Identifying biological pathways that underlie primordial short stature using network analysis

Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M ‘interactome’, to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure

Optimised processing of faba bean (<i>Vicia faba L.</i>) kernels as a brewing adjunct

Pulse (Fabaceae) grains, such as peas and beans, are derived from crops that are usually cultivated in the absence of mineral nitrogen fertiliser as these crops can obtain their nitrogen requirement naturally from the air via biological nitrogen fixation. Therefore, pulses present a significantly lower greenhouse gas (GHG) footprint than crops demanding nitrogen fertiliser, whilst also offering significant quantities of starch for the brewing and distilling industries. Mitigation of agriculture derived GHG emissions through utilisation of pulses can have a positive environmental impact. To this end, the potential of exploiting dry, dehulled faba bean (Vicia faba L.) kernel flour as an adjunct for beer production was evaluated. The impact of different temperature regimes and commercial enzymes were assessed for their effect on wort: viscosity; run-off rate; primary amino nitrogen content and, fermentability. Faba beans demonstrated insufficient endogenous enzyme capacity for starch conversion and generated a viscous wort. However, using a stepped temperature mashing regime and exogenous enzyme additions, the faba bean wort was comparable in processability and fermentability to that of 100% malted barley wort. The faba based beer and co-product qualities demonstrate the environmental, nutritional and commercial potential of pulses in brewing.</p

Poster Abstract:Deploying a 6LoWPAN, CoAP, low power, wireless sensor network

In order to integrate equipment from different vendors, wireless sensor networks need to become more standardized. Using IP as the basis of low power radio networks, together with application layer standards designed for this purpose is one way forward. This research focuses on implementing and deploying a system using Contiki, 6LoWPAN over an 868 MHz radio network, together with CoAP as a standard application layer protocol. A system was deployed in the Cairngorm mountains in Scotland as an environmental sensor network, measuring streams, temperature profiles in peat and periglacial features. It was found that RPL provided an effective routing algorithm, and that the use of UDP packets with CoAP proved to be an energy efficient application layer. This combination of technologies can be very effective in large area sensor networks

Britain’s highest bog: can we unlock its secrets?

The Glenfeshie Mòine Mhór (Great Moss) is Britain’s highest bog, the largest bog in the Cairngorm Mountains (Scotland) and a water source area for the River Spey. The area was managed primarily for sport hunting for about two centuries, but deer numbers have been heavily reduced in the last decade to allow regeneration of natural woodland and the return to more natural condition of all ecosystems including peatland. However, it may not be realistic to expect spontaneous improvement in peatland condition and ecosystem services provision in the harsh environment of the Mòine Mhór, which retains snow cover for more than half the year and differs floristically from lower-altitude bogs. To understand whether and where management intervention may be required, we need first to understand how the system works at scales ranging from microform to macrotope, and from sub-catchment to whole-system level. Multi-disciplinary condition and process studies (involving various collaborators) are in progress, with a current emphasis on streamflow generation and fluvial carbon loads. This presentation develops two sub-themes. First, ground survey and GIS analysis are used to address the questions: what are the special features of this bog; what is the nature and extent of degradation; and what are the implications for water delivered to the outflow streams? Secondly, a striking feature is the bare peat patches which were favourite resting places for deer on warm, dry summer days. The occurrence of seasonally extreme surface conditions seems a likely factor in preventing their recolonisation by bog plants now. Information about these conditions that cannot readily be accessed through direct observation, originating from temperature sensors and delivered at 60-minute intervals via a low power internet link, is explored in this context. Finally, we discuss aspects of the suitability of our investigation methods for remote and intermittently accessible field sites such as the Mòine Mhór

Utilization of low nitrogen barley for production of distilling quality malt

The potential to utilize low nitrogen barley for production of distilling quality malt was studied. This presents an opportunity to reduce the environmental impact of nitrogen fertilizer applications. Malting barley (cv. Octavia) was grown without the application of inorganic nitrogen fertilizer, to produce grain with a relatively low nitrogen concentration (1.16%, dry weight basis). Following micro-malting trials, dextrinizing units (58 DU) obtained from low nitrogen malt were much higher than a typical specification of 45 DU for malt with a conventional nitrogen concentration (&lt;1.5%). A higher soluble nitrogen ratio (SNR) or index of modification (IoM) of 49 indicated greater modification of the low nitrogen barley, resulting in higher extract released into the wort. Additionally, much lower levels of β-glucan were found in low nitrogen malt wort (64 mg/L compared with over 100 mg/L in wort of conventional nitrogen malt). Low nitrogen malt also produced higher predicted spirit yields following wort fermentation and wash distillation. These findings indicate that lower nitrogen concentration barley can be processed without negatively impacting malt quality for distilling applications. The implication of these findings to help realize more environmentally sustainable production of barley for malting and use in distilling is discussed.</p

Improved Two-level Voltage Source Converter for High-Voltage Direct Current Transmission Systems

this paper presents an improved two-level voltage source converter for dc transmission systems with relatively low rated power and dc operating voltage. Unlike conventional two-level converter, the presented converter employs two distributed cell capacitors per three-phase; thus, do not contribute any current when converter is blocked during dc short circuit fault as in modular multilevel converter case. The use of three-phase cells is proven to be beneficial because the arm currents do not contain 2nd order harmonic currents, and cell capacitors tend to be small as they only experience high-order harmonic current associated with the switching frequency. For the same rated dc link voltage and switching devices, the rated power of the improved two-level converter will be twice that of the conventional two-level converter. Average, switching function and electromagnetic transient simulation models of the improved two-level converter are discussed and validated against detailed switch model. The viability of the improved two-level converter for HVDC applications is examined, considering dc and ac short circuit faults. Besides, reduced complexity of the control and power circuit of the improved two-level converter, it has been found that its transient responses to ac and dc faults are similar to that of the modular multilevel converter

Correction: Substituent interference on supramolecular assembly in urea gelators: synthesis, structure prediction and NMR

Correction for ‘Substituent interference on supramolecular assembly in urea gelators: synthesis, structure prediction and NMR’ by Francesca Piana et al., Soft Matter, 2016, 12, 4034–4043

Substituent interference on supramolecular assembly in urea gelators: synthesis, structure prediction and NMR

Eighteen N-aryl-N?-alkyl urea gelators were synthesised in order to understand the effect of head substituents on gelation performance. Minimum gelation concentration values obtained from gel formation studies were used to rank the compounds and revealed the remarkable performance of 4-methoxyphenyl urea gelator 15 in comparison to 4-nitrophenyl analogue 14, which could not be simply ascribed to substituent effects on the hydrogen bonding capabilities of the urea protons. Crystal structure prediction calculations indicated alternative low energy hydrogen bonding arrangements between the nitro group and urea protons in gelator 14, which were supported experimentally by NMR spectroscopy. As a consequence, it was possible to relate the observed differences to interference of the head substituents with the urea tape motif, disrupting the order of supramolecular packing. The combination of unbiased structure prediction calculations with NMR is proposed as a powerful approach to investigate the supramolecular arrangement in gel fibres and help understand the relationships between molecular structure and gel formation

The Effect of Heat Waves on Mental Health in a Temperate Australian City

Objective: The goal of this study was to identify mental, behavioral, and cognitive disorders that may be triggered or exacerbated during heat waves, predisposing individuals to heat-related morbidity and mortality. Design: Using health outcome data from Adelaide, South Australia, for 1993–2006, we estimated the effect of heat waves on hospital admissions and mortalities attributed to mental, behavioral, and cognitive disorders. We analyzed data using Poisson regression accounting for overdispersion and controlling for season and long-term trend, and we performed threshold analysis using hockey stick regression. Results: Above a threshold of 26.7°C, we observed a positive association between ambient temperature and hospital admissions for mental and behavioral disorders. Compared with non–heat-wave periods, hospital admissions increased by 7.3% during heat waves. Specific illnesses for which admissions increased included organic illnesses, including symptomatic mental disorders ; dementia ; mood (affective) disorders ; neurotic, stress related, and somatoform disorders ; disorders of psychological development ; and senility. Mortalities attributed to mental and behavioral disorders increased during heat waves in the 65- to 74-year age group and in persons with schizophrenia, schizotypal, and delusional disorders. Dementia deaths increased in those up to 65 years of age. Conclusion: Our results suggest that episodes of extreme heat pose a salient risk to the health and well-being of the mentally ill. Relevance to Clinical or Professional Practice: Improvements in the management and care of the mentally ill need to be addressed to avoid an increase in psychiatric morbidity and mortality as heat waves become more frequent.Alana Hansen, Peng Bi, Monika Nitschke, Philip Ryan, Dino Pisaniello and Graeme Tucke

Cost-benefit of outcome adjudication in nine randomised stroke trials

Background: Central adjudication of outcomes is common for randomised trials and should control for differential misclassification. However, few studies have estimated the cost of the adjudication process.Methods: We estimated the cost of adjudicating the primary outcome in nine randomised stroke trials (25,436 participants). The costs included adjudicators’ time, direct payments to adjudicators, and co-ordinating centre costs (e.g. uploading cranial scans and general set-up costs). The number of events corrected after adjudication was our measure of benefit. We calculated cost per corrected event for each trial and in total.Results: The primary outcome in all nine trials was either stroke or a composite that included stroke. In total, the adjudication process associated with this primary outcome cost in excess of £100,000 for a third of the trials (3/9). Mean cost per event corrected by adjudication was £2295.10 (standard deviation: £1482.42).Conclusions: Central adjudication is a time-consuming and potentially costly process. These costs need to be considered when designing a trial and should be evaluated alongside the potential benefits adjudication brings to determine whether they outweigh this expense