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Summary: The recent extension of genetic tools to the domestic cat, together with the serendipitous consequences of selective breeding, have been essential to the study of the genetic diseases that affect them. Cats are increasingly presented for veterinary surveillance and share many of human's heritable diseases, allowing them to serve as natural models of these conditions. Feline diabetes mellitus is a common condition in domestic cats that bears close pathological and clinical resemblance to type 2 diabetes in humans, including pancreatic β‐cell dysfunction and peripheral insulin resistance. In Australia, New Zealand and Europe, diabetes mellitus is almost four times more common in cats of the Burmese breed than in other breeds. This geographically based breed predisposition parallels familial and population clustering of type 2 diabetes in humans. As a genetically isolated population, the Australian Burmese breed provides a spontaneous, naturally occurring genetic model of type 2 diabetes. Genetically isolated populations typically exhibit extended linkage disequilibrium and increased opportunity for deleterious variants to reach high frequencies over many generations due to genetic drift. Studying complex diseases in such populations allows for tighter control of confounding factors including environmental heterogeneity, allelic frequencies and population stratification. The homogeneous genetic background of Australian Burmese cats may provide a unique opportunity to either refine genetic signals previously associated with type 2 diabetes or identify new risk factors for this disease. [ABSTRACT FROM AUTHOR]

The underlying drivers of variation in the colouration (colour and pattern) of animals can be genetic, non-genetic, or more likely, a combination of both. Understanding the role of heritable genetic elements, as well as non-genetic factors such as age, habitat or temperature, in shaping colouration can provide insight into the evolution and function of these traits, as well as the speed of response to changing environments. This project examined the genetic and non-genetic drivers of continuous variation in colouration in a lizard, the jacky dragon (Amphibolurus muricatus). We leveraged a large captive experiment that manipulated parental and offspring thermal environment to simultaneously estimate the genetic and non-genetic drivers of variation in colouration. We found that the overall brightness, the elongation of the longitudinal stripes on the dorsum and the contrast between light and dark patches of the pattern were all heritable. Colouration varied according to the age of the hatchling; however, the thermal environment of neither the parents nor offspring contributed significantly to colouration. It appears that developmental plasticity and maternal effects associated with temperature are not important drivers of variation in our measures of colouration., (© 2022 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)

Although Giardia duodenalis is considered a parasite of mammals, different genotypes have been identified as infecting several species of freshwater and marine fish in Australia. Establishment of G. duodenalis infection in common laboratory zebrafish ( Danio rerio), could provide an excellent tool for a range of studies on Giardia. We conducted preliminary experiments to investigate this possibility. Zebrafish were inoculated with viable G. duodenalis cysts from two different Assemblages (A and D) using a modified oro-gastric tube. Direct microscopy and immunofluorescent antibody test were used to check for Giardia cysts/trophozoites in the intestine, and histology was performed on intestinal mucosa to evaluate possible pathological changes. Giardia cysts were successfully deposited in the zebrafish alimentary tract using a modified oro-gastric tube, and were maintained in the fish gut for at least 8 days. Although a single trophozoite was observed in one fish three days post-exposure, we were unable to demonstrate established, propagative infection under the conditions tested. [ABSTRACT FROM AUTHOR]

Most quantitative traits are thought to exhibit high levels of genetic variance and evolutionary potential. However, this conclusion may be biased by a lack of studies on nonmodel organisms and may not generalize to restricted species. A recent study on a single, southern population of the rainforest-restricted Drosophila birchii failed to find significant additive genetic variance for the desiccation resistance trait; however, it is unclear whether this pattern extends to other D. birchii populations or to other rainforest species. Here we use an animal model design to show very low levels of additive genetic variance for desiccation resistance in multiple populations of two highly sensitive rainforest species of Drosophila from tropical northeastern Australia. In contrast, relatively high levels of genetic variance were found for morphological traits in all populations of the species tested. This indicates limited evolutionary potential for evolving increased desiccation resistance in these rainforest restricted species. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an emerging virus that has caused significant human morbidity and mortality since its detection in late 2019. With the rapid emergence has come an unprecedented programme of vaccine development with at least 300 candidates under development. Ferrets have proven to be an appropriate animal model for testing safety and efficacy of SARS-CoV-2 vaccines due to quantifiable virus shedding in nasal washes and oral swabs. Here, we outline our efforts early in the SARS-CoV-2 outbreak to propagate and characterize an Australian isolate of the virus in vitro and in an ex vivo model of human airway epithelium, as well as to demonstrate the susceptibility of domestic ferrets (Mustela putorius furo) to SARS-CoV-2 infection following intranasal challenge., (© 2021 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

The host defense peptide caerin 1.9 was originally isolated from skin secretions of an Australian tree frog and inhibits the growth of a wide range of bacteria in vitro . In this study, we demonstrated that caerin 1.9 shows high bioactivity against several bacteria strains, such as Staphylococcus aureus, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus haemolyticus in vitro . Importantly, unlike the antibiotic Tazocin, caerin 1.9 does not induce bacterial resistance after 30 rounds of in vitro culture. Moreover, caerin 1.1, another peptide of the caerin family, has an additive antibacterial effect when used together with caerin 1.9. Furthermore, caerin 1.1 and 1.9 prepared in the form of a temperature-sensitive gel inhibit MRSA growth in a skin bacterial infection model of two murine strains. These results indicate that caerin 1.1 and 1.9 peptides could be considered an alternative for conventional antibiotics. IMPORTANCE Antibiotic-resistant bacteria cause severe problems in the clinic. We show in our paper that two short peptides isolated from an Australian frog and prepared in the form of a gel are able to inhibit the growth of antibiotic-resistant bacteria in mice, and, unlike antibiotics, these peptides do not lead to the development of peptide-resistant bacteria strains.

Tildrakizumab (also known as MK-3222), is a high-affinity, humanized, immunoglobin G1κ monoclonal antibody targeting the p19 subunit of interleukin-23 recently approved for the treatment of moderate to severe plaque psoriasis in the US, Europe, and Australia. The safety profile of tildrakizumab was characterized in nonclinical studies using a pharmacologically relevant cynomolgus monkey model. In repeat-dose toxicity studies, cynomolgus monkeys were chronically treated with subcutaneous (SC) injections of 100 mg/kg of tildrakizumab every 2 weeks up to 9 months. Tildrakizumab was well tolerated, with no toxicological findings (including assessment of reproductive organs; hormonal effects; and cardiovascular, respiratory, and central nervous system function) at systemic exposures approximately 90 times higher than the recommended human dose of 100 mg. An embryofetal developmental study conducted in pregnant monkeys revealed no treatment-related effects to the developing fetus following SC administration of tildrakizumab 100 mg/kg. In a pre- and postnatal development study, 2 neonatal deaths due to potential viral infection at 100 mg/kg were considered of uncertain relationship to the treatment based on a lack of historical data on the occurrence of viral infection in neonate cynomolgus monkeys. The results of this comprehensive nonclinical safety program support the safe use of tildrakizumab. • The anti–IL-23p19 mAb tildrakizumab is approved for moderate-to-severe plaque psoriasis in the US, EU, and Australia. • Safety of subcutaneously administered tildrakizumab was characterized using a pharmacologically relevant cynomolgus monkey. • Tildrakizumab was well tolerated, with no toxicological findings in repeat-dose toxicity or embryofetal development studies. • No neonatal deaths were noted following in utero exposure at 7x the recommended human dose. • The results of this comprehensive nonclinical safety program support the safe use of tildrakizumab. [ABSTRACT FROM AUTHOR]

Non-human vertebrate animals, primarily domestic pigs, have been widely used in forensic science research as analogues for humans due to ethical and logistical constraints. Yet the suitability of pigs to mimic human decomposition and entomological patterns remains largely untested, and explicit comparative research in this area is lacking. We compared the decomposition rates and insect communities found at pig and human remains during summer and winter at the Australian Facility for Taphonomic Experimental Research (AFTER). Pigs decomposed faster than humans, with pigs entering active decay earlier in both summer and winter, and humans undergoing desiccation rather than skeletonisation. There was also a delay in the colonisation of humans by both flies and beetles. Species richness of these necrophagous taxa was between two and five times higher during the first two weeks of decomposition on pigs compared to humans during both summer and winter. Insect species composition was also significantly different between pigs and humans in each season. We interpret our findings to mean that the difference between humans and pigs, such as their mass, diet, medical history, or their microbiomes, might be causing different decomposition processes and altered timing or production of chemical cues for insect colonisation. Although preliminary, our results suggest that pigs might not be accurate substitutes for humans in particular fields of taphonomy and forensic entomology. Our findings also have broader implications for the reliability of forensic studies using pigs as models for humans, and highlight the need to recognise intrinsic differences between animal models and humans., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595-9940 ) is a previously reported recessively inherited disorder in Australian Poll Merino/Merino sheep. Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2. Here we report the identification of a likely disease-causing variant and propose an ovine model for human 3M syndrome-2., Results: Eight positional candidate genes were identified among the 39 genes in the approximately 1 Mb interval to which the disease was mapped previously. Obscurin like cytoskeletal adaptor 1 (OBSL1) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220472248delC within OBSL1. Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant. A genotyping assay was developed to genotype 583 animals from the original flock, giving an estimated allele frequency of 5%., Conclusions: The identification of a likely disease-causing variant resulting in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein has enabled improved breeding management of the implicated flock. The opportunity for an ovine model for human 3M syndrome and ensuing therapeutic research is promising given the availability of carrier ram semen for BCRHS.

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants in at least 13 genes underlie different forms of NCL, almost all of which are recessively inherited. To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breeds in which they result in progressive neurological disorders similar to human NCLs. Canine NCLs can serve as models for preclinical evaluation of therapeutic interventions for these disorders. In most NCLs, the onset of neurological signs occurs in childhood, but some forms have adult onsets. Among these is CLN12 disease, also known as Kufor-Rakeb syndrome, PARK9, and spastic paraplegia78. These disorders result from variants in ATP13A2 which encodes a putative transmembrane ion transporter important for lysosomal function. Three Australian Cattle Dogs (a female and two of her offspring) were identified with a progressive neurological disorder with an onset of clinical signs at approximately 6 years of age. The affected dogs exhibited clinical courses and histopathology characteristic of the NCLs. Whole genome sequence analysis of one of these dogs revealed a homozygous c.1118C > T variant in ATP13A2 that predicts a nonconservative p.(Thr373Ile) amino acid substitution. All 3 affected dogs were homozygous for this variant, which was heterozygous in 42 of 394 unaffected Australian Cattle Dogs, the remainder of which were homozygous for the c.1118C allele. The high frequency of the mutant allele in this breed suggests that further screening for this variant should identify additional homozygous dogs and indicates that it would be advisable to perform such screening prior to breeding Australian Cattle Dogs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)