Does ursodeoxycholic acid change the proliferation of the colorectal mucosa? A randomized, placebo-controlled study

Background: In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans. Methods: Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography. Results: The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%, 14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 mumol/l, 0.9-1.8) than in group B (0.7 mumol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups. Conclusions: In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation. Copyright (C) 2003 S. Karger AG, Basel

Introduction: the politicisation of permanent crisis in Europe

Taking stock of the numerous crises that have confronted Europe in the last decade, this special issue investigates the relationship between crisis and the politicisation of the process of European integration. It draws attention in so doing to the epistemic construction of crises. In this conceptual overview, we discuss first, how crises are framed and reframed in relation to the constitutive elements of a political community. Second, we explore the extent to which, and how, the emergence of different understandings of crisis and the ensuing frame competition between them contribute to such politicisation. By elucidating the link between the politics of a now seemingly permanent crisis in Europe and the politicisation of European integration, this introduction sets the framework informing all of the articles in this special issue

The genetic architecture of petal number in Cardamine hirsuta

International audienceInvariant petal number is a characteristic of most flowers and is generally robust to genetic and environmental variation. We took advantage of the natural variation found in Cardamine hirsuta petal number to investigate the genetic basis of this trait in a case where robustness was lost during evolution. We used quantitative trait locus (QTL) analysis to characterize the genetic architecture of petal number. Αverage petal number showed transgressive variation from zero to four petals in five C. hirsuta mapping populations, and this variation was highly heritable. We detected 15 QTL at which allelic variation affected petal number. The effects of these QTL were relatively small in comparison with alleles induced by mutagenesis, suggesting that natural selection may act to maintain petal number within its variable range below four. Petal number showed a temporal trend during plant ageing, as did sepal trichome number, and multi-trait QTL analysis revealed that these age-dependent traits share a common genetic basis. Our results demonstrate that petal number is determined by many genes of small effect, some of which are age-dependent, and suggests a mechanism of trait evolution via the release of cryptic variation

Stochastic variation in Cardamine hirsuta petal number

Background and Aims Floral development is remarkably robust in terms of the identity and number of floral organs in each whorl, whereas vegetative development can be quite plastic. This canalization of flower development prevents the phenotypic expression of cryptic genetic variation, even in fluctuating environments. A cruciform perianth with four petals is a hallmark of the Brassicaceae family, typified in the model species Arabidopsis thaliana. However, variable petal loss is found in Cardamine hirsuta, a genetically tractable relative of A. thaliana. Cardamine hirsuta petal number varies in response to stochastic, genetic and environmental perturbations, which makes it an interesting model to study mechanisms of decanalization and the expression of cryptic variation. Methods Multitrait quantitative trait locus (QTL) analysis in recombinant inbred lines (RILs) was used to identify whether the stochastic variation found in C. hirsuta petal number had a genetic basis. Key Results Stochastic variation (standard error of the average petal number) was found to be a heritable phenotype, and four QTL that influenced this trait were identified. The sensitivity to detect these QTL effects was increased by accounting for the effect of ageing on petal number variation. All QTL had significant effects on both average petal number and its standard error, indicating that these two traits share a common genetic basis. However, for some QTL, a degree of independence was found between the age of the flowers where allelic effects were significant for each trait. Conclusions Stochastic variation in C. hirsuta petal number has a genetic basis, and common QTL influence both average petal number and its standard error. Allelic variation at these QTL can, therefore, modify petal number in an age-specific manner via effects on the phenotypic mean and stochastic variation. These results are discussed in the context of trait evolution via a loss of robustness

Morphogenetic Theory and the Constructivist Institutionalist Challenge

This article engages with two meta-theoretical approaches to social analysis, ‘morphogenetic theory’ and ‘constructivist institutionalism’, and specifically explores how the former fares under the critical scrutiny of the latter. The key proponent of constructivist institutionalism, Colin Hay, has offered two detailed critiques of morphogenesis that criticise its position on the foundational sociological issues of structure-agency and material-ideational. Although Hay’s critiques are largely rejected in an overall defence of the morphogenetic approach, the process of engagement is seen to be particularly useful for morphogenetic theory because it allows a number of important clarifications to be made and it also opens up space for theoretical development. In the course of this debate, accessible introductions are given to both theories, and the similarities and differences between them are outlined, providing clarity to both. Therefore, although this article ultimately operates as a defence of morphogenetic theory, especially in the form proposed by Margaret Archer and Douglas Porpora, it finds a great deal of fruitful discussion in the constructivist institutionalist challenge

Globalization, the ambivalence of European integration and the possibilities for a post-disciplinary EU studies

Using the work of Manuel Castells as a starting point, this article explores the ambivalent relationship between globalization and European integration and the variety of ways in which the mainstream political science of the EU has attempted to deal with this issue. The analysis here suggests that various 'mainstreaming' disciplinary norms induce types of work that fail to address fully the somewhat paradoxical and counter-intuitive range of possible relationships between globalization and European integration. The article explores critically four possible analytical ways out of this paradox—abandonment of the concept of globalization, the development of definition precision in globalization studies, the reorientation of work to focus on globalization as discourse, and inter- and post-disciplinarity. The argument suggests that orthodox discussions of the relationship require a notion of social geography that sits at odds with much of the literature on globalization and while greater dialogue between disciplines is to be welcomed, a series of profound epistemological questions need to be confronted if studies of the interplay between global and social process are to be liberated from their disciplinary chains

Rapid turnover of the recirculating lymphocyte pool in vivo

Lymphocytes are unique among blood cells in their capacity to continually recirculate between blood and the tissues via the lymph. Previous estimates of lymphocyte lifespan in vivo and the turnover of the recirculating lymphocyte pool have been deduced from indirect labeling techniques. Using the fluorescent dye PKH-26, individual labeled cells have been tracked in sheep for periods >2 months. By direct measurement their lifespan was calculated. This label was found to be stable in vivo, allowing long-term analysis of the characteristics of the recirculating lymphocyte pool. It Is possible to calculate the rate of turnover of cells of the recirculating pool based on the rate at which labeled cells disappear from the lymphatic circulation. The recirculating lymphocyte pool was found to repopulate itself every 16.5 ± 3.0 days. Using this label, it was estimated that recirculating lymphocytes divide on average once every 29.8 ± 6.8 days. Labeled erythrocytes were also examined and found to have an average lifespan of 153 days, demonstrating no dye loss over the 2 month period of observation. These data suggest that the recirculating lymphocyte pool is a highly dynamic compartment, with a high rate of turnover and peripheral cell division in vivo. This is the first report of the direct measurement of the in vivo turnover of recirculating lymphocyte pools, and this method may now be used to further analyze the lifespan of individual lymphocyte subsets and the in vivo lifespan of other cell types in viv

Inverse Medea as a Novel Gene Drive System for Local Population Replacement: A Theoretical Analysis

One strategy to control mosquito-borne diseases, such as malaria and dengue fever, on a regional scale is to use gene drive systems to spread disease-refractory genes into wild mosquito populations. The development of a synthetic Medea element that has been shown to drive population replacement in laboratory Drosophila populations has provided encouragement for this strategy but has also been greeted with caution over the concern that transgenes may spread into countries without their consent. Here, we propose a novel gene drive system, inverse Medea, which is strong enough to bring about local population replacement but is unable to establish itself beyond an isolated release site. The system consists of 2 genetic components—a zygotic toxin and maternal antidote—which render heterozygous offspring of wild-type mothers unviable. Through population genetic analysis, we show that inverse Medea will only spread when it represents a majority of the alleles in a population. The element is best located on an autosome and will spread to fixation provided any associated fitness costs are dominant and to very high frequency otherwise. We suggest molecular tools that could be used to build the inverse Medea system and discuss its utility for a confined release of transgenic mosquitoes

External and internal noise surveys of London primary schools

Internal and external noise surveys have been carried out around schools in London, UK, to provide information on typical levels and sources to which children are exposed while at school. Noise levels were measured outside 142 schools, in areas away from flightpaths into major airports. 86% of the schools surveyed were exposed to noise from road traffic, the average external noise level outside a school being 57 dB LAeq. Detailed internal noise surveys have been carried out in 140 classrooms in 16 schools, together with classroom observations. It was found that noise levels inside classrooms depend upon the activities in which the children are engaged, with a difference of 20 dB LAeq between the 'quietest' and 'noisiest' activities. The average background noise level in classrooms exceeds the level recommended in current standards. The number of children in the classroom was found to affect noise levels. External noise influenced internal noise levels only when children were engaged in the quietest classroom activities. The effects of the age of the school buildings and types of window upon internal noise were examined but results were inconclusive

Bioinformatics tools for marine biotechnology: A practical tutorial with a metagenomic approach

Background: Bioinformatics has pervaded all fields of biology and has become an indispensable tool for almost all research projects. Although teaching bioinformatics has been incorporated in all traditional life science curricula, practical hands-on experiences in tight combination with wet-lab experiments are needed to motivate students. Results: We present a tutorial that starts from a practical problem: finding novel enzymes from marine environments. First, we introduce the idea of metagenomics, a recent approach that extends biotechnology to non-culturable microbes. We presuppose that a probe for the screening of metagenomic cosmid library is needed. The students start from the chemical structure of the substrate that should be acted on by the novel enzyme and end with the sequence of the probe. To attain their goal, they discover databases such as BRENDA and programs such as BLAST and Clustal Omega. Students' answers to a satisfaction questionnaire show that a multistep tutorial integrated into a research wet-lab project is preferable to conventional lectures illustrating bioinformatics tools. Conclusion: Experimental biologists can better operate basic bioinformatics if a problem-solving approach is chosen