The bile acid receptor TGR5 does not interact with β-arrestins or traffic to endosomes but transmits sustained signals from plasma membrane rafts.

TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid, DCA, taurolithocholic acid, TLCA) and the selective agonists oleanolic acid (OA) and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide (CCDC) stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, assessed by confocal microscopy. DCA, TLCA and OA did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, determined by bioluminescence resonance energy transfer. CCDC stimulated a low level of TGR5 interaction with β-arrestin2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of extracellular signal regulated kinase (ERK1/2). BRET analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists.

Storytelling in song: television music, narrative and allusion in 'The O.C.'

Television’s long-form storytelling has the potential to allow the rippling of music across episodes and seasons in interesting ways. In the integration of narrative, music and meaning found in The O.C. (Fox, FOX 2003-7), popular song’s allusive and referential qualities are drawn upon to particularly televisual ends. At times embracing its ‘disruptive’ presence, at others suturing popular music into narrative, at times doing both at once. With television studies largely lacking theories of music, this chapter draws on film music theory and close textual analysis to analyse some of the programme's music moments in detail. In particular it considers the series-spanning use of Jeff Buckley’s cover of ‘Hallelujah’ (and its subsequent oppressive presence across multiple televisual texts), the end of episode musical montage and the use of recurring song fragments as theme within single episodes. In doing so it highlights music's role in the fragmentation and flow of the television aesthetic and popular song’s structural presence in television narrative. Illustrating the multiplicity of popular song’s use in television, these moments demonstrate song’s ability to provide narrative commentary, yet also make particular use of what Ian Garwood describes as the ability of ‘a non-diegetic song to exceed the emotional range displayed by diegetic characters’ (2003:115), to ‘speak’ for characters or to their feelings, contributing to both teen TV’s melodramatic affect and narrative expression.

Priority research questions for the UK food system

The rise of food security up international political, societal and academic agendas has led to increasing interest in novel means of improving primary food production and reducing waste. There are however, also many ‘post-farm gate’ activities that are critical to food security, including processing, packaging, distributing, retailing, cooking and consuming. These activities all affect a range of important food security elements, notably availability, affordability and other aspects of access, nutrition and safety. Addressing the challenge of universal food security, in the context of a number of other policy goals (e.g. social, economic and environmental sustainability), is of keen interest to a range of UK stakeholders but requires an up-to-date evidence base and continuous innovation. An exercise was therefore conducted, under the auspices of the UK Global Food Security Programme, to identify priority research questions with a focus on the UK food system (though the outcomes may be broadly applicable to other developed nations). Emphasis was placed on incorporating a wide range of perspectives (‘world views’) from different stakeholder groups: policy, private sector, non-governmental organisations, advocacy groups and academia. A total of 456 individuals submitted 820 questions from which 100 were selected by a process of online voting and a three-stage workshop voting exercise. These 100 final questions were sorted into 10 themes and the ‘top’ question for each theme identified by a further voting exercise. This step also allowed four different stakeholder groups to select the top 7–8 questions from their perspectives. Results of these voting exercises are presented. It is clear from the wide range of questions prioritised in this exercise that the different stakeholder groups identified specific research needs on a range of post-farm gate activities and food security outcomes. Evidence needs related to food affordability, nutrition and food safety (all key elements of food security) featured highly in the exercise. While there were some questions relating to climate impacts on production, other important topics for food security (e.g. trade, transport, preference and cultural needs) were not viewed as strongly by the participants.

Massive Science with VO and Grids

There is a growing need for massive computational resources for the analysis of new astronomical datasets. To tackle this problem, we present here our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, AstroGrid) and the computa- tional grid (e.g. TeraGrid, COSMOS etc.). We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of compu- tational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We discuss our planned usages of the VOTechBroker in computing a huge number of n–point correlation functions from the SDSS data and mas- sive model-fitting of millions of CMBfast models to WMAP data. We also discuss other applications including the determination of the XMM Cluster Survey selection function and the construction of new WMAP maps.

Statistical computations with AstroGrid and the Grid

We outline our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, Astro- Grid) and the computational grid. We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of computational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We present our planned usage of the VOTechBroker in computing a huge number of n–point correlation functions from the SDSS, as well as fitting over a million CMBfast models to the WMAP data.

The effect of salmon consumption during pregnancy on maternal and infant faecal microbiota, sIgA and calprotectin

The infant gut microbiota plays an important role in the development of the infant immune and gastrointestinal systems. We investigated whether increased salmon consumption during pregnancy, maternal weight gain during pregnancy or infant mode of feeding alter markers of gut immune defence and inflammation. Women (n = 123) who rarely ate oily fish were randomly assigned to remain on their habitual diet or to consume two 150 g portions of farmed salmon per week from 20 weeks pregnancy until delivery. At 38 weeks gestation the women (n = 75) provided a faecal sample and on days 7, 14, 28 and 84 post-partum, faecal samples were collected from the infants (n = 38). Fluorescence in situ hybridisation was used to determine the composition of the faecal microbiota and ELISA to measure faecal sIgA and calprotectin concentrations. There was no effect of salmon consumption on the faecal microbiota of the mothers or on faecal sIgA and calprotectin concentrations in either mothers or infants. Degree of weight gain influenced the maternal faecal microbiota and mode of infant feeding influenced the infant faecal microbiota. Faecal samples from infants in the salmon group tended to have lower counts of Atopobium cluster compared with those in the control group (P = 0.097). This difference was significant in formula-fed infants (P < 0.05), but not exclusively breast-fed infants. In conclusion, the impact of oily fish consumption during pregnancy on maternal and infant gut microbiota composition is limited, but significant differences were associated with maternal weight gain during pregnancy and infant mode of feeding.

Socially anxious mothers’ narratives to their children, and their relation to child representations and adjustment

Anxious mothers’ parenting, particularly transfer of threat information, has been considered important in their children’s risk for social anxiety disorder (SAnxD), and maternal narratives concerning potential social threat could elucidate this contribution. Maternal narratives to their pre-school 4-5 year-old children, via a picture book about starting school, were assessed in socially anxious (N=73), and non-anxious (N=63) mothers. Child representations of school were assessed via Doll Play (DP). After one school term, mothers (CBCL) and teachers (TRF) reported on child internalizing problems, and child SAnxD was assessed via maternal interview. Relations between these variables, infant behavioral inhibition, and attachment, were examined. Socially anxious mothers showed more negative (higher threat attribution), and less supportive (lower encouragement) narratives, than controls, and their children’s DP representations, SAnxD and CBCL scores were more adverse. High narrative threat predicted child SAnxD; lower encouragement predicted negative child CBCL scores and, particularly for behaviorally inhibited children, TRF scores and DP representations. In securely attached children, CBCL scores and risk for SAnxD were affected by maternal anxiety and threat attributions, respectively. Low encouragement mediated the effects of maternal anxiety on child DP representations, and CBCL scores. Maternal narratives are affected by social anxiety, and contribute to adverse child outcome.

A lagged response to the 11 year solar cycle in observed winter Atlantic/European weather patterns

The surface response to 11 year solar cycle variations is investigated by analyzing the long-term mean sea level pressure and sea surface temperature observations for the period 1870–2010. The analysis reveals a statistically significant 11 year solar signal over Europe, and the North Atlantic provided that the data are lagged by a few years. The delayed signal resembles the positive phase of the North Atlantic Oscillation (NAO) following a solar maximum. The corresponding sea surface temperature response is consistent with this. A similar analysis is performed on long-term climate simulations from a coupled ocean-atmosphere version of the Hadley Centre model that has an extended upper lid so that influences of solar variability via the stratosphere are well resolved. The model reproduces the positive NAO signal over the Atlantic/European sector, but the lag of the surface response is not well reproduced. Possible mechanisms for the lagged nature of the observed response are discussed.

Nonlinear regional warming with increasing CO₂ concentration

When considering adaptation measures and global climate mitigation goals, stakeholders need regional-scale climate projections, including the range of plausible warming rates. To assist these stakeholders, it is important to understand whether some locations may see disproportionately high or low warming from additional forcing above targets such as 2 K (ref. 1). There is a need to narrow uncertainty2 in this nonlinear warming, which requires understanding how climate changes as forcings increase from medium to high levels. However, quantifying and understanding regional nonlinear processes is challenging. Here we show that regional-scale warming can be strongly superlinear to successive CO2 doublings, using five different climate models. Ensemble-mean warming is superlinear over most land locations. Further, the inter-model spread tends to be amplified at higher forcing levels, as nonlinearities grow—especially when considering changes per kelvin of global warming. Regional nonlinearities in surface warming arise from nonlinearities in global-mean radiative balance, the Atlantic meridional overturning circulation, surface snow/ice cover and evapotranspiration. For robust adaptation and mitigation advice, therefore, potentially avoidable climate change (the difference between business-as-usual and mitigation scenarios) and unavoidable climate change (change under strong mitigation scenarios) may need different analysis methods.

Satellite-supported flood forecasting in river networks: a real case study

Satellite-based (e.g., Synthetic Aperture Radar [SAR]) water level observations (WLOs) of the floodplain can be sequentially assimilated into a hydrodynamic model to decrease forecast uncertainty. This has the potential to keep the forecast on track, so providing an Earth Observation (EO) based flood forecast system. However, the operational applicability of such a system for floods developed over river networks requires further testing. One of the promising techniques for assimilation in this field is the family of ensemble Kalman (EnKF) filters. These filters use a limited-size ensemble representation of the forecast error covariance matrix. This representation tends to develop spurious correlations as the forecast-assimilation cycle proceeds, which is a further complication for dealing with floods in either urban areas or river junctions in rural environments. Here we evaluate the assimilation of WLOs obtained from a sequence of real SAR overpasses (the X-band COSMO-Skymed constellation) in a case study. We show that a direct application of a global Ensemble Transform Kalman Filter (ETKF) suffers from filter divergence caused by spurious correlations. However, a spatially-based filter localization provides a substantial moderation in the development of the forecast error covariance matrix, directly improving the forecast and also making it possible to further benefit from a simultaneous online inflow error estimation and correction. Additionally, we propose and evaluate a novel along-network metric for filter localization, which is physically-meaningful for the flood over a network problem. Using this metric, we further evaluate the simultaneous estimation of channel friction and spatially-variable channel bathymetry, for which the filter seems able to converge simultaneously to sensible values. Results also indicate that friction is a second order effect in flood inundation models applied to gradually varied flow in large rivers. The study is not conclusive regarding whether in an operational situation the simultaneous estimation of friction and bathymetry helps the current forecast. Overall, the results indicate the feasibility of stand-alone EO-based operational flood forecasting.

Regional climate impacts of a possible future grand solar minimum

Any reduction in global mean near-surface temperature due to a future decline in solar activity is likely to be a small fraction of projected anthropogenic warming. However, variability in ultraviolet solar irradiance is linked to modulation of the Arctic and North Atlantic Oscillations, suggesting the potential for larger regional surface climate effects. Here, we explore possible impacts through two experiments designed to bracket uncertainty in ultraviolet irradiance in a scenario in which future solar activity decreases to Maunder Minimum-like conditions by 2050. Both experiments show regional structure in the wintertime response, resembling the North Atlantic Oscillation, with enhanced relative cooling over northern Eurasia and the eastern United States. For a high-end decline in solar ultraviolet irradiance, the impact on winter northern European surface temperatures over the late twenty-first century could be a significant fraction of the difference in climate change between plausible AR5 scenarios of greenhouse gas concentrations.

The polychaete worm Nereis diversicolor increases mercury lability and methylation in intertidal mudflats

The polychaete worm Nereis diversicolor engineers its environment by creating oxygenated burrows in anoxic intertidal sediments. The authors carried out a laboratory microcosm experiment to test the impact of polychaete burrowing and feeding activity on the lability and methylation of mercury in sediments from the Bay of Fundy, Canada. The concentration of labile inorganic mercury and methylmercury in burrow walls was elevated compared to worm-free sediments. Mucus secretions and organic detritus in worm burrows increased labile mercury concentrations. Worms decreased sulfide concentrations, which increased Hg bioavailability to sulfate-reducing bacteria and increased methylmercury concentrations in burrow linings. Because the walls of polychaete burrows have a greater interaction with organisms, and the overlying water, the concentrations of mercury and methylmercury they contain is more toxicologically relevant to the base of a coastal food web than bulk samples. The authors recommend that researchers examining Hg in marine environments account for sediment dwelling invertebrate activity to more fully assess mercury bioavailability.

Improving the TanDEM-X Digital Elevation Model for flood modelling using flood extents from Synthetic Aperture Radar images

The topography of many floodplains in the developed world has now been surveyed with high resolution sensors such as airborne LiDAR (Light Detection and Ranging), giving accurate Digital Elevation Models (DEMs) that facilitate accurate flood inundation modelling. This is not always the case for remote rivers in developing countries. However, the accuracy of DEMs produced for modelling studies on such rivers should be enhanced in the near future by the high resolution TanDEM-X WorldDEM. In a parallel development, increasing use is now being made of flood extents derived from high resolution Synthetic Aperture Radar (SAR) images for calibrating, validating and assimilating observations into flood inundation models in order to improve these. This paper discusses an additional use of SAR flood extents, namely to improve the accuracy of the TanDEM-X DEM in the floodplain covered by the flood extents, thereby permanently improving this DEM for future flood modelling and other studies. The method is based on the fact that for larger rivers the water elevation generally changes only slowly along a reach, so that the boundary of the flood extent (the waterline) can be regarded locally as a quasi-contour. As a result, heights of adjacent pixels along a small section of waterline can be regarded as samples with a common population mean. The height of the central pixel in the section can be replaced with the average of these heights, leading to a more accurate estimate. While this will result in a reduction in the height errors along a waterline, the waterline is a linear feature in a two-dimensional space. However, improvements to the DEM heights between adjacent pairs of waterlines can also be made, because DEM heights enclosed by the higher waterline of a pair must be at least no higher than the corrected heights along the higher waterline, whereas DEM heights not enclosed by the lower waterline must in general be no lower than the corrected heights along the lower waterline. In addition, DEM heights between the higher and lower waterlines can also be assigned smaller errors because of the reduced errors on the corrected waterline heights. The method was tested on a section of the TanDEM-X Intermediate DEM (IDEM) covering an 11km reach of the Warwickshire Avon, England. Flood extents from four COSMO-SKyMed images were available at various stages of a flood in November 2012, and a LiDAR DEM was available for validation. In the area covered by the flood extents, the original IDEM heights had a mean difference from the corresponding LiDAR heights of 0.5 m with a standard deviation of 2.0 m, while the corrected heights had a mean difference of 0.3 m with standard deviation 1.2 m. These figures show that significant reductions in IDEM height bias and error can be made using the method, with the corrected error being only 60% of the original. Even if only a single SAR image obtained near the peak of the flood was used, the corrected error was only 66% of the original. The method should also be capable of improving the final TanDEM-X DEM and other DEMs, and may also be of use with data from the SWOT (Surface Water and Ocean Topography) satellite.

Effects of coastal managed retreat on mercury biogeochemistry

We investigated the impact of managed retreat on mercury (Hg) biogeochemistry at a site subject to diffuse contamination with Hg. We collected sediment cores from an area of land behind a dyke one year before and one year after it was intentionally breached. These sediments were compared to those of an adjacent mudflat and a salt marsh. The concentration of total mercury (THg) in the sediment doubled after the dyke was breached due to the deposition of fresh sediment that had a smaller particle size, and higher pH. The concentration of methylmercury (MeHg) was 27% lower in the sediments after the dyke was breached. We conclude that coastal flooding during managed retreat of coastal flood defences at this site has not increased the risk of Hg methylation or bioavailability during the first year. As the sediment becomes vegetated, increased activity of Hg-methylating bacteria may accelerate Hg-methylation rate.