Using molecular networking for microbial secondary metabolite bioprospecting

The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149-2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations

Perception of risk of HIV and sexual risk behaviours among students in the United States, Turkey and South Africa

The aim of this study was to examine HIV sexual risk behaviours and perception of HIV risk among 1 095 students from the United States of America (US), Turkey and South Africa. Randomly selected students who were enrolled in general education courses completed a structured questionnaire. Results revealed statistically significant differences in specific HIV-related sexual behaviours among students from the three countries and among male and female students in each country. A higher percentage of US and South African students engage in HIV risky sexual behaviours compared with their Turkish counterparts, and a higher percentage of female students in the US and South Africa engage in HIV sexual risk behaviours compared with their male colleagues. A higher proportion of Turkish male students engaged in sexual risk behaviours compared with their female counterparts. The perception of HIV risk was low among US and Turkish students, and high among South African students. There was no agreement between engaging in risky sexual behaviour and self-perception of HIV risk among South African female students, while agreement was poor for US male and female students, Turkish male and female students, and South African male students. The observed optimistic bias needs to be considered in the design and implementation of HIV prevention programmes for these populations.Department of HE and Training approved lis

Images of Germany: a theory-based approach to the classification, analysis, and critique of British attitudes towards Germany, 1890-1940

The thesis attempts to set sources broadly representative of the range of British attitudes to Germany and the Germans - from Spender, Low, Maxse and Dillon, to Bowse, Namier, Vansittart, Gollancz and Barraclough in a framework informed by multidisciplinary theory. There are five main themes: the classification of attitudes; the analysis of content; the identification of a relatively constant British self-image; the potential for attitudinal dilemmas and cognitive dissonance inherent in that self-image; national character as a concept and as a descriptor. Although dealt with in this order the themes interrelate. For example, the first phase of content analysis [chapters 4 to 8], where the emphasis is on the way in which sources differ, anticipates the discussion in chapter 10 of the differences in their approaches to the modal distribution of cultural and individual characteristics in Germany; the classificatory model proposed as an alternative to the Idealist-Realist dichotomy in chapter 2 [and 'tested' in a brief case study in chapter 3] is consistent with the definition of the self-image and facilitates discussion on cognitive dissonance. It is proposed that a classificatory system based on an Idealist-Realist dichotomy with respective pro and anti-German sub-sets does not adequately highlight the nuances and ambiguities which often informed group or individual attitudes toward Germany. It is argued that such a system cannot readily deal with the views of realists who were ideologically neutral [i. e. not ideologically anti-German] in their definition of Germany as the enemy, of idealists who were ideologically opposed to Germany, or of others who were equivocal. An alternative model is offered in the form of partially congruent parallel continuums of competition and cooperation, travelling in opposite directions in relation to respective minimum and maximum positions. In chapters 4 to 8 the content analysis of sources focuses on their different perceptions of Germany and the Germans: whether they made distinctions between Germans - and what form such distinctions took - or regarded them as 'all of a kind.' It is argued that underlying expressed attitudes to Germany and the Germans from the British side was a notion of self, incorporating two main components: a pragmatic component defining Britain as a material competitor in a competitive world, and an ideological component defining a package of traits and values associated with the cultural condition 'being British. ' The ideological component of the self-image was commonly validated and served as an assessment instrument for making judgements on Germans. It is argued that the intellectual and psychological need to maintain a consistent relationship between expressed attitudes and declared values, particularly when the values were central to the self-image, led to the use of dissonance reducing mechanisms. The ways in which one national culture may reasonably be said to differ from another, and the methodological requirements for tenable cross-cultural analysis, are explored through critical consideration of the concept 'national character.' A theoretical framework is devised for the critical analysis of the views presented by the sources on the national character of the Germans. This framework relates their perception of modal structure [unimodal, bimodal, multimodal] to their level of commitment - positive or negative - to propositions on cultural homogeneity, differential sharing, the causal autonomy of situational factors, the significance of international cultural influences, the innate nature of characteristics, and concern for methodological rigour. An image of the configurations and features in the German cultural profile is formulated. Recognition of the partial and provisional nature of this image, and discussion of what it omits and lacks in terms of texture, is used to demonstrate the deficiencies of the Schwarzweissmalerei approach to Germany and the Germans

Can positive inquiry strengthen obstetric referral systems in Cambodia?

Maternal death remains high in low resource settings. Current literature on obstetric referral that sets out to tackle maternal death tends to focus on problematization. We took an alternative approach and rather asked what works in contemporary obstetric referral in a low income setting to find out if positive inquiry could generate original insights on referral that could be transformative. We documented and analysed instances of successful referral in a rural province of Cambodia that took place within the last year. Thirty women, their families, healthcare staff and community volunteers were purposively sampled for in‐depth interviews, conducted using an appreciative inquiry lens. We found that referral at its best is an active partnership between families, community and clinicians that co‐constructs care for labouring women during referral and delivery. Given the short time frame of the project we cannot conclude if this new understanding was transformative. However, we can show that acknowledging positive resources within contemporary referral systems enables health system stakeholders to widen their understanding of the kinds of resources that are available to them to direct and implement constructive change for maternal health

Constitutivism

A brief explanation and overview of constitutivism

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Using molecular networking for microbial secondary metabolite bioprospecting

\ua9 2016 by the authors; licensee MDPI, Basel, Switzerland. The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemicaL profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149–2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations

Cytokeratin-18 is a sensitive biomarker of alanine transaminase increase in a placebo-controlled, randomized, crossover trial of therapeutic paracetamol dosing (PATH-BP Biomarker sub-study)

Drug-induced liver injury (DILI) is a challenge in clinical medicine and drug development. Highly sensitive novel biomarkers have been identified for detecting DILI following a paracetamol overdose. The study objective was to evaluate biomarker performance in a 14-day trial of therapeutic dose paracetamol.The PATH-BP trial was a double-blind, placebo-controlled, crossover study. Individuals (n=110) were randomized to receive 1g paracetamol 4×daily or matched placebo for 2 weeks followed by a 2-week washout before crossing over to the alternate treatment. Blood was collected on days 0 (baseline), 4, 7 and 14 in both arms. Alanine transaminase (ALT) activity was measured in all patients. MicroRNA-122 (miR-122), cytokeratin-18 (K18) and glutamate dehydrogenase (GLDH) were measured in patients who had an elevated ALT on paracetamol treatment (50% from baseline). ALT increased in 49 individuals (45%). All 3 biomarkers were increased at the time of peak ALT (K18 paracetamol arm:18.9±9.7ng/mL, placebo arm:11.1±5.4ng/mL, ROC-AUC = 0.80, 95%CI 0.71-0.89; miR-122: 15.1±12.9fM V 4.9±4.7fM, ROC-AUC = 0.83, 0.75-0.91; and GLDH:24.6±31.1U/L V 12.0±11.8U/L, ROC-AUC = 0.66,0.49-0.83). All biomarkers were correlated with ALT (K18 r=0.68, miR-122 r=0.67, GLDH r=0.60). To assess sensitivity, biomarker performance was analyzed on the visit preceding peak ALT (mean 3 days earlier). K18 identified the subsequent ALT increase (K18 ROC-AUC=0.70, 0.59-0.80; miR-122 ROC-AUC=0.60,0.49-0.72, ALT ROC-AUC=0.59,0.48-0.70; GLDH ROC-AUC=0.70,0.50-0.90). Variability was lowest for ALT and K18. In conclusion, K18 was more sensitive than ALT, miR-122 or GLDH and has potential significant utility in the early identification of DILI in trials and clinical practice.<br/

Cervicovaginal Microbiota Predicts Neisseria gonorrhoeae Clinical Presentation

Neisseria gonorrhoeae infection of the female lower genital tract can present with a spectrum of phenotypes ranging from asymptomatic carriage to symptomatic cervical inflammation, or cervicitis. The factors that contribute to the development of asymptomatic or symptomatic infections are largely uncharacterized. We conducted a pilot study to assess differences in the cervicovaginal microbial community of patients presenting with symptomatic vs. asymptomatic N. gonorrhoeae infections to a sexually transmitted infections (STI) clinic. DNA was isolated from cervicovaginal swab specimens from women who tested positive for N. gonorrhoeae infection using a clinical diagnostic nucleic acid amplification test. We performed deep sequencing of 16S ribosomal RNA gene amplicons, followed by microbiome analyses with QIIME, and species-specific real-time PCR to assess the composition of microbial communities cohabitating the lower genital tract with the infecting N. gonorrhoeae. Specimens collected from asymptomatic individuals with N. gonorrhoeae infection and no co-infection with Chlamydia trachomatis and/or Trichomonas vaginalis carried Lactobacillus-dominant microbial communities more frequently than symptomatic patients without co-infection. When compared to asymptomatic individuals, symptomatic women had microbial communities characterized by more diverse and heterogenous bacterial taxa, typically associated with bacterial vaginosis (BV) [Prevotella, Sneathia, Mycoplasma hominis, and Bacterial Vaginosis-Associated Bacterium-1 (BVAB1)/“Candidatus Lachnocurva vaginae”]. Both symptomatic and asymptomatic N. gonorrhoeae patients with additional STI co-infection displayed a BV-like microbial community. These findings suggest that Lactobacillus-dominant vaginal microbial community may protect individuals from developing symptoms during lower genital tract infection with N. gonorrhoeae