The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

Chemical Defenses Against Fish Predation in Three Brazilian Octocorals: 11β,12β-Epoxypukalide as a Feeding Deterrent in Phyllogorgia dilatata

The feeding-deterrence properties of crude extracts of three Brazilian octocoral species, Neospongodes atlantica Kükenthal (Alcyonacea, Nephtheidae), Plexaurella regia Castro (Gorgonacea, Plexauridae), and Phyllogorgia dilatata Esper (Gorgonacea, Gorgoniidae), were investigated. All the extracts were incorporated into food strips at the concentrations occurring in the living organisms. Crude extract and its ethyl acetate fraction obtained from P. dilatata collected in Armação dos Búzios (Rio de Janeiro State), when incorporated into artificial diets and tested in the habitat of origin, reduced consumption of food strips by fishes, relative to controls. Crude extracts from two octocoral species collected at the National Marine Park of Abrolhos (Bahia State), N. atlantica and P. regia, had no apparent feeding-deterrence properties; in fact, they seemed to stimulate feeding. Bioassay-guided fractionation of the bioactive P. dilatata crude extract revealed that the deterrent property was restricted to a medium polarity fraction. Field palatability experiments with two pure compounds isolated from this fraction revealed that the furanocembranolide 11,12-epoxypukalide is a potent feeding deterrent produced by P. dilatata against fish. Apparently, furanocembranolides are a particular class of compounds with feeding deterrent properties, protecting some octocorals from potential fish predator species in both tropical and temperate environments.     

Measuring the reach‐scale geomorphic diversity of streams: application to a stream disturbed by a sediment slug

There is increasing evidence that greater physical diversity in a stream leads to a greater diversity of habitats, and hence species. Human impact has reduced the physical diversity within many stream systems. This paper reviews a range of techniques used to measure the physical diversity of a stream reach and specifically examines variability measures of a stream's thalweg, cross‐section and sediment size at the scale of millimetres to metres. Each measure was evaluated against synthetic data with different levels of diversity. From the original thirteen, eight measures were considered appropriate for application to data measured in the field. Creightons Creek (Victoria, Australia) was selected as a test site as it contains areas that are in their original geomorphic condition, as well as sections that have been disturbed by increased bed‐load in the form of a sediment slug. All eight measures showed that the area impacted by the sediment slug was less diverse in terms of its geomorphic variability than the unimpacted reaches. This suggests that massive increases in sediment load to streams will reduce the geomorphic complexity of a stream, and in turn, the diversity of habitat for biological communities. Copyright © 2005 John Wiley & Sons, Ltd.     

Brown Superfund Basic research Program: a multistakeholder partnership addresses real-world problems in contaminated communities

The NIEHS funds several basic and applied research programs, many of which also require research translation or outreach. This paper reports on a project by the Brown University Superfund Basic Research Program (SBRP), in which outreach and research translation teams collaborated with state regulatory agency personnel and community activists on a legislative initiative to mitigate the financial impacts of living in a contaminated community. The Environmentally Compromised Home Ownership (ECHO) program makes home equity loans of up to $25,000 available to qualified applicants. This collaboration provides a case study in community engagement and demonstrates how research translation and outreach activities that are clearly differentiated yet well-integrated can improve a suite of basic and applied research. Although engaging diverse constituencies can be difficult community-engaged translation and outreach have the potential to make research findings more useful to communities, address some of the social impacts of contamination, and empower stakeholders to pursue their individual and collectively held goals for remediation. The NIEHS has recently renewed its commitment to community-engaged research and advocacy, making this an optimal time to reflect on how basic research programs that engage stakeholders through research translation and outreach can add value to the overall research enterprise.     

Terrain-derived measures for basin conservation and restoration planning

Centuries of human development have altered the connectivity of rivers, adversely impacting ecosystems and the services they provide. Significant investments in natural resource projects are made annually with the goal of restoring function to degraded rivers and floodplains and protecting freshwater resources. Yet restoration projects often fall short of their objectives, in part due to the lack of systems-based strategic planning. To evaluate channel-floodplain (dis)connectivity and erosion/incision hazard at the basin scale, we calculate Specific Stream Power (SSP), an estimate of the energy of a river, using a topographically based, low-complexity hydraulic model. Other basin-wide SSP modeling approaches neglect reach-specific geometric information embedded in Digital Elevation Models. Our approach leverages this information to generate reach-specific SSP-flow curves. We extract measures from these curves that describe (dis)connected floodwater storage capacity and erosion hazard at individual design storm flood stages and demonstrate how these measures may be used to identify watershed-scale patterns in connectivity. We show proof-of-concept using 25 reaches in the Mad River watershed in central Vermont and demonstrate that the SSP results have acceptable agreement with a well-calibrated process-based model (2D Hydraulic Engineering Center's River Analysis System) across a broad range of design events. While systems-based planning of regional restoration and conservation activities has been limited, largely due to computational and human resource requirements, measures derived from low-complexity models can provide an overview of reach-scale conditions at the regional level and aid planners in identifying areas for further restoration and/or conservation assessments.     

Effects of organic carbon supply rates on uranium mobility in a previously bioreduced contaminated sediment

Bioreduction-based strategies for remediating uranium (U)-contaminated sediments face the challenge of maintaining the reduced status of U for long times. Because groundwater influxes continuously bring in oxidizing terminal electron acceptors (O2, NO3(-)), it is necessary to continue supplying organic carbon (OC) to maintain the reducing environment after U bioreduction is achieved. We tested the influence of OC supply rates on mobility of previously microbial reduced uranium U(IV) in contaminated sediments. We found that high degrees of U mobilization occurred when OC supply rates were high, and when the sediment still contained abundant Fe(III). Although 900 days with low levels of OC supply minimized U mobilization, the sediment redox potential increased with time as did extractable U(VI) fractions. Molecular analyses of total microbial activity demonstrated a positive correlation with OC supply and analyses of Geobacteraceae activity (RT-qPCR of 16S rRNA) indicated continued activity even when the effluent Fe(II) became undetectable. These data support our hypothesis on the mechanisms responsible for remobilization of U under reducing conditions; that microbial respiration caused increased (bi)carbonate concentration and formation of stable uranyl carbonate complexes, thereby shifted U(IV)/U(VI) equilibrium to more reducing potentials. The data also suggested that low OC concentrations could not sustain the reducing condition of the sediment for much longer time. Bioreduced U(IV) is not sustainable in an oxidizing environment for a very long time.     

Exploratory studies of modeling approaches for hydrogen triple flames

A review of triple flame modeling is first presented, which demonstrates the need for additional work in this area. Building on previous methods described in the literature, a hybrid model that uses a weighted average of one-dimensional premixed and diffusion flamelet reaction rates has been proposed and evaluated for a hydrogen triple flame. Results indicated that some type of progress variable is needed for application of the diffusion flamelet contribution. Weighting the premixed flamelet reaction rate contribution at 100%, it is shown that peak temperatures between the model and a case employing detailed chemistry vary 7.5%, while heat release rate, flame speed, and mass fraction contours agree well.A second model, based on a library of reaction rates built from numerical studies which directly resolve the propagating triple flame has also been tested. Computational time for the baseline case is shown to be reduced by a factor of 3 ½ in comparison to use of detailed chemistry. The role of scalar dissipation rate as a necessary independent variable to the library has also been investigated using simulations with variable mixing layer thicknesses. Overall, it is found that large changes in local mixture fraction gradient cause rather small changes in propagation speed and total heat release rate of the hydrogen triple flame. This implies that such a model may be useful for CFD simulations that do not employ spatial resolution capable of resolving the triple flame itself.     

ENDOW (efficient development of offshore wind farms): modelling wake and boundary layer interactions

While experience gained through the offshore wind energy projects currently operating is valuable, a major uncertainty in estimating power production lies in the prediction of the dynamic links between the atmosphere and wind turbines in offshore regimes. The objective of the ENDOW project was to evaluate, enhance and interface wake and boundary layer models for utilization offshore. The project resulted in a significant advance in the state of the art in both wake and marine boundary layer models, leading to improved prediction of wind speed and turbulence profiles within large offshore wind farms. Use of new databases from existing offshore wind farms and detailed wake profiles collected using sodar provided a unique opportunity to undertake the first comprehensive evaluation of wake models in the offshore environment. The results of wake model performance in different wind speed, stability and roughness conditions relative to observations provided criteria for their improvement. Mesoscale model simulations were used to evaluate the impact of thermal flows, roughness and topography on offshore wind speeds. The model hierarchy developed under ENDOW forms the basis of design tools for use by wind energy developers and turbine manufacturers to optimize power output from offshore wind farms through minimized wake effects and optimal grid connections. The design tools are being built onto existing regional‐scale models and wind farm design software which was developed with EU funding and is in use currently by wind energy developers. Copyright © 2004 John Wiley & Sons, Ltd.     

Rainproof cities in the Netherlands: approaches in Dutch water governance to climate-adaptive urban planning

Abstract

Due to increasingly frequent incidents of pluvial flooding of public spaces and private properties, climate-adaptive building and urban water management are gaining momentum in Dutch water governance. This study assesses the Dutch approach to urban water management by looking at the governance approaches of three of the largest Dutch municipalities: Amsterdam, Rotterdam and Utrecht. By analyzing the municipalities’ governance approaches in a holistic way, paying attention to knowledge, organization and implementation, the research provides good practices in terms of different aspects of resilience as well as lessons regarding setting performance indicators in service levels, clarifying responsibility division, applying binding rules instead of soft policies, and more.