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Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn’s disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles. Inflammatory bowel disease (IBD) has been linked to host-microbiota interactions. Here, the authors investigate mucosa-associated microbiota using endoscopically-targeted biopsies from inflamed and non-inflamed colon in patients with Crohn’s disease and ulcerative colitis, finding associations with inflammation and host epigenomic alterations.

We examine the impact of the first phase of the Bank of England's quantitative easing (QE) programme during March 2009—January 2010 on the UK government bond (gilt) market, using high-frequency, disaggregated data on individual gilts. We find that: QE announcements took varying amounts of time to get incorporated into market prices and had significant effects on the shape of the term structure; the Bank's reverse auctions were initially associated with additional yield reductions; and, allowing for fiscal news and the changing macroeconomic outlook, QE appears to have had persistent effects on gilt yields.

The operation of the portfolio balance channel has been emphasized by monetary policymakers as a key channel through which quantitative easing (QE) policies work. We assess whether the investment behavior of insurance companies and pension funds in the United Kingdom during the global financial crisis was consistent with such an effect by analyzing both sectoral and institution-level data. Our results suggest QE led to institutional investors shifting their portfolios away from government bonds toward corporate bonds but did not lead to a shift into equities.

BackgroundDistinct sets of microbes contribute to colorectal cancer (CRC) initiation and progression. Some occur due to the evolving intestinal environment but may not contribute to disease. In contrast, others may play an important role at particular times during the tumorigenic process. Here, we describe changes in the microbiota and host over the course of azoxymethane (AOM)-induced tumorigenesis.MethodsMice were administered AOM or PBS and were euthanised 8, 12, 24 and 48 weeks later. Samples were analysed using 16S rRNA gene sequencing, UPLC-MS and qRT-PCR.ResultsThe microbiota and bile acid profile showed distinct changes at each timepoint. The inflammatory response became apparent at weeks 12 and 24. Moreover, significant correlations between individual taxa, cytokines and bile acids were detected. One co-abundance group (CAG) differed significantly between PBS- and AOM-treated mice at week 24. Correlation analysis also revealed significant associations between CAGs, bile acids and the bile acid transporter, ASBT. Aberrant crypt foci and adenomas were first detectable at weeks 24 and 48, respectively.ConclusionThe observed changes precede host hyperplastic transformation and may represent early therapeutic targets for the prevention or management of CRC at specific timepoints in the tumorigenic process.

During the recent financial crisis the Bank of England, like many other central banks, loosened monetary policy using both conventional and unconventional measures. The main unconventional measure used by the Bank was the policy of asset purchases—mainly of government bonds—financed by the creation of central bank money, so-called quantitative easing (QE). During March 2009 to January 2010 and October 2011 to May 2012, the Bank completed asset purchases of £ 200 billion (QE1) and £ 125 billion (QE2), respectively. The decision to resume purchases in July 2012 will mean that by November 2012 the Bank will have bought a total of £ 375 billion of assets, equivalent to around 25 per cent of annual GDP. This article reviews the transmission channels through which asset purchases operate and assesses the impact of QE1 and QE2 on financial markets.

A new entomopathogenic nematode species from Australia, Heterorhabditis gerrardi n. sp. (Nematoda: Heterorhabditidae) is described. Morphological and molecular studies together with cross-hybridization tests indicated that this nematode represents a new undescribed species, closely related to members in the ‘indica-group’. However, the new species can be distinguished from other species in this genus by a combination of several qualitative and quantitative morphological traits. Key diagnostic features include: body size and excretory pore position of the third-stage infective juveniles; male bursa with a reduction of bursal rays, usually affecting the terminal set of papillae, with symmetrical or asymmetrical loss of one or two pairs; vulva of hermaphrodites more anteriorly located than in other species in the indica-group (V% average: 43), with non-protruding or slightly protruding lips, and longer tail length (average: 106 μm). The new species can be further characterized by molecular traits of sequence data from the internal transcribed spacer (ITS) region of ribosomal DNA. Additionally, the bacterial symbiont of this new species, Photorhabdus asymbiotica Kingscliff strain, was phenotypically characterized and compared with other P. asymbiotica strains. The Kingscliff strain revealed many characters not present in other strains of this species. We hypothesize that the newly found traits may contribute to the maintenance of this mutualistic association of the bacterium with its nematode host.

Statins are widely prescribed cholesterol-lowering medications and act through inhibition of the human enzyme 3-methylglutaryl coenzyme A reductase (HMG-R) which produces mevalonate (MVAL), a key substrate for cholesterol biosynthesis. Some important microbial species also express an isoform of HMG-R; however, the nature of the interaction between statins and bacteria is currently unclear and studies would benefit from protocols to quantify MVAL in complex microbial environments. The objective of this study was to develop a protocol for the analytical quantification of MVAL in bacterial systems and to utilise this approach to analyse the effects of Rosuvastatin (RSV) on bacterial MVAL formation. To determine the effective concentration range of RSV, we examined the dose-dependent inhibition of growth in the HMG-R + bacterial pathogens Listeria monocytogenes , Staphylococcus aureus and Enterococcus faecium at various concentrations of pure RSV. Growth inhibition generally correlated with a reduction in bacterial MVAL levels, particularly in culture supernatants at high RSV concentrations, as determined using our ultra-performance liquid chromatography mass spectrometry protocol. This work therefore outlines a refined protocol for the analysis of MVAL in microbial cultures and provides evidence for statin-mediated inhibition of bacterial HMG-R. Furthermore, we show that MVAL is readily transported and secreted from bacterial cells into the growth media.

Providing a favourable and comfortable living environment for the population is one of the main tasks of optimising urban development. The level of comfort is formed with the territorial interaction of natural and socio-economic conditions for the region’s development. This interaction is especially manifested in large industrial centres, characterised by a strong negative anthropogenic impact on the environment. The territorial assessment of the comfort of the living environment involves a comprehensive spatial analysis of the population comfort main factors. The purpose of this work is a spatial analysis of the population living comfort of one of the most industrialised regions not only Ukraine, but also Europe – the city of Kryvyi Rih. Functional zoning was carried out using GIS Map Info with the allocation of the following areas: residential zones, public and business zones, industry and warehouse zones, resort and recreation zones. The distribution of the residential area according to the level of comfort of the population living environment was carried out according to 3 groups of factors: transport accessibility, development of social infrastructure and ecological state. The first group characterises the habitat from the point of view of the city’s provision with transport routes for various types of public transport. The second group characterises the population’s social conditions, namely the number of educational, cultural and medical institutions. The third block includes the ecological state of the territory according to the criterion of atmospheric pollution. The method of scoring made it possible to compare individual parts of the area under study across the entire range of natural, ecological and social population comfort. The combination of indicators of the totality of all three groups factors was carried out using overlay operations. As a result of the research, a map characterising the spatial differentiation of indicators of the living comfort in the city of Kryvyi Rih has been created. The specialisation of the city as a large industrial centre has determined the leading role of the group of environmental indicators in the situational model of the living environment comfort in the region.

We used a randomized clinical trial to investigate the interaction of two patient personality characteristics (quality of object relations [QOR] and psychological mindedness [PM]) with two forms of time-limited, short-term group therapy (interpretive and supportive) for 139 psychiatric outpatients with complicated grief. Findings differed depending on the outcome variable (e.g., grief symptoms, general symptoms) and the statistical criterion (e.g., statistical significance, clinical significance, magnitude of effect). Patients in both therapies improved. For grief symptoms, a significant interaction effect was found for QOR. High-QOR patients improved more in interpretive therapy and low-QOR patients improved more in supportive therapy. A main effect was found for PM. High-PM patients improved more in both therapies. For general symptoms, clinical significance favored interpretive therapy over supportive therapy. Clinical implications concerning patient-treatment matching are discussed.