Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors

Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE), which encode the adhesin intimin, a type III secretion system (T3SS) and six effectors, including the essential translocated intimin receptor (Tir). Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages. Here, using a stepwise approach, we generated an EPEC mutant lacking the entire effector genes (EPEC0) and intermediate mutants. We show that EPEC0 contains a functional T3SS. An EPEC mutant expressing intimin but lacking all the LEE effectors but Tir (EPEC1) was able to trigger robust actin polymerization in HeLa cells and mucin-producing intestinal LS174T cells. However, EPEC1 was unable to form A/E lesions on human intestinal in vitro organ cultures (IVOC). Screening the intermediate mutants for genes involved in A/E lesion formation on IVOC revealed that strains lacking non-LEE effector/s have a marginal ability to form A/E lesions. Furthermore, we found that Efa1/LifA proteins are important for A/E lesion formation efficiency in EPEC strains lacking multiple effectors. Taken together, these results demonstrate the intricate relationships between T3SS effectors and the essential role non-LEE effectors play in A/E lesion formation on mucosal surfaces

Modulation of host cell processes by T3SS effectors

Two of the enteric Escherichia coli pathotypes-enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC)-have a conserved type 3 secretion system which is essential for virulence. The T3SS is used to translocate between 25 and 50 bacterial proteins directly into the host cytosol where they manipulate a variety of host cell processes to establish a successful infection. In this chapter, we discuss effectors from EPEC/EHEC in the context of the host proteins and processes that they target-the actin cytoskeleton, small guanosine triphosphatases and innate immune signalling pathways that regulate inflammation and cell death. Many of these translocated proteins have been extensively characterised, which has helped obtain insights into the mechanisms of pathogenesis of these bacteria and also understand the host pathways they target in more detail. With increasing knowledge of the positive and negative regulation of host signalling pathways by different effectors, a future challenge is to investigate how the specific effector repertoire of each strain cooperates over the course of an infection

Climate change impacts on human health over Europe through its effect on air quality

Abstract This review examines the current literature on the effects of future emissions and climate change on particulate matter (PM) and O3 air quality and on the consequent health impacts, with a focus on Europe. There is considerable literature on the effects of climate change on O3 but fewer studies on the effects of climate change on PM concentrations. Under the latest Intergovernmental Panel on Climate Change (IPCC) 5th assessment report (AR5) Representative Concentration Pathways (RCPs), background O3 entering Europe is expected to decrease under most scenarios due to higher water vapour concentrations in a warmer climate. However, under the extreme pathway RCP8.5 higher (more than double) methane (CH4) abundances lead to increases in background O3 that offset the O3 decrease due to climate change especially for the 2100 period. Regionally, in polluted areas with high levels of nitrogen oxides (NOx), elevated surface temperatures and humidities yield increases in surface O3 – termed the O3 climate penalty – especially in southern Europe. The O3 response is larger for metrics that represent the higher end of the O3 distribution, such as daily maximum O3. Future changes in PM concentrations due to climate change are much less certain, although several recent studies also suggest a PM climate penalty due to high temperatures and humidity and reduced precipitation in northern mid-latitude land regions in 2100. A larger number of studies have examined both future climate and emissions changes under the RCP scenarios. Under these pathways the impact of emission changes on air quality out to the 2050s will be larger than that due to climate change, because of large reductions in emissions of O3 and PM pollutant precursor emissions and the more limited climate change response itself. Climate change will also affect climate extreme events such as heatwaves. Air pollution episodes are associated with stagnation events and sometimes heat waves. Air quality during the 2003 heatwave over Europe has been examined in numerous studies and mechanisms for enhancing O3 have been identified. There are few studies on health effects associated with climate change impacts alone on air quality, but these report higher O3-related health burdens in polluted populated regions and greater PM2.5 health burdens in these emission regions. Studies that examine the combined impacts of climate change and anthropogenic emissions change under the RCP scenarios report reductions in global and European premature O3-respiratory related and PM mortalities arising from the large decreases in precursor emissions. Under RCP 8.5 the large increase in CH4 leads to global and European excess O3-respiratory related mortalities in 2100. For future health effects, besides uncertainty in future O3 and particularly PM concentrations, there is also uncertainty in risk estimates such as effect modification by temperature on pollutant-response relationships and potential future adaptation that would alter exposure risk

Modeling regional air quality and climate: Improving organic aerosol and aerosol activation processes in WRF/Chem version 3.7.1

Air quality and climate influence each other through the uncertain processes of aerosol formation and cloud droplet activation. In this study, both processes are improved in the Weather, Research and Forecasting model with Chemistry (WRF/Chem) version 3.7.1. The existing Volatility Basis Set (VBS) treatments for organic aerosol (OA) formation in WRF/Chem are improved by considering the following: the secondary OA (SOA) formation from semi-volatile primary organic aerosol (POA), a semi-empirical formulation for the enthalpy of vaporization of SOA, and functionalization and fragmentation reactions for multiple generations of products from the oxidation of VOCs. Over the continental US, 2-month-long simulations (May to June 2010) are conducted and results are evaluated against surface and aircraft observations during the Nexus of Air Quality and Climate Change (CalNex) campaign. Among all the configurations considered, the best performance is found for the simulation with the 2005 Carbon Bond mechanism (CB05) and the VBS SOA module with semivolatile POA treatment, 25% fragmentation, and the emissions of semi-volatile and intermediate volatile organic compounds being 3 times the original POA emissions. Among the three gas-phase mechanisms (CB05, CB6, and SAPRC07) used, CB05 gives the best performance for surface ozone and PM2.5 concentrations. Differences in SOA predictions are larger for the simulations with different VBS treatments (e.g., nonvolatile POA versus semivolatile POA) compared to the simulations with different gas-phase mechanisms. Compared to the simulation with CB05 and the default SOA module, the simulations with the VBS treatment improve cloud droplet number concentration (CDNC) predictions (normalized mean biases from -40.8% to a range of -34.6 to -27.7%), with large differences between CB05-CB6 and SAPRC07 due to large differences in their OH and HO2 predictions. An advanced aerosol activation parameterization based on the Fountoukis and Nenes (2005) series reduces the large negative CDNC bias associated with the default Abdul Razzak and Ghan (2000) parameterization from -35.4% to a range of -0.8 to 7.1%. However, it increases the errors due to overpredictions of CDNC, mainly over the northeastern US. This work indicates a need to improve other aerosol-cloud-radiation processes in the model, such as the spatial distribution of aerosol optical depth and cloud condensation nuclei, in order to further improve CDNC predictions. © Author(s) 2017

Decadal evaluation of regional climate, air quality, and their interactions over the continental US and their interactions using WRF/Chem version 3.6.1

The Weather Research and Forecasting model with Chemistry (WRF/Chem) v3.6.1 with the Carbon Bond 2005 (CB05) gas-phase mechanism is evaluated for its first decadal application during 2001–2010 using the Representative Concentration Pathway 8.5 (RCP 8.5) emissions to assess its capability and appropriateness for long-term climatological simulations. The initial and boundary conditions are downscaled from the modified Community Earth System Model/Community Atmosphere Model (CESM/CAM5) v1.2.2. The meteorological initial and boundary conditions are bias-corrected using the National Center for Environmental Protection's Final (FNL) Operational Global Analysis data. Climatological evaluations are carried out for meteorological, chemical, and aerosol–cloud–radiation variables against data from surface networks and satellite retrievals. The model performs very well for the 2 m temperature (T2) for the 10-year period, with only a small cold bias of −0.3 °C. Biases in other meteorological variables including relative humidity at 2 m, wind speed at 10 m, and precipitation tend to be site- and season-specific; however, with the exception of T2, consistent annual biases exist for most of the years from 2001 to 2010. Ozone mixing ratios are slightly overpredicted at both urban and rural locations with a normalized mean bias (NMB) of 9.7 % but underpredicted at rural locations with an NMB of −8.8 %. PM_2.5 concentrations are moderately overpredicted with an NMB of 23.3 % at rural sites but slightly underpredicted with an NMB of −10.8 % at urban/suburban sites. In general, the model performs relatively well for chemical and meteorological variables, and not as well for aerosol–cloud–radiation variables. Cloud-aerosol variables including aerosol optical depth, cloud water path, cloud optical thickness, and cloud droplet number concentration are generally underpredicted on average across the continental US. Overpredictions of several cloud variables over the eastern US result in underpredictions of radiation variables (such as net shortwave radiation – GSW – with a mean bias – MB – of −5.7 W m⁻²) and overpredictions of shortwave and longwave cloud forcing (MBs of  ∼  7 to 8 W m⁻²), which are important climate variables. While the current performance is deemed to be acceptable, improvements to the bias-correction method for CESM downscaling and the model parameterizations of cloud dynamics and thermodynamics, as well as aerosol–cloud interactions, can potentially improve model performance for long-term climate simulations

CESM/CAM5 improvement and application: comparison and evaluation of updated CB05_GE and MOZART-4 gas-phase mechanisms and associated impacts on global air quality and climate

Atmospheric chemistry plays a key role in determining the amounts and distributions of oxidants and gaseous precursors that control the formation of secondary gaseous and aerosol pollutants; all of those species can interact with the climate system. To understand the impacts of different gas-phase mechanisms on global air quality and climate predictions, in this work, a comprehensive comparative evaluation is performed using the Community Atmosphere Model (CAM) Version 5 with comprehensive tropospheric and stratospheric chemistry (CAM5-chem) within the Community Earth System Model (CESM) with the two most commonly used gas-phase chemical mechanisms: the 2005 Carbon Bond mechanism with Global Extension (CB05_GE) and the Model of OZone and Related chemical Tracers version 4 (MOZART-4) mechanism with additional updates (MOZART-4x). MOZART-4x and CB05_GE use different approaches to represent volatile organic compounds (VOCs) and different surrogates for secondary organic aerosol (SOA) precursors. MOZART-4x includes a more detailed representation of isoprene chemistry compared to CB05_GE. CB05_GE includes additional oxidation of SO₂ by O₃ over the surface of dust particles, which is not included in MOZART-4x. The results show that the two CAM5-chem simulations with CB05_GE and MOZART-4x predict similar chemical profiles for major gases (e.g., O₃, CO, and NO_<i>x</i>) compared to the aircraft measurements, with generally better agreement for NO_<i>y</i> profiles by CB05_GE than MOZART-4x. The concentrations of SOA at four sites in the continental US (CONUS) and organic carbon (OC) over the IMPROVE sites are well predicted by MOZART-4x (with normalized mean biases (NMBs) of −1.9 and 2.1 %, respectively) but moderately underpredicted by CB05_GE (with NMBs of −23.1 and −20.7 %, respectively). This is mainly due to the higher biogenic emissions and OH levels simulated with MOZART-4x than with CB05_GE. The concentrations of OC over Europe are largely underpredicted by both MOZART-4x and CB05_GE, with NMBs of −73.0 and −75.1 %, respectively, indicating the uncertainties in the emissions of precursors and primary OC and relevant model treatments such as the oxidations of VOCs and SOA formation. Uncertainties in the emissions and convection scheme can contribute to the large bias in the model predictions (e.g., SO₂, CO, black carbon, and aerosol optical depth). The two simulations also have similar cloud/radiative predictions, with a slightly better performance of domain average cloud condensation nuclei (CCN) at supersaturation of 0.5 % by CB05_GE, but slightly better agreement with observed CCN (at supersaturation of 0.2 %) profile over Beijing by MOZART-4x. The two gas-phase mechanisms result in a global average difference of 0.5 W m⁻² in simulated shortwave cloud radiative forcing, with significant differences (e.g., up to 13.6 W m⁻²) over subtropical regions

Development and initial application of the global-through-urban weather research and forecasting model with chemistry (GU-WRF/Chem)

A unified model framework with online-coupled meteorology and chemistry and consistent model treatments across spatial scales is required to realistically simulate chemistry-aerosol-cloud-radiation-precipitation-climate interactions. In this work, a global-through-urban WRF/Chem model (i.e., GU-WRF/Chem) has been developed to provide such a unified model framework to simulate these important interactions across a wide range of spatial scales while reducing uncertainties from the use of offline-coupled model systems with inconsistent model treatments. Evaluation against available observations shows that GU-WRF/Chem is capable of reproducing observations with comparable or superior fidelity than existing mesoscale models. The net effect of atmospheric aerosols is to decrease shortwave and longwave radiation, NO2 photolysis rate, near-surface temperature, wind speed at 10-m, planetary boundary layer height, and precipitation as well as to increase relative humidity at 2-m, aerosol optical depths, column cloud condensation nuclei, cloud optical thickness, and cloud droplet number concentrations at all scales. As expected, such feedbacks also change the abundance and lifetimes of chemical species through changing radiation, atmospheric stability, and the rates of many meteorologically- dependent chemical and microphysical processes. The use of higher resolutions in progressively nested domains from the global to local scale notably improves the model performance of some model predictions (especially for chemical predictions) and also captures spatial variability of aerosol feedbacks that cannot be simulated at a coarser grid resolution. Simulated aerosol, radiation, and cloud properties exhibit small-to-high sensitivity to various nucleation and aerosol activation parameterizations. Representing one of the few unified global-through-urban models, GU-WRF/Chem can be applied to simulate air quality and its interactions with meteorology and climate and to quantify the impact of global change on urban/regional air quality across various spatial scales. © 2012. American Geophysical Union. All Rights Reserved