Pushing the boundaries: integration of multi-source digital elevation model data for seamless geological mapping of the UK's coastal zone

Recent advances in marine acoustic survey and land-based topographic monitoring technologies have resulted in increasingly cost-effective data acquisition in coastal areas. The DEFRA-funded National Network of Regional Coastal Monitoring Programmes of England are, for example, utilising swath bathymetry and airborne light detection and ranging (LiDAR) technology more routinely to survey the coastal zone around the coastline of England. The demand for data processing, visualisation and interpretation techniques to keep pace with such advances in data acquisition is clear. This study discusses collection and processing techniques for such data on the south coast of Dorset, England, which have enabled the production of a seamless, high spatial resolution digital elevation model across the coastal zone. Case studies demonstrate how this elevation model can be viewed and analysed using state-of-the-art digital techniques to allow geological mapping to be extended from onshore to offshore in unprecedented detail, effectively eliminating what is known as the ‘White Ribbon’ for coastal geological mapping. The potential for rolling out such techniques for wider surveying programmes across many environmental disciplines is significant, which could contribute towards improving the multi-disciplinary scientific evidence base in the complex coastal zone

Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo

Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX “coating” also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting

Interpreting monitoring data for shoreline and geohazard mapping

The demand for marine-related spatial information has become increasingly apparent in recent years at a European and national scale, due to the increased pressures on the sea-floor environments and marine resources of UK territorial waters. The advent of economically viable swath bathymetry data acquisition in the coastal zone and effective collaborative partnerships between the Channel Coastal Observatory, Maritime and Coastguard Agency, UK Hydrographic Office, British Geological Survey and academic institutions, have opened up new opportunities to produce a robust scientific evidence base to inform integrated coastal zone management objectives and contribute to wider scientific initiatives. Interpretation of high-quality bathymetric data, acoustic backscatter and ground-truthing data allows zones of exposed bedrock, rock outcrops and pinnacles to be identified, along with areas of mobility or stability of surficial sediments. Temporal and spatial analyses of coastal and marine monitoring datasets also contribute to improved understanding of interactions between natural coastal process and coastal-defence and beach-management operations. Furthermore, developments in three-dimensional mapping techniques and visualisation technologies have enabled seamless high-resolution coastal geology maps to be re-interpreted and extended offshore, providing a more complete picture of the baseline geology, physical properties, structure and geohazards in the coastal and nearshore zone. The full paper details the methodology developed to produce a range of indicative marine mapping layers, and presents examples from eastern and southern England where marine-related spatial data has contributed to the multi-disciplinary scientific evidence base to inform development of UK marine policy and planning, coastal management and coastal zone geological mappin

Targeted nanoparticle binding & detection in petroleum hydrocarbon impacted porous media

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.chemosphere.2018.10.046 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Targeted nanoparticle binding has become a core feature of experimental pharmaceutical product design which enables more efficient payload delivery and enhances medical imaging by accumulating nanoparticles in specific tissues. Environmental remediation and geophysical monitoring encounter similar challenges which may be addressed in part by the adoption of targeted nanoparticle binding strategies. This study illustrates that engineered nanoparticles can bind to crude oil-impacted silica sand, a selective adsorption driven by active targeting based on an amphiphilic polymer coating. This coating strategy resulted in 2 mg/kg attachment to clean silica sand compared to 8 mg/kg attachment to oil-impacted silica sand. It was also shown that modifying the surface coating influenced the binding behaviour of the engineered nanoparticles – more hydrophobic polymers resulted in increased binding. Successful targeting of Pluronic-coated iron oxide nanoparticles to a crude oil and silica sand mixture was demonstrated through a combined quantitative Orbital Emission Spectroscopy mass analysis supported by Vibrating Scanning Magnetometer magnetometry, and a qualitative X-ray micro-computed tomography (CT) visualization approach. These non-destructive characterization techniques facilitated efficient analysis of nanoparticles in porous medium samples with minimal sample preparation, and in the case of X-Ray CT, illustrated how targeted nanoparticle binding may be used to produce 3-D images of contaminated porous media. This work demonstrated successful implementation of nanoparticle targeted binding toward viscous LNAPL such as crude oil in the presence of a porous medium, a step which opens the door to successful application of targeted delivery technology in environmental remediation and monitoring.Natural Sciences and Engineering Research Council of Canad

Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein

Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators of innate immune signalling. VACV protein N1 is an intracellular homodimer that contributes to virus virulence and was reported to inhibit nuclear factor (NF)-κB signalling. However, analysis of NF-κB signalling in cells infected with recombinant viruses with or without the N1L gene showed no difference in NF-κB-dependent gene expression. Given that N1 promotes virus virulence, other possible functions of N1 were investigated and this revealed that N1 is an inhibitor of apoptosis in cells transfected with the N1L gene and in the context of VACV infection. In support of this finding virally expressed N1 co-precipitated with endogenous pro-apoptotic Bcl-2 proteins Bid, Bad and Bax as well as with Bad and Bax expressed by transfection. In addition, the crystal structure of N1 was solved to 2.9 Å resolution (0.29 nm). Remarkably, although N1 shows no sequence similarity to cellular proteins, its three-dimensional structure closely resembles Bcl-xL and other members of the Bcl-2 protein family. The structure also reveals that N1 has a constitutively open surface groove similar to the grooves of other anti-apoptotic Bcl-2 proteins, which bind the BH3 motifs of pro-apoptotic Bcl-2 family members. Molecular modelling of BH3 peptides into the N1 surface groove, together with analysis of their physico-chemical properties, suggests a mechanism for the specificity of peptide recognition. This study illustrates the importance of the evolutionary conservation of structure, rather than sequence, in protein function and reveals a novel anti-apoptotic protein from orthopoxviruses