Impact of steroid hormone signals on Drosophila cell cycle during development

Metamorphosis of Drosophila involves proliferation, differentiation and death of larval tissues in order to form the adult fly. The major steroid hormone implicated in the larval-pupal transition and adult tissue modelling is ecdysone. Previous reviews have draw together studies connecting ecdysone signaling to the processes of apoptosis and differentiation. Here we discuss those reports connecting the ecdysone pulse to developmentally regulated cell cycle progression

The infinite in early modern philosophy

The calculus was developed in the seventeenth and eighteenth centuries in order to solve certain mathematical problems. In ‘The Analyst’ Berkeley gave his objections to the calculus. In particular, he objected to its dependence upon infinitesimals. He argued that these infinitely small distances were contradictory. Further he objected that the calculus, despite leading to true conclusions was not genuine science. So, although the calculus worked, it raised philosophical problems. I will look at Berkeley’s objections, both logical and metaphysical and explore how philosophically problematic they are. I will then consider what consequences arise from these objections. Specifically, I will look at the consequences for mathematical realism, and aim to answer the following questions: If Berkeley’s philosophical arguments are valid how can we explain that the calculus enables us to derive useful results? If we rely on non-entities such as infinitesimals in our mathematical proofs, does this mean that platonism cannot be the true metaphysical framework? If we reject platonism, does the dependence upon nonentities in the proofs of the calculus mean that all forms of mathematical realism are off the table? Or, is this methodology consistent with non-platonic forms of mathematical realism such as truth-value realism. Or, must we look to an alternative picture, such as fictionalism

Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for healthcare policy and decision making

Objective: Network meta-analyses have extensively been used to compare the effectiveness of multiple interventions for healthcare policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. Study design and setting: Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE <25/30 and <27/30, and MoCA <22/30 and <26/30. Using Markov Chain Monte Carlo (MCMC) methods, we fitted a bivariate network meta-analysis model incorporating constraints on increasing test threshold, and accounting for the correlations between multiple test accuracy measures from the same study. Results: We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold <26/30 appeared to have the best true positive rate, whilst MMSE at threshold <25/30 appeared to have the best true negative rate. Conclusion: The combined analysis of multiple tests at multiple thresholds allowed for more rigorous comparisons between competing diagnostics tests for decision making

Organic-Conventional Dairy Systems Trial in New Zealand: Four Years’ Results

The Organic-Conventional Comparative Dairy Systems trial at Massey University began in August 2001, and the organic farmlet achieved certification in August 2003. The trial is unique because it is the only comparative grassland-based open grazing dairy study in the world. The organic and conventional systems are managed individually according to best practice, and both are intensively monitored for production, animal health, and environmental impacts. The systems remained similar for the first two years, but began to diverge in the third and fourth years. Production has been 10-20% lower on the organic farm, but environmental impacts appear to be less than on the conventional unit, and net incomes would be similar given a 20% price premium for the organic product. Animal health issues have been manageable on the organic farmlet, and not too dissimilar from the conventional farmlet. Full results after four years of the trial will be available and presented at the conference

The infinite in early modern philosophy

The calculus was developed in the seventeenth and eighteenth centuries in order to solve certain mathematical problems. In ‘The Analyst’ Berkeley gave his objections to the calculus. In particular, he objected to its dependence upon infinitesimals. He argued that these infinitely small distances were contradictory. Further he objected that the calculus, despite leading to true conclusions was not genuine science. So, although the calculus worked, it raised philosophical problems. I will look at Berkeley’s objections, both logical and metaphysical and explore how philosophically problematic they are. I will then consider what consequences arise from these objections. Specifically, I will look at the consequences for mathematical realism, and aim to answer the following questions: If Berkeley’s philosophical arguments are valid how can we explain that the calculus enables us to derive useful results? If we rely on non-entities such as infinitesimals in our mathematical proofs, does this mean that platonism cannot be the true metaphysical framework? If we reject platonism, does the dependence upon nonentities in the proofs of the calculus mean that all forms of mathematical realism are off the table? Or, is this methodology consistent with non-platonic forms of mathematical realism such as truth-value realism. Or, must we look to an alternative picture, such as fictionalism

The Ecdysone receptor constrains wingless expression to pattern cell cycle across the Drosophila wing margin in a cyclin B-dependent manner

Background: Ecdysone triggers transcriptional changes via the ecdysone receptor (EcR) to coordinate developmental programs of apoptosis, cell cycle and differentiation. Data suggests EcR affects cell cycle gene expression indirectly and here we identify Wingless as an intermediary factor linking EcR to cell cycle. Results: We demonstrate EcR patterns cell cycle across the presumptive Drosophila wing margin by constraining wg transcription to modulate CycB expression, but not the previously identified Wg-targets dMyc or Stg. Furthermore co-knockdown of Wg restores CycB patterning in EcR knockdown clones. Wg is not a direct target of EcR, rather we demonstrate that repression of Wg by EcR is likely mediated by direct interaction between the EcR-responsive zinc finger transcription factor Crol and the wg promoter. Conclusions: Thus we elucidate a critical mechanism potentially connecting ecdysone with patterning signals to ensure correct timing of cell cycle exit and differentiation during margin wing development

Mismatched prenatal and postnatal maternal depressive symptoms and child behaviours: a sex-dependent role for NR3C1 DNA methylation in the Wirral Child Health and Development Study

Evolutionary hypotheses predict that male fetuses are more vulnerable to poor maternal conditions (Sex-biased Maternal Investment), but female fetuses are at greater risk of glucocorticoid-mediated disorders where there is a mismatch between fetal and postnatal environments (Predictive Adaptive Response). Self-reported prenatal and postnatal depression and maternal report of child anxious-depressed symptoms at 2.5, 3.5 and 5.0 years were obtained from an ‘extensive’ sample of first-time mothers (N = 794). Salivary NR3C1 1-F promoter methylation was assayed at 14 months in an ‘intensive’ subsample (n = 176) and stratified by psychosocial risk. Generalised structural equation models were fitted and estimated by maximum likelihood to allow the inclusion of participants from both intensive and extensive samples. Postnatal depression was associated with NR3C1 methylation and anxious-depressed symptoms in daughters of mothers with low prenatal depression (prenatal-postnatal depression interaction for methylation, p 0.001; for child symptoms, p = 0.011). In girls, NR3C1 methylation mediated the association between maternal depression and child anxious-depressed symptoms. The effects were greater in girls than boys: the test of sex differences in the effect of the prenatal-postnatal depression interaction on both outcomes gave X2 (2) = 5.95 (p = 0.051). This was the first human study to show that epigenetic and early behavioural outcomes may arise through different mechanisms in males and females

Using An Evaluation Framework to Direct Public Engagement Work:2017-2022 with Case Studies

We are the School of Life Sciences Public Engagement team. This team encompasses the Schools Outreach Organiser and Public Engagement and Communications Officer as well as the WCAIR Public Engagement Manager and Public Engagement Officer and the Academic Lead. We provide support for the staff and students within the School of Life Sciences in engaging with the public, including training, resource development, administrative support, and specialist expertise. We have staff and student development, and social purpose at the heart of all that we do.In 2017 we defined four main aims as part of our new Public Engagement with Research Strategy:→ Build on our creative partnerships to deliver a high-quality, innovative engagement programme. This will inspire participation in and understanding of our research, making science relevant for everyone.→ Engage a diverse range of people with our research.→ Consult with our local communities to widen our reach and meet their needs.→ Promote and support a culture of active participation in public engagement within our life sciences community.In 2018, we worked with Evaluation Support Scotland to set up our evaluation framework. Some of the evaluation outcomes, and their associated indicators, were set to evidence the good work we were already doing. Some were set to drive us to improve our practice.Over the past five years, we have used the framework to monitor our work. Each annual reflection gave us confidence in some areas but also pushed us to re-examine some of our long-standing practices and assumptions and refine the framework to meet changing needs.Here we showcase how we used the evaluation framework to guide our work and in doing so, provide a flavour of the public engagement activities the School of Life Sciences undertakes. We demonstrate how we knew if we were being successful, where we had more work to do, and where we were unrealistic with our expectations