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Sulphonylureas as Adjunct Therapeutic Agents in the Treatment of Autoimmune Conditions: A Narrative Review
No full textA rapid and cost-effective arm of the drug discovery and development process is finding new uses for existing drugs. Initially used as antibacterial agents, sulphonylureas were repurposed for the treatment of type 2 diabetes due to their hypoglycemic side effects. Their primary mechanism of action is mediated by binding to sulphonylurea receptors (SUR), which are atypical adenosine triphosphate binding cassette transporters in pancreatic beta cells. This interaction inhibits ATP-sensitive potassium channels to promote insulin release. Off-target actions of sulphonylureas identified in recent studies have demonstrated a range of anti-inflammatory properties mediated by modulation of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 inflammasomes. Inflammasomes are cytosolic protein complexes that assemble in response to infection or stress-associated stimuli, activating inflammatory responses, and are the primary source of pro-inflammatory cytokines. Sulphonylureas and their derivatives have been shown to inhibit various stages of inflammasome activation, leading to the reduction of pro-inflammatory mediators, including IL-1β and IL-18. Recent evidence demonstrates that these agents reduced inflammatory responses, disease severity, and progression in various preclinical autoimmune and inflammatory models. In this narrative review, we consider the complexity of autoimmune conditions and the limited treatment options, and highlight the potential value of repurposing sulphonylureas and their derivatives as adjunct therapeutics for autoimmune conditions
Social influence on the effectiveness of virtual fencing in sheep
No full textEarly virtual fencing trials have effectively contained small groups of sheep within set areas of a paddock when all animals were wearing manual electronic collars. With sheep farming commonly involving large flocks, a potential cost-effective application of virtual fencing would involve applying equipment to only a proportion of the flock. In this study, we tested the ability of virtual fencing to control a small flock of sheep with differing proportions of the group exposed to the virtual fence (VF). Thirty-six Merino sheep were identified as leaders, middle or followers by moving them through a laneway. The sheep were then allocated to groups balanced for order of movement. The groups (n = 9 per group) included applying the VF to the following proportions of animals within each group: (1) 100% (n = 9 VF) (2) 66% (n = 6 VF; n = 3 no VF) (3) 33% (n = 3 VF; n = 6 no VF) (4) 0% (no VF; free to roam the paddock). The groups were given access to their own paddock (80 × 20 m) for two consecutive days, six hours per day, with the VF groups prevented from entering an exclusion zone that covered 50% of the north side of the paddock. During these hours, VF interactions, behavioural time budgets, and body temperature were recorded as measures of stress, and location was tracked with GPS. Group 100% VF and Control were tested on the first two days and groups 33% VF and 66% VF were tested on the following two days. During VF implementation the 100% VF and 66% VF group were successfully prevented from entering the exclusion zone. Having only 33% of the flock exposed to the virtual fence was not successful, with the sheep pushing forward through the VF to join flock mates in the exclusion zone. For learning to respond to the audio cue, sheep in the 33% group received more electrical stimuli with a 0.51 proportion for the ratio of electrical stimuli to audio cue, compared to 0.22 and 0.28 for the 100% and 66% groups, respectively. There were small differences in behavioural patterns of standing and lying on both days of testing, with the 100% VF and 66% VF groups spending more time lying. Although stress-induced hyperthermia did not occur in any of the VF groups, body temperature differed in the 33% VF group. There were no differences in temperature measures between the control and 100% VF animals. This study demonstrates that for a short period, controlling two-thirds of the flock was equally as effective as virtually fencing all animals, while controlling one-third of a flock with a virtual fence was not effective. For the short term, it appears that implementing the VF to a proportion of the flock can be an effective method of containment. Due to the limitations of this study, these results warrant further testing with larger flocks and for longer periods
Combined LambPlan: Expanding the mulit-breed nature of the LambPlan evaluation
No full textThe Australian sheep industry continues to mix breeds across all sectors, including ram breeding. Genetic evaluation needs to change with industry and provide relevant comparisons across breeds. This has prompted a development to combine the LAMBPLAN Terminal and Maternal evaluations. Combining analyses will provide a single breeding value ‘language’ across non-Merino breeds and continue to allow breeders to access selection tools to meet their breeding objectives irrespective of breed. This study summarises the key technical enhancements to deliver the Combined LAMBPLAN analysis, including: business decisions around data usage, formation of lifetime contemporary groups, genetic group structure and the use of a meta-founder model, fixed effects models, heterosis adjustments and parameter re-estimation. The combined evaluation will provide an improved utility of ASBVs for the Australian prime lamb industry
Welcome to the Machine: Artificial Intelligence on Screen
No full textArtificial intelligence has been a topic of fascination for film and television since the earliest appearances of robots on our screens, bringing with them questions about ethics, sentience, and the long-term fate of humanity. This article explores depictions of artificial intelligence on screen from a thematic rather than chronological viewpoint. Themes explored include the popular sci-fi trope of robot rebellion, androids as worker/slaves, and intimate relationships between humans and AI. The article also raises philosophical questions of why we wish to create robots in our own image, and what AI sentience, in both android bodies and more elusive disembodied forms, could look like. A range of films and television series—from the Terminator franchise to HBO's Westworld—are used to unpack humanity's dreams and nightmares of how AI could shape our future
Accuracy of genomic predictions for beef eating quality traits
No full textEating quality is the primary factor influencing consumer purchasing decisions for beef products. Consumer-derived sensory eating quality traits capture the actual eating experience and are directly aligned with consumer expectations. Accurate genomic prediction of these traits can enable selective breeding, allowing for continuous genetic improvement and consistent consumer satisfaction. In this study we used an international dataset from Australia, the USA and Ireland to estimate genetic parameters for five meat eating quality traits and to evaluate the accuracy of genomic estimated breeding values under different cross-validation scenarios. Heritability estimates ranged from 0.19 to 0.31 for Australia, 0.07 to 0.20 for the USA, 0.09 to 0.17 for Ireland, and 0.14 to 0.22 for the combined dataset. Prediction accuracies for all traits were moderate when using the Australia-only reference population but increased to high accuracies when international data were included. This highlights the value of incorporating international data into the reference population, creating a larger and more diverse dataset, and ultimately improving prediction accuracies
How biochar works, and when it doesn't: A review of mechanisms controlling soil and plant responses to biochar
No full textWe synthesized 20 years of research to explain the interrelated processes that determine soil and plant responses to biochar. The properties of biochar and its effects within agricultural ecosystems largely depend on feedstock and pyrolysis conditions. We describe three stages of reactions of biochar in soil: dissolution (1–3 weeks); reactive surface development (1–6 months); and aging (beyond 6 months). As biochar ages, it is incorporated into soil aggregates, protecting the biochar carbon and promoting the stabilization of rhizodeposits and microbial products. Biochar carbon persists in soil for hundreds to thousands of years. By increasing pH, porosity, and water availability, biochars can create favorable conditions for root development and microbial functions. Biochars can catalyze biotic and abiotic reactions, particularly in the rhizosphere, that increase nutrient supply and uptake by plants, reduce phytotoxins, stimulate plant development, and increase resilience to disease and environmental stressors. Meta-analyses found that, on average, biochars increase P availability by a factor of 4.6; decrease plant tissue concentration of heavy metals by 17%–39%; build soil organic carbon through negative priming by 3.8% (range −21% to +20%); and reduce non-CO2 greenhouse gas emissions from soil by 12%–50%. Meta-analyses show average crop yield increases of 10%–42% with biochar addition, with greatest increases in low-nutrient P-sorbing acidic soils (common in the tropics), and in sandy soils in drylands due to increase in nutrient retention and water holding capacity. Studies report a wide range of plant responses to biochars due to the diversity of biochars and contexts in which biochars have been applied. Crop yields increase strongly if site-specific soil constraints and nutrient and water limitations are mitigated by appropriate biochar formulations. Biochars can be tailored to address site constraints through feedstock selection, by modifying pyrolysis conditions, through pre- or post-production treatments, or co-application with organic or mineral fertilizers. We demonstrate how, when used wisely, biochar mitigates climate change and supports food security and the circular economy
Deliberately introduced dung beetles in Australia: 12 years of occurrence and abundance records from 2001 to 2022
No full textSince 1968, the Australian Dung Beetle Project has carried out field releases of 43 deliberately introduced dung beetle species for the biological control of livestock dung and dung-breeding pests. Of these, 23 species are known to have become established. For most of these species, sufficient time has elapsed for population expansion to fill the extent of their potential geographic range through both natural and human-assisted dispersal. Consequently, over the last 20 years, extensive efforts have been made to quantify the current distribution of these introduced dung beetles, as well as the seasonal and spatial variation in their activity levels. Much of these data and their associated metadata have remained unpublished, and they have not previously been synthesized into a cohesive dataset. Here, we collate and report data from the three largest dung beetle monitoring projects from 2001 to 2022. Together, these projects encompass data collected from across Australia, and include records for all 23 species of established dung beetles introduced for biocontrol purposes. In total, these data include 22,718 presence records and 213,538 absence records collected during 10,272 sampling events at 546 locations. Most presence records (97%) include abundance data. In total, 1,752,807 dung beetles were identified as part of these data. The distributional occurrence and abundance data can be used to explore questions such as factors influencing dung beetle species distributions, dung beetle biocontrol, and insect-mediated ecosystem services
Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease
No full textAlzheimer’s disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems worldwide. The pathogenesis of AD is being extensively investigated, yet several unknown key components remain. Therefore, we aimed to extract new knowledge from existing data. Ten gene expression datasets from different brain regions including the hippocampus, cerebellum, entorhinal, frontal and temporal cortices of 820 AD cases and 626 healthy controls were analyzed using the robust rank aggregation (RRA) method. Our results returned 1713 robust differentially expressed genes (DEGs) between five brain regions of AD cases and healthy controls. Subsequent analysis revealed pathways that were altered in each brain region, of which the GABAergic synapse pathway and the retrograde endocannabinoid signaling pathway were shared between all AD affected brain regions except the cerebellum, which is relatively less sensitive to the effects of AD. Furthermore, we obtained common robust DEGs between these two pathways and predicted three miRNAs as potential candidates targeting these genes; hsa-mir-17-5p, hsa-mir-106a-5p and hsa-mir-373-3p. Three transcription factors (TFs) were also identified as the potential upstream regulators of the robust DEGs; ELK-1, GATA1 and GATA2. Our results provide the foundation for further research investigating the role of these pathways in AD pathogenesis, and potential application of these miRNAs and TFs as therapeutic and diagnostic targets
Optimising the hatching success of artificially incubated eggs for use in a conservation program for the western saw-shelled turtle (Myuchelys bellii)
No full textArtificial incubation of eggs and the release of hatchlings into the wild is a common conservation intervention designed to augment threatened turtle populations. We investigate a range of incubation temperatures to establish an optimal temperature for maximum hatching success of western saw-shelled turtle (Myuchelys bellii) eggs. We report on the influence of incubation temperature on incubation duration and hatching success and describe two experimental incubation methods which, for the same incubation temperature (27°C), resulted in 77% and 97% hatching success, respectively. Eggs were incubated at constant temperatures (27°C, 28°C and 29°C) to determine the influence of temperature on incubation period, hatchling morphology and external residual yolk. Incubation duration was negatively correlated with incubation temperature. We report on the morphology of eggs and hatchlings and show that their dimensions are positively correlated with maternal adult size and mass. A constant incubation temperature of 27°C produced the highest hatching success and smallest external residual yolk on hatching and is therefore recommended for incubation of eggs for population reinforcement programs. Our study is the first to optimise artificial incubation procedures for M. bellii and will be a valuable resource for M. bellii and other threatened freshwater turtle conservation initiatives
Expanding Australian sheep genomic reference population
No full textAllele frequencies play a crucial role in multi-breed genetic evaluations by enabling the construction of a breed-adjusted genomic relationship matrix (GRM), which can be derived from a genomic reference population. This study aimed to update the Australian sheep genomic reference population for a combined Terminal and Maternal LAMBPLAN genetic evaluation. The analysis incorporated genotypic data from sheep across maternal, terminal, shedding, and Merino breeds, as well as smaller breeds and composite populations. Population structure analysis identified 27 genetic clusters among terminal, maternal and shedding breeds and five clusters within Merino sheep. The findings demonstrate that genomic data and unsupervised clustering methods can improve breed composition accuracy and facilitate a comprehensive multi-breed genetic evaluation, reducing the need for strictly straight-bred reference populations