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

Variational bridge constructs for approximate Gaussian process regression

This paper introduces a method to approximate Gaussian process regression by representing the problem as a stochastic differential equation and using variational inference to approximate solutions. The approximations are compared with full GP regression and generated paths are demonstrated to be indistinguishable from GP samples. We show that the approach extends easily to non-linear dynamics and discuss extensions to which the approach can be easily applied

Summary report on the geology of the proposed HS2 Route (3) in the Chesham and Amersham Constituency

This brief open-file report summarises the information available from the British Geological Survey (BGS), a component body of the Natural Environment Research Council (NERC), on the geology, hydrogeology and potential geological hazards of the proposed HS2 Route 3 within the Chesham and Amersham Constituency, and surrounding areas. The report summarises the geology and hydrogeology of the district and highlights geological and hydrogeological considerations that may need further investigation along the route. Further review and analysis of existing data and possible field investigation would be required to confirm details of the local geology. The report was requested by Mrs Cheryl Gillan MP following a meeting with Dr Martin Smith, Head of Geology & Landscapes programme, on Monday 16th May 2011 at the offices of the Secretary of State for Wales in Whitehall

Variational bridge constructs for grey box modelling with Gaussian processes

Latent force models are systems whereby there is a mechanistic model describing the dynamics of the system state, with some unknown forcing term that is approximated with a Gaussian process. If such dynamics are non-linear, it can be difficult to estimate the posterior state and forcing term jointly, particularly when there are system parameters that also need estimating. This paper uses black-box variational inference to jointly estimate the posterior, designing a multivariate extension to local inverse autoregressive flows as a flexible approximater of the system. We compare estimates on systems where the posterior is known, demonstrating the effectiveness of the approximation, and apply to problems with non-linear dynamics, multi-output systems and models with non-Gaussian likelihoods

Ethane-beta-Sultam Modifies the Activation of the Innate Immune System Induced by Intermittent Ethanol Administration in Female Adolescent Rats

Intermittent ethanol abuse or ‘binge drinking’ during adolescence induces neuronal damage, which may be associated with cognitive dysfunction. To investigate the neurochemical processes involved, rats were administered either 1 g/kg or 2 g/kg ethanol in a ‘binge drinking’ regime. After only 3 weeks, significant activation of phagocytic cells in the peripheral (alveolar macrophages) and the hippocampal brain region (microglia cells) was present,as exemplified by increases in the release of pro-inflammatory cytokines in the macrophages and of iNOS in the microglia. This was associated with neuronal loss in the hippocampus CA1 region. Daily supplementation with a taurine prodrug, ethane-β-sultam, 0.028 g/kg, during the intermittent ethanol loading regime, supressed the release of the pro-inflammatory cytokines and of reactive nitrogen species, as well as neuronal loss, particularly in the rats administered the lower dose of ethanol, 1 g/kg. Plasma, macrophage and hippocampal taurine levels increased marginally after ethane-β-sultam supplementation. The ‘binge drinking’ ethanol rats administered 1 g/kg ethanol showed increased latencies to those of the control rats in their acquisition of spacial navigation in the Morris Water Maze, which was normalised to that of the controls values after ethane-β-sultam administration. Such results confirm that the administration of ethane-β-sultam to binge drinking rats reduces neuroinflammation in both the periphery and the brain, suppresses neuronal loss, and improved working memory of rats in a water maze study

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

Collective T=0 pairing in N=Z nuclei? Pairing vibrations around 56Ni revisited

We present a new analysis of the pairing vibrations around 56Ni, with emphasis on odd-odd nuclei. This analysis of the experimental excitation energies is based on the subtraction of average properties that include the full symmetry energy together with volume, surface and Coulomb terms. The results clearly indicate a collective behavior of the isovector pairing vibrations and do not support any appreciable collectivity in the isoscalar channel.Comment: RevTeX, two-column, 5 pages, 4 figure

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

N=1 super-Chern-Simons coupled to parity-preserving matter from Atiyah-Ward space-time

In this letter, we present the Parkes-Siegel formulation for the massive Abelian $N$$=$$1$ super-{\QED} coupled to a self-dual supermultiplet, by introducing a chiral multiplier superfield. We show that after carrying out a suitable dimensional reduction from ($2$$+$$2$) to ($1$$+$$2$) dimensions, and performing some necessary truncations, the simple supersymmetric extension of the ${\tau}_{3}$QED$_{1+2}$ coupled to a Chern-Simons term naturally comes out.Comment: 7 pages, latex, no figure