Microbial species involved in production of 1,2-sn-diacylglycerol and effects of phosphatidylcholine on human fecal microbiota

1,2-sn-Diacylglycerols (DAGs) are activators of protein kinase C (PKQ, which is involved in the regulation of colonic mucosal proliferation. Extracellular DAG has been shown to stimulate the growth of cancer cell lines in vitro and may therefore play an important role in tumor promotion. DAG has been detected in human fecal extracts and is thought to be of microbial origin. Hitherto, no attempts have been made to identify the predominant fecal bacterial species involved in its production. We therefore used anaerobic batch culture systems to determine whether fecal bacteria could utilize phosphatidylcholine (0.5% [wt/vol]) to produce DAG. Production was found to be dependent upon the presence of the substrate and was enhanced in the presence of high concentrations of deoxycholate (5 and 10 mM) in the growth medium. Moreover, its production increased with the pH, and large inter- and intraindividual variations were observed between cultures seeded with inocula from different individuals. Clostridia and Escherichia coli multiplied in the fermentation systems, indicating their involvement in phosphatidylcholine metabolism. On the other hand, there was a significant decrease in the number of Bifidobacterium spp. in the presence of phosphatidylcholine. Pure-culture experiments showed that 10 of the 12 strains yielding the highest DAG levels (>50 nmol/ml) were isolated from batch culture enrichments run at pH 8.5. We found that the strains capable of producing large amounts of DAG were predominantly Clostridium bifermentans (8 of 12), followed by Escherichia coli (2 of 12). Interestingly, one DAG-producing strain was Bifidobacterium infantis, which is often considered a beneficial gut microorganism. Our results have provided further evidence that fecal bacteria can produce DAG and that specific bacterial groups are involved in this process. Future strategies to reduce DAG formation in the gut should target these species.

Role of quercetin and its in vivo metabolites in protecting H9c2 cells against oxidative stress

The aim of this study was to investigate the potential of quercetin and two of its "in vivo" metabolites, 3'-O-methyl quercetin and 4'-O-methyl quercetin, to protect H9c2 cardiomyoblasts against H2O2-induced oxidative stress. As limited data are available regarding the potential uptake and cellular effects of quercetin and its metabolites in cardiac cells, we have evaluated the cellular association/uptake of the three compounds and their involvement in the modulation of two pro-survival signalling pathways: ERK1/2 signalling cascade and PI3K/Akt pathway. The three flavonols associated with cells to differing extents. Quercetin and its two O-methylated metabolites were able to reduce intracellular ROS production but only quercetin was able to counteract H2O2 cell damage, as measured by MTT reduction assay, caspase-3 activity and DNA fragmentation assays. Furthermore, only quercetin was observed to modulate pro-survival signalling through ERK1/2 and PI3K/Akt pathway. In conclusion we have demonstrated that quercetin, but not its O-methylated metabolites, exerts protective effects against H2O2 cardiotoxicity and that the mechanism of its action involves the modulation of PI3K/Akt and ERK1/2 signalling pathways. (c) 2006 Elsevier Masson SAS. All rights reserved.

fMRI delineation of working memory for emotional prosody in the brain: commonalities with the lexico-semantic emotion network

Decoding emotional prosody is crucial for successful social interactions, and continuous monitoring of emotional intent via prosody requires working memory. It has been proposed by Ross and others that emotional prosody cognitions in the right hemisphere are organized in an analogous fashion to propositional language functions in the left hemisphere. This study aimed to test the applicability of this model in the context of prefrontal cortex working memory functions. BOLD response data were therefore collected during performance of two emotional working memory tasks by participants undergoing fMRI. In the prosody task, participants identified the emotion conveyed in pre-recorded sentences, and working memory load was manipulated in the style of an N-back task. In the matched lexico-semantic task, participants identified the emotion conveyed by sentence content. Block-design neuroimaging data were analyzed parametrically with SPM5. At first, working memory for emotional prosody appeared to be right-lateralized in the PFC, however, further analyses revealed that it shared much bilateral prefrontal functional neuroanatomy with working memory for lexico-semantic emotion. Supplementary separate analyses of males and females suggested that these language functions were less bilateral in females, but their inclusion did not alter the direction of laterality. It is concluded that Ross et al.'s model is not applicable to prefrontal cortex working memory functions, that evidence that working memory cannot be subdivided in prefrontal cortex according to material type is increased, and that incidental working memory demands may explain the frontal lobe involvement in emotional prosody comprehension as revealed by neuroimaging studies. (c) 2007 Elsevier Inc. All rights reserved.

Drivers' ratings of different components of their own driving skill: a greater illusion of superiority for skills that relate to accident involvement

Different components of driving skill relate to accident involvement in different ways. For instance, while hazard-perception skill has been found to predict accident involvement, vehicle-control skill has not. We found that drivers rated themselves superior to both their peers and the average driver on 18 components of driving skill (N = 181 respondents). These biases were greater for hazard-perception skills than for either vehicle-control skills or driving skill in general. Also, ratings of hazard-perception skill related to self-perceived safety after overall skill was controlled for. We suggest that although drivers appear to appreciate the role of hazard perception in safe driving, any safety benefit to be derived from this appreciation may be undermined by drivers' inflated opinions of their own hazard-perception skill. We also tested the relationship between illusory beliefs about driving skill and risk taking and looked at ways of manipulating drivers' illusory beliefs.

A universal primer for isolation of fragments of a gene encoding phytoene desaturase for use in virus-induced gene silencing (VIGS) studies

We have been using Virus-Induced Gene Silencing (VIGS) to test the function of genes that are candidates for involvement in floral senescence. Although VIGS is a powerful tool for assaying the effects of gene silencing in plants, relatively few taxa have been studied using this approach, and most that have are in the Solanaceae. We typically use silencing of phytoene desaturase (PDS) in preliminary tests of the feasibility of using VIGS. Silencing this gene, whose product is involved in carotene biosynthesis, results in a characteristic photobleaching phenotype in the leaves. We have found that efficient silencing requires the use of fragments that are more than 90% homologous to the target gene. To simplify testing the effectiveness of VIGS in a range of species, we designed a set of universal primers to a region of the PDS gene that is highly conserved among species, and that therefore allows an investigator to isolate a fragment of the homologous PDS gene from the species of interest. We report the sequences of these primers and the results of VIGS experiments in horticultural species from the Asteraceae, Leguminosae, Balsaminaceae and Solanaceae.

Motivations for innovation in the built environment: new directions for research

Innovation in the built environment involves multiple actors with diverse motivations. Policy-makers find it difficult to promote changes that require cooperation from these numerous and dispersed actors and to align their sometimes divergent interests. Established research traditions on the economics and management of innovation pay only limited attention to stakeholder choices, engagement and motivation. This paper reviews the insights that emerge as research in these traditions comes into contact with work on innovation from sociological and political perspectives. It contributes by highlighting growing areas of research on user involvement in complex innovation, collective action, distributed innovation and transition management. To differing extents, these provide approaches to incorporate the motivations of different actors into theoretical understanding. These indicate new directions for research that promise to enrich understanding of innovation.

Fora, networks and public examinations: the role and significance of public participation in the new regional plan for South East England

This paper overviews the main conceptual frameworks for understanding participatory approaches to land use planning and explores their utility in analysing the experience of a recent regional planning exercise in South East England. In particular it examines the contribution of recent ‘New Institutionalist’ ideas to our understanding of participatory processes and the implications for practice of using them to build strategies of public involvement in policy-making and implementation.

An investigation of the expression and adhesin function of H7 flagella in the interaction of Escherichia coli O157: H7 with bovine intestinal epithelium

Enterohaemorrhagic Escherichia coli O157 : H7 is a bacterial pathogen that can cause haemorrhagic colitis and haemolytic uremic syndrome. In the primary reservoir host, cattle, the terminal rectum is the principal site of E. coli O157 colonization. In this study, bovine terminal rectal primary epithelial cells were used to examine the role of H7 flagella in epithelial adherence. Binding of a fliC(H7) mutant O157 strain to rectal epithelium was significantly reduced as was binding of the flagellated wild-type strain following incubation with H7-specific antibodies. Complementation of fliC(H7) mutant O157 strain with fliC(H7) restored the adherence to wild-type levels; however, complementation with fliC(H6) did not restore it. High-resolution ultrastructural and imunofluorescence studies demonstrated the presence of abundant flagella forming physical contact points with the rectal epithelium. Binding to terminal rectal epithelium was specific to H7 by comparison with other flagellin types tested. In-cell Western assays confirmed temporal expression of flagella during O157 interaction with epithelium, early expression was suppressed during the later stages of microcolony and attaching and effacing lesion formation. H7 flagella are expressed in vivo by individual bacteria in contact with rectal mucosa. Our data demonstrate that the H7 flagellum acts as an adhesin to bovine intestinal epithelium and its involvement in this crucial initiating step for colonization indicates that H7 flagella could be an important target in intervention strategies.

Effects of psychotherapy for anxiety in children and adolescents: a meta-analytic review

This paper provides a comprehensive quantitative review of high quality randomized controlled trials of psychological therapies for anxiety disorders in children and young people. Using a systematic search for randomized controlled trials which included a control condition and reported data suitable for meta-analysis, 55 studies were included. Eligible studies were rated for methodological quality and outcome data were extracted and analyzed using standard methods. Trial quality was variable, many studies were underpowered and adverse effects were rarely assessed; however, quality ratings were higher for more recently published studies. Most trials evaluated cognitive behavior therapy or behavior therapy and most recruited both children and adolescents. Psychological therapy for anxiety in children and young people was moderately effective overall, but effect sizes were small to medium when psychological therapy was compared to an active control condition. The effect size for non-CBT interventions was not significant. Parental involvement in therapy was not associated with differential effectiveness. Treatment targeted at specific anxiety disorders, individual psychotherapy, and psychotherapy with older children and adolescents had effect sizes which were larger than effect sizes for treatments targeting a range of anxiety disorders, group psychotherapy, and psychotherapy with younger children. Few studies included an effective follow-up. Future studies should follow CONSORT reporting standards, be adequately powered, and assess follow-up. Research trials are unlikely to address all important clinical questions around treatment delivery. Thus, careful assessment and formulation will remain an essential part of successful psychological treatment for anxiety in children and young people.

Managing the duality of IHRM: unravelling the strategy and perceptions of key actors in South Korean MNCs

This research aims to extend our understanding of the duality between global integration and local responsiveness in multinational corporations (MNCs) by exploring the perceptions of corporate HR actors regarding the intra-organisational factors that alter the balance between these pressures. It examines the perceptions and actions of key actors in the context of two Korean MNCs. The study shows the importance attributed to a range of socio-procedural factors by corporate actors and which, therefore, inform the practical management of the dual forces, notably: HR expertise, social ties, trustworthy relationships and co-involvement in decision processes.

The "Fair trade nation": market-oriented development in devolved European regions

Scholars have largely ignored the roles played by government and public sector institutions in the fair trade movement. This article addresses the knowledge gap through examining government involvement in fair trade networks in the context of European devolution and the localization of international development action. Proposing a relational view of fair trade networks, and considering the Fair Trade Nation as a social category for development, it highlights how power sources outside the centralized nation-state permit a political community to associate itself with fair trade. Research from Wales demonstrates that government acts in a leadership role rather than as regulator, conferring political voice and finance while enhancing its international credentials and contributing to the politics of nation-building. Our conclusion is cautious; campaigners celebrate political commitment to fair trade embodied within the category of the Fair Trade Nation, but evidence suggests that government reliance on the market as a vehicle for decentralized development action is limited by how the Fair Trade Nation is currently executed.

Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells

The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50th percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually.

The researcher-farmer interface in the rice-wheat system: moving from agricultural productivity to livelihoods

This chapter explores some of the implications of adopting a research approach that focuses on people and their livelihoods in the rice-wheat system of the Indo-Gangetic Plains. We draw on information from a study undertaken by the authors in Bangladesh and then consider the transferability of our findings to other situations. We conclude that if our research is to bridge the researcher-farmer interface, ongoing technical research must be supported by research that explores how institutional, policy, and communication strategies determine livelihood outcomes. The challenge that now faces researchers is to move beyond their involvement in participatory research to understand how to facilitate a process in which they provide information and products for others to test. Building capacity at various levels for openness in sharing information and products–seeing research as a public good for all–seems to be a prerequisite for more effective dissemination of the available information and technologies.

Randomized controlled trial of parent-enhanced CBT compared with individual CBT for obsessive-compulsive disorder in young people

Objective: Obsessive-compulsive disorder (OCD) in young people can be effectively treated with Cognitive Behavior Therapy (CBT). Practice guidelines in the United Kingdom recommend that CBT be delivered with parental or family involvement; however, there is no evidence from randomized trials that this enhances effectiveness. The aim of this trial was to assess if CBT with high parental involvement was more effective than CBT with low parental involvement (individual CBT) in reducing symptoms of OCD. Method: Fifty young people ages 12–17 years with OCD were randomly allocated to individual CBT or parent-enhanced CBT. In parent-enhanced CBT parents attended all treatment sessions; in individual CBT, parents attended only Sessions 1, 7, and the final session. Participants received up to 14 sessions of CBT. Data were analyzed using intent-to-treat and per-protocol methods. The primary outcome measure was the Children’s Yale-Brown Obsessive Compulsion Scale (Scahill et al., 1997). Results: Both forms of CBT significantly reduced symptoms of OCD and anxiety. Change in OCD symptoms was maintained at 6 months. Per-protocol analysis suggested that parent-enhanced CBT may be associated with significantly larger reductions in anxiety symptoms. Conclusions: High and low parental involvement in CBT for OCD in young people were both effective, and there was no evidence that 1 method of delivery was superior on the primary outcome measure. However, this study was small. Future trials should be adequately powered and examine interactions with the age of the young person and comorbid anxiety disorders.

Influence of SNPs in nutrient-sensitive candidate genes and gene–diet interactions on blood lipids: the DiOGenes study

Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene–diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP–diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect), and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP–dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of − 0·26 mmol/l per A-allele/protein unit (95 % CI − 0·38, − 0·14, P= 0·000043). In conclusion, we investigated SNP–diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.