neglected tropical diseases such as, lymphatic filariasis caused by Wuchereria bancrofti and Brugia spp., as well as loiasis caused by Loa loa. Moreover, some emerging or difficult-to-eliminate filarioid pathogens are zoonotic using animals like canines as reservoir hosts, for example Dirofilaria sp. 'hongkongensis'. Diagnosis of filariasis through commonly available methods, like microscopy, can be challenging as microfilaremia may wane below the limit of detection. In contrast, conventional PCR methods are more sensitive and specific but may show limited ability to detect coinfections as well as emerging and/or novel pathogens. Use of deep-sequencing technologies obviate these challenges, providing sensitive detection of entire parasite communities, whilst also being better suited for the characterisation of rare or novel pathogens. Therefore, we developed a novel long-read metabarcoding assay for deep-sequencing the filarial nematode cytochrome c oxidase subunit I gene on Oxford Nanopore Technologies' (ONT) MinION™ sequencer. We assessed the overall performance of our assay using kappa statistics to compare it to commonly used diagnostic methods for filarial worm detection, such as conventional PCR (cPCR) with Sanger sequencing and the microscopy-based modified Knott's test (MKT). RESULTS: We confirmed our metabarcoding assay can characterise filarial parasites from a diverse range of genera, including, Breinlia, Brugia, Cercopithifilaria, Dipetalonema, Dirofilaria, Onchocerca, Setaria, Stephanofilaria and Wuchereria. We demonstrated proof-of-concept for this assay by using blood samples from Sri Lankan dogs, whereby we identified infections with the filarioids Acanthocheilonema reconditum, Brugia sp. Sri Lanka genotype and zoonotic Dirofilaria sp. 'hongkongensis'. When compared to traditionally used diagnostics, such as the MKT and cPCR with Sanger sequencing, we identified an additional filarioid species and over 15% more mono- and coinfections. CONCLUSIONS: Our developed metabarcoding assay may show broad applicability for the metabarcoding and diagnosis of the full spectrum of filarioids from a wide range of animal hosts, including mammals and vectors, whilst the utilisation of ONT' small and portable MinION™ means that such methods could be deployed for field use.
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Item'Bingo'-a large language model- and graph neural network-based workflow for the prediction of essential genes from protein data(Oxford University Press, 2024-01)The identification and characterization of essential genes are central to our understanding of the core biological functions in eukaryotic organisms, and has important implications for the treatment of diseases caused by, for example, cancers and pathogens. Given the major constraints in testing the functions of genes of many organisms in the laboratory, due to the absence of in vitro cultures and/or gene perturbation assays for most metazoan species, there has been a need to develop in silico tools for the accurate prediction or inference of essential genes to underpin systems biological investigations. Major advances in machine learning approaches provide unprecedented opportunities to overcome these limitations and accelerate the discovery of essential genes on a genome-wide scale. Here, we developed and evaluated a large language model- and graph neural network (LLM–GNN)-based approach, called ‘Bingo’, to predict essential protein-coding genes in the metazoan model organisms Caenorhabditis elegans and Drosophila melanogaster as well as in Mus musculus and Homo sapiens (a HepG2 cell line) by integrating LLM and GNNs with adversarial training. Bingo predicts essential genes under two ‘zero-shot’ scenarios with transfer learning, showing promise to compensate for a lack of high-quality genomic and proteomic data for non-model organisms. In addition, the attention mechanisms and GNNExplainer were employed to manifest the functional sites and structural domain with most contribution to essentiality. In conclusion, Bingo provides the prospect of being able to accurately infer the essential genes of little- or under-studied organisms of interest, and provides a biological explanation for gene essentiality.
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ItemNo Preview AvailableMaternal contact and positive human interactions during lactation impacts piglet performance and behaviour during lactation(Frontiers Media S.A., 2023)Introduction: Early life interactions with the sow or humans can have lifelong consequences on welfare and performance in pigs. It was hypothesised that piglets that received increased maternal contact and positive human contact would display improved responses to stressful events and improved performance. Methods: Ninety-eight litters were allocated to a 2 x 2 factorial design for maternal contact (MC+)/restricted maternal contact (MC-); and positive human contact (HC+)/no additional human contact (HC-). Modified farrowing crates were used to restrict maternal contact (MC-) and litters in the HC+ treatment received five minutes of daily positive human interaction (stroking). Behavioural and physiological responses were assessed during processing at three days of age and during a behaviour test in which piglets were introduced to an empty arena, novel object, human hand and human standing in the arena at 18 days of age. Observations of behaviour in the home pen and growth and survival of piglets to weaning were also assessed. Results: At processing, MC- piglets had more squeals (P = 0.015), tended to have more grunts (P = 0.063) and struggle attempts (P = 0.079), and had increased plasma cortisol concentrations (P = 0.009) after processing than MC+ piglets. During the behaviour test, HC+ piglets were more active (P = 0.014) and had more vocalisations (P < 0.05) in the empty arena than HC piglets. Furthermore, HC+ piglets were more likely to approach a human standing in the arena (P = 0.006) than HC- piglets. MC- piglets were less active (P = 0.008) and were less likely to approach the novel object (P = 0.049) than MC+ piglets. MC+ piglets tended to have higher weaning weights (P = 0.055) and more MC+ piglets were successfully weaned (P = 0.022) than MC- piglets. There was no significant effect of HC on piglet performance. Discussion: While positive handling did not affect behavioural and physiological stress response to processing, HC+ reduced fear of novelty and humans. These findings highlight the importance of early life experiences has on stress resilience early in life.