Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination

Progressive telomere shortening from cell division (replicative aging) provides a barrier for human tumor progression. This program is not conserved in laboratory mice, which have longer telomeres and constitutive telomerase. Wild species that do ⁄ do not use replicative aging have been reported, but the evolution of different phenotypes and a conceptual framework for understanding their uses of telomeres is lacking. We examined telomeres ⁄ telomerase in cultured cells from > 60 mammalian species to place different uses of telomeres in a broad mammalian context. Phylogeny-based statistical analysis reconstructed ancestral states. Our analysis suggested that the ancestral mammalian phenotype included short telomeres (< 20 kb, as we now see in humans) and repressed telomerase. We argue that the repressed telomerase was a response to a higher mutation load brought on by the evolution of homeothermy. With telomerase repressed, we then see the evolution of replicative aging. Telomere length inversely correlated with lifespan, while telomerase expression co-evolved with body size. Multiple independent times smaller, shorter-lived species changed to having longer telomeres and expressing telomerase. Trade-offs involving reducing the energetic ⁄ cellular costs of specific oxidative protection mechanisms (needed to protect < 20 kb telomeres in the absence oftelomerase) could explain this abandonment of replicative aging. These observations provide a conceptual framework for understanding different uses of telomeres in mammals, support a role for human-like telomeres in allowing longer lifespans to evolve, demonstrate the need to include telomere length in the analysis of comparative studies of oxidative protection in the biology of aging, and identify which mammals can be used as appropriate model organisms for the study of the role of telomeres in human cancer and aging. Key words: evolution of telomeres; immortalization; telomerase; replicative aging; senescence.

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammation

Salts responsive nanovesicles through π-stacking induced self-assembly of backbone modified tripeptides

A set of backbone modified peptides of general formula Boc-Xx-m-ABA-Yy-OMe where m-ABA is meta-aminobenzoic acid and Xx and Yy are natural amino acids such as Phe, Gly, Pro, Leu, Ile, Tyr and Trp etc., are found to self-assemble into soft nanovesicular structures in methanol-water solution (9:1 by v/v). At higher concentration the peptides generate larger vesicles which are formed through fusion of smaller vesicles. The formation of vesicles has been facilitated through the participation of various noncovalent interactions such as aromatic pi-stacking, hydrogen bonding and hydrophobic interactions. Model study indicates that the pi-stacking induced self-assembly, mediated by m-ABA is essential for well structured vesicles formation. The presence of conformationally rigid m-ABA in the backbone of the peptides also helps to form vesicular structures by restricting the conformational entropy. The vesicular structures get disrupted in presence of various salts such as KCl, CaCl(2), N(n-Bu)(4)Br and (NH(4))(2)SO(4) in methanol-water solution. Fluorescence microscopy and UV studies reveal that the soft nanovesicles encapsulate organic dye molecules such as Rhodamine B and Acridine Orange which could be released through salts induced disruption of vesicles.

Edward Bond & the celebrity of exile

A shibboleth has grown up around the work of Edward Bond. The tag ‘controversial dramatist’ has continued to dog both the man and his work. This article will hope to explore some of the contradictory, and sometimes frustrating manifestations that such ‘celebrity’ has produced. Since the reception of The War Plays [1985] by the Royal Shakespeare Company at the National Theatre Bond has largely withdrawn his work from mainstream British theatre. Since the late 1990s he has looked to a new home – La Colline Theatre – in France, to premiere new work and run retrospective seasons of older plays. Here, Bond's celebrity is of a different kind, and has allowed him to enhance and develop his work as a playwright, director and writer about theatre. While this article draws on secondary sources it also uses material based on personal correspondence with Edward Bond.

Britain and the Commonwealth: confronting the past - imagining the future

This is an extended version of Philip Murphy's inaugural lecture as director of the Institute of Commonwealth Studies, delivered on 23 February 2011. It traces the relationship of the UK with the wider Commonwealth over 40 years, paying particular attention to the rhetoric of governments and opposition parties from Wilson and Heath to Cameron. It examines the reasons for the Commonwealth being relegated to a peripheral role in British foreign policy, especially European preoccupations and the issues of Rhodesia and South Africa. It argues that the Commonwealth remains of considerable practical and enormous symbolic importance to the UK. The British government should engage with the Commonwealth more than it has done in the recent past and the Commonwealth should be both open to and critical of its imperial past.

The Greenland Ice Sheet's surface mass balance in a seasonally sea-ice free Arctic

General circulation models predict a rapid decrease in sea ice extent with concurrent increases in near surface air temperature and precipitation in the Arctic over the 21st century. This has led to suggestions that some Arctic land ice masses may experience an increase in accumulation due to enhanced evaporation from a seasonally sea ice free Arctic Ocean. To investigate the impact of this phenomenon on Greenland ice sheet climate and surface mass balance (SMB) a regional climate model, HadRM3, was used to force an insolation-temperature melt SMB model. A set of experiments designed to investigate the role of sea ice independently from sea surface temperature (SST) forcing are described. In the warmer and wetter SI + SST simulation Greenland experiences a 23% increase in winter SMB but 65% reduced summer SMB, resulting in a net decrease in the annual value. This study shows that sea ice decline contributes to the increased winter balance, causing 25% of the increase in winter accumulation; this is largest in eastern Greenland as the result of increased evaporation in the Greenland Sea. These results indicate that the seasonal cycle of Greenland's SMB will increase dramatically as global temperatures increase, with the largest changes in temperature and precipitation occurring in winter. This demonstrates that the accurate prediction of changes in sea ice cover is important for predicting Greenland SMB and ice sheet evolution.

Sir Bernard Spilsbury: a survey and catalogue of his autopsy case cards from the Wellcome Library, London

During his lifetime, Sir Bernard Spilsbury was referred to as the ‘‘father of forensic medicine.’’ He became a household name as a result of several famous cases. Several articles have been written about his life and work, but an objective assessment has proved difficult because of the lack of available material that Spilsbury himself produced. His main legacy has been a series of case cards, but for many years these were unavailable to the researcher. In 2008, a collection of some 4000 of Spilsbury’s case cards was bought by The Wellcome Library in London and therefore entered the public domain. In this article, we report our study of 650 of these cards. We discuss trends in Spilsbury’s work and several specific cases in more detail. These cards allow an objective view to be taken of Spilsbury’s everyday work, and we feel that some reappraisal of his legacy is now timely

Widespread supplementary feeding in domestic gardens explains the return of reintroduced Red Kites Milvus milvus to an urban area

Reintroductions are used worldwide to mitigate biodiversity loss. One prominent case is a charismatic raptor of conservation concern, the Red Kite Milvus milvus. This species has been reintroduced across the UK over the last 25 years following its near extinction after centuries of persecution. The species was not expected to recolonize urban areas; its historical association with human settlements is attributed to scavenging on human waste and refuse, a resource now greatly reduced on the streets of modern Western cities. However, the species has become a common day-time visitor to a large conurbation centred on the town of Reading, southern England, approximately 20 km from the first English reintroduction site. Given a near-absence of breeding and roost sites, we investigated foraging opportunities and habitat associations that might explain use by Red Kites of this urban area. Surveys of discarded human foods and road-kill suggested that these could support at most 13−29 kites/day. Face-to-face surveys of a cross-section of residents revealed that 4.5% (equivalent to 4349 households) provided supplementary food for kites. Using estimates of per-household resource provision from another study, we calculated that this level is potentially sufficient to provision 142−320 kites, a substantial proportion of the total estimated to visit the conurbation each day (between 140 and 440). Road transects found positive associations between Red Kites and residential areas. We therefore suggest that the decision made by thousands of individuals to provide supplementary food for Red Kites is the primary factor explaining their day-time abundance in this urban area.

Bioinspired autonomous visual vertical control of a quadrotor unmanned aerial vehicle

Near-ground maneuvers, such as hover, approach, and landing, are key elements of autonomy in unmanned aerial vehicles. Such maneuvers have been tackled conventionally by measuring or estimating the velocity and the height above the ground, often using ultrasonic or laser range finders. Near-ground maneuvers are naturally mastered by flying birds and insects because objects below may be of interest for food or shelter. These animals perform such maneuvers efficiently using only the available vision and vestibular sensory information. In this paper, the time-tocontact (tau) theory, which conceptualizes the visual strategy with which many species are believed to approach objects, is presented as a solution for relative ground distance control for unmanned aerial vehicles. The paper shows how such an approach can be visually guided without knowledge of height and velocity relative to the ground. A control scheme that implements the tau strategy is developed employing only visual information from a monocular camera and an inertial measurement unit. To achieve reliable visual information at a high rate, a novel filtering system is proposed to complement the control system. The proposed system is implemented onboard an experimental quadrotor unmannedaerial vehicle and is shown to not only successfully land and approach ground, but also to enable the user to choose the dynamic characteristics of the approach. The methods presented in this paper are applicable to both aerial and space autonomous vehicles.

Object-love at the Science Museum: cultural geographies of museum storerooms

The field of museum geography is taking on new significance as geographers and museum-studies scholars make sense of the spatial relations between the people, things, practices and buildings that make and remake museums. In order to strengthen this spatial interest in museums, this paper makes important connections between recent work in cultural geography and museum studies on love, materiality and the museum effect. This paper marks a departure from the preoccupation with the public spaces of museums to go behind the scenes of the Science Museum in London to explore its rarely visited, but nonetheless lively, small-to-medium-sized object storerooms at Blythe House. Incorporating field diary entries and interview extracts from two research projects based upon the museum storerooms at Blythe House, this paper brings to life the social interactions that take place between museum curators and conservators and the objects they care for. This focus on object-love enables scholars to consider anew what museums are and what they are for, the life of the museum object in the storeroom, and the emotional practices of professional curatorship and conservation. This journey into the storeroom at Blythe House makes explicit how object-love shapes museum space.

Treatment non-adherence in teenage and young adult patients with cancer

Adhering to treatment can be a significant issue for many patients diagnosed with chronic health conditions and this has been reported to be greater during the adolescent years. However, little is known about treatment adherence in teenage and young adult (TYA) patients with cancer. To increase awareness of the adherence challenges faced by these patients, we have reviewed the published work. The available evidence suggests that a substantial proportion of TYA patients with cancer do have difficulties, with reports that up to 63% of patients do not adhere to their treatment regimens. However, with inconsistent findings across studies, the true extent of non-adherence for these young patients is still unclear. Furthermore, it is apparent that there are many components of the cancer treatment regimen that have yet to be assessed in relation to patient adherence. Factors that have been shown to affect treatment adherence in TYA patients include patient emotional functioning (depression and self-esteem), patient health beliefs (perceived illness severity and vulnerability), and family environment (parental support and parent–child concordance). Strategies that foster greater patient adherence are also identified. These strategies are multifactorial, targeting not only the patient, but the health professional, family, and treatment regimen. This review highlights the lack of interventional studies addressing treatment adherence in TYA patients with cancer, with only one such intervention being identified: a video game intervention focusing on behavioural issues related to cancer treatment and care. Methodological issues in measuring adherence are addressed and suggestions for improving the design of future adherence studies highlighted, of which there is a great need.

Standing on the shoulders of giants: an examination of the interdisciplinary foundation of relationship marketing

In the 20th century, the scholarly study of human relationships both grew dramatically and simultaneously fragmented into various disciplines and subdisciplines. Although diversity of thought is generally considered helpful for the evolution of scientific fields, the value accrued from interdisciplinary discourse depends on the ability of scholars to integrate multiple perspectives and synthesize foundational works in a systematic manner. The goal of this study is to synthesize foundational theories from social and behavioral sciences that have contributed to an understanding of relationship marketing. In seeking to provide a holistic understanding of the field, we incorporate contributions from the disciplines of marketing, management, psychology, and sociology. In building on our analysis, we synthesize our findings into a conceptual model that examines the systematic dimensions of relationship marketing. The article concludes by identifying key themes for contributors to the Journal of Relationship Marketing to consider going forward.

Mining in Ghana’s forests: cross-sectoral linkages and the prospects for REDD

Strategies to Reduce Emissions from Deforestation and Degradation (REDD) are being pursued in numerous developing countries. Proponents contest that REDD mechanisms could deliver sustainable development by contributing to both environmental protection and economic development, particularly in poor forest communities. However, among the challenges to REDD, and natural resource management more generally, is the need to develop a comprehensive understanding of cross-sectoral linkages and addressing how they impact the pursuit of sustainable development. Drawing on an exploratory case-study of Ghana, this paper aims to outline the linkages between the forestry and minerals sectors. It is argued that contemporary debates give incommensurate attention to the reclamation of large-scale mine sites located in forest reserves, and neglect to consider more nuanced links which characterise the forestry-mining nexus in Ghana. A review of key stakeholders further elucidates the complex networks which characterise these linkages and highlights the important role of traditional authorities in governing across sectors. If the multiple roles of local resource users and traditional authorities continue to be neglected in policy mechanisms, schemes such as REDD will continue to fall short of achieving sustainable development.

Adaptation of Rhizobium leguminosarum to pea, alfalfa and sugar beet rhizospheres investigated by comparative transcriptomics

Background The rhizosphere is the microbe-rich zone around plant roots and is a key determinant of the biosphere's productivity. Comparative transcriptomics was used to investigate general and plant-specific adaptations during rhizosphere colonization. Rhizobium leguminosarum biovar viciae was grown in the rhizospheres of pea (its legume nodulation host), alfalfa (a non-host legume) and sugar beet (non-legume). Gene expression data were compared to metabolic and transportome maps to understand adaptation to the rhizosphere. Results Carbon metabolism was dominated by organic acids, with a strong bias towards aromatic amino acids, C1 and C2 compounds. This was confirmed by induction of the glyoxylate cycle required for C2 metabolism and gluconeogenesis in all rhizospheres. Gluconeogenesis is repressed in R. leguminosarum by sugars, suggesting that although numerous sugar and putative complex carbohydrate transport systems are induced in the rhizosphere, they are less important carbon sources than organic acids. A common core of rhizosphere-induced genes was identified, of which 66% are of unknown function. Many genes were induced in the rhizosphere of the legumes, but not sugar beet, and several were plant specific. The plasmid pRL8 can be considered pea rhizosphere specific, enabling adaptation of R. leguminosarum to its host. Mutation of many of the up-regulated genes reduced competitiveness for pea rhizosphere colonization, while two genes specifically up-regulated in the pea rhizosphere reduced colonization of the pea but not alfalfa rhizosphere. Conclusions Comparative transcriptome analysis has enabled differentiation between factors conserved across plants for rhizosphere colonization as well as identification of exquisite specific adaptation to host plants.