Animal research is saving lives, but funding is needed to improve welfare: Submission to the New South Wales parliamentary inquiry

Many kinds of animal research are occurring in New South Wales (NSW), with biomedical research among the most prominent. As behavioural neuroscientists, we study the neural mechanisms of motivation and cognition in rodents, which is important for developing new treatments for a range of psychological disorders, such as substance use disorder, as well as neurodegenerative diseases such as Alzheimer’s. The welfare and wellbeing of the animals we study is of critical importance, not only to ensure the quality of our data but to our sense of morality as compassionate human beings. Biomedical animal research is highly regulated and the pharmacological and biological tools we use pose negligible risks to the public. Meanwhile, our research brings enormous benefits to NSW by building expertise and supporting biotechnology companies. Although research on complex behaviours cannot be replaced by non-animal procedures, we believe that there is much scope for refinement and improvement in animal welfare in NSW. For example, investing in a local breeding facility to produce animals used in NSW research projects would significantly reduce the stress associated with importing animals from interstate or overseas. Additionally, standard animal housing could be improved through targeted and ongoing investment to refit animal facilities and support additional caretaker and veterinary staff to provide higher degrees of welfare

The influence of maternal unhealthy diet on maturation of offspring gut microbiota in rat

Background Despite well-known effects of diet on gut microbiota diversity, relatively little is known about how maternal diet quality shapes the longitudinal maturation of gut microbiota in offspring. To investigate, we fed female rats standard chow (Chow) or a western-style, high-choice cafeteria diet (Caf) prior to and during mating, gestation and lactation. At weaning (3 weeks), male and female offspring were either maintained on their mother’s diet (ChowChow, CafCaf groups) or switched to the other diet (ChowCaf, CafChow). Fecal microbial composition was assessed in dams and longitudinally in offspring at 3, 7 and 14 weeks of age. Results The effect of maternal diet on maturation of offspring gut microbiota was assessed by α- and β-diversities, Deseq2/LEfSe, and SourceTracker analyses. Weanling gut microbiota composition was characterised by reduced α- and β-diversity profiles that clustered away from dams and older siblings. After weaning, offspring gut microbiota came to resemble an adult-like gut microbiota, with increased α-diversity and reduced dissimilarity of β-diversity. Similarly, Deseq2/LEfSe analyses found fewer numbers of altered operational taxonomic units (OTUs) between groups from weaning to adulthood. SourceTracker analyses indicated a greater overall contribution of Caf mothers’ microbial community (up to 20%) to that of their offspring than the contribution of Chow mothers (up to 8%). Groups maintained on the maternal diet (ChowChow, CafCaf), versus those switched to the other diet (ChowCaf, CafChow) post-weaning significantly differed from each other at 14 weeks (Permutational Multivariate Analysis of Variance), indicating interactive effects of maternal and post-weaning diet on offspring gut microbiota maturation. Nevertheless, this developmental trajectory was unaffected by sex and appeared consistent between ChowChow, CafCaf, ChowCaf and CafChow groups. Conclusions Introducing solid food at weaning triggered the maturation of offspring gut microbiota to an adult-like profile in rats, in line with previous human studies. Postweaning Caf diet exposure had the largest impact on offspring gut microbiota, but this was modulated by maternal diet history. An unhealthy maternal Caf diet did not alter the developmental trajectory of offspring gut microbiota towards an adult-like profile, insofar as it did not prevent the age-associated increase in α-diversity and reduction in β-diversity dissimilarity

Design considerations for workflow management systems use in production genomics research and the clinic

Abstract The changing landscape of genomics research and clinical practice has created a need for computational pipelines capable of efficiently orchestrating complex analysis stages while handling large volumes of data across heterogeneous computational environments. Workflow Management Systems (WfMSs) are the software components employed to fill this gap. This work provides an approach and systematic evaluation of key features of popular bioinformatics WfMSs in use today: Nextflow, CWL, and WDL and some of their executors, along with Swift/T, a workflow manager commonly used in high-scale physics applications. We employed two use cases: a variant-calling genomic pipeline and a scalability-testing framework, where both were run locally, on an HPC cluster, and in the cloud. This allowed for evaluation of those four WfMSs in terms of language expressiveness, modularity, scalability, robustness, reproducibility, interoperability, ease of development, along with adoption and usage in research labs and healthcare settings. This article is trying to answer, which WfMS should be chosen for a given bioinformatics application regardless of analysis type?. The choice of a given WfMS is a function of both its intrinsic language and engine features. Within bioinformatics, where analysts are a mix of dry and wet lab scientists, the choice is also governed by collaborations and adoption within large consortia and technical support provided by the WfMS team/community. As the community and its needs continue to evolve along with computational infrastructure, WfMSs will also evolve, especially those with permissive licenses that allow commercial use. In much the same way as the dataflow paradigm and containerization are now well understood to be very useful in bioinformatics applications, we will continue to see innovations of tools and utilities for other purposes, like big data technologies, interoperability, and provenance

Metabolic effects of access to sucrose drink in female rats and transmission of some effects to their offspring

The aims of this study were, first, to examine the metabolic consequences for female rats of having unrestricted access to 10% sucrose solution and, second, to test for effects of this dietary intervention on their offspring. In Stage 1 females were mated following a 4-week period in which one group was given the sucrose in addition to their normal chow and a control group was given chow and water only. Sucrose was removed at parturition and the pups monitored until weaning. Despite the development of glucose intolerance in sucrose-fed mothers, no effects were detected on litter size or pup weights. In Stage 2 voluntary activity of offspring was assessed over postnatal days (PND) 51-60 and their glucose tolerance measured at PND89-94. Again no effect of maternal diet was detected. Only male offspring were used in Stage 3, which began when they were 13 weeks old. Four groups were given 10% sucrose solution for 48 days in a 2 x 2 design, in which one factor was maternal diet and the other was whether they were given 2-h access to an activity wheel on alternate days. Higher fasting glucose levels were found in offspring of sugar-fed mothers. Exercise increased insulin sensitivity in these rats but not in offspring of control mothers. Behavioural measures of memory in Stage 3 did not reveal any effects of maternal diet or exercise. Overall, this study suggested that, while providing 10% sucrose solution ad-libitum was sufficient to impair maternal metabolism, the impact of this dietary manipulation on offspring may be revealed only when the offspring’s diet is similarly manipulated

Contexts paired with junk food impair goal-directed behaviour in rats: implications for decision making in obesogenic environments

The high prevalence of obesity and related metabolic diseases calls for greater understanding of the factors that drive excess energy intake. Calorie-dense palatable foods are readily available and often are paired with highly salient environmental cues. These cues can trigger food-seeking and consumption in the absence of hunger. Here we examined the effects of palatable food-paired environmental cues on control of instrumental food-seeking behaviour. In Experiment 1, adult male rats received exposures to one context containing three ‘junk’ foods (JF context) and another containing chow (Chow context). Next, rats were food-deprived and trained to perform instrumental responses (lever-press) for two novel food rewards in a third, distinct context. Contextual influences on flexible control of food-seeking behaviour were then assessed by outcome devaluation tests held in the JF, chow, and training contexts. Devaluation was achieved using specific satiety and test order was counterbalanced. Rats exhibited goal-directed control over behaviour when tested in the training and chow-paired contexts. Notably, performance was habitual (insensitive to devaluation) when tested in the JF context. In Experiment 2 we tested whether the impairment found in the JF context could be ameliorated by the presentation of a discrete auditory cue paired with the chow context, relative to a second cue paired with the JF context. Consistent with the results of Experiment 1, the devaluation effect was not significant when rats were tested in the JF context with the JF cue. However, presenting the chow cue increased the impact of the devaluation treatment leading to a robust devaluation effect. Further tests confirmed that performance in the chow context was goal-directed and that sensory-specific satiety in the JF context was intact. These results show that environments paired with palatable foods can impair goal-directed control over food-seeking behaviour, but that this deficit was improved by a cue paired with chow. This has promising implications for assisting individuals in controlling their eating behaviour in environments designed to dysregulate it

Switching from Sugar- to Artificially-Sweetened Beverages: A 12-Week Trial

Background: Consumption of sugar-sweetened beverages (SSBs) forms the primary source of added sugar intake and can increase the risk of metabolic disease. Evidence from studies in humans and rodents also indicates that consumption of SSBs can impair performance on cognitive tests, but that removing SSB access can ameliorate these effects. Methods: The present study used an unblinded 3-group parallel design to assess the effects of a 12-week intervention in which young healthy adults (mean age = 22.85, SD = 3.89; mean BMI: 23.2, SD = 3.6) who regularly consumed SSBs were instructed to replace SSB intake with artificially-sweetened beverages (n = 28) or water (n = 25), or (c) to continue SSB intake (n = 27). Results: No significant group differences were observed in short-term verbal memory on the Logical Memory test or the ratio of waist circumference to height (primary outcomes), nor in secondary measures of effect, impulsivity, adiposity, or glucose tolerance. One notable change was a significant reduction in liking for strong sucrose solutions in participants who switched to water. Switching from SSBs to ‘diet’ drinks or water had no detectable impact on cognitive or metabolic health over the relatively short time frame studied here. This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001004550; Universal Trial Number: U1111-1170-4543)

Retroperitoneal fat in Stage 3.

<p>Fat pad mass did not differ between the four experimental groups, but was lower in the Added group than in the Sucrose-Sedentary group.</p