The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, beingsignificantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression.

The role of glycans in the development and progression of prostate cancer

Prostate cancer is a unique and heterogeneous disease. Currently, a major unmet clinical need exists to develop biomarkers that enable indolent disease to be distinguished from aggressive disease. The prostate is an abundant secretor of glycoproteins of all types, and alterations in glycans are, therefore, attractive as potential biomarkers and therapeutic targets. Despite progress over the past decade in profiling the genome and proteome, the prostate cancer glycoproteome remains relatively understudied. A wide range of alterations in the glycoproteins on prostate cancer cells can occur, including increased sialylation and fucosylation, increased O-β-N-acetylglucosamine (GlcNAc) conjugation, the emergence of cryptic and high-mannose N-glycans and alterations to proteoglycans. Glycosylation can alter protein function and has a key role in many important biological processes in cancer including cell adhesion, migration, interactions with the cell matrix, immune surveillance, cell signalling and cellular metabolism; altered glycosylation in prostate cancer might modify some, or all of these processes. In the past three years, powerful tools such as glycosylation-specific antibodies and glycosylation gene signatures have been developed, which enable detailed analyses of changes in glycosylation. Thus, emerging data on these often overlooked modifications have the potential to improve risk stratification and therapeutic strategies in patients with prostate cancer.

The life of the Rev. Elisha Macurdy.

Mode of access: Internet.

Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability

Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl Lewis(X) (SLe(X)), O-GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.

Nowhere Landscape, for Clarinets, Trombones, Percussion, Violins, and Electronics and “The Map and the Territory: Documenting David Dunn’s Sky Drift”

1. nowhere landscape, for clarinets, trombones, percussion, violins, and electronics

nowhere landscape is an eighty-minute work for nine performers, composed of acoustic and electronic sounds. Its fifteen movements invoke a variety of listening strategies, using slow change, stasis, layering, coincidence, and silence to draw attention to the sonic effects of the environment—inside the concert hall as well as the world outside of it. The work incorporates a unique stage set-up: the audience sits in close proximity to the instruments, facing in one of four different directions, while the musicians play from a number of constantly-shifting locations, including in front of, next to, and behind the audience.

Much of nowhere landscape’s material is derived from a collection of field recordings

made by the composer during a road trip from Springfield, MA to Douglas, WY along US- 20, a cross-country route made effectively obsolete by the completion of I-90 in the mid- 20th century. In an homage to artist Ed Ruscha’s 1963 book Twentysix Gasoline Stations, the composer made twenty-six recordings at gas stations along US-20. Many of the movements of nowhere landscape examine the musical potential of these captured soundscapes: familiar and anonymous, yet filled with poignancy and poetic possibility.

2. “The Map and the Territory: Documenting David Dunn’s Sky Drift”

In 1977, David Dunn recruited twenty-six musicians to play his work Sky Drift in the

Anza-Borrego Desert in Southern California. This outdoor performance was documented with photos and recorded with four stationary microphones to tape. A year later, Dunn presented the work in New York City as a “performance/documentation,” playing back the audio recording and projecting slides. In this paper I examine the consequences of this kind of act: what does it mean for a recording of an outdoor work to be shared at an indoor concert event? Can such a complex and interactive experience be successfully flattened into some kind of re-playable documentation? What can a recording capture and what must it exclude?

This paper engages with these questions as they relate to David Dunn’s Sky Drift and to similar works by Karlheinz Stockhausen and John Luther Adams. These case-studies demonstrate different solutions to the difficulty of documenting outdoor performances. Because this music is often heard from a variety of equally-valid perspectives—and because any single microphone only captures sound from one of these perspectives—the physical set-up of these kind of pieces complicate what it means to even “hear the music” at all. To this end, I discuss issues around the “work itself” and “aura” as well as “transparency” and “liveness” in recorded sound, bringing in thoughts and ideas from Walter Benjamin, Howard Becker, Joshua Glasgow, and others. In addition, the artist Robert Irwin and the composer Barry Truax have written about the conceptual distinctions between “the work” and “not- the-work”; these distinctions are complicated by documentation and recording. Without the context, the being-there, the music is stripped of much of its ability to communicate meaning.

New light on the early history of the greater Northwest. The manuscript journals of Alexander Henry ... and of David Thompson ... 1799-1814. Exploration and adventure among the Indians on the Red, Saskatchewan, Missouri and Columbia rivers.

v. 1. The Red river of the North.--v. 2. The Saskatchewan and Columbia rivers.--v. 3. Index and maps.

The politics of literacy in David Almond and Dave McKean’s "The Savage" (2008)

Competency in language and literacy are central to contemporary debates about education in Anglophone nations around the world. This paper suggests that such debates are informing not just educational policy but children’s literature itself as can be seen in Almond and McKean’s The Savage. This hybrid text combines prose and graphic narrative and narration in order to tell the story of Blue, a young British boy negotiating his identity in the aftermath of his father's death. While foregrounding a narrative of ideal masculinity, The Savage enacts and privileges a formal and thematic ideal of literacy as index of individual agency and development. Almond and McKean produce a politicised understanding of language and literacy that simultaneously positions The Savage in a textual tradition of socio-culturally disenfranchised youth, and intervenes in that tradition to (perhaps ironically) affirm the very conditions previously critiqued by that very tradition. Where earlier authors such as Barry Hines sought to challenge normative accounts of language and literacy in order to indict educational policy and praxes, Almond and McKean work to naturalise the very logics of education and agency by which their protagonist has been disenfranchised. In doing so, The Savage exemplifies current approaches to education which claim to value social and cultural diversity while imposing national standardised testing predicated on assumptions about the legitimacy of uniform standards and definitions of literacy.

David Hicks and Cathie Holden (eds.) (2007). Teaching The Global Dimension. London: Routledge, Taylor & Francis Group, 212 pages.

Teaching The Global Dimension (2007) is intended for primary and secondary teachers, pre-service teachers and educators interested in fostering global concerns in the education system. It aims at linking theory and practice and is structured as follows. Part 1, the global dimension, proposes an educational framework for understanding global concerns. Individual chapters in this section deal with some educational responses to global issues and the ways in which young people might become, in Hick’s terms, more “world-minded”. In the first two chapters, Hicks presents first, some educational responses to global issues that have emerged in recent decades, and second, an outline of the evolution of global education as a specific field. As with all the chapters in this book, most of the examples are drawn from the United Kingdom. Young people’s concerns, student teachers’ views and the teaching of controversial issues, comprise the other chapters in this section. Taken collectively, the chapters in Part 2 articulate the conceptual framework for developing, teaching and evaluating a global dimension across the curriculum. Individual chapters in this section, written by a range of authors, explore eight key concepts considered necessary to underpin appropriate learning experiences in the classroom. These are conflict, social justice, values and perceptions, sustainability, interdependence, human rights, diversity and citizenship. These chapters are engaging and well structured. Their common format consists of a succinct introduction, reference to positive action for change, and examples of recent effective classroom practice. Two chapters comprise the final section of this book and suggest different ways in which the global dimension can be achieved in the primary and the secondary classroom.

An interview with Professor David Held : exploring the concepts of cosmopolitanism and democracy

David Held is the Graham Wallace Chair in Political Science, and co-director of LSE Global Governance, at the London School of Economics. He is the author of many works, such as Cosmopolitanism: Ideals and Realities (2010); The Cosmopolitanism Reader (2010), with Garrett Brown; Globalisation/AntiGlobalisation (2007), Models of Democracy (2006), Global Covenant (2004) and Global Transformations: Politics, Economics and Culture (1999). Professor Held is also the co-founder, alongside Lord Professor Anthony Giddens, of Polity Press. Professor Held is widely known for his work concerning cosmopolitan theory, democracy, and social, political and economic global improvement. His Global Policy Journal endeavours to marry academic developments with practitioner realities, and contributes to the understanding and improvement of our governing systems.

David F. Treagust : congenial soul, science educator, and international research leader

For almost a half century David F. Treafust has been an exemplary science educator who has contributed through his dedication and commitments to students, curriculum development and collaboration with teachers, and cutting edge research in science education that has impacted the field globally, nationally and locally. A hallmark of his outstanding career is his collaborative style that inspires others to produce their best work.

'In the hands of the Receivers': The Politics of Literacy in The Savage by David Almond and Dave McKean

David Almond and Dave McKean's The Savage is a hybrid prose and graphic novel which tells the story of one young man’s maturation through literacy. The protagonist learns to deal with the death of his father and his own 'savage' self by writing a graphic novel. This article reads The Savage in the context of earlier, 'Northern' literacy narrative - particularly Tony Harrison's poem "Them & [uz]" and Barry Hines' Kes — through the discourse of neoliberalism and the notion of the reluctant boy reader. It is suggested that Almond and McKean are influenced by currently dominant ideologies of gender and literacy.