Robustness from flexibility in the fungal circadian clock

Background Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa. Results The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq) gene inhibits its transcriptional activator white collar-1 (wc-1), interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on the circuit by the interlocking loop structure. Conclusions Our model shows that the behaviour of the fungal clock in light-dark cycles can be accounted for by a transcription-translation feedback model of the central FRQ-WC oscillator. More generally, we provide an example of a biological circuit in which greater flexibility yields improved robustness, while also introducing novel sensitivity analysis techniques applicable to a broader range of cellular oscillators

Morphology of the recently re-classified Tasman masked booby (Sula dactylatra tasmani) breeding on the Kermadec Islands

Once thought to be extinct, the Tasman Booby Sula tasmani has recently been re-classified as a subspecies of the Masked Booby S. dactylatra on the basis of genetic data. This re-classification raises the issue of whether this novel clade has a distinct morphology. Morphological differences in size, as well as coloration of integuments, bill and iris have been found in other subspecies of the Masked Booby but have not yet been reported for live Kermadec Islands breeding individuals. Museum specimens from this breeding location have been separated from other Pacific breeding subspecies by their longer wings. We sampled a total of 21 individuals from North Meyer Islet, Kermadec Group, New Zealand, and applied molecular sexing to obtain sex-specific morphometric measurements. We matched dimorphism in vocalization with genetic sexing results and photographic documentation of human-assessed bill, foot and eye coloration. While culmen measurements were consistent with reports from museum specimens, wing chords from living specimens of Tasman Masked Boobies were 3% and 4% larger in males and females, respectively. Females had larger culmens and wings than males, consistent with the low extent of sexual dimorphism reported from museum skins. Adult Tasman Masked Boobies had yellow to buff-yellow feet, while fledglings, as in most sulids, had grey to greyish-yellow feet. Our findings confirm the distinctively long wing and particular iris coloration previously reported for the taxon and provide the first description of integument coloration of live specimens. This study highlights the importance of including in situ assessment in taxon descriptions

Learning About Development at A-Level

Young people’s interest in development issues has been the focus of numerous studies but there has been little research that looks at the impact of learning of a specific educational course. This research paper looks at the impact of studying A-level World Development on young people in England and Wales. It summarises the outcomes of research by Bowes in 2011 and a further survey in 2012 with students who have completed the course. This study looks specifically at the relevance, effectiveness and impact of the course on students. The evidence suggests that the A-level is popular and seen as relevant to young people’s lives and views about the world. Both teachers and students state that the themes discussed are up-to-date and accessible to study. In terms of effectiveness of the course overall, there is evidence of understanding of the key issues in development, although the priorities given to particular themes varied from school and college. Programmes and projects on learning about development have often been promoted because there is an assumption that mere engagement with these themes has an impact on young people’s learning in terms of changing their behaviour and attitudes towards taking action to reduce global poverty. The evidence from this research shows a complex picture of impact with the emphasis appearing to be more on the social and moral aspects of development than the political. The research indicates positive changes in perceptions of global poverty and inequality in the world, but less so on the more social and political aspects. There is evidence that studying the A-level has had an impact upon the students’ future learning in higher education with Geography and Development Studies becoming more popular. The first full World Development A-level began in 2008 so the examination is still relatively new. The sample taken for this study and the research by Bowes covered a relatively small number of students. However, what is clear from this research is that an A-level of this type can play an important contribution in deepening a young person’s learning and understanding about development and that it is a subject that is seen as popular and relevant to their lives

Investigating the DNA-Binding Site for VirB, a Key Transcriptional Regulator of Shigella Virulence Genes, Using an In Vivo Binding Tool

The transcriptional anti-silencing and DNA-binding protein, VirB, is essential for the virulence of Shigella species and, yet, sequences required for VirB-DNA binding are poorly understood. While a 7-8 bp VirB-binding site has been proposed, it was derived from studies at a single VirB-dependent promoter, icsB. Our previous in vivo studies at a different VirB-dependent promoter, icsP, found that the proposed VirB-binding site was insufficient for regulation. Instead, the required site was found to be organized as a near-perfect inverted repeat separated by a single nucleotide spacer. Thus, the proposed 7-8 bp VirB-binding site needed to be re-evaluated. Here, we engineer and validate a molecular tool to capture protein-DNA binding interactions in vivo. Our data show that a sequence organized as a near-perfect inverted repeat is required for VirB-DNA binding interactions in vivo at both the icsB and icsP promoters. Furthermore, the previously proposed VirB-binding site and multiple sites found as a result of its description (i.e., sites located at the virB, virF, spa15, and virA promoters) are not sufficient for VirB to bind in vivo using this tool. The implications of these findings are discussed