Pathogen-host reorganization during Chlamydia invasion revealed by cryo-electron tomography

Invasion of host cells is a key early event during bacterial infection, but the underlying pathogen-host interactions are yet to be fully visualised in three-dimensional detail. We have captured snapshots of the early stages of bacterial-mediated endocytosis in situ by exploiting the small size of chlamydial elementary bodies (EBs) for whole cell cryo-electron tomography. Chlamydiae are obligate intracellular bacteria that infect eukaryotic cells and cause sexually transmitted infections and trachoma, the leading cause of preventable blindness. We demonstrate that Chlamydia trachomatis LGV2 EBs are intrinsically polarised. One pole is characterised by a tubular inner membrane invagination, while the other exhibits asymmetric periplasmic expansion to accommodate an array of type III secretion systems (T3SSs). Strikingly, EBs orient with their T3SS-containing pole facing target cells, enabling the T3SSs to directly contact the cellular plasma membrane. This contact induces enveloping macropinosomes, actin-rich filopodia and phagocytic cups to zipper tightly around the internalising bacteria. Once encapsulated into tight early vacuoles, EB polarity and the T3SSs are lost. Our findings reveal previously undescribed structural transitions in both pathogen and host during the initial steps of chlamydial invasion

Regulatory practice and transport modelling for nitrate pollution in groundwater

This report forms the first deliverable of a project jointly funded by BGS and the Environment Agency to consider the potential for incorporating the outputs from the BGS unsaturated zone travel time work in assessing the risks to water from nitrate. This is to help to inform the nitrate vulnerable zones (NVZs) designation process. In England, the Environment Agency advises Defra on identifying areas for designation as NVZs. Over time, the designation process has developed and become more complex since the first round of designations in 1996. The designation process for groundwater initially used only public supply monitoring data and the associated source catchment area. In December 2000, the European Court of Justice held that the UK had failed to designate sufficient NVZs for the protection of all waters, not just for drinking water sources. This resulted in the development of revised methodologies for the designation of NVZs which separately address surface waters, groundwater and waters at risk of eutrophication. This was implemented in 2002. Further reviews have been carried out in 2008 and 2012 and as a result, modifications and improvements to methods have been made at each designation round. For groundwater the Environment Agency developed a numerical risk assessment procedure that uses a range of risk factors including both nitrate concentration data and nitrate-loading data to assess the risk of nitrate pollution. The loading data is based on farm census returns made to Defra and combined using the NEAP-N methodology developed by ADAS (Lord and Anthony, 2000). The overall risk assessment considers both current observed concentrations and predicted future concentrations as well as current loadings. However, this approach has a number of disadvantages including a lack of a specific term for the time of travel to the water table and emergence of pollutant both into groundwater and to groundwater discharge points that support surface water features. Instead, these issues are considered at the conceptual level in workshops with local EA hydrogeologists. A key question for Defra and the Agency is how long it will take for nitrate concentrations to peak and then stabilise at an acceptable, lower level, in response to existing and future land management control measures. This is most important for soils, for aquifers, for lakes and for groundwater-fed wetland systems that respond less quickly to changes in loading. Groundwater and lake catchment numerical models can provide first-order estimates of likely response times, but can be difficult and costly to set-up for many different situations and are difficult to apply consistently at the national scale. A previous review of nitrate vulnerable zones suggests a range of further needs: • to understand the recent developments in nitrate pollution simulation and particularly the potential to understand/characterise past nitrate loading from changing land management practices and correlate these with observed nitrate concentrations over time; • to evaluate the retention of nitrate in catchments, particularly in the unsaturated zone of soils and aquifers; • to simulate the recent and future anticipated decreases in nitrate loading by sectors within the UK; • to understand the likely time taken for nitrate concentrations to peak and then stabilise at an acceptable, lower level, in response to existing and future control measures. Without evidence of how long it may take systems to recover it is difficult to evaluate the effectiveness of existing measures or decide whether additional measures are necessary. The aim of this project is to investigate the use of new models to inform decision-making on nitrate pollution in groundwater and the potential for incorporating unsaturated zone processes in future NVZ designations. The work described here forms the first task of this project and aims to review NVZ methodology and recent designation experience. As part of this we will: • collate information from the Agency on the recent application of the methodology; • provide case study examples of designation in different time-lag settings and/or where these are not corroborated by water quality

Quantification of nitrate storage in the vadose (unsaturated) zone: a missing component of terrestrial N budgets

National terrestrial nitrogen budgets for many developed countries have been calculated as part of the management of impacts of N on the environment, but these rarely represent the subsurface explicitly. Using estimates of vadose zone travel time and agricultural nitrate loading, we quantify, for the first time, the total mass of nitrate contained in the vadose zone of aquifers in England and Wales. This mass peaked in 2008 at 1400 kt N (800 to >1700 kt N from sensitivity analyses) which is approximately 2.5 to 6 times greater than saturated zone estimates for this period and indicates that the subsurface is an important store of reactive nitrogen. About 70% of the nitrate mass is estimated to be in the Chalk, with the remainder split between the Permo-Triassic sandstones, the Jurassic Oolitic limestones and minor aquifers. Current controls on fertiliser application mean that the vadose zone is now a nitrate source and in 2015 we estimate the net flux from the unsaturated zone to groundwater to be 72 kt N/annum. The mass of nitrate in the vadose zone should be included in future terrestrial nitrogen budgets at national and global scales to improve ecosystem management. This article is protected by copyright. All rights reserved

Modelling the groundwater nitrate legacy

This report details the findings of a project jointly funded by the British Geological Survey (BGS)and Defra through the Environment Agency. The overall aim of the work was to investigate the use of new models to inform decision-making on nitrate pollution in groundwater and the potential for incorporating unsaturated zone processes into the model currently used by the Environment Agency to delineate Nitrate Vulnerable Zones (NVZs). The potential application as supporting evidence for the Water Framework Directive has also been considered as nitrate pollution of groundwater remains the most significant reason for failure of WFD environmental objectives across England. The background to the nitrate legacy in groundwater and to the approaches to NVZ designation is described in Stuart et al. (2016). A series of developments to the BGS Nitrate Time Bomb (NTB) model have been made to improve a number of areas and approaches used in the first version of the model. The improvements included a spatially and temporally distributed nitrate input function, improved unsaturated zone thickness estimation, travel time attribution using a 1:250,000 geological map, estimating nitrate velocity in the unsaturated zone using groundwater recharge and aquifer properties, and introducing nitrate transport processes in low permeability superficial deposits and the saturated zones. These now allow the model to be applied at sub national scale. Using the improved model we have also made the first estimate of the mass of nitrate stored within the unsaturated zone and how this will change over time to improve UK nitrate budget estimates. The new version of the BGS NTB approach was applied in three case studies at different scales which compared its outcomes to the results from other modelling to demonstrate that the model can be benchmarked against the other nitrate modelling approaches: • For a basin-scale model of the Thames Chalk (Howden et al., 2010 & 2011). The NTB model gave comparable results to the original study back to 1925 provided that the same nitrate input function was used. Both models failed to predict nitrate concentrations in the Thames after the mid-1980s. • At the multi-borehole scale in the Permo-Triassic. A similar approach was used to the BGS model in the Eden Valley. This replicated the existing model for the area used by the Environment Agency both in terms of trend assessment and in the lack of dilution available within the aquifer block for blending purposes. • At the single borehole scale in the Chalk of the South Downs. The existing Environment and National Park model constructed by AMEC treated the unsaturated zone very similarly to the NTB model. This model provided a good fit to observed concentrations and confirmed the importance of estimating unsaturated zone delays. The assessment of modelled travel time from different areas of the catchment clearly illustrated the arable areas that would give a relatively rapid respond to changes in nitrate management. To illustrate the potential application of the BGS NTB model to support the Environment Agency’s NVZ designation methodology, areas of England were identified where unsaturated zone lags may be significant and where there is uncertainty in the NVZ designation. A major advantage of the BGS NTB model is that it covers the whole of England (and Wales) in a consistent way. A national overview of areas of designation uncertainty identified large areas of England, in particular the chalk outcrop of southern and eastern England. These were compared to areas with significant unsaturated zone travel time indicating where travel time may be contributing to designation uncertainty. The results suggest that the model may be useful both for identifying currently impacted groundwater which reflects legacy fertilizer application and also where additional designation could be needed as impacts have not yet emerged. Application of the model to support implementation of the WFD has also been considered and whilst no quantitative analysis has yet been carried out there are a number of ways that the model could be of significant benefit. For example, the model could be used to estimate when trend reversal would be expected to occur as a result of measures (at a specific location or across a groundwater body) and the time required to achieve good chemical status (alternative objective setting). A further application could be for scenario testing such as evaluating the effects of different land use/management measures as part of cost benefit analysis or considering the long term impacts of climate change through changing fertiliser use and/or recharge

AgroCycle – developing a circular economy in agriculture

Continuing population growth and increasing consumption are driving global food demand, with agricultural activity expanding to keep pace. The modern agricultural system is wasteful, with Europe generating some 700 million tonnes of agrifood (agricultural and food) waste each year. The Agricultural Centre for Sustainable Energy Systems (ACSES) at Harper Adams University is involved in a major research and innovation project (AgroCycle) on the application of the ‘circular economy’ across the agri-food sector. In the context of the agrifood chain, the ‘circular economy’ aims to reduce waste while also making best use of the ‘wastes’ produced by using economically viable processes and procedures to increase their value . Led by University College Dublin, AgroCycle is a Horizon 2020 collaborative project with 26 partners. AgroCycle will address such opportunities directly by implementation of the ‘circular economy’ across the agri-food sector. The authors will present (a) a summary of the AgroCycle project and (b) the role played by Harper Adams in the project in evaluating the potential for small-scale anaerobic digestion (AD) technology that can be applied on farm to provide local heat, energy and nutrient recovery from mixed agricultural wastes

Psychophysiological measures of driver distraction and workload while intoxicated

The crash risk associated with cell phone use while driving is a contentious issue. Many states are introducing Advanced Traveler Information Systems (ATIS) that may be accessed with cell phones while driving (e.g., 511 Traveler Information Services). In these contexts, there is a need for relevant research to determine the risk of cell phone use. This study compared driver performance while conversing on a hands-free cell phone to conditions of operating common in-vehicle controls (e.g., radio, fan, air conditioning) and alcohol intoxication (BAC 0.08). In addition, the study examined the combined effects of being distracted and being intoxicated given that there may be a higher risk of a crash if the driver engages in a combination of risk factors. During simulated traffic scenarios, resource allocation was assessed through an eventrelated potential (ERP) novelty oddball paradigm. Intoxicated drivers were less attentive to all stimuli and drivers engaged in secondary tasks had weaker responses to unexpected novel sounds in brain regions associated with evaluative processing. Drivers conversing on the cell phone and in-vehicle tasks while sober had lower accuracy during the target tone task than intoxicated drivers not completing any secondary task

Developing Tautai Lavea‘i, a Breast Cancer Patient Nativation Program in American Samoa

This article focuses on development of the psychosocial-cultural components of a breast cancer patient navigation program (PNP) in the medically underserved, albeit culturally-rich Territory of American Samoa. Efforts to reduce cancer morbidity and mortality in American Samoa must necessarily consider the territory’s limited cancer resources and indigenous culture, as well as the individuals at risk for poor health outcomes and premature death. Within this complex set of challenges resides the prospect of health equity and opportunities for advancing service innovations that meaningfully plait native ways of knowing with Western evidencebased practice. Increasing adherence to diagnostic and treatment procedures is of significant concern to the American Samoa Cancer Community Network who initiated this inquiry to assess patients lost to follow-up, describe treatment-seeking influences, and identify cultural preferences for inclusion in a PNP tailored on fa‘aSamoa or the Samoan worldview

The changing trend in nitrate concentrations in major aquifers due to historical nitrate loading from agricultural land across England and Wales from 1925 to 2150

Nitrate is necessary for agricultural productivity, but can cause considerable problems if released into aquatic systems. Agricultural land is the major source of nitrates in UK groundwater. Due to the long time-lag in the groundwater system, it could take decades for leached nitrate from the soil to discharge into freshwaters. However, this nitrate time-lag has rarely been considered in environmental water management. Against this background, this paper presents an approach to modelling groundwater nitrate at the national scale, to simulate the impacts of historical nitrate loading from agricultural land on the evolution of groundwater nitrate concentrations. An additional process-based component was constructed for the saturated zone of significant aquifers in England and Wales. This uses a simple flow model which requires modelled recharge values, together with published aquifer properties and thickness data. A spatially distributed and temporally variable nitrate input function was also introduced. The sensitivity of parameters was analysed using Monte Carlo simulations. The model was calibrated using national nitrate monitoring data. Time series of annual average nitrate concentrations along with annual spatially distributed nitrate concentration maps from 1925 to 2150 were generated for 28 selected aquifer zones. The results show that 16 aquifer zones have an increasing trend in nitrate concentration, while average nitrate concentrations in the remaining 12 are declining. The results are also indicative of the trend in the flux of groundwater nitrate entering rivers through baseflow. The model thus enables the magnitude and timescale of groundwater nitrate response to be factored into source apportionment tools and to be taken into account alongside current planning of land-management options for reducing nitrate losses

The Hopf algebra of Feynman graphs in QED

We report on the Hopf algebraic description of renormalization theory of quantum electrodynamics. The Ward-Takahashi identities are implemented as linear relations on the (commutative) Hopf algebra of Feynman graphs of QED. Compatibility of these relations with the Hopf algebra structure is the mathematical formulation of the physical fact that WT-identities are compatible with renormalization. As a result, the counterterms and the renormalized Feynman amplitudes automatically satisfy the WT-identities, which leads in particular to the well-known identity $Z_1=Z_2$.Comment: 13 pages. Latex, uses feynmp. Minor corrections; to appear in LM