Induction of tetraploidy through loss of p53 and upregulation of Plk1 by Human Papillomavirus type-16 E6

Cancer cells are insensitive to many signals that inhibit growth of untransformed cells. Here, we show that primary human epithelial cells expressing human papillomavirus (HPV) type-16 E6/E7 bypass arrest caused by the DNA-damaging drug adriamycin and become tetraploid. To determine the contribution of E6 in the context of E7 to the resistance of arrest and induction of tetraploidy, we used an E6 mutant unable to degrade p53 or RNAi targeting p53 for knockdown. The E6 mutant fails to generate tetraploidy; however, the presence of E7 is sufficient to bypass arrest while the p53 RNAi permits both arrest insensitivity and tetraploidy. We published previously that polo-like kinase 1 (Plk1) is upregulated in E6/E7-expressing cells. We observe here that abnormal expression of Plk1 protein correlates with tetraploidy. Using the p53 binding-defective mutant of E6 and p53 RNAi, we show that p53 represses Plk1, suggesting that loss of p53 results in tetraploidy through upregulation of Plk1. Consistent with this hypothesis, overexpression of Plk1 in cells generates tetraploidy but does not confer resistance to arrest. These results support a model for transformation caused by HPV-16 where bypass of arrest and tetraploidy are separable consequences of p53 loss with Plk1 required only for the latter effect.

Depressed mood and dietary fish intake: Direct relationship or indirect relationship as a result of diet and lifestyle?

Previous studies have suggested an association between depressed mood and the dietary intake of fish. In all cases, however, dietary fish intake has been considered at the exclusion of all other aspects of the diet. This analysis investigates associations between depressed mood and dietary fish intake, while also concurrently investigating intake of a number of other dietary components. The analysis is conducted on data from 10,602 men from Northern Ireland and France screened for inclusion into the PRIME cohort study. Depressed mood was assessed using a self-report questionnaire based on the Welsh Pure Depression sub-scale of the Minnesota Multiphasic Personality Inventory, diet was assessed using a Food Frequency Questionnaire, and limited demographics were also measured. Using regression, depressed mood is initially inversely associated with dietary fish intake. On inclusion of all other dietary variables, the strength of this relationship reduces but remains, and significant associations with a number of other foods are also found. On additional inclusion of all demographic variables, the strength of the above relationships again reduces, and associations with various measures of socio-economic status and education are also significant. These findings suggest that depressed mood is associated with fish intake both directly, and indirectly as part of a diet that is associated with depression and as part of a lifestyle that is associated with depression. Additional support for these conclusions is also provided in the pattern of associations between depressed mood and diet in the two countries. The relative contributions of fish intake to depressed mood both directly and indirectly are yet to be determined. However, while diet is not measured and until lifestyle can be adequately measured, the potential roles of diet and lifestyle in the association between depressed mood and dietary fish intake should not be ignored.

Rarity and decline in bumblebees - A test of causes and correlates in the Irish fauna

Bees are believed to be in decline across many of the world's ecosystems. Recent studies on British bumblebees proposed alternative theories to explain declines. One study suggested that greater dietary specialization among the rarer bumblebee species makes them more susceptible to decline. A second study disputed this theory and found that declines in British bumblebees were correlated with the size of species' European ranges, leading to the suggestion that climate and habitat specialization may be better indicators of the risk of decline. Here we use a new and independent dataset based on Irish bumblebees to test the generality of these theories. We found that most of the same bumblebee species are declining across the British Isles, but that, within Ireland, a simple food-plant specialization model is inadequate to explain these declines. Furthermore, we found no evidence of a relationship between declines in Irish bumblebees and the size of species' European ranges. However, we demonstrate that the late emerging species have declined in Ireland (and in Britain), and that these species show a statistically significant westward shift to the extremity of their range, probably as a result of changing land use. Irish data support the finding that rare and declining bumblebees are later nesting species, associated with open grassy habitats. We suggest that the widespread replacement of hay with silage in the agricultural landscape, which results in earlier and more frequent mowing and a reduction in late summer wildflowers, has played a major role in bumblebee declines. (C) 2006 Elsevier Ltd. All rights reserved.

Lifestyle limitations of children and young people with severe cerebral palsy: a population study protocol

Aim.  This paper is a presentation of a study protocol to establish the prevalence of orthopaedic problems (hip dislocation, pelvic obliquity, spinal deformity and contractures) and their impact on pain, function, participation and health in a population of children and young people with severe cerebral palsy.

Background.  Cerebral palsy is the commonest cause of motor impairment in childhood and is associated with life-long disability. An estimated 30% of people with cerebral palsy have severe forms and are non-ambulant. Although the underlying neurological damage is not amenable to correction, many health services are dedicated to providing therapeutic and adaptive support to help people with the condition reach their potential.

Method.  A cross-sectional survey of children and young people, aged 4–25 years with severe, non-ambulant cerebral palsy as defined using the Gross Motor Function Classification System (Levels IV and V). Study participants will be identified from a pre-existing, geographically defined case register and recruited via a healthcare professional known to them. Two assessments will be undertaken: one involving parents/carers at home and using questionnaires; the other involving the child/young person ideally in one of three settings and including X-rays if clinically indicated.

Discussion.  This study will contribute to our knowledge of the history and epidemiology of orthopaedic problems in children and young people with cerebral palsy and how these problems accumulate and impact on participation, health and well-being. The study will also identify unmet need and make recommendations for good practice in relation to the orthopaedic care and management for people with severe cerebral palsy

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care.

Background Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers’ and participants’ experiences of its implementation and to inform future strategies to maximise recruitment and retention. Methods In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection. Results We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners’ contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention. Conclusions Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.

Adjusting to Life After Esophagectomy: The Experience of Survivors and Carers

Following surgery for esophageal cancer, patients can experience complex physical, social, and emotional changes. Investigation of these challenges, particularly from the perspective of the patient and his or her carer, has been limited. The current study explored the emotional and cognitive experiences of esophageal cancer survivors and those of their carers, using focus groups conducted with members of a patient support group. Analysis of the patients’ data yielded three themes: coping with a death sentence, adjusting to and accepting an altered self, and the unique benefits of peer support. Analysis of the carers’ data also yielded three themes: the carer as buffer, representations of recovery and recurrence, and normalizing experiences through peer support. Esophageal cancer patients and their carers require holistic support in their efforts to adjust to the social, emotional, and physical consequences of esophagectomy. Peers could be an effective channel for the support of patients and carers.

Predicting intentions to purchase organic food: The role of affective and moral attitudes in the Theory of Planned Behaviour

This study examined the usefulness of integrating measures of affective and moral attitudes into the Theory of Planned Behaviour (TPB)-model in predicting purchase intentions or organic foods. Moral attitude was operationalised Lis positive self-rewarding feelings of doing the right thing. Questionnaire data were gathered in three countries: Italy (N = 202), Finland (N = 270) and UK (N = 200) in March 2004. Questions focussed on intentions to purchase organic apples and organic ready-to-cook pizza instead of their conventional alternatives. Data were analysed using Structural Equation Modelling by simultaneous multi-group analysis of the three Countries. Along with attitudes, moral attitude and subjective norms explained considerable shares of variances in intentions. The relative influences of these variables varied between the Countries, such that in the UK and Italy moral attitude rather than subjective norms had stronger explanatory power. In Finland it was other way around. Inclusion of moral attitude improved the model fit and predictive ability of the model, although only marginally in Finland. Thus the results partially Support the usefulness of incorporating moral measures as well as affective items for attitude into the framework of TPB. (c) 2007 Elsevier Ltd. All rights reserved.

Sources of Software Requirements Change from the Perspectives of Development and Maintenance

Changes to software requirements occur during initial development and subsequent to delivery, posing a risk to cost and quality while at the same time providing an opportunity to add value. Provision of a generic change source taxonomy will support requirements change risk visibility, and also facilitate richer recording of both pre- and post-delivery change data. In this paper we present a collaborative study to investigate and classify sources of requirements change, drawing comparison between those pertaining to software development and maintenance. We begin by combining evolution, maintenance and software lifecycle research to derive a definition of software maintenance, which provides the foundation for empirical context and comparison. Previously published change ‘causes’ pertaining to development are elicited from the literature, consolidated using expert knowledge and classified using card sorting. A second study incorporating causes of requirements change during software maintenance results in a taxonomy which accounts for the entire evolutionary progress of applications software. We conclude that the distinction between the terms maintenance and development is imprecise, and that changes to requirements in both scenarios arise due to a combination of factors contributing to requirements uncertainty and events that trigger change. The change trigger taxonomy constructs were initially validated using a small set of requirements change data, and deemed sufficient and practical as a means to collect common requirements change statistics across multiple projects.

Managing time: integration of care and paid work amongst low income families and the role of the United Kingdom’s tax credit system

Under the New Labour Governments in the UK, successive reforms of the tax and benefit system sought to improve the financial benefits of paid work. Drawing on two waves of qualitative interviews with low-income working families this article examines the role of the UK tax credit system in shaping decisions about employment and unpaid care work. The article suggests that the financial support provided for lone parent participants by the tax credit system enhanced their temporal autonomy, permitting participation in paid work to align more closely with temporally situated notions of parental responsibility for caring. For couple families however, parental perceptions of responsibility for pre-school children, along with childcare constraints and the structure of the tax credit system served to constrain the autonomy of the main carer and implicitly encourage a gendered specialisation in caring or employment.

Translating ‘gaytown’: the collision of global and local in bringing Australian queer play Bison to Belfast.

Sydney playwright Lachlan Philpott’s Bison (2000/2009) is immersed in a sweaty, summery Antipodean scene of bronzed and toned bodies. It is located in the flora and fauna of gum trees and biting ants. Yet, despite this, it could be argued that at its heart it is not a specifically Australian site, but an all-too translatable scene that seems to be played out in gay clubs, bars, chatrooms and saunas around the Western world: men repeating patterns, looking for sex or love; checking out bodies, craving perfection; avoiding, and occasionally seeking, disease. At least, that was my assumption when I decided to direct the play in Belfast, Northern Ireland, in 2009. Philpott came to Belfast to workshop the play with the actors and, as a group, we restructured the play and tried to find a way to ‘de-Australianise’ it without necessarily placing it in a new geographical place - Northern Ireland - through linguistic clues in the text. As Philpott put it: ‘Let’s not make this play about Belfast or Sydney or London or anywhere because it is not a fair reflection of these scenes. Maybe we should just identify the generic elements of this world and then make Bison a play that reflects gaytown – because the rituals are all the same in Western society’. The experience of doing the play in Belfast made clear, however, that ideas of a global gay identity/experience –though highly marketed – fail to account for the vastly different situations of embodied gay experience. And the Northern Irish gay experience, while it has imported the usual ‘generic’ tropes of gayness, sits within a specific cultural context in which the farsighted legislation on equality for gays (imposed by either London or the EU) vastly outstrips wider societal thinking. For many in Northern Ireland, erstwhile MP Iris Robinson’s comments about homosexuality being an ‘abomination’ were a reason to support her, rather than to reject her. For me, the comments were the catalyst to doing Bison in Belfast.

Deep molluscan phylogeny: synthesis of palaeontological and neontological data

The position of the earliest-derived living molluscs, the Polyplacophora ( chitons) and shell-less vermiform Aplacophora, remains highly contentious despite many morphological, developmental and molecular studies of extant organisms. These two groups are thought to represent either a basal molluscan grade or a clade (Aculifera) sister to the 'higher' molluscs (Conchifera). These incompatible hypotheses result in very different predictions about the earliest molluscs. A new cladistic analysis incorporating both Palaeozoic and extant molluscs is presented here. Our results support the monophyly of Aculifera and suggest that extant aplacophorans and polyplacophorans both derive from a disparate group of multivalved molluscs in two major clades. Reanalysis of the critical Ordovician taxon 'Helminthochiton' thraivensis shows that this animal lacks a true foot despite bearing polyplacophoran-like valves. Its position within our phylogenetic reconstruction indicates that many fossil 'polyplacophorans' in the order Palaeoloricata are likely to represent footless stem-group aplacophorans. 'H.' thraivensis and similar forms such as Acaenoplax may be morphological stepping stones between chitons and the shell-less aplacophorans. Our results imply that crown-group molluscan synapomorphies include serial repetition, the presence of a foot, a mineralized scleritome and a creeping rather than worm-like mode of life.

Potential output in a rapidly developing economy: the case of China and a comparison with the United States and the European Union

The authors use a growth accounting framework to examine growth of the rapidly developing Chinese economy. Their findings support the view that, although feasible in the intermediate term, China's recent pattern of extensive growth is not sustainable in the long run. The authors believe that China will be able to sustain a growth rate of 8 to 9 percent for an extended period if it moves from extensive to intensive growth. They next compare potential growth in China with historical developments in the United States and the European Union. They discuss the differences in production structure and level of development across the three economies that may explain the countries' varied intermediate-term growth prospects. Finally, the authors provide an analysis of "green" gross domestic product and the role of natural resources in China's growth. © 2009, The Federal Reserve Bank of St. Louis.

The role of infrequent and extraordinary deep dives in leatherback turtles (Dermochelys coriacea)

Infrequent and exceptional behaviours can provide insight into the ecology and physiology of a particular species. Here we examined extraordinarily deep (300-1250 m) and protracted (>1h) dives made by critically endangered leatherback turtles (Dermochelys coriacea) in the context of three previously suggested hypotheses: predator evasion, thermoregulation and exploration for gelatinous prey. Data were obtained via satellite relay data loggers attached to adult turtles at nesting beaches (N=11) and temperate foraging grounds (N=2), constituting a combined tracking period of 9.6 years (N=26,146 dives) and spanning the entire North Atlantic Ocean. Of the dives, 99.6% (N=26,051) were to depths <300 m with only 0.4% (N=95) extending to greater depths (subsequently termed 'deep dives'). Analysis suggested that deep dives: (1) were normally distributed around midday; (2) may exceed the inferred aerobic dive limit for the species; (3) displayed slow vertical descent rates and protracted durations; (4) were much deeper than the thermocline; and (5) occurred predominantly during transit, yet ceased once seasonal residence on foraging grounds began. These findings support the hypothesis that deep dives are periodically employed to survey the water column for diurnally descending gelatinous prey. If a suitable patch is encountered then the turtle may cease transit and remain within that area, waiting for prey to approach the surface at night. If unsuccessful, then migration may continue until a more suitable site is encountered. Additional studies using a meta-analytical approach are nonetheless recommended to further resolve this matter.

'Rule of Law and Politics of Anti-Corruption Campaigns in a Post-Authoritarian State- The Nigerian Case'

This article evaluates the anti-corruption campaign instituted in Nigeria following on the post-authoritarian transition in the country, with specific focus on political corruption. The anti-corruption campaign is being prosecuted within a context where law is as critical a factor as politics. This article examines whether the judiciary, in view of its accountability deficit, can offer legitimacy to the campaign. How has its questionable credentials impacted on its involvement in the campaign to sanitise public life? What has been the impact of the judicial role on the rule of law? These are some of the important questions this article seeks to answer. The inquiry in this article demonstrates how the guardian institution of the rule of law faces an uphill task in the performance of that role in a post-authoritarian context.

Dietary intake of fruits and vegetables improves microvascular function in hypertensive subjects in a dose-dependent manner

Background— Observational evidence has consistently linked increased fruit and vegetable consumption with reduced cardiovascular morbidity; however, there is little direct trial evidence to support the concept that fruit and vegetable consumption improves vascular function. This study assessed the dose-dependent effects of a fruit and vegetable intervention on arterial health in subjects with hypertension.

Methods and Results— After a 4-week run-in period during which fruit and vegetable intake was limited to 1 portion per day, participants were randomized to consume either 1, 3, or 6 portions daily for the next 8 weeks. Endothelium-dependent and -independent arterial vasodilator responses were assessed by venous occlusion plethysmography in the brachial circulation before and after intervention. Compliance was monitored with serial contemporaneous 4-day food records and by measuring concentrations of circulating dietary biomarkers. A total of 117 volunteers completed the 12-week study. Participants in the 1-, 3-, and 6-portions/d groups reported consuming on average 1.1, 3.2, and 5.6 portions of fruit and vegetables, respectively, and serum concentrations of lutein and ß-cryptoxanthin increased across the groups in a dose-dependent manner. For each 1-portion increase in reported fruit and vegetable consumption, there was a 6.2% improvement in forearm blood flow responses to intra-arterial administration of the endothelium-dependent vasodilator acetylcholine (P=0.03). There was no association between increased fruit and vegetable consumption and vasodilator responses to sodium nitroprusside, an endothelium-independent vasodilator.

Conclusions— The present study illustrates that among hypertensive volunteers, increased fruit and vegetable consumption produces significant improvements in an established marker of endothelial function and cardiovascular prognosis.