Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential

The human Werner and Bloom syndromes (WS and BS) are caused by deficiencies in the WRN and BLM RecQ helicases, respectively. WRN, BLM and their Saccharomyces cerevisiae homologue Sgs1, are particularly active in vitro in unwinding G-quadruplex DNA (G4-DNA), a family of non-canonical nucleic acid structures formed by certain G-rich sequences. Recently, mRNA levels from loci containing potential G-quadruplex-forming sequences (PQS) were found to be preferentially altered in sgs1Δ mutants, suggesting that G4-DNA targeting by Sgs1 directly affects gene expression. Here, we extend these findings to human cells. Using microarrays to measure mRNAs obtained from human fibroblasts deficient for various RecQ family helicases, we observe significant associations between loci that are upregulated in WS or BS cells and loci that have PQS. No such PQS associations were observed for control expression datasets, however. Furthermore, upregulated genes in WS and BS showed no or dramatically reduced associations with sequences similar to PQS but that have considerably reduced potential to form intramolecular G4-DNA. These findings indicate that, like Sgs1, WRN and BLM can regulate transcription globally by targeting G4-DNA

Procurement impacts on construction supply chains: UK experiences

SCM has long been advocated as a means of improving the performance of supply chains in construction. SCM can be defined as a network of different organisations, linked upstream and downstream in a chain, aiming to produce quality and value in the services and products for the end consumers through integrated processes and activities. The drive for SCM has frequently come from the public and private sector client base. With one of the purposes being to achieve increased levels of integration of the whole supply chain, the industry has had to respond to drivers embedded in the changed procurement arrangements that have been implemented. This paper reports on an investigation into the impact of changed procurement systems on supply chain firms in the UK. It will discuss different initiatives by clients and by the UK government in order to drive some form of supply chain integration

Interventions to manage trust in construction projects

Trust is described as an elusive concept, difficult to describe, understand, and therefore manage. The Trust in Construction project undertook five exploratory case studies in order to understand how trust is formed and the impact this has on project performance. The authors propose a model of the different forms of trust and the drivers and barriers to its development. Through this model, different approaches are identified that can either manage trust directly or mitigate the factors that may cause its breakdown within project teams. The research looks at the role of procurement mechanisms and the tools that are available to manage issues of project and commercial and relationship uncertainty, such as open book arrangements or partnering workshops, and sees how they can drive the level of trust within the project team. Based on both literature and experience of the case studies, the model identifies the risks to the development of trust and how they may be addressed through these tools