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.

A burning issue? Governance and anti-incinerator campaigns in Ireland, North and South

The decades of conflict in Northern Ireland created divisions between communities, with few opportunities for cooperation. However, in the 1990s opposition to a proposed cross-border incinerator brought the divided communities together. The 1990s economic boom in the Republic of Ireland generated a waste management crisis as the by-products of rampant consumerism overwhelmed the state's rudimentary waste disposal system. Three Irish anti-incinerator campaigns which have pitted local communities against the Irish state or the Northern Ireland Department of the Environment are examined. Community attempts to gain leverage within the political governance frameworks in operation on both sides of the border are examined and the various ways in which environmental movements respond to the crisis of waste management under different governance regimes are illuminated.

Large acoustic solitons and double layers in plasmas with two positive ion species

Large nonlinear acoustic waves are discussed in a plasma made up of cold supersonic and adiabatic subsonic positive ions, in the presence of hot isothermal electrons, with the help of Sagdeev pseudopotential theory. In this model, no solitons are found at the acoustic speed, and no compositional parameter ranges exist where solutions of opposite polarities can coexist. All nonlinear modes are thus super-acoustic, but polarity changes are possible. The upper limits on admissible structure velocities come from different physical arguments, in a strict order when the fractional cool ion density is increased: infinite cold ion compression, warm ion sonic point, positive double layers, negative double layers, and finally, positive double layers again. However, not all ranges exist for all mass and temperature ratios. Whereas the cold and warm ion sonic point limitations are always present over a wide range of mass and temperature ratios, and thus positive polarity solutions can easily be obtained, double layers have a more restricted existence range, specially if polarity changes are sought. (C) 2011 American Institute of Physics. [doi:10.1063/1.3579397]

Mushroom: An Oracular Sound Processor

Composers of digital music today have a bewildering variety of sound-processing tools and techniques at their disposal. At their best, these tools allow composers to hone a sound to perfection. However, they can also lead us into a routine which bypasses avenues of experimentation, simply because the known tools work so well and their sonic output is so attractive. An alternative strategy is oracular sound processing. An oracular sound processor creates a derived version of its input whose characteristics could not have been fully predicted, while affording the user little or no parametric control over the process.

Evocative Listening : Mediated Practices in Everyday Life

The history of sonic arts is charged with transgressive practices that seek to expose the social, aural and cultural thresholds across various listening experiences, posing new questions in terms of the dialogue between listener and place. Recent work in sonic art exposes the need for an experiential understanding of listening that foregrounds the use of new personal technologies, environmental philosophy and the subject–object relationship. This paper aims to create a vocabulary that better contextualises recent installations and performances produced within the context of everyday life, by researchers and artists at the Sonic Arts Research Centre at Queen's University Belfast.

Dispelling the Myth of the Naive Investor during the British Railway Mania, 1845–46

Anecdotal evidence from the British Railway Mania and other historical financial bubbles suggests that many investors during such episodes are naive, thus contributing to the asset price boom. Using extensive investor records, we find that very few investors during the Railway Mania can be categorized as such. Although some interpretations of the Mania suggest that naive investors were expropriated by railway insiders, our evidence is inconsistent with this view as railway insiders contributed substantial amounts of capital, and their investments performed no better than those made by other experienced investors.

Soundweaving: Writings on Improvisation

This book consists of eight chapters with writings on improvisation and an introduction by one of the most intriguing improvisers of our generation – Evan Parker.
The initial discussions for this book were carried out during the “Two Thousand + TEN” symposium, which took place on the 6th of November 2010 at the Sonic Arts Research Centre in Belfast. The symposium’s theme was ‘improvisation’. Georgina Born and David Borgo gave keynote addresses, alongside many other excellent speakers, several of who are included in this book.
My contribution is a novel way of editing texts, as I have woven all chapters into an overall piece of writing, interlaced with my own contribution of around 40 pages.

Rock hyrax middens: A palaeoenvironmental archive for southern African drylands

Like many of the world's subtropical regions, southern Africa is highly sensitive to changes in the earth's climate system, but a dearth of reliable palaeoenvironmental records means that relatively little is known about how regional environments have been affected over centennial to multi-millennial timescales. To a large extent this sensitivity is a function of the position of these regions at the interface between temperate and tropical circulation systems. The resulting seasonality and irregularity of rainfall have limited the development of suitable archives, such as lakes and wetlands, for the preservation of palaeoenvironmental proxies.

This paper reviews and evaluates the value of rock hyrax middens as novel palaeoenvironmental archives in southern Africa. Considered are (1) the contemporary taxonomy, distribution and ecology of hyraxes, (2) the mechanisms of hyrax midden development, their physical and chemical structure, rates of accumulation and age; and (3) the palaeoenvironmental proxies preserved within hyrax middens, including fossil pollen, stable isotopes and biomarkers. The interpretive constraints and opportunities offered by these various midden characteristics are assessed with a view to demonstrating the potential of these deposits, widespread as they are through arid and semi-arid southern Africa, in providing a more detailed and chronologically resolved view of late Quaternary palaeoenvironments across the subcontinent. (C) 2012 Elsevier Ltd. All rights reserved.