5,625 research outputs found

    Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration.

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    UnlabelledTreatment with streptomycin enhances the growth of human commensal Escherichia coli isolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as "colonization resistance." However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression of Nos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth of E. coli by nitrate respiration in a Nos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance to E. coli colonization after streptomycin treatment.ImportanceOur intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers "colonization resistance" through unknown mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting the Nos2-dependent growth of commensal Escherichia coli by nitrate respiration. These data point to the generation of alternative electron acceptors as a by-product of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such as E. coli

    Global and regional estimates of cancer mortality and incidence by site: I. Application of regional cancer survival model to estimate cancer mortality distribution by site

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    BACKGROUND: The Global Burden of Disease 2000 (GBD 2000) study starts from an analysis of the overall mortality envelope in order to ensure that the cause-specific estimates add to the total all cause mortality by age and sex. For regions where information on the distribution of cancer deaths is not available, a site-specific survival model was developed to estimate the distribution of cancer deaths by site. METHODS: An age-period-cohort model of cancer survival was developed based on data from the Surveillance, Epidemiology, and End Results (SEER). The model was further adjusted for the level of economic development in each region. Combined with the available incidence data, cancer death distributions were estimated and the model estimates were validated against vital registration data from regions other than the United States. RESULTS: Comparison with cancer mortality distribution from vital registration confirmed the validity of this approach. The model also yielded the cancer mortality distribution which is consistent with the estimates based on regional cancer registries. There was a significant variation in relative interval survival across regions, in particular for cancers of bladder, breast, melanoma of the skin, prostate and haematological malignancies. Moderate variations were observed among cancers of colon, rectum, and uterus. Cancers with very poor prognosis such as liver, lung, and pancreas cancers showed very small variations across the regions. CONCLUSIONS: The survival model presented here offers a new approach to the calculation of the distribution of deaths for areas where mortality data are either scarce or unavailable

    A full-scale composite tidal blade fatigue test using single and multiple actuators

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    In order to perform fatigue testing on tidal turbine blades, it is necessary to apply cyclic loads that do not match the blade's natural frequency. This is due to the high stiffness of the blades and the thermal challenges associated with testing composite materials at frequencies typically around 18–20 Hz. To overcome this challenge, auxiliary systems are used to load the blades. However, conventional hydraulic systems commonly used for this purpose are known to be energy-intensive and inefficient. In this work, we present results obtained at the FastBlade fatigue testing facility, which utilises a regenerative digital displacement hydraulic pump system to address these issues. This innovative system has proven to be highly efficient, resulting in up to 75% energy savings compared to standard hydraulic systems. To perform these tests, we first performed a series of Reynolds-Averaged Navier–Stokes (RANS) simulations using on-site water velocity data to determine equivalent target hydrodynamic loads. These target loads are applied to the blades using initially a single contact point and, later, three load contact points. The FastBlade facility showcases an effective approach to fatigue testing during these tests. Throughout the testing process, comprehensive measurements are taken to evaluate the response of the blades and the FastBlade test structure itself. These measurements provide valuable insights into the mechanical behaviour of the blades when a single or multi-actuator setup is used to match the root bending moment and contribute to the refinement of testing practices. Notably, the blades successfully endured the equivalent of 20 years of tides in an accelerated fatigue loading test without experiencing catastrophic failure. The data obtained from these tests will enable the identification of improvements in testing procedures, including control strategies, load introduction methods, instrumentation layout, instrument calibration, and test design. This knowledge will lead to enhanced performance and reliability of the FastBlade facility, further advancing the field of tidal turbine blade testing

    Dynamics of Marine Bacterial Community Diversity of the Coastal Waters of the Reefs, Inlets, and Wastewater Outfalls of Southeast Florida

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    Coastal waters adjacent to populated southeast Florida possess different habitats (reefs, oceanic inlets, sewage outfalls) that may affect the composition of their inherent microbiomes. To determine variation according to site, season, and depth, over the course of 1 year, we characterized the bacterioplankton communities within 38 nearshore seawater samples derived from the Florida Area Coastal Environment (FACE) water quality survey. Six distinct coastal locales were profiled – the Port Everglades and Hillsboro Inlets, Hollywood and Broward wastewater outfalls, and associated reef sites using culture-independent, high-throughput pyrosequencing of the 16S rRNA V4 region. More than 227,000 sequences helped describe longitudinal taxonomic profiles of marine bacteria and archaea. There were 4447 unique operational taxonomic units (OTUs) identified with a mean OTU count of 5986 OTUs across all sites. Bacterial taxa varied significantly by season and by site using weighted and unweighted Unifrac, but depth was only supported by weighted Unifrac, suggesting a change due to presence/absence of certain OTUs. Abundant microbial taxa across all samples included Synechococcus, Pelagibacteraceae, Bacteroidetes, and various Proteobacteria. Unifrac analysis confirmed significant differences at inlet sites relative to reef and outfalls. Inlet-based bacterioplankton significantly differed in greater abundances of Rhodobacteraceae and Cryomorphaceae, and depletion of SAR406 sequences. This study also found higher counts of Firmicutes, Chloroflexi, and wastewater associated SBR1093 bacteria at the outfall and reef sites compared to inlet sites. This study profiles local bacterioplankton populations in a much broader context, beyond culturing and quantitative PCR, and expands upon the work completed by the National Oceanic and Atmospheric Administration FACE program

    Validation of the Symptom Pattern Method for Analyzing Verbal Autopsy Data

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    Chris Murray and colleagues propose and, using data from China, validate a new strategy for analyzing verbal autopsy data that combines the advantages of previous methods

    The relationship between values and knowledge in visioning for landscape management : relevance for a collaborative approach

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    Respecting connections between the diversity of values and forms of knowledge is essential to support a decision-making that fosters relationships between ecosystems and people. However, little theory has been developed for clarifying interactions between values and knowledge, and their relevance for environmental policy. We surfaced the overlooked relationship between values and knowledge by studying individual cognitive and emotional processes during a guided visioning exercise in the context of the multifunctional landscapes of Ostergotland, Sweden. We investigated these cognitive processes using 30 semi-structured interviews and questionnaires organized around three types of relationships: vision. values, vision. knowledge, and especially values. knowledge. The analysis of the relationship between vision and values reveals that all types of values including core human values, relational, and intrinsic values are important in shaping the decision-making context in which landscape management visions arise. The relationship between vision and knowledge uncovers the mix of experiential and theoretical knowledge that informs the decisionmaking context. Interviews unfold three modalities in terms of how values and knowledge relate: i) linked and not necessarily connected (e.g. when individuals perceive a high conflict between their knowledge and their values leading to one construct silencing the other); ii) mutually reinforcing (e.g. when values and knowledge are seen as feeding into one another); and iii) intertwined (e.g. when individuals perceive that values and knowledge can co-exist). We discuss our findings in the context of their relevance for a collaborative decision-making process for balancing consensus and dissensus in multifunctional landscapes.Peer reviewe
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