Extracellular BMP-antagonist regulation in development and disease: tied up in knots

Developmental processes are regulated by the bone morphogenetic protein (BMP) family of secreted molecules. BMPs bind to serine/threonine kinase receptors and signal through the canonical Smad pathway and other intracellular effectors. Integral to the control of BMPs is a diverse group of secreted BMP antagonists that bind to BMPs and prevent engagement with their cognate receptors. Tight temporospatial regulation of both BMP and BMP-antagonist expression provides an exquisite control system for developing tissues. Additional facets of BMP-antagonist biology, such as crosstalk with Wnt and Sonic hedgehog signaling during development, have been revealed in recent years. In addition, previously unappreciated roles for the BMP antagonists in kidney fibrosis and cancer have been elucidated. This review provides a description of BMP-antagonist biology, together with highlights of recent novel insights into the role of these antagonists in development, signal transduction and human disease.

RUNX3 protein is overexpressed in human basal cell carcinomas

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

Sonic Geography, Place and Race in the Formation of Local Identity: Liverpool and Scousers

The concept of identity has attracted significant academic attention. This article unpacks what constitutes the Scouse identity, how it is constructed and its different dimensions, with particular reference to place, phonology and race. Its novelty lies in developing the underused concept of “sonic geography” to examine the extent to which sound, for example a distinctive accent and/or dialect, affects the construction of local identity. Empirically this is conducted through a detailed analysis of the Scouse, or Liverpudlian, identity. The article also deploys the concept of “sonic exclusion” to examine the role a distinguishing vernacular plays in shaping local identity and the extent to which it determines “who is in” and “who is out” as a Scouser. The conclusion is that an effective understanding of a Scouser is not only spatial – someone born in Liverpool – because the sonoric landscape of spoken Scouse, and thereby Scouse identity, extends beyond the contemporary political and geographic boundaries of the City of Liverpool.

THE PRIMARY STRUCTURE OF PANCREATIC-POLYPEPTIDE FROM A PRIMITIVE INSECTIVOROUS MAMMAL, THE EUROPEAN HEDGEHOG (ERINACEOUS-EUROPAEUS)

Pancreatic polypeptide (PP) has been isolated from extracts of the pancreas of the European hedgehog (Erinaceous europaeus) which is a representative of the order Insectivora, deemed to be the most primitive group of placental mammals. Pancreatic tissues were extracted in acidified ethanol and the peptide was purified chromatographically using a PP C-terminal hexapeptide amide specific radioimmunoassay to monitor purification. Two major PP-immunoreactive peptides were baseline-resolved following the final analytical reverse phase HPLC fractionation. Each was separately subjected to plasma desorption mass spectroscopy (PDMS) and gas-phase sequencing. The molecular masses of each peptide were similar: (I) 4237.6 +/- 4 Da and (II) 4238.2 +/- 4 Da. The full primary structures of each peptide were deduced and these were identical: VPLEPVYPGDNATPEQMAHYAAELRRYINMLTRPRY. The peptides were deemed to be amidated due to their full molar cross-reactivity with the amide-requiring PP antiserum employed in radioimmunoassay. The molecular mass (4233.8 Da) calculated from the sequence was in close agreemeent with PDMS estimates and the reason for the different retention times of each peptide is unknown at present. Hedgehog PP exhibits only 2 unique amino acid substitutions, at positions 1 (Val) and 19 (His), when compared with other mammalian analogues.

"Variations on Psycho Killer" - Musical Score. Commissioned by Pauline Kim Harris. A virtuosic set of variations on the famous Talking Heads song for solo violin. General information State: Unpublished Organisations: School of Creative Arts, Sonic Arts, UOA35 - Music, Drama, Dance and Performing Arts Authors: Lyon, E. Keywords: (Talking Heads, Violin Music) Publication date: 2012

Musical Score. Commissioned by Pauline Kim Harris. A virtuosic set of variations on the famous Talking Heads song for solo violin.

"The End" for piano and computer. Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC. General information State: Published Organisations: School of Creative Arts, Sonic Arts, UOA35 - Music, Drama, Dance and Performing Arts Authors: Lyon, E.

Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC.

Every Situation has its Rhythm: Acoustic Mimesis and Sonic Exoticism in Tambours Sur La Digue.

This article examines the soundscapes of Ariane Mnouchkine’s Tambours Sur La Digue and explores the concept of acoustic mimesis located in the performance as a dramaturgical strategy to create, aurally, an imagined Far East. In Tambours, mimesis is the performative principle exemplified by the presentation of the mise en scène, and most distinctly Mnouckine’s decision to adapt the Japanese performance tradition of Bunraku through a process of 'reversed' mimicry (in which human bodies simulate the wooden marionettes of the Japanese style). Mimesis pervades the acoustemologies of the performance as it is heard in the extracted sounds, styles, and rhythms of Asian musical modes and movements that consequently become dislocated from context; the sounds become imitated, iconicised and exoticised as sonic signatures as they reify the Orientalist spectacle. The 'oriental' soundscape, reverberating with exotic overtones, becomes the means by which the production creates an imaginary Orient – one in which the Orient Other is silenced, and is resounded only through the musical sensibilities of the Occidental Self.

Big Ears – sonic art for public ears: Reflections on collaborative training

This text critically reflects on the higher education public engagement training program, entitled ‘Big Ears – sonic art for public ears’. The authors detail the objectives and aims as well as the benefits of this initiative for the enhancement of the student learning experience. We consider Schmidt’s (Schmidt, 2012) notion of mis-listening and Christopher Small’s concept of ‘musicking’ (Small, 1998), and develop a critical argument on how public engagement has changed researchers’ views and attitudes about their own research. The text explores how the creative interaction with a young audience has had great impact on the students’ learning experience as well as on their employability/transferable skills, because Big Ears stresses the importance of pulling practice as research away from the academic argument of why artists should be supported inside an institution, and into the realm of the real – what to do when making art, how to make it relevant and applicable to audiences.

Inhabiting Sound: Tactile-sonic links in musical meaning

Connections can be suggested between music’s occupation of physical space, its relative ‘presence’ (using Edward Hall’s notion of proxemics), and the various senses of movement which pervade it. Movement might be seen to operate with respect to music at a variety of levels of metaphorisation – as increasingly complex chains of analogy which point back to our early physical experience of the world. But of course music is, fundamentally, action. Humans put energy into systems - external or internal to themselves - which transduce that energy into the movement of air. At the acoustic level music is, emphatically and unmetaphorically, movement. Perhaps such simple physical perceptions form one route through which we might understand and explore shared senses of meaning and their capacity for ‘transduction’ between multiple individuals. Our (developmentally) early sensory models of the world, built from encounters with its physical resistances and affordances, might be a route to understanding our more clearly encultured and abstracted ('higher' level) understandings of music.