Characterization of subsurface media from locations up- and down-gradient of a uranium-contaminated aquifer.

The processing of sediment to accurately characterize the spatially-resolved depth profiles of geophysical and geochemical properties along with signatures of microbial density and activity remains a challenge especially in complex contaminated areas. This study processed cores from two sediment boreholes from background and contaminated core sediments and surrounding groundwater. Fresh core sediments were compared by depth to capture the changes in sediment structure, sediment minerals, biomass, and pore water geochemistry in terms of major and trace elements including pollutants, cations, anions, and organic acids. Soil porewater samples were matched to groundwater level, flow rate, and preferential flows and compared to homogenized groundwater-only samples from neighboring monitoring wells. Groundwater analysis of nearby wells only revealed high sulfate and nitrate concentrations while the same analysis using sediment pore water samples with depth was able to suggest areas high in sulfate- and nitrate-reducing bacteria based on their decreased concentration and production of reduced by-products that could not be seen in the groundwater samples. Positive correlations among porewater content, total organic carbon, trace metals and clay minerals revealed a more complicated relationship among contaminant, sediment texture, groundwater table, and biomass. The fluctuating capillary interface had high concentrations of Fe and Mn-oxides combined with trace elements including U, Th, Sr, Ba, Cu, and Co. This suggests the mobility of potentially hazardous elements, sediment structure, and biogeochemical factors are all linked together to impact microbial communities, emphasizing that solid interfaces play an important role in determining the abundance of bacteria in the sediments

Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis

publishedVersio

Analysis of Hypoxia and Hypoxia-Like States through Metabolite Profiling

In diverse organisms, adaptation to low oxygen (hypoxia) is mediated through complex gene expression changes that can, in part, be mimicked by exposure to metals such as cobalt. Although much is known about the transcriptional response to hypoxia and cobalt, little is known about the all-important cell metabolism effects that trigger these responses.Herein we use a low molecular weight metabolome profiling approach to identify classes of metabolites in yeast cells that are altered as a consequence of hypoxia or cobalt exposures. Key findings on metabolites were followed-up by measuring expression of relevant proteins and enzyme activities. We find that both hypoxia and cobalt result in a loss of essential sterols and unsaturated fatty acids, but the basis for these changes are disparate. While hypoxia can affect a variety of enzymatic steps requiring oxygen and heme, cobalt specifically interferes with diiron-oxo enzymatic steps for sterol synthesis and fatty acid desaturation. In addition to diiron-oxo enzymes, cobalt but not hypoxia results in loss of labile 4Fe-4S dehydratases in the mitochondria, but has no effect on homologous 4Fe-4S dehydratases in the cytosol. Most striking, hypoxia but not cobalt affected cellular pools of amino acids. Amino acids such as aromatics were elevated whereas leucine and methionine, essential to the strain used here, dramatically decreased due to hypoxia induced down-regulation of amino acid permeases.These studies underscore the notion that cobalt targets a specific class of iron proteins and provide the first evidence for hypoxia effects on amino acid regulation. This research illustrates the power of metabolite profiling for uncovering new adaptations to environmental stress

Changes in level of household car ownership: The role of life events and spatial context

Recent longitudinal studies of household car ownership have examined factors associated with increases and decreases in car ownership level. The contribution of this panel data analysis is to identify the predictors of different types of car ownership level change (zero to one car, one to two cars and vice versa) and demonstrate that these are quite different in nature. The study develops a large scale data set (n=19,334), drawing on the first two waves (2009–2011) of the UK Household Longitudinal Study (UKHLS). This has enabled the generation of a comprehensive set of life event and spatial context variables. Changes to composition of households (people arriving and leaving) and to driving licence availability are the strongest predictors of car ownership level changes, followed by employment status and income changes. Households were found to be more likely to relinquish cars in association with an income reduction than they were to acquire cars in association with an income gain. This may be attributed to the economic recession of the time. The effect of having children differs according to car ownership state with it increasing the probability of acquiring a car for non-car owners and increasing the probability of relinquishing a car for two car owners. Sensitivity to spatial context is demonstrated by poorer access to public transport predicting higher probability of a non-car owning household acquiring a car and lower probability of a one-car owning household relinquishing a car. While previous panel studies have had to rely on comparatively small samples, the large scale nature of the UKHLS has provided robust and comprehensive evidence of the factors that determine different car ownership level changes

Deep Sequencing Whole Transcriptome Exploration of the σE Regulon in Neisseria meningitidis

Bacteria live in an ever-changing environment and must alter protein expression promptly to adapt to these changes and survive. Specific response genes that are regulated by a subset of alternative σ70-like transcription factors have evolved in order to respond to this changing environment. Recently, we have described the existence of a σE regulon including the anti-σ-factor MseR in the obligate human bacterial pathogen Neisseria meningitidis. To unravel the complete σE regulon in N. meningitidis, we sequenced total RNA transcriptional content of wild type meningococci and compared it with that of mseR mutant cells (ΔmseR) in which σE is highly expressed. Eleven coding genes and one non-coding gene were found to be differentially expressed between H44/76 wildtype and H44/76ΔmseR cells. Five of the 6 genes of the σE operon, msrA/msrB, and the gene encoding a pepSY-associated TM helix family protein showed enhanced transcription, whilst aniA encoding a nitrite reductase and nspA encoding the vaccine candidate Neisserial surface protein A showed decreased transcription. Analysis of differential expression in IGRs showed enhanced transcription of a non-coding RNA molecule, identifying a σE dependent small non-coding RNA. Together this constitutes the first complete exploration of an alternative σ-factor regulon in N. meningitidis. The results direct to a relatively small regulon indicative for a strictly defined response consistent with a relatively stable niche, the human throat, where N. meningitidis resides

Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative

Pelvic exenteration is a complex operation performed for locally advanced and recurrent pelvic cancers. The goal of surgery is to achieve clear margins, therefore identifying adjacent or involved organs, bone, muscle, nerves and/or vascular structures that may need resection. While these extensive resections are potentially curative, they can be associated with substantial morbidity. Recently, there has been a move to centralize care to specialized units, as this facilitates better multi-disciplinary care input. Advancements in pelvic oncology and surgical innovation have redefined the boundaries of pelvic exenterative surgery. Combined with improved neoadjuvant therapies, advances in diagnostics, and better reconstructive techniques have provided quicker recovery and better quality of life outcomes, with improved survival This article provides highlights of the current management of advanced pelvic cancers in terms of surgical strategy and potential future developments

Ornithodoros moubata complement inhibitor (OmCI)—A novel and efficient C5 inhibitor in the pig

Complement and CD14/TLR4 are two important upstream components of innate immunity. Inflammation induced by these danger sensors may be excessive and detrimental in conditions such as sepsis. Inhibition of complement or CD14/TLR4 differentially attenuate experimentally induced inflammation. Combined inhibition has a more pronounced effect, almost abolishing Escherichia coli (E. coli)-induced cytokine release, oxidative burst and expression of the cell-surface marker CD11b in vitro in human studies. We recently showed that an anti-CD14 antibody attenuated proinflammatory cytokines, granulocyte activation and hypercoagulation in E. coli-induced sepsis in vivo in pigs. Combination with a complement inhibitor might enhance the antiinflammatory effect. The aim of the present study was to explore the efficacy in pig of the Ornithodoros moubata complement inhibitor (OmCI) that specifically binds C5 and prevents release of C5a and formation of the terminal complement complex (TCC). Porcine serum and whole blood anticoagulated with lepuridin was incubated with increasing doses of OmCI and activated with E. coli. A pilot study was additionally conducted in vivo in pigs, whereby sepsis was induced by E. coli and the effect of OmCI on the inflammatory response was investigated. Inhibition of complement activity, as evaluated by functional assay of the three initial pathways, was complete at a dose of 2.5 μg OmCI/mL in vitro and 1 mg OmCI/kg in vivo. TCC formation induced by E. coli was abolished in vitro at 5 μg OmCI/mL whole blood, while expression of wCD11R3, the pig analog of human CD11b, was reduced by more than 50% at 5 μg OmCI/mL whole blood. In vivo, OmCI attenuated the increase in IL-8 and TNF-α, and partly protected against the fall in leukocytes seen in the sepsis control group. In conclusion, OmCI efficiently inhibited pig complement activation, showed additional anti-inflammatory effects and is a promising candidate inhibitor for further sepsis studies in vivo