Disruption of 3D MCF-12A breast cell cultures by estrogens - An in vitro model for ER-mediated changes indicative of hormonal carcinogenesis

Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.Introduction: Estrogens regulate the proliferation of normal and neoplastic breast epithelium. Although the intracellular mechanisms of estrogens in the breast are largely understood, little is known about how they induce changes in the structure of the mammary epithelium, which are characteristic of breast cancer. In vitro three dimensional (3D) cultures of immortalised breast epithelial cells recapitulate features of the breast epithelium in vivo, including formation of growth arrested acini with hollow lumen and basement membrane. This model can also reproduce features of malignant transformation and breast cancer, such as increased cellular proliferation and filling of the lumen. However, a system where a connection between estrogen receptor (ER) activation and disruption of acini formation can be studied to elucidate the role of estrogens is still missing. Methods/Principal Findings: We describe an in vitro 3D model for breast glandular structure development, using breast epithelial MCF-12A cells cultured in a reconstituted basement membrane matrix. These cells are estrogen receptor (ER)α, ERβ and G-protein coupled estrogen receptor 1 (GPER) competent, allowing the investigation of the effects of estrogens on mammary gland formation and disruption. Under normal conditions, MCF-12A cells formed organised acini, with deposition of basement membrane and hollow lumen. However, treatment with 17β-estradiol, and the exogenous estrogens bisphenol A and propylparaben resulted in deformed acini and filling of the acinar lumen. When these chemicals were combined with ER and GPER inhibitors (ICI 182,780 and G-15, respectively), the deformed acini recovered normal features, such as a spheroid shape, proliferative arrest and luminal clearing, suggesting a role for the ER and GPER in the estrogenic disruption of acinar formation. Conclusion: This new model offers the opportunity to better understand the role of the ER and GPER in the morphogenesis of breast glandular structure as well as the events implicated in breast cancer initiation and progression.This study was partly funded by a School of Pharmacy Studentship

Enlightenment versus Counter-Enlightenment: Isaiah Berlin's account on the sciences and the humanities

Isaiah Berlin, one of the most renowned liberal intellectuals of the twentieth century, dedicated his life to the study of ideas, demonstrating how their power influenced and changed world history. A defender of value pluralism, Berlin was against a priori, absolute truths and axiomatic premises safeguarded by the empiricist philosophers of the seventeenth and eighteenth centuries. This being said, in this paper I intend to give account of Isaiah Berlin’s ideas in regards to the divorce between the sciences and the humanities, which started with the seventeenth and eighteenth centuries’ champions of reason whose sole purpose was ‘to bring everything before the bar of reason’. Berlin gives us a very acute and precise lesson on how this growing tension and great divorce became clear since the seventeenth century up to the present day. An admirer of the Counter-Enlightenment philosophers – Vico, Herder and Hamann – Berlin denies the existence of a perfect world so much sought by the Enlightenment philosophes. This dichotomy will therefore be highlighted as a means to present Berlin’s position, that of agonistic liberalism and value-pluralism, always struggling for the importance of both the sciences and the humanities

Transformations of citizenship: politics of membership in Britain

Dating back from the French revolution, citizenship means a status that confers entitlements and benefits as well as obligations towards the state. Being a citizen is the legal state requirement to become part of the nation. National identity means inclusiveness and identifying oneself with a collective whole. Nonetheless, one can argue that concept has somehow transformed itself in its basic core. What is now the status of citizenship, in a world of gradually more deterritorialised politics? How is citizenship being reconfigured under contemporary conditions? Is postnational cosmopolitan solidarity, so proclaimed nowadays, really possible to attain? As a consequence of the world’s latest terrorist attacks, both in London and in Madrid, European governments are instigating a more controlled defence of the national territory. Therefore, new immigration laws are created within this new social and political context. This paper’s main purpose is to reflect on the politics of membership in Britain and the steps immigrants and ethnic minorities have to take in their journey to citizenship. Special emphasis will thus be put on the law and system of control which governs immigration and asylum in the UK. We will also make reference to the politics of membership carried on in other European countries, such as Portugal, Spain and France, in order to try to understand and compare the theory and practice of citizenship in different European countries

Living the British dream? Immigration, identity and the idea of citizenship in 21st century Britain

Based on the assumption that everyone should have the opportunity to live the British dream, Michael Howard’s 2005 Conservative Manifesto outlines a sense of nationhood, admiring excellence and encouraging ambition, whatever the background or colour of people’s skin. Would this be possible? Can’t we perceive in it a utopian desire to create a monoculture society? Would the same chances be given to everyone? Nonetheless, one of the main projects of the Conservative party is to set a limit on immigration in Britain. This paper’s main purpose is to reflect upon the causes and consequences of immigration in Britain and what the government intends to do to integrate multicultural and multiethnic societies in the mainstream culture. Special focus will be put on a specific community in Britain: the Pakistanis. The central concern of this paper is basically to highlight similarities and differences in the concept and exercise of citizenship in Britain.Fundação para a Ciência e a Tecnologi

Hoverfly (Diptera: Syrphidae) diversity in Tapada da Ajuda, Lisbon - a preliminary study

Hoverflies are holometabolic insects, whose adults are pollinators feeding on nectar and pollen. Frequently, they are confused with wasps, bees and bumblebees. In the larval stage, some of them prey other insects, specially aphids (Hemiptera), and others are saprophagous. For this reason, they are important biological control agents. In this study, we carried out the prospection and specific identification of hoverflies in four habitats in Tapada da Ajuda (olive grove, a field of Apiaceae, herbaceous vegetation near Lagoa Branca and plum orchard), between March and May 2017. Hoverfly adults were mostly captured with an entomologic net, but also with jar and plastic bags. A preliminary evaluation on the importance of ecologic infrastructure fava bean inter-row in the plum orchard was also performed. For this purpose, we observed fava plants and plum trees, collecting eggs, larvae and pupae of hoverflies that we reared in the laboratory until the emergence of the adult of hoverfly or parasitoid. A total of 12 species were identified, being the most frequent and abundant Episyrphus balteatus and Sphaerophoria scripta. Species richness was higher in the Apiaceae field although this habitat was sampled only during the last fortnight of the study. In the hoverfly immature collected in the plum orchard we detected hymenopteran parasitoids belonging to Diplazontinae and Pteromalidaeinfo:eu-repo/semantics/publishedVersio

Isaiah Berlin and the role of education: from Riga to Oxford

Being the result of a lecture to Latvian students in May 2011, this article aims at introducing Isaiah Berlin, who was born in Riga in 1909. The focus will be on the man and the intellectual, how his life experience (his childhood in Russia and the fact that he was an emigrant in Britain) affected his intellectual route, and how he became a defender of liberalism and value-pluralism. Furthermore, special attention will also be given to Berlin’s opinions on Education, the way he regarded the educational problems of his time and how education should be enhanced in order to escape from obscurantism and dogmatism towards a freer intellectual life and also to develop capacities for thought and feeling. Berlin believed education, and particularly university education, could be a powerful means to achieve these ends

On India de John Stuart Mill: barbárie versus civilização e a política de não intervenção

A defender of free-trade and an opponent of monopoly, John Stuart Mill advocated direct rule by the British in India and intended, like his father, to promote good and useful government. In his belief, the Indian native states needed someone who could guide them towards civilization. However, by the mid 1840s, Mill changed to a more moderate position. He thus defended non-intervention and indirect rule by the British in India. This paper’s main aim is therefore to assess Mill’s views on Indian society and on the nature and progress of British rule in India. Furthermore, we intend to highlight some contradictions on Mill’s defence of liberty in India and of his political ideas namely his liberal imperialism. John Stuart Mill (1806-1873) afigura-se um dos representantes máximos do liberalismo e um dos pensadores mais influentes do século XIX. Defendendo uma perspectiva política liberal da sociedade e assumindo-se como um utilitarista (Mill, Autobiography 181), Mill acreditava na importância fundamental da liberdade individual para o alcance da felicidade de cada um e para o progresso do conhecimento humano. Mill guiava-se igualmente por um espírito empirista, influenciado por Locke (1632-1704) e Hume (1711-1776), na prossecução da descoberta das verdades (Mill Autobiography 233). Contudo, distanciava-se do racionalismo calculista e desprovido de emoções em que o pai, James Mill (1773-1836), o educara. Todavia, deve ao pai o facto de lhe ter incutido valores morais como a justiça, a moderação, a perseverança, a preocupação com o bem público (Mill, Autobiography 49), que iriam guiá-lo ao longo da sua vida. Além disso, a possibilidade ilimitada do progresso da condição intelectual e moral da humanidade através da educação constitui talvez a doutrina mais importante herdada de seu pai e que Mill aplicou sempre nas suas teorias políticas e filosóficas (Mill, Autobiography 111).Fundação para a Ciência e para a Tecnologi

Liberal imperialism and the origins of Israel: the position of Isaiah Berlin

Isaiah Berlin, a British philosopher and historian of ideas,positioaed in favour oftfae creation ofthe State of Israel in 1948. Himself a Russian Jew, yet confessedly an anglophile, Berlin accounted for the advantages for the Jews ofhaving a place which they could call home. Claiming that Jews had no geography, only history, Berlm saw fhe creation of Israel as the emancipation of Jewish slavery and as the chance for the Jews to have their own nation, with coinmon national and cultural pattems, despite the difficulties it implied. Even though the state of Israel emerged with attributes quite different from those which anyone had previously mtended, there were by the time of its formation, several positions which were anticipated by the Jewish Diaspora in the world. On the one side, there were the Westem Jews and on the other the Bastem European Jews.Based on Berlia's own defence of Israel, it is this paper's main objective to analyse these distinct positions, focusing mainly on the British liberal conception of Israel, in its attempts to establish a civilising mission in the rather barbarous and undeveloped communities of the East

Cosmopolitanism and patriotism: questions of identity, membership and belonging

Must we choose between cosmopolitanism and patriotism or, as A. Kwame Appiah defends, can we be cosmopolitan patriots or rooted cosmopolitans? This paper’s main purpose is to reflect upon the similarities and differences of cosmopolitanism and patriotism, focussing on the problems of world citizenship and accounting for the role of local identities, nowadays