Studying the Human Gut Microbiota in the Trans-Omics Era - Focus on Metagenomics and Metabonomics

The human gut microbiota comprises a diverse microbial consortium closely co-evolved with the human genome and diet. The importance of the gut microbiota in regulating human health and disease has however been largely overlooked due to the inaccessibility of the intestinal habitat, the complexity of the gut microbiota itself and the fact that many of its members resist cultivation and are in fact new to science. However, with the emergence of 16S rRNA molecular tools and "post-genomics" high resolution technologies for examining microorganisms as they occur in nature without the need for prior laboratory culture, this limited view of the gut microbiota is rapidly changing. This review will discuss the application of molecular microbiological tools to study the human gut microbiota in a culture independent manner. Genomics or metagenomics approaches have a tremendous capability to generate compositional data and to measure the metabolic potential encoded by the combined genomes of the gut microbiota. Another post-genomics approach, metabonomics, has the capacity to measure the metabolic kinetic or flux of metabolites through an ecosystem at a particular point in time or over a time course. Metabonomics thus derives data on the function of the gut microbiota in situ and how it responds to different environmental stimuli e.g. substrates like prebiotics, antibiotics and other drugs and in response to disease. Recently these two culture independent, high resolution approaches have been combined into a single "transgenomic" approach which allows correlation of changes in metabolite profiles within human biofluids with microbiota compositional metagenomic data. Such approaches are providing novel insight into the composition, function and evolution of our gut microbiota.

Impact of apoE genotype on oxidative stress, inflammation and disease risk

Although in developing countries an apolipoprotein E4 (apoE4) genotype may offer an evolutionary advantage, as it has been shown to offer protection against certain infectious disease, in Westernised societies it is associated with increased morbidity and mortality, and represents a significant risk factor for cardiovascular disease, late-onset Alzheimer's disease and other chronic disorders. ApoE is an important modulator of many stages of lipoprotein metabolism and traditionally the increased risk was attributed to higher lipid levels in E4 carriers. However, more recent evidence demonstrates the multifunctional nature of the apoE protein and the fact that the impact of genotype on disease risk may be in large part due to an impact on oxidative status or the immunomodulatory/anti-inflammatory properties of apoE. An increasing number of studies in cell lines, targeted replacement rodents and human volunteers indicate higher oxidative stress and a more pro-inflammatory state associated with the F,4 allele. The impact of genotype on the antioxidant and immunomodulatory/anti-inflammatory properties of apoE is the focus of the current review. Furthermore, current information on the impact of environment (diet, exercise, smoking status, alcohol) on apoE genotype-phenotype associations are discussed with a view to identifying particular lifestyle strategies that could be adapted to counteract the 'at-risk' E4 genotype.

Introduction to the DISRUPT postprandial database: subjects, studies and methodologies

Dysregulation of lipid and glucose metabolism in the postprandial state are recognised as important risk factors for the development of cardiovascular disease and type 2 diabetes. Our objective was to create a comprehensive, standardised database of postprandial studies to provide insights into the physiological factors that influence postprandial lipid and glucose responses. Data were collated from subjects (n = 467) taking part in single and sequential meal postprandial studies conducted by researchers at the University of Reading, to form the DISRUPT (DIetary Studies: Reading Unilever Postprandial Trials) database. Subject attributes including age, gender, genotype, menopausal status, body mass index, blood pressure and a fasting biochemical profile, together with postprandial measurements of triacylglycerol (TAG), non-esterified fatty acids, glucose, insulin and TAG-rich lipoprotein composition are recorded. A particular strength of the studies is the frequency of blood sampling, with on average 10-13 blood samples taken during each postprandial assessment, and the fact that identical test meal protocols were used in a number of studies, allowing pooling of data to increase statistical power. The DISRUPT database is the most comprehensive postprandial metabolism database that exists worldwide and preliminary analysis of the pooled sequential meal postprandial dataset has revealed both confirmatory and novel observations with respect to the impact of gender and age on the postprandial TAG response. Further analysis of the dataset using conventional statistical techniques along with integrated mathematical models and clustering analysis will provide a unique opportunity to greatly expand current knowledge of the aetiology of inter-individual variability in postprandial lipid and glucose responses.

Dethroning the myth: cognitive dissociations and innate modularity in Williams syndrome

Despite increasing empirical data to the contrary, it continues to be claimed that morphosyntax and face processing skills of people with Williams syndrome are intact, This purported intactness, which coexists with mental retardation, is used to bolster claims about innately specified, independently functioning modules, as if the atypically developing brain were simply a normal brain with parts intact and parts impaired. Yet this is highly unlikely, given the dynamics of brain development and the fact that in a genetic microdeletion syndrome the brain is developing differently from the moment of conception, throughout embryogenesis, and during postnatal brain growth. In this article, we challenge the intactness assumptions, using evidence from a wide variety of studies of toddlers, children, and adults with Williams syndrome.

Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment

Background Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans. Methods We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment. Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key “punishment” areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect. Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment.

The distribution of interplanetary dust between 0.96 and 1.04 au as inferred from impacts on the STEREO spacecraft observed by the heliospheric imagers

The distribution of dust in the ecliptic plane between 0.96 and 1.04 au has been inferred from impacts on the two Solar Terrestrial Relations Observatory (STEREO) spacecraft through observation of secondary particle trails and unexpected off-points in the heliospheric imager (HI) cameras. This study made use of analysis carried out by members of a distributed web-based citizen science project Solar Stormwatch. A comparison between observations of the brightest particle trails and a survey of fainter trails shows consistent distributions. While there is no obvious correlation between this distribution and the occurrence of individual meteor streams at Earth, there are some broad longitudinal features in these distributions that are also observed in sources of the sporadic meteor population. The different position of the HI instrument on the two STEREO spacecraft leads to each sampling different populations of dust particles. The asymmetry in the number of trails seen by each spacecraft and the fact that there are many more unexpected off-points in the HI-B than in HI-A indicates that the majority of impacts are coming from the apex direction. For impacts causing off-points in the HI-B camera, these dust particles are estimated to have masses in excess of 10−17 kg with radii exceeding 0.1 μm. For off-points observed in the HI-A images, which can only have been caused by particles travelling from the anti-apex direction, the distribution is consistent with that of secondary ‘storm’ trails observed by HI-B, providing evidence that these trails also result from impacts with primary particles from an anti-apex source. Investigating the mass distribution for the off-points of both HI-A and HI-B, it is apparent that the differential mass index of particles from the apex direction (causing off-points in HI-B) is consistently above 2. This indicates that the majority of the mass is within the smaller particles of this population. In contrast, the differential mass index of particles from the anti-apex direction (causing off-points in HI-A) is consistently below 2, indicating that the majority of the mass is to be found in larger particles of this distribution.

Interpolation of Hilbert and Sobolev spaces: quantitative estimates and counterexamples

This paper provides an overview of interpolation of Banach and Hilbert spaces, with a focus on establishing when equivalence of norms is in fact equality of norms in the key results of the theory. (In brief, our conclusion for the Hilbert space case is that, with the right normalisations, all the key results hold with equality of norms.) In the final section we apply the Hilbert space results to the Sobolev spaces Hs(Ω) and tildeHs(Ω), for s in R and an open Ω in R^n. We exhibit examples in one and two dimensions of sets Ω for which these scales of Sobolev spaces are not interpolation scales. In the cases when they are interpolation scales (in particular, if Ω is Lipschitz) we exhibit examples that show that, in general, the interpolation norm does not coincide with the intrinsic Sobolev norm and, in fact, the ratio of these two norms can be arbitrarily large.

Recognition, assessment and treatment of social anxiety disorder: summary of NICE guidance

Social anxiety disorder is one of the most persistent and common of the anxiety disorders, with lifetime prevalence rates in Europe of 6.7% (range 3.9-13.7%).1 It often coexists with depression, substance use disorder, generalised anxiety disorder, panic disorder, and post-traumatic stress disorder.2 It can severely impair a person’s daily functioning by impeding the formation of relationships, reducing quality of life, and negatively affecting performance at work or school. Despite this, and the fact that effective treatments exist, only about half of people with this condition seek treatment, many after waiting 10-15 years.3 Although about 40% of those who develop the condition in childhood or adolescence recover before adulthood,4 for many the disorder persists into adulthood, with the chance of spontaneous recovery then limited compared with other mental health problems. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on recognising, assessing, and treating social anxiety disorder in children, young people, and adults.5

Intertextuality, authenticity, and gonzo selves in Anya Ulinich’s 'Lena Finkle’s Magic Barrel'

This article traces the intertextual relationships between Anya Ulinich’s graphic novel Lena Finkle’s Magic Barrel, Bernard Malamud’s short story ‘The Magic Barrel’ and a number of works by Philip Roth. Through these relationships and her construction of a number of variations on what Miriam Libicki has called a ‘gonzo self’ Ulinich explores the tensions between life and art, fact and fiction, and autobiography and the novel, mediating the aesthetic imperatives of what Roth has called the ‘written world’ and the ethical obligations of the ‘unwritten world’ in order to arrive at an authentic sense of herself as an artist and writer.

Approximation algorithms and hardness results for the clique packing problem

For a fixed family F of graphs, an F-packing in a graph G is a set of pairwise vertex-disjoint subgraphs of G, each isomorphic to an element of F. Finding an F-packing that maximizes the number of covered edges is a natural generalization of the maximum matching problem, which is just F = {K(2)}. In this paper we provide new approximation algorithms and hardness results for the K(r)-packing problem where K(r) = {K(2), K(3,) . . . , K(r)}. We show that already for r = 3 the K(r)-packing problem is APX-complete, and, in fact, we show that it remains so even for graphs with maximum degree 4. On the positive side, we give an approximation algorithm with approximation ratio at most 2 for every fixed r. For r = 3, 4, 5 we obtain better approximations. For r = 3 we obtain a simple 3/2-approximation, achieving a known ratio that follows from a more involved algorithm of Halldorsson. For r = 4, we obtain a (3/2 + epsilon)-approximation, and for r = 5 we obtain a (25/14 + epsilon)-approximation. (C) 2008 Elsevier B.V. All rights reserved.

FT-Raman, FTIR and density functional theory studies of a hydrogen-bonded formamide: pyridine complex

Raman and IR experiments have been carried out on formamide (FA) and pyridine (Py) mixtures at different compositions. The appearance of a new Raman band at 996 cm(-1) (nu(1) region of Py), whose intensity depends on the FA concentration, is assigned to an FA: Py adduct and this result is in excellent agreement with those of other authors who employed noisy light-based coherent Raman scattering spectroscopy (I((2)) CARS). Another band at 1587 cm(-1) (nu(8) region of Py) has been observed for the first time by using Raman and IR spectroscopies. Its intensity shows the same dependence on the FA concentration and this fact allows us to also attribute it to an FA: Py adduct. The good relationship between the Raman and IR data demonstrates the potential of the vibrational spectroscopy for this kind of study. Owing to higher absolute Raman scattering cross section, the nu(1) region of Py has been chosen for the quantitative analysis and a stoichiometry of 1 : 1 FA: Py is reported. The experimental data are very well supported by the density functional theory (OFT) calculation, which was employed for the first time to the present system. Furthermore, the actual investigation shows an excellent agreement with those reported from computational calculations for similar systems. A comparison with our previous studies confirms that: the solvent dielectric constant determines the stoichiometry of a given Lewis acid-base adduct in the infinite dilution limit. Copyright (C) 2009 John Wiley & Sons, Ltd.

Ethical behaviour: the means for creating and maintaining better reputations in arts organisations

Arts organisations, unsure of the level of continued government funding available and confronted with the need ever to improve, are seeking new ideas upon which they can focus. At a time when leadership and governance in arts organisations have changed in line with cultural expectations, how is their ethical stance assessed? How does their ethical stance impact on reputation? The challenge to build a good reputation starts at the top of the organisation; however, traditionally, one type of arts organisation, art museums, has focused on the activities level. In an age of globalisation, economic restructuring and technological change, museums therefore may be seen as a contradiction. Traditionally seen as temples for the muses, today’s museums are being challenged to be ethical for society and to build their reputation. As a solution, proposes a cooperative model of cultural organisational ethics that attempts to provide a framework by which arts organisations can put in place ethical artefacts that enhance organisational reputation, rather than detract from it.

State sovereignty and migration control: the ultimate act of discrimination?

Nations zealously guard their borders and carefully vet migrants. This consigns many people to live in states not of their choice and often diminishes their opportunities and their level of flourishing. In some cases it is the difference between life and death. The practice of imposing migration controls is discriminatory. In fact it is the ultimate form of discrimination: 'super-discrimination.' There is no logical or moral reason why non-nationals of a state should not have the same opportunities and freedoms as nationals in that state. One of the most common forms of discrimination is race - treating a person differently simply because of their place of birth. This is one of the clearest and most repugnant forms of discrimination because the location where a person is born is of course merely a happy or unhappy circumstance over which the individual has no control. An accident of birth should not qualify a person for extra privileges or opportunities. The world is a fairer place if to the maximum extent possible luck is taken out of the process for allocating benefits and burdens - which ought to be distributed on the basis of merit and dessert. This paper examines whether there are sound reasons for restricting the flow of world-wide people movement. The main arguments in favour of this policy, relating to security and national building, are ultimately flawed. This exposes a tragic irony given the great efforts that many Western states - which typically have the strongest migration controls - make to stamp out discrimination at the domestic level, and the vast array of international law anti-discrimination instruments, loudly trumpeted by Western nations. This is hypocrisy nearing its finest. The substratum of sovereign states upon which available international law is built is inherently discriminatory and in fact is probably responsible for more harm as a result of the innately discriminatory immigration policies than results from the cumulative operation of all domestic discrimination. The world should move towards loosening migration controls. This would have an enormous number of humanistic benefits, not the least of which is largely eradicating world hunger and poverty.

Quality-of-life measurement in patients undergoing radiation therapy for head and neck cancer: a Hong Kong experience

The aims of this study are (1) to establish a reliable and valid quality-of-life (QOL) questionnaire for Chinese patients with head and neck (H&N) cancer who are treated with radiation therapy and (2) to evaluate the impact of the immediate side effects of treatment on the QOL of these patients. The 39-item "Quality of Life Radiation Therapy Instrument with Head and Neck Companion Module" (QOL-RTI/H&N) was translated into Chinese. In the reliability evaluation phase (study module 1), the questionnaire was administered twice to 56 H&N cancer patients, 7 days apart, during the second and third week of radiation therapy. In the validity evaluation phase (study module 2), 138 patients completed the QOL-RTI/H&N before starting and at the end of radiation therapy. Sixty-nine of these 138 patients also completed the QOL-RTI/H&N during the second week of their radiation therapy, at the same time as completing the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire. Cronbach alpha coefficients were 0.88 for the general-tool QOL-RTI and 0.90 for the H&N subscale. Test-retest reliability was satisfactory with intraclass correlation coefficients of 0.89 for the general-tool QOL-RTI and 0.75 for the H&N subscale. The instrument can discriminate between patients with stage I or II disease and those with stage III or IV disease (P < .05). Concurrent validity was established by the good agreement with the FACT-H&N (r = 0.86, P < .001). A highly significant deterioration was in the QOL from the baseline to the end of treatment (mean difference for general tool = 1.95, P < .001; mean difference for H&N subscale = 4.85, P < .001). The Chinese QOL-RTI/H&N is a reliable and valid tool for determining the QOL in H&N cancer patients receiving radiation therapy. The immediate side effects of treatment had a significantly negative impact on the patients' QOL. The impact was relatively large for the functional and treatment-site aspects.

Earth bound: the rise and fall of a ground-breaking venture

Earth Sanctuaries Ltd (ESL) intends to offer its entire asset base for sale. ESL's primary objective is to conserve Australia's biodiversity, by breeding and preserving fauna profitably by running sanctuaries, environmental consultancies and related tourist facilities. This "ailing company" is also undergoing a management restructuring and attempting cost reduction. ESL was was one of the first firms to adopt AASB 1037. The implications for the accounting profession are discussed.