Comparative analysis of dna methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Previous reports have shown that DNA methylation profiles within primary human malignant tissues are altered when these cells are transformed into cancer cell lines. However, it is unclear if similar differences in DNA methylation profiles exist between DNA derived from peripheral blood leukocytes (PBLs) and corresponding Epstein-Barr Virus transformed lymphoblastoid cell lines (LCLs). To assess the utility of LCLs as a resource for methylation studies we have compared DNA methylation profiles in promoter and 5' regions of 318 genes in PBL and LCL sample pairs from patients with type 1 diabetes with or without nephropathy. We identified a total of 27 (similar to 8%) genes that revealed different DNA methylation profiles in PBL compared with LCL-derived DNA samples. In conclusion, although the profiles for most promoter regions were similar between PBL-LCL pairs, our results indicate that LCL-derived DNA may not be suitable for DNA methylation studies at least in diabetic nephropathy.

Restraing Regulatory Capture? Anglo America, Crisis Politics and Trajectories of Change in Global Financial Governance

A growing number of respected commentators now argue that regulatory capture of public agencies and public policy by leading banks was one of the main causal factors behind the financial crisis of 2007–2009, resulting in a permissive regulatory environment. This regulatory environment placed a faith in banks own internal risk models, contributed to pro-cyclical behaviour and turned a blind eye to excessive risk taking. The article argues that a form of ‘multi-level regulatory capture’ characterized the global financial architecture prior to the crisis. Simultaneously, regulatory capture fed off, but also nourished the financial boom, in a fashion that mirrored the life cycle of the boom itself. Minimizing future financial booms and crises will require continuous, conscious and explicit efforts to restrain financial regulatory capture now and into the future. The article assesses the extent to which this has been achieved in current global financial governance reform efforts and highlights some of the persistent difficulties that will continue to hamper efforts to restrain regulatory capture. The evidence concerning the extent to which regulatory capture is being effectively restrained is somewhat mixed, and where it is happening it is largely unintentional and accidental. Recent reforms have overlooked the political causes of the crisis and have failed to focus explicitly or systematically on regulatory capture.

Acoustic solitary waves in dusty and/or multi-ion plasmas with cold, adiabatic, and hot constituents

Large nonlinear acoustic waves are discussed in a four-component plasma, made up of two superhot isothermal species, and two species with lower thermal velocities, being, respectively, adiabatic and cold. First a model is considered in which the isothermal species are electrons and ions, while the cooler species are positive and/or negative dust. Using a Sagdeev pseudopotential formalism, large dust-acoustic structures have been studied in a systematic way, to delimit the compositional parameter space in which they can be found, without restrictions on the charges and masses of the dust species and their charge signs. Solitary waves can only occur for nonlinear structure velocities smaller than the adiabatic dust thermal velocity, leading to a novel dust-acoustic-like mode based on the interplay between the two dust species. If the cold and adiabatic dust are oppositely charged, only solitary waves exist, having the polarity of the cold dust, their parameter range being limited by infinite compression of the cold dust. However, when the charges of the cold and adiabatic species have the same sign, solitary structures are limited for increasing Mach numbers successively by infinite cold dust compression, by encountering the adiabatic dust sonic point, and by the occurrence of double layers. The latter have, for smaller Mach numbers, the same polarity as the charged dust, but switch at the high Mach number end to the opposite polarity. Typical Sagdeev pseudopotentials and solitary wave profiles have been presented. Finally, the analysis has nowhere used the assumption that the dust would be much more massive than the ions and hence, one or both dust species can easily be replaced by positive and/or negative ions and the conclusions will apply to that plasma model equally well. This would cover a number of different scenarios, such as, for example, very hot electrons and ions, together with a mix of adiabatic ions and dust (of either polarity) or a very hot electron-positron mix, together with a two-ion mix or together with adiabatic ions and cold dust (both of either charge sign), to name but some of the possible plasma compositions.

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.