Biotransformation of zearalenone and zearalenols to their major glucuronide metabolites reduces estrogenic activity

Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. Once ingested, ZEN may be absorbed andmetabolised to a- and b-zearalenol (a-ZOL, b-ZOL), and to a lesser extent a- and b-zearalanol (a-ZAL,b-ZAL). Further biotransformation to glucuronide conjugates also occurs to facilitate the elimination ofthese toxins from the body. Unlike ZEN and its metabolites, information regarding the estrogenic activityof these glucuronide conjugates in various tissues is lacking. ZEN-14-O-glucuronide, a-ZOL-14-O-glucuronide,a-ZOL-7-O-glucuronide, b-ZOL-14-O-glucuronide and b-ZOL-16-O-glucuronide, previouslyobtained as the major products from preparative enzymatic synthesis, were investigated for their potentialto cause endocrine disruption through interference with estrogen receptor transcriptional activity.All five glucuronide conjugates showed a very weak agonist response in an estrogen responsive reportergene assay (RGA), with activity ranging from 0.0001% to 0.01% of that of 17b-estradiol, and also lessthan that of ZEN, a-ZOL and b-ZOL which have previously shown estrogenic potencies of the order 17bestradiol> a-ZOL > ZEN > b-ZOL. Confirmatory mass spectrometry revealed that any activity observedwas likely a result of minor deconjugation of the glucuronide moiety. This study confirms that formationof ZEN and ZOL glucuronides is a detoxification reaction with regard to estrogenicity, serving as a potentialhost defence mechanism against ZEN-induced estrogenic activity.

Multidrug transporter proteins of the major facilitator superfamily: not only for drug efflux

Multidrug resistance in prokaryotes is due primarily to efflux of offending antimicrobials from the cell by representatives of several different families of integral membrane transporter proteins. Clearly, in evolutionary terms, these proteins did not arise specifically to pump human-made antimicrobials out of the cell and thereby confer resistance. Despite this, often only their role in antibiotic resistance is characterised and highlighted.
In recent years, however, a transition from the traditional anthropocentric perception of antibiotic resistance mechanisms in microorganisms has occurred, with naturally produced antimicrobials now generally regarded as physiologically important signalling molecules or sources of nutrition for bacteria rather than antimicrobial agents, and bacterial multidrug efflux proteins not merely as a defensive response to antimicrobials but as important players in fundamental physiological processes such as cellular homeostasis.
This emerging perspective supports the notion that a better understanding of the complexities of infection and multidrug resistance in bacteria can be achieved via a more detailed understanding of those physiological processes. In this chapter, we review the ‘true’ physiological roles of multidrug efflux proteins of the largest non-ATP-hydrolysing family of membrane transporters, the major facilitator superfamily, and explore the evidence for their function in processes such as pH and metal homeostasis, import and export of metabolites and biofilm formation

The British conservative party and Europe:The choosing of John Major

This article provides an empirical analysis of voting behaviour in the second ballot of the 1990 Conservative leadership contest that resulted in John Major becoming party leader and prime minister. Seven hypotheses of voting behaviour are generated from the extant literature relating voting to socio-economic variables (occupational and educational background), political variables (parliamentary experience, career status, age and electoral marginality) and ideological variables (drawn from survey data on MPs' positions on economic, European and moral issues). These hypotheses are tested using data on voting intentions gathered from published lists of MPs' declarations, interviews with each of the leadership campaign teams, and correspondence with MPs. Bivariate relationships are presented, followed by logistic regression analysis to isolate the unique impact that each variable had on voting. This shows that educational background, parliamentary experience and (especially) attitudes to Europe were the key factors determining voting. The importance of Europe in the contest is particularly instructive: the severe problems for Major's leadership which were caused by the issue can be attributed to, and understood in the context of, the 1990 contest in which he became leader.

Interacting supernovae and supernova impostors. SN 2007sv: the major eruption of a massive star in UGC 5979

We report the results of the photometric and spectroscopic monitoring campaign of the transient SN 2007sv. The observables are similar to those of Type IIn supernovae, a well-known class of objects whose ejecta interact with pre-existing circumstellar material (CSM). The spectra show a blue continuum at early phases and prominent Balmer lines in emission; however, the absolute magnitude at the discovery of SN 2007sv (M-R=-14.25 +/- 0.38) indicate it to be most likely a supernova impostor. This classification is also supported by the lack of evidence in the spectra of very high velocity material as expected in supernova ejecta. In addition, we find no unequivocal evidence of broad lines of alpha- and/or Fe-peak elements. The comparison with the absolute light curves of other interacting objects (including Type IIn supernovae) highlights the overall similarity with the prototypical impostor SN 1997bs. This supports our claim that SN 2007sv was not a genuine supernova, and was instead a supernova impostor, most likely similar to the major eruption of a luminous blue variable.

Retinopathy in type 1 diabetes mellitus: Major differences between rural and urban dwellers in northwest Ethiopia

Aim: To audit levels of diabetes-related eye disease in Type 1 diabetes mellitus (T1DM) patients in northwest Ethiopia. In particular to establish whether, despite identical clinical goals, major differences between the physically demanding life-style of rural subsistence farmers and the sedentary life-style of urban dwellers would influence the prevalence of diabetes-related eye complications. 

Methods: A robust infrastructure for chronic disease management that comprehensively includes all rural dwellers was a pre-requisite for the investigation. A total of 544 T1DM were examined, representing 80% of all T1DM patients under regular review at both the urban and rural clinics and representative of patient age and gender (62.1% male, 37.9% female) of T1DM patients from this region; all were supervised by the same clinical team. Eye examinations were performed for visual acuity, cataract and retinal changes (retinal photography). HbA1c levels and the presence or absence of hypertension were recorded. 

Results/conclusions: Urban and rural groups had similar prevalences of severe visual impairment/blindness (7.0% urban, 5.2% rural) and cataract (7.3% urban, 7.1% rural). By contrast, urban dwellers had a significantly higher prevalence of retinopathy compared to rural patients, 16.1% and 5.0%, respectively (OR 2.9, p <. 0.02, after adjustment for duration, age, gender and hypertension). There was a 3-fold greater prevalence of hypertension in urban patients, whereas HbA1c levels were similar in the two groups. Since diabetic retinopathy is closely associated with microvascular disease and endothelial dysfunction, the possible influences of hypertension to increase and of sustained physical activity to reduce endothelial dysfunction are discussed.

A revised age of AD 667-699 for the latest major eruption at Rabaul

The most recent major eruption at Rabaul was one of the largest known events at this complex system, having a VEI rating of 6. The eruption generated widespread airfall pumice lapilli and ash deposits and ignimbrites of different types. The total volume of pyroclastic material produced in the eruption exceeded 11 km3 and led to a new phase of collapse within Rabaul Caldera. Initial 14C dating of the eruptive products yielded an age of about 1400 yrs BP, and the eruption became known as the "1400 BP" eruption. Previous analyses of the timing of the eruption have linked it to events in AD 536 and AD 639. However, we have re-evaluated the age of the eruption using the Bayesian wiggle-match radiocarbon dating method, and the eruption is now thought to
have occurred in the interval AD 667-699. The only significant equatorial eruptions recorded in both Greenland and Antarctic ice during this interval are at AD 681 and AD 684, dates that coincide with frost rings in bristlecone pines of western USA in the same years. Definitively linking the Rabaul eruption to this narrow age range will require identification of Rabaul tephra in the ice records. However, it is proposed that a new working hypothesis for the timing of the most recent major eruption at Rabaul is that it occurred in the interval AD 681-684.

The first major step in the peace process’? Exploring the impact of the Anglo-Irish Agreement on Irish Republican thinking

This article supports interpretations of the Anglo-Irish Agreement of 1985 as a significant factor contributing to the development of the Northern Ireland peace process. However, it also emphasises a certain serendipity in the Agreement's effect on northern nationalist, and more specifically republican, politics in the region. In particular, it stresses that a specific interpretation of the Agreement promoted by the Social Democratic and Labour Party inspired a dialogue with republicanism, encouraging an ongoing reappraisal within the latter about the nature of Britain's role in Northern Ireland. This, the article argues, reinforced the movement towards a more political approach that republicans had begun in the 1980s, and encouraged their eventual embrace of a constitutional strategy in the 1990s. However, in advancing this argument, the article notes that such an outcome was far from the minds of the British and Irish officials who negotiated the Anglo-Irish Agreement. The Agreement was intended to marginalise rather than accommodate republicans. Despite this, it provided an inadvertent incentive to draw militant republicanism into the democratic process in Northern Ireland.

The first major step in the peace process’? Exploring the impact of the Anglo-Irish Agreement on Irish republican thinking

This article supports interpretations of the Anglo-Irish Agreement of 1985 as a significant factor contributing towards the development of the Northern Ireland peace process. However, it also emphasises a certain serendipity in the Agreement’s effect on northern nationalist, and more specifically republican, politics in the region. In particular, it stresses that a specific interpretation of the Agreement promoted by the SDLP inspired a dialogue with republicanism, encouraging an ongoing re-appraisal within the latter about the nature of Britain’s role in Northern Ireland. This, the article argues, reinforced the movement towards a more political approach that republicans had begun in the 1980s, and encouraged their eventual embrace of a constitutional strategy in the 1990s. However, in advancing this argument, the article notes that such an outcome was far from the minds of the British and Irish officials who negotiated the Anglo-Irish Agreement. The Agreement was intended to marginalise rather than accommodate republicans. Despite this, it provided an inadvertent incentive to draw militant republicanism into the democratic process in Northern Ireland.