An atlas of gene regulatory networks reveals multiple three-gene mechanisms for interpreting morphogen gradients

Although >450 different topologies can achieve the same multicellular patterning function, they can be grouped into six main classes, which operate using different underlying dynamics.Alternative designs for the same functions can therefore split into two types: (a) topology alterations that retain the same underlying dynamics and (b) alterations that utilize a completely different underlying dynamical mechanism.This segregation of networks into distinct dynamical mechanisms can be revealed by the shape of the topology atlas itself.Cell–cell communication is not usually part of the causal mechanism underlying a band-pass response during morphogen interpretation, but it can tune the result or increase robustness

Not Exactly Dragon\u27s Den: Enterprise Challenges can Enhance Psychological Literacy.

Enterprise challenges are teaching activities that allow students to develop and pitch a creative idea in response to a real-life challenge, usually posed by a charitable organisation. Students work in teams to develop their ideas and draw on their subject knowledge, as well as entrepreneurial processes, to articulate their product or service that addresses the challenge. These activities have the potential to enhance psychological literacy as they provide an opportunity to utilise psychological knowledge and skills in novel and unfamiliar ways and urges students to find creative solutions to societal problems. This article presents the rationale and structure to design an enterprise challenge in psychology teaching and uses two case studies to show diverse ways of delivering these teaching events. Evaluation data from six previous challenges show that students self-rate their perceived psychological literacy and entrepreneurial orientation higher after having participated in an enterprise challenge. These teaching activities present a propitious way of enhancing psychological literacy in the curriculum and supporting students on their journey to develop as global citizens

Effects of the neonicotinoid pesticide thiamethoxam at field-realistic levels on microcolonies of Bombus terrestris worker bumble bees

Copyright © 2013 Elsevier. Notice: this is the author’s version of a work that was accepted for publication in Ecotoxicology and Environmental Safety. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Ecotoxicology and Environmental Safety, 2014, Vol. 100, pp. 153-158 at: http://dx.doi.org/10.1016/j.ecoenv.2013.10.027Neonicotinoid pesticides are currently implicated in the decline of wild bee populations. Bumble bees, Bombus spp., are important wild pollinators that are detrimentally affected by ingestion of neonicotinoid residues. To date, imidacloprid has been the major focus of study into the effects of neonicotinoids on bumble bee health, but wild populations are increasingly exposed to alternative neonicotinoids such as thiamethoxam. To investigate whether environmentally realistic levels of thiamethoxam affect bumble bee performance over a realistic exposure period, we exposed queenless microcolonies of Bombus terrestris L. workers to a wide range of dosages up to 98 μg kg−1 in dietary syrup for 17 days. Results showed that bumble bee workers survived fewer days when presented with syrup dosed at 98 μg thiamethoxam kg−1, while production of brood (eggs and larvae) and consumption of syrup and pollen in microcolonies were significantly reduced by thiamethoxam only at the two highest concentrations (39, 98 μg kg−1). In contrast, we found no detectable effect of thiamethoxam at levels typically found in the nectars of treated crops (between 1 and 11 μg kg−1). By comparison with published data, we demonstrate that during an exposure to field-realistic concentrations lasting approximately two weeks, brood production in worker bumble bees is more sensitive to imidacloprid than thiamethoxam. We speculate that differential sensitivity arises because imidacloprid produces a stronger repression of feeding in bumble bees than thiamethoxam, which imposes a greater nutrient limitation on production of brood.Natural Environment Research Council (NERC

The management of children with bronchiolitis in the Australasian hospital setting: Development of a clinical practice guideline

© 2018 The Author(s). Background: Bronchiolitis is the commonest respiratory infection in children less than 12 months and cause of hospitalisation in infants under 6 months of age in Australasia. Unfortunately there is substantial variation in management, despite high levels of supporting evidence. This paper reports on the process, strengths and challenges of the hybrid approach used to develop the first Australasian management guideline relevant to the local population. Method: An adaption of the nine steps recommended by the National Health and Medical Research Council (NHMRC) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology were utilised. Following establishment of the Guideline Development Committee (GDC), we identified the population, intervention, comparator, outcomes and time of interest (PICOt) questions, undertook a systematic literature search and graded the evidence and recommendations using the NHMRC and GRADE processes. Using Nominal Group Techniques (NGT), consensus was sought in formulating the clinical practice recommendations and practice points. Key health professional bodies were consulted to ensure relevance in the Australasian emergency and ward settings. Results: From 33 PICOT questions, clinical recommendations for practice that were deemed relevant to the Australasian population were identified. Specific considerations for the management of Australian and New Zealand indigenous infants in relation to the use of azithromycin and risk factors for more serious illness are included. Using NGT, consensus demonstrated by a median Likert score > 8 for all recommendations was achieved. The guideline presents clinical guidance, followed by the key recommendations and evidence review behind each recommendation. Conclusion: Developing evidence-based clinical guidelines is a complex process with considerable challenges. Challenges included having committee members located over two countries and five time zones, large volume of literature and variation of member's knowledge of grading of evidence and recommendations. The GRADE and NHMRC processes provided a systematic and transparent approach ensuring a final structure including bedside interface, and a descriptive summary of the evidence base and tables for each key statement. Involvement of stakeholders who will ultimately be end-users as members of the GDC provided valuable knowledge. Lessons learnt during this guideline development process provide valuable insight for those planning development of evidence-based guidelines

A spontaneous mutation in MutL-Homolog 3 (HvMLH3) affects synapsis and crossover resolution in the barley desynaptic mutant des10

Although meiosis is evolutionarily conserved, many of the underlying mechanisms show species-specific differences. These are poorly understood in large genome plant species such as barley (Hordeum vulgare) where meiotic recombination is very heavily skewed to the ends of chromosomes. The characterization of mutant lines can help elucidate how recombination is controlled. We used a combination of genetic segregation analysis, cytogenetics, immunocytology and 3D imaging to genetically map and characterize the barley meiotic mutant DESYNAPTIC 10 (des10). We identified a spontaneous exonic deletion in the orthologue of MutL-Homolog 3 (HvMlh3) as the causal lesion. Compared with wild-type, des10 mutants exhibit reduced recombination and fewer chiasmata, resulting in the loss of obligate crossovers and leading to chromosome mis-segregation. Using 3D structured illumination microscopy (3D-SIM), we observed that normal synapsis progression was also disrupted in des10, a phenotype that was not evident with standard confocal microscopy and that has not been reported with Mlh3 knockout mutants in Arabidopsis. Our data provide new insights on the interplay between synapsis and recombination in barley and highlight the need for detailed studies of meiosis in nonmodel species. This study also confirms the importance of early stages of prophase I for the control of recombination in large genome cereals.Isabelle Colas, Malcolm Macaulay, James D. Higgins, Dylan Phillips, Abdellah Barakate ... Robbie Waugh ... et al

The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis

Oriented cell behaviors likely have a more important role in limb bud elongation during development than previously suggested by the “growth-based morphogenesis” hypothesis

p53 Gene Repair with Zinc Finger Nucleases Optimised by Yeast 1-Hybrid and Validated by Solexa Sequencing

The tumor suppressor gene p53 is mutated or deleted in over 50% of human tumors. As functional p53 plays a pivotal role in protecting against cancer development, several strategies for restoring wild-type (wt) p53 function have been investigated. In this study, we applied an approach using gene repair with zinc finger nucleases (ZFNs). We adapted a commercially-available yeast one-hybrid (Y1H) selection kit to allow rapid building and optimization of 4-finger constructs from randomized PCR libraries. We thus generated novel functional zinc finger nucleases against two DNA sites in the human p53 gene, near cancer mutation ‘hotspots’. The ZFNs were first validated using in vitro cleavage assays and in vivo episomal gene repair assays in HEK293T cells. Subsequently, the ZFNs were used to restore wt-p53 status in the SF268 human cancer cell line, via ZFN-induced homologous recombination. The frequency of gene repair and mutation by non-homologous end-joining was then ascertained in several cancer cell lines, using a deep sequencing strategy. Our Y1H system facilitates the generation and optimisation of novel, sequence-specific four- to six-finger peptides, and the p53-specific ZFN described here can be used to mutate or repair p53 in genomic loci