Exploring the most common lesion of Australian farmed saltwater crocodile (Crocodylus porosus) belly skin in the Northern Territory.

This is the first descriptive study to characterise and identify the most common lesions on harvested Australian saltwater crocodiles (Crocodylus porosus). 88 skins were examined over a 17-month period as part of normal farming practices, 2901 lesions identified, with scale location, location of the lesion on the scale, and characteristics (contour, keratin normality, translucency and colour) recorded. The study determined that linear lesions accounted for 68.25 % of lesions followed by foci lesions 17.24 %. Lesions were distributed on the upper proportion of the belly skin (77.8 %) and along the midline (72 %). The most common lesion identified was a single translucent linear lesion across the scale that otherwise appeared normal (58.95 %). While there is extensive research into pathogenic agents, further research is recommended to explore further causation of linear lesions, and factors that may contribute to their prevention. Given the subjective nature of crocodile skin grading, it is recommended future research into lesions is required to ensure the sustainability and profitability of the industry.

Photoperiod and metabolic health: evidence, mechanism, and implications.

Circadian rhythms are evolutionarily programmed biological rhythms that are primarily entrained by the light cycle. Disruption of circadian rhythms is an important risk factor for several metabolic disorders. Photoperiod is defined as total duration of light exposure in a day. With the extended use of indoor/outdoor light, smartphones, television, computers, and social jetlag people are exposed to excessive artificial light at night increasing their photoperiod. Importantly long photoperiod is not limited to any geographical region, season, age, or socioeconomic group, it is pervasive. Long photoperiod is an established disrupter of the circadian rhythm and can induce a range of chronic health conditions including adiposity, altered hormonal signaling and metabolism, premature ageing, and poor psychological health. This review discusses the impact of exposure to long photoperiod on circadian rhythms, metabolic and mental health, hormonal signaling, and ageing and provides a perspective on possible preventive and therapeutic approaches for this pervasive challenge.

Circulating MicroRNAs as Prognostic Molecular Biomarkers in Human Head and Neck Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Circulating microRNAs (miRNAs) are potential molecular biomarkers for cancer detection; however, little is known about their prognostic role in head and neck cancer. This current study is aimed at evaluating the role of novel miRNAs in the survival of head and neck cancer patients. MATERIALS AND METHODS: We performed a systematic literature search using online databases for articles published between December 2006 and February 2019. A meta-analysis was conducted to assess the correlation between miRNA expressions and overall survival (OS) among the selected head and neck cancer studies. After multilevel screening by reviewers, meta-analysis was performed using hazard ratios (HR) and associated 95% confidence interval (CI) of survival to calculate a pooled effect size. RESULT: A total of 1577 patients across 13 studies were included in the literature review, with 18 miRNAs upregulated and 4 miRNAs downregulated predicting a poor overall survival. The forest plot generated using cumulated survival data resulted in a pooled HR value of 2.943 (95% CI: 2.394-3.618) indicating a strong association of dysregulated miRNA expression with a poor outcome. Only 2 miRNAs-low levels of miR-9 and high levels of miR-483-5p-were observed in two studies, both showing a significant association with overall cancer survival. CONCLUSION: To our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the prognostic role of circulating miRNAs from blood in head and neck cancer patients. The combined effect estimates a HR across multiple studies and also supports the previous individual findings that an alteration in miRNA expression is highly associated with poor prognosis. This has the potential to use serum and/or plasma miRNAs as biomarkers and become novel tools for predicting the prognosis of head and neck cancer patients in the near future.

Molecular characterization of the first saltwater crocodilepox virus genome sequences from the world's largest living member of the Crocodylia.

Crocodilepox virus is a large dsDNA virus belonging to the genus Crocodylidpoxvirus, which infects a wide range of host species in the order Crocodylia worldwide. Here, we present genome sequences for a novel saltwater crocodilepox virus, with two subtypes (SwCRV-1 and -2), isolated from the Australian saltwater crocodile. Affected belly skins of juvenile saltwater crocodiles were used to sequence complete viral genomes, and perform electron microscopic analysis that visualized immature and mature virions. Analysis of the SwCRV genomes showed a high degree of sequence similarity to CRV (84.53% and 83.70%, respectively), with the novel SwCRV-1 and -2 complete genome sequences missing 5 and 6 genes respectively when compared to CRV, but containing 45 and 44 predicted unique genes. Similar to CRV, SwCRV also lacks the genes involved in virulence and host range, however, considering the presence of numerous hypothetical and or unique genes in the SwCRV genomes, it is completely reasonable that the genes encoding these functions are present but not recognized. Phylogenetic analysis suggested a monophyletic relationship between SwCRV and CRV, however, SwCRV is quite distinct from other chordopoxvirus genomes. These are the first SwCRV complete genome sequences isolated from saltwater crocodile skin lesions.

Dermatological conditions of farmed Crocodilians: A review of pathogenic agents and their proposed impact on skin quality.

The control of pathogens that target crocodilian skin is essential to the long-term success and sustainability of intensive farming operations worldwide. To understand the impact these pathogens may have on the skin, a brief overview of skin histology is given. A review of the known viral, bacterial, fungal and helminth taxa associated with skin conditions in commercially significant crocodilian species is presented. Best management practices are discussed, with an emphasis on addressing extrinsic factors that influence transmission and pathogenicity. It is argued that, in the past, reduced immune function arising from inadequate thermal regulation was the leading cause of skin disease in captive crocodilians. Consequently, innovations such as temperature control, coupled with the adoption of more stringent hygiene standards, have greatly reduced the prevalence of many infectious skin conditions in intensively farmed populations. However, despite improvements in animal husbandry and disease management, viral pathogens such as West Nile virus, herpesvirus and poxvirus continue to afflict crocodilians in modern captive production systems.

Prognostic Role of MicroRNAs in Human Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: MicroRNAs (miRNAs) have been found to play an important role in the development and outcomes for multiple human cancers. Their role as a prognostic biomarker in non-small-cell lung cancer (NSCLC) remains unclear. This meta-analysis aims to clarify the role of various miRNAs in the survival of NSCLC patients. MATERIALS AND METHODS: All studies were identified through medical database search engines. A meta-analysis was conducted to assess the correlation between miRNAs expressions and overall survival among those NSCLC studies. Relevant data were extracted from each eligible study regarding baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and P value, which were utilized to calculate a pooled effect size. RESULT: Thirty-two studies were included in the meta-analysis. Using a random effect model, the combined HR and 95% CI for overall survival (OS) was calculated as 1.59 (1.39-1.82), predicting a poor overall survival. Five miRNAs (miR-21, miR-155, miR-let-7, miR-148a, and miR-148b) were found to be of significance for predicting OS in at least two studies, hence, selected for subgroup analysis. Subgroup analysis disclosed that elevated levels of miR-21 and miR-155 in both cancer tissue and blood samples were associated with worse OS. Compared to American studies (I-squared: <0.001% and P value: 0.94), Asian and European studies exhibited greater heterogeneity in miRNA expression and relationship to OS (I-squared, P values were approximately 78.85%, <0.001 and 61.28%, 0.006, respectively). These subgroup analyses also highlighted that elevated expression of miR-21 and miR-155 and low levels of expression of miR-148a, miR-148b, and miR-let-7 were associated with poor prognosis in NSCLC. CONCLUSION: miR-21, miR-155, miR-148a, miR-148b, and miR-let-7 are consistently up- or downregulated in NSCLC and are associated with poor OS. These miRNAs show potential as useful prognostic biomarkers in the diagnosis, treatment, and follow-up of NSCLC.

Impact of poxvirus lesions on saltwater crocodile (Crocodylus porosus) skins.

Cutaneous poxvirus infections are common in several crocodilian species and are of importance in crocodile farming due to their potential impact on the tanned hide. To confirm poxvirus infection and understand the impact on saltwater crocodile (Crocodylus porosus) skin, fourteen animals from different age groups (five hatchlings, five yearlings and four grow-outs) were selected based on a criterion of ten poxvirus-like lesions per animal. One lesion on each animal was extruded for genetic analysis and transmission electron microscopy. Both methods confirmed poxvirus so the remainder of lesions were re-examined every six weeks over a 24 week study period. Each lesion went through four distinct phases: early active, active, expulsion and healing. To understand how these lesions impact on the final skin product, one crocodile from each age group was euthanised and the lesions examined. Using standard skin grading techniques (light-table), the early phase (early active - expulsion) lesions were all translucent and would lead to downgrading of the skin or, at worst, rendering them unsaleable. At the later stages of healing, the translucency reduces. Histological examination of the phases confirm that the basement membrane is not breached by the infection further indicating that poxvirus lesions, given enough time, will eventually have no detrimental effect on skin quality. This is obviously dependent upon no more lesions developing in the interim.

Sequence analysis and characterisation of virally induced viperin in the saltwater crocodile (Crocodylus porosus).

A number of pathogens have been detected in crocodiles, however little is known about their ability to control these pathogens. The interferon stimulated gene (ISG), viperin, has gained attention recently as an important host protein involved in multiple arms of the immune response. Viperin in concert with a number of other ISGs was upregulated in response to viral nucleic acid mimics and sendai virus in the C. porosus cell line, LV-1, indicating an intact early innate response to viral infection in these animals for the first time. Viperin was cloned from the LV-1 cell line and shown to have similar localisation patterns as human viperin, as well as demonstrating extremely high conservation with the human orthologue, excepting at the N-terminus. Interestingly, C. porosus viperin was also able to inhibit Dengue virus replication in vitro, showing a high level of intact functionality for this protein across divergent animal species, and perhaps demonstrating its importance in the early innate response to pathogens in the animal kingdom.

Pulmonary cytochrome P450 enzymes belonging to the CYP4B subfamily from an Australian marsupial, the tammar wallaby (Macropus eugenii).

Cytochromes P450 (CYPs) are critically important in the oxidative metabolism of a diverse array of xenobiotics and endogenous substrates. We have previously reported the cloning and characterisation of the koala CYP4A15, the first reported member of the CYP4 family from marsupials, and have demonstrated important species differences in CYP4A activity and tissue expression. In the present study, the cloning of CYP4B1 in the wallaby (Macropus eugenii) and their expression across marsupials is described. Rabbit anti-mouse CYP4B1 antibody detected immunoreactive proteins in lung and liver microsomes from all test marsupials, with relative weak signal detected from the koala, suggesting a species-specific expression. Microsomal 2-aminofluorene bio-activation (a CYP4B1 marker) in wallaby lung was comparable to that of rabbit, with significant higher activities detected in wallaby liver and kidneys compared to rabbit. A 1548bp wallaby lung CYP4B complete cDNA, designated CYP4B1, which encodes a protein of 510 amino acids and shares 72% nucleotide and 69% amino acid sequence identity to human CYP4B1, was cloned by polymerase chain reaction approaches. The results demonstrate the presence of wallaby CYP4B1 that shares several common features with other published CYP4Bs; however the wallaby CYP4B1 cDNA contains four extra amino acid residues at the NH2-terminal, a fundamentally conserved transmembrane anchor of all eukaryote CYPs.