Molecular dynamics studies of the STAT3 homodimer:DNA complex: relationships between STAT3 mutations and protein-DNA recognition.

Signal Transducers and Activators of Transcription (STAT) proteins are a group of latent cytoplasmic transcription factors involved in cytokine signaling. STAT3 is a member of the STAT family and is expressed at elevated levels in a large number of diverse human cancers and is now a validated target for anticancer drug discovery.. Understanding the dynamics of the STAT3 dimer interface, accounting for both protein-DNA and protein-protein interactions, with respect to the dynamics of the latent unphosphorylated STAT3 monomer, is important for designing potential small-molecule inhibitors of the activated dimer. Molecular dynamics (MD) simulations have been used to study the activated STAT3 homodimer:DNA complex and the latent unphosphorylated STAT3 monomer in an explicit water environment. Analysis of the data obtained from MD simulations over a 50 ns time frame has suggested how the transcription factor interacts with DNA, the nature of the conformational changes, and ways in which function may be affected. Examination of the dimer interface, focusing on the protein-DNA interactions, including involvement of water molecules, has revealed the key residues contributing to the recognition events involved in STAT3 protein-DNA interactions. This has shown that the majority of mutations in the DNA-binding domain are found at the protein-DNA interface. These mutations have been mapped in detail and related to specific protein-DNA contacts. Their structural stability is described, together with an analysis of the model as a starting-point for the discovery of novel small-molecule STAT3 inhibitors.

Two Views of ‘Subordination’: the Personal Scope of Employment Discrimination Law in Jivraj v Hashwani

In Jivraj v Hashwani, the Supreme Court considered what requirements are necessary for a relationship to be considered as an employment relationship for the purposes of determining the scope of domestic employment discrimination law. The Court held that an element of subordination was necessary for the relationship to be considered employment under a contract personally to do work. This article discusses what the Court in Jivraj meant by this requirement, contrasting two differing views of subordination. It examines some implications of the decision for the relationship between employment law and anti-discrimination law, and for recent debates on the scope of employment law more generally.

Private equity, the minimalist organization and the quality of employment relations

This article develops a firm-level analysis of how the quality of employment relations following acquisition by private equity firms (PEFs) is contingent upon the strategic intent of those firms and the post-acquisition organizational choices they make. The efficiency gains that PEFs seek in acquired companies are expected to encourage restructuring towards a minimalist organization. However, the form such an organization takes is seen to depend on whether PEF strategy is oriented primarily towards extracting short-term value from acquired assets rather than towards renewing and developing those assets. Contrasts in the process of restructuring and in organizational form associated with these two strategies will have different implications for the quality of employment relations. The way in which PEFs restructure the companies or units they acquire is the key intervening factor between the strategic intent of PEFs and impact they have on the quality of employment relations. © The Author(s) 2010.

Relationships between lameness and feeding behaviour in cubicle-housed Holstein-Friesian dairy cows

The relationship between lameness and feeding behaviour in dairy cows is not yet fully understood. This study examined the effect of lameness on feeding behaviour at two points during lactation. Forty-five Holstein–Friesian dairy cows (average parity 3.3) were housed in cubicle accommodation after calving and fed a total mixed ration (TMR). At approximately 60 and 120 days post partum, 48 h of information on feeding behaviour (including number of meals eaten, meal duration, meal size and feeding rate) was collected for each animal using feed boxes fitted to a data recording system. At the same time points, locomotion scores were recorded for each cow as a measure of lameness (1.0-sound to 4.5-severely lame). Relationships between feeding behaviour and locomotion score were analysed using Residual Maximum Likelihood (REML) analysis. At both time points, cows with higher locomotion scores ate fewer (P < 0.001), larger meals (P < 0.001) and had a shorter total feeding time (P < 0.001). At day 60 post partum, an increase in locomotion score was associated with a decrease in dry matter intake (P < 0.05), but at day 120 post partum no relationship was found between locomotion score and DMI. No relationship was found at either time point between locomotion score and mean meal duration or rate of feeding. The results of this study suggest that the effect of lameness on feeding behaviour in dairy cows does not remain constant across lactation.

“They might as well be walking around the inside of a biscuit tin”: Barriers to Employment and Reintegration for ‘Politically Motivated’ Former Prisoners in Northern Ireland

The prisoner provisions under the Northern Ireland Peace Agreement clearly emphasised the importance of the reintegration and civic inclusion of ‘politically motivated’ former prisoners; however, numerous barriers to full reintegration remain. Even though these prisoners were released as part of a peace process, based on principles of conflict transformation and reconciliation, there were still The prisoner provisions under the Northern Ireland Peace Agreement emphasised the importance of the reintegration and civic inclusion of ‘politically motivated’ former prisoners; however, numerous barriers to full reintegration remain. Notwithstanding the fact that these prisoners were released as part of a peace process, based on principles of conflict transformation and reconciliation, there were still numerous conditions placed upon them as part of their release process and they continued to hold a ‘criminal’ record upon release. As with ‘ordinary’ ex-prisoners, these ‘politically motivated’ former prisoners have subsequently faced numerous obstacles in their attempts to reintegrate back into society, particularly in the area of employment. Recognising that they needed to deal with the consequences of imprisonment, ‘politically motivated’ former prisoners formed numerous self-help organisations to assist in the reintegration process and have mobilised to lobby for protection against the discrimination and unequal treatment experienced by ex-prisoners seeking employment. This article explores the remaining barriers to employment for ‘politically motivated’ former prisoners and the consequences of these barriers. The article moves to assess how prisoner groups have subsequently used a ‘rights based’ discourse to engage local government in their struggle to overcome existing obstacles before finally concluding that any piecemeal attempt to remove barriers to full reintegration will only impede the longer term conflict transformation process in Northern Ireland.

Severity staging by early features of age-related maculopathy exhibits weak relationships with functional deficits on SWS grating acuity

To examine the relationship between short-wavelength-sensitive (SWS) resolution acuity and epidemiologically defined stages of early age-related maculopathy (ARM).