Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma

The t(4;14)(p16;q32) translocation seen in c. 18% of newly diagnosed multiple myeloma (MM) cases, results in FGFR3 activation and creation of an IGH/MMSET fusion transcript. We have recently shown that FGFR3 is activated in only 75% of t(4;14)(+) cases, suggesting that alternative genes near the breakpoint may be involved in the transforming event. The gene, TACC3, located just 50 kb telomeric of FGFR3, with transforming capacity, therefore represented a candidate gene. Using a real-time quantitative polymerase chain reaction-based approach on a cohort of 54 patients, we found a statistically significant, twofold increase in TACC3 expression in t(4;14)(+) cases. TACC3, MMSET and p21 values were positively correlated in all cases and, of particular interest, six patient samples [three t(4;14)(-), three t(4;14)(+)] samples showed a joint up-regulation of TACC3, MMSET and p21. Although a poor prognosis is linked with elevated MMSET expression, an extended follow-up period will be required to evaluate the significance of elevated TACC3 and p21 expression in this subgroup of MM.

AINT/ERIC/TACC: an expanding family of proteins with C-terminal coiled coil domains:an expanding family of proteins with C-terminal coiled coil domains

The AINT/ERIC/TACC genes encode novel proteins with a coiled coil domain at their C-terminus. The founding member of this expanding family of genes, transforming acidic coiled coil 1 (TACC1), was isolated from a BAC contig spanning the breast cancer amplicon-1 on 8p11. Transfection of cells in vitro with TACC1 resulted in anchorage-independent growth consistent with a more "neoplastic" phenotype. Database searches employing the human TACC1 sequence revealed other novel genes, TACC2 and TACC3, with substantial sequence homology particularly in the C-terminal regions encoding the coiled coil domains. TACC2, located at 10q26, is similar to anti-zuai-1 (AZU-1), a candidate breast tumour suppressor gene, and ECTACC, an endothelial cell TACC which is upregulated by erythropoietin (Epo). The murine homologue of TACC3, murine erythropoietin-induced cDNA (mERIC-1) was also found to be upregulated by Epo in the Friend virus anaemia (FVA) model by differential display-PCR. Human ERIC-1, located at 4p16.3, has been cloned and encodes an 838-amino acid protein whose N- and C-terminal regions are highly homologous to the shorter 558-amino acid murine protein, mERIC-1. In contrast, the central portions of these proteins differ markedly. The murine protein contains four 24 amino acid imperfect repeats. ARNT interacting protein (AINT), a protein expressed during embryonic development in the mouse, binds through its coiled coil region to the aryl hydrocarbon nuclear translocator protein (ARNT) and has a central portion that contains seven of the 24 amino acid repeats found in mERIC-1. Thus mERIC-1 and AINT appear to be developmentally regulated alternative transcripts of the gene. Most members of the TACC family discovered so far contain a novel nine amino acid putative phosphorylation site with the pattern [R/K]-X(3)-[E]-X(3)-Y. Genes with sequence homology to the AINT/ERIC/TACC family in other species include maskin in Xenopus, D-TACC in Drosophila and TACC4 in the rabbit. Maskin contains a peptide sequence conserved among eIF-4E binding proteins that is involved in oocyte development. D-TACC cooperates with another conserved microtubule-associated protein Msps to stabilise spindle poles during cell division. The diversity of function already attributed to this protein family, including both transforming and tumour suppressor properties, should ensure that a new and interesting narrative is about to unfold.

Contesting public accountability: A dialogical exploration of accountability and social housing

This paper analyses the interaction between neoliberal inspired reforms of public services and the mechanisms for achieving public accountability. Where once accountability was exercised through the ballot box, now in the neoliberal age managerial and market based forms of accountability predominate. The analysis identifies resistance from civil society campaigns to the neoliberal restructuring of public services which leads to public accountability (PA) becoming a contested arena. To develop this analysis a re-theorisation of PA, as a relationship where civil society seeks to control the state, is explored in the context of social housing in England over the past thirty years. Central to this analysis is a dialogical analysis of key documents from a social housing regulator and civil society campaign. The analysis shows that the current PA practices are an outcome of both reforms from the government and resistance from civil society (in the shape of tenants’ campaigns). The outcome of which is to tell the story of the changes in PA (and accountability) centring on an analysis of discourse. Thus, the paper moves towards answering the question – what has happened to PA during the neoliberal age?

Investigating Hydraulically Active Fractures in A Shallow Meta-Sedimentary Bedrock Aquifer Using Single Well Tracer Testing, Mount Stewart, Northern Ireland

Knowledge of groundwater flow/mass transport, in poorly productive aquifers which underlie over 65% of the island of Ireland, is necessary for effective management of catchment water quality and aquatic ecology. This research focuses on a fractured low-grade Ordovician/Silurian greywacke sequence which underlies approximately 25% of the northern half of Ireland. Knowledge of the unit’s hydrogeological properties remain largely restricted to localised single well open hole “transmissivity” values. Current hydrogeological conceptual models of the Greywacke view the bulk of groundwater flowing through fractures in an otherwise impermeable bedrock mass.
Core analysis permits fracture characterisation, although not all identified fractures may be involved in groundwater flow. Traditional in-situ hydraulic characterisation relies on cumbersome techniques such as packer testing or geophysical borehole logging (e.g. flowmeters). Queen’s University Belfast is currently carrying out hydraulic characterization of 16 boreholes at its Greywacke Hydrogeological Research Site at Mount Stewart, Northern Ireland.
Development of dye dilution methods, using a recently-developed downhole fluorometer, provided a portable, user-friendly, and inexpensive means of detecting hydraulically active intervals in open boreholes. Measurements in a 55m deep hole, three days following fluorescent dye injection, demonstrated the ability of the technique to detect two discrete hydraulically active intervals corresponding to zones identified by caliper and heat-pulse flowmeter logs. High resolution acoustic televiewer logs revealed the zones to correspond to two steeply dipping fractured intervals. Results suggest the rock can have effective porosities of the order of 0.1%.
Study findings demonstrate dye dilution’s utility in characterizing groundwater flow in fractured aquifers. Tests on remaining holes will be completed at different times following injection to identify less permeable fractures and develop an improved understanding of the structural controls on groundwater flow in the uppermost metres of competent bedrock.