Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay

Background: The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents. Methods: In this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal compounds for potential anti-cancer stem cell (CSC) activity in vitro. Results: MCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days growth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an increase in the proportion of CD44high/CD24low marker-bearing cells and Oct4 expression compared to those in the bulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for the ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the polyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum, both of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed breast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the brown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent MCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel appeared to enhance mammosphere formation and development, a finding which is consistent with the reported resistance of CSCs to traditional chemotherapeutic agents. Conclusion: Due to the proposed clinical significance of CSC in terms of tumour initiation and metastasis, the identification of agents able to inhibit this subpopulation has clinical significance

A multi-model approach to stakeholder engagement in complex environmental problems

We describe the different types of models we used as part of an effort to inform policy-making aiming at the management of the Ningaloo coast in the Gascoyne region, Western Australia. This provides an overview of how these models interact, the different roles they cover, how they fit into a full decision making process and what we learnt about the stakeholders involved in our project via their use. When modelling is explicitly used to address socio-ecological issues, the key determinant of success is whether the models, their results and recommendations are taken up by stakeholders; such uptake in turn depends on addressing stakeholders’ concerns, on engaging them in the project, on ensuring they feel ownership of the decision process at large, and that they understand and trust the modelling effort. This observation has guided our approach and has resulted in treating ‘building a model’ as the catalyst, rather than the final aim, of the process. In other words, extensive interactions in order to introduce, showcase, discuss and tune the model used for final decision making have represented both a requirement and an opportunity to ensure (i) model relevance, (ii) its acceptance, (iii) that all information available in the stakeholder team was accounted for and (iv) that stakeholders holding different levels of understanding of modelling, what it does and what it can provide to decision-making could develop an informed opinion on its use. To fulfil these roles we developed five broad classes of models: conceptual models, toy-models, singlesystem models, shuttle-models and a full-system model. In conceptual models the main drivers of a system are highlighted for subsequent representation as components of the full-system model. This usually results in a diagram summarising our understanding of how the system works. In toy-models a problem is simplified in such a way that only a handful of components are included. The purpose of these models is mostly educational: we want to understand how each component affects the problem and in order to achieve this, we temporarily renounce a satisfactory understanding of the overall problem. In single-system models we include a fairly detailed representation of a single component of the system (in our case recreational fishing and tourism); these models can be used to introduce stakeholders to modelling, provide temporary results from the study of a single activity, which will feed into the development of the final full-system model, or address sector-specific issues. In shuttle-models, we include the minimum number of processes we believe are crucial for a basic understanding of the overall problem. We know these models are still too simple for full system description, but they provide a sufficient understanding to enable us to contemplate, build and use the more complex models needed for full problem description. The term ‘shuttle’ refers to taking us from a minimum to a full description of the problem, a journey which is necessary both to developers in model definition and parameterisation and to stakeholders in the interpretation of the final full-system model results. Finally, the full-system model includes all information collected through the project and addresses all scenarios of stakeholders concern, and whose definition has been greatly eased by use of the ‘simpler’ models. As an example, a conceptual model may identify fishing and tourism as the main drivers of a region; a toymodel may describe how catches affect fish stocks; a single-system model may include the effect of gear, regulations and other processes affecting recreational fishing; a shuttle-model may include a simplified representation of the interaction between fishing, tourism, and infrastructure development on the overall health of the local ecosystem; this will gradually ‘take’ us to comprehend the ‘full’ model which may include tourism pressure, fish market values, climate effect, larger food-webs, etc

'They’ve Got Their Wine Bars, We’ve Got Our Pubs’: Housing, diversity and community in two south London neighbourhoods

This chapter explores how housing policies and the nature of housing stock have conditioned residential geographies and diversity patterns in two south London neighbourhoods, Bermondsey and Camberwell. The key drivers are policy changes to social housing allocation and the post-industrial reconfiguration of urban space expressed in processes of gentrification and the redevelopment of riverside docklands into expensive housing units. These developments have challenged existing narratives of community, but they have also shifted the focus of analytical enquiry towards emerging us-them divides based on class and generation. Within the context of diversity and social cohesion, both neighbourhoods are characterized by a comparatively unproblematic day-to-day muddling along with difference, but also a generally declining level of civic engagement and neighbourhood cohesion, expressed by a sense of ‘living together apart

Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay:

The cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents

"Women's rights, the European Court and Supranational Constitutionalism"

This analysis examines supranational constitutionalism in the European Union. In particular, the study focuses on the role of the European Court of Justice in the creation of women’s rights. I examine the interaction between the Court and member state governments in legal integration, and also the integral role that women’s advocates – both individual activists and groups – have played in the development of EU social provisions. The findings suggest that this litigation dynamic can have the effect of fueling the integration process by creating new rights that may empower social actors and EU organizations, with the ultimate effect of diminishing member state government control over the scope and direction of EU law. This study focuses specifically on gender equality law, yet provides a general framework for examining the case law in subsequent legal domains, with the purpose of providing a more nuanced understanding of supranational governance and constitutionalism

Effect of Parameters on Oxychlorination of Tert-Butyl Ethers

The effect of concentration, molar ratios of reagents, pH, and temperature on formation of chloro-organic products in reaction of tert-butyl ethers with chloride ions and hydrogen peroxide has been determined. A significant effect of Cl− ions and H2O2 molar ratios on the rate of chloro-organic product formation has been observed. Studies on oxychlorination of tert-butylethyl ether (ETBE) at pH 7, 3.5, and 2.5 have been carried out. It was found that introduction of hydronium ions into the reaction system considerably hastened the process of chloro-organic product formation. Hydronium ions contribute to the formation of the reactive tert-butyl carbocation, which undergoes secondary reactions in the presence of reactive forms of chlorine and oxygen. Moreover, the effect of temperature on ETBE (tert-butylethyl ether) and MTBE (tert-butylmethyl ether) conversions was verified. The reactions of MTBE and ETBE oxychlorination were carried out at temperatures of 5°C, 20°C, and 35°C

Modern Special Collections Cataloguing: A University of London Case Study

Recent years have seen a growing emphasis on modern special collections (in themselves no new phenomenon), with a dichotomy between guidance for detailed cataloguing in Descriptive Cataloging of Rare Materials (Books) (DCRM(B), 2007) and the value of clearing cataloguing backlogs expeditiously. This article describes the De la Mare Family Archive of Walter de la Mare's Printed Oeuvre at Senate House Library, University of London, as an example of a modern author collections in an institutional library. It sets out the particular cataloguing challenges faced, looking at both general and copy-specific features and discussing the relation between bibliography and catalogue when no comprehensive bibliography exists. It confirms the adequacy of AACR2 for general cataloguing purposes, while noting the benefit of DCRM(B)’s more expansive copy-specific instructions

Extracellular Hsp90 and TGFP regulate adhesion, migration and anchorage independent growth in a paired colon cancer cell line model

Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-ß pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-ß pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown

Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The yield of charged particles associated with high-$p_{\rm T}$ trigger particles ($8 < p_{\rm T} < 15$ GeV/$c$) is measured with the ALICE detector in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jet-like correlation peaks in azimuthal di-hadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta $p_{\rm T}> 3$ GeV/$c$ on the away-side drops to about 60% of that observed in pp collisions, while on the near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388