Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders.

Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 through Stimulation of E2-Ubiquitin Thioester Hydrolysis.

Mouse double minute 2 (MDM2) has a phosphorylation site within a lid motif at Ser17 whose phosphomimetic mutation to Asp17 stimulates MDM2-mediated polyubiquitination of p53. MDM2 lid deletion, but not Asp17 mutation, induced a blue shift in the λmax of intrinsic fluorescence derived from residues in the central domain including Trp235, Trp303, Trp323, and Trp329. This indicates that the Asp17 mutation does not alter the conformation of MDM2 surrounding the tryptophan residues. In addition, Phe235 mutation enhanced MDM2 binding to p53 but did not stimulate its ubiquitination function, thus uncoupling increases in p53 binding from its E3 ubiquitin ligase function. However, the Asp17mutation inMDM2 stimulated its discharge of the UBCH5a-ubiquitin thioester adduct (UBCH5a is a ubiquitin-conjugating enzyme E2D 1 UBC4/5 homolog yeast). This stimulation of ubiquitin discharge fromE2 was independent of the p53 substrate. There are now four known effects of the Asp17 mutation on MDM2: (i) it alters the conformation of the isolated N-terminus as defined by NMR; (ii) it induces increased thermostability of the isolated N-terminal domain; (iii) it stimulates the allosteric interaction ofMDM2 with the DNA-binding domain of p53; and (iv) it stimulates a novel protein–protein interaction with the E2-ubiquitin complex in the absence of substrate p53 that, in turn, increases hydrolysis of theE2-ubiquitin thioester bond. These data also suggest a new strategy to disrupt MDM2 function by targeting the E2-ubiquitin discharge reaction.

Understanding what drives informal learning at work: A resource-based view.

The resource-based view identifies a number of factors that may influence employees’ informal learning. In a cross-sectional survey of 113 German employees in the energy sector, we examined a number of potential predictors of informal learning and a more positive informal learning attitude. The results showed that proactive help-seeking and professional self-efficacy were positive predictors of informal learning. Employees who were older, who enjoyed learning, sought help and were self-efficacious learners had a more positive attitude towards formal learning. Employees who had a more positive attitude about informal learning rated organisational learning provisions as less important, potentially due to being proactive help-seekers. Managers rated organisational learning resources as less important than non-managerial employees. However, managers also reported higher professional self-efficacy. These circumstances may also influence their decision-making regarding the need to provide learning resources to others in the workplace.

Improving the operational skills of the health personnel working in the emergency departments. A useful tool to give concrete answers to EU policies on patients' safety and to create new working opportunities” (VS/2013/0430) finanziato dalla Commissione Europea nell'ambito del programma PROGRESS.

A useful tool to give concrete answers to EU policies on patients' safety and to create new working opportunities (VS / 2013/0430

Road traffic pollution and its effect on the internal environment of buildings.

Indoor and outdoor concentrations of various pollutants were measured in a naturally ventilated building in the West End of Edinburgh during and after the period of the Commonwealth Heads of Government Meeting (CHOGM) to assess the effect upon indoor pollution levels of the closure of some streets in the city. The relationships between indoor and outdoor air qualities in respect of traffic-generated pollutants were studied and the building’s relative attenuation of external pollution levels investigated. The peak concentrations of some of the external pollutants were attenuated by the building and the internal concentrations showed a reduction of up to 30% in some periods. During periods of reduced traffic, the early analyses indicate that the daily mean concentrations of the pollutants were not significantly different from those measured at other times.

An Integrated approach to street canyon pollution modelling.

An integrated method for the prediction of the spatial pollution distribution within a street canyon directly from a microscopic traffic simulation model is outlined. The traffic simulation package Paramics is used to model the flow of vehicles in realistic traffic conditions on a real road network. This produces details of the amount of pollutant produced by each vehicle at any given time. The authors calculate the dispersion of the pollutant using a particle tracking diffusion method which is superimposed on a known velocity and turbulence field. This paper shows how these individual components may be integrated to provide a practical street canyon pollution model. The resulting street canyon pollution model provides isoconcentrations of pollutant within the road topography.

Natural Language Generation enhances human decision-making with uncertain information.

Decision-making is often dependent on uncertain data, e.g. data associated with confidence scores or probabilities. We present a comparison of different informa- tion presentations for uncertain data and, for the first time, measure their effects on human decision-making. We show that the use of Natural Language Genera- tion (NLG) improves decision-making un- der uncertainty, compared to state-of-the- art graphical-based representation meth- ods. In a task-based study with 442 adults, we found that presentations using NLG lead to 24% better decision-making on av- erage than the graphical presentations, and to 44% better decision-making when NLG is combined with graphics. We also show that women achieve significantly better re- sults when presented with NLG output (an 87% increase on average compared to graphical presentations).