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No description available.

No description available.

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No description available.

SUMO-1/2/3 are members of the ubiquitin-like family of protein modifiers. These proteins are covalently attached to numerous proteins in a directed and controlled manner. SUMO conjugation primarily occurs to proteins containing an exposed SUMO conjugation motif, (I, V, L, F)KxE, where x represents any amino acid. SUMO conjugation is controlled by key enzymes, a SUMO activating enzyme, SAE1/2 and a SUMO conjugating enzyme, Ubc9, which is responsible for substrate recognition, and the efficiency of this pathway can be increased by one of many SUMO ligase enzymes. This modification alters the substrate's characteristics and results in a change of state, such as stability, localisation, or activity. p300, a transcriptional co-activator, contains an evolutionary conserved tandem SUMO modification motif, located in a transcriptional repression domain. p300 was efficiently conjugated, both in vitro and in vivo, by SUMO-1/2/3, within this repression domain to both SUMO conjugation motifs. The SUMO conjugation to p300 correlated with p300 ability to repress transcription, requiring both SUMO conjugation motifs for full transcription repression activity. This repression activity was mediated through SUMO recruitment of histone deacetylase 6. Repression could be alleviated through co-expression of a SUMO-specific protease thereby suggesting a potential regulatory mechanism for transcription control of SUMO modified substrates. Despite utilising the same conjugation machinery, there remained the potential for distinct roles for the SUMO isoforms. SUMO -2/3, which form a distinct group from SUMO-1, were shown to preferentially mediate the transcription repression abilities of a number of known SUMO modifiable substrates: p300, Elk-1, and SP3. Further differences were observed in the ability of SUMO-1 and SUMO-2/3 to influence the nuclear organisation of p80 coilin.

Systematic review Executive dysfunction is commonly reported following stroke with most research in this area focused on frontal lobe lesions. A systematic review was carried out to evaluate the evidence of executive dysfunction following stroke as compared to control groups. It was found that executive functions are consistently impaired following stroke and is not limited to frontal lobe lesions. Processing speed, mental flexibility, attention and working memory impairments were found to be the most common executive functioning impairments following stroke. Given the impact executive dysfunction may have on successful rehabilitation, relationships, return to work and quality of life, a comprehensive assessment of such difficulties is important following stroke to aid in the development of appropriate and effective rehabilitation strategies. Future research should use larger samples and a wide range of measures to assess different aspects of executive functioning. Introduction Mood disorders and psychological distress are common following stroke, and depression and emotional lability have been studied extensively. There has, however, been little research into difficulties in emotion regulation following stroke and whether this is associated with emotional or cognitive difficulties. The current study investigated emotion regulation difficulties following stroke and their relationship with quality of life, executive functions, anxiety and depression. Method Fifty participants who had suffered a stroke and forty five age matched controls completed the Difficulties in Emotion Regulation Scale, the Hospital Anxiety and Depression Scale, the World Health Organization Quality of Life assessment – Brief version and the National Adult Reading Test. In addition individuals with stroke completed four measures of executive functioning – Color Trails Test, Verbal Fluency, Brixton Spatial Anticipation Test and the Hayling Sentence Completion Test. Results Individuals with stroke had significantly greater difficulties in emotion regulation compared to age matched controls and this was significantly associated with lower self reported quality of life and increased levels of both anxiety and depression. No significant associations were found between emotion regulation and executive functions or between executive dysfunction and lower self reported quality of life. Discussion The current study found evidence that individuals who have suffered a stroke have more difficulties in emotion regulation than an age matched control group. This is clinically important as emotion regulation difficulties are found in mood disorders and it may be that such difficulties precipitate and/or maintain depression following stroke. The absence of an association between difficulties in emotion regulation and executive functioning suggests that other factors may influence such difficulties, such as the trauma of having a stroke. Future research should explore emotion regulation difficulties further following stroke, particularly investigating whether the course of these difficulties changes over time and if they are linked to type of stroke or lesion location.

The leukocyte immunoglobulin like receptors (LILRs) are a group of receptors with immunomodulatory effects. Group 1 LILRs comprise of LILRB1, among others, and bind to class 1 MHC molecules and transmits inhibitory signals. Studies have shown that LILRB1 ligation during the monocyte differentiation process into dendritic cells (DCs) results in the generation of a population of cells that are tolerogenic. Here we hypothesize that this tolerogenic nature of the resultant cells is due to the high expression of nuclear factor kappa – light chain enhancer of activated B cells (NF-κB) inhibitor – A20 binding inhibitor of NF-κB signalling 1 (ABIN1). In this study we analyzed the effect that ABIN1 exerts on the maturation of DCs and CD14+HLA-DRlow/- monocytes - a population of cells that have been recently been identified as myeloid derived suppressor cells (MDSCs) in humans. LILRB1 ligated DCs and CD14+HLA-DRlow/- monocytes, when treated with ABIN1 siRNA, displayed an increase in the expression of antigen presentation and co-stimulatory molecules such as CD80, CD86, HLA-DR and HLA-ABC and displayed a greater capacity to produce cytokines like IL-12 and IFN-α. Additionally, they displayed a greater capacity to stimulate the adaptive component of the immune system in terms of IFN-γ production, cell proliferation and adapter molecule and mitogen activated protein kinase (MAPK) activation in T cells. Based on the results we obtained, it can be concluded that ABIN1 plays a significant role in maintaining the immature and suppressive phenotype of immature myeloid cells (IMCs) by dampening NF-κB signalling, while also exerting a negative effect on antiviral signalling.

This is a normative research on how best to structure financial regulatory agencies and principles consistently with the core objectives of financial regulation in such a manner that can yield an effective regulatory framework for Nigeria. It moves forward the debate on what an effective financial regulatory ought to be relative to a country's national context, its developmental stage and how international financial regulatory best practice principles can be 'woven' into the design of an enduring regulatory architecture in a developing economy such as Nigeria. The thesis contributes to three areas namely: the literature on comparative financial regulation, financial legal transplantation, and financial regulatory reform. On comparative financial regulation, it contributes a developing world perspective on the legal and institutional challenges of financial regulation and how to deal with these challenges. On financial regulatory transplantation, it contributes to the debate on how best to conceptualise a financial regulatory architecture that mirror contemporary international best practices and that fits into the Nigerian context. In relation to financial regulatory reform, the thesis makes two major sub-contributions. First, it links financial regulation in Nigeria with robust and multi-layered regulatory accountability mechanisms including judicial and democratic accountability. Second, it generates principles that can be transformed into laws and policies to achieve the following: (a) the imposition of mandatory inter-agency co-ordination among financial regulators; (b) imposition of a statutory duty on financial regulators to prevent regulatory failure; (c) the imposition of liability for a supervisory failure induced collapse of a financial institution and (or) a financial crisis; (d) the use of irreversible convertible debentures as a corporate governance disciplinary mechanism to deter imprudent business model and to serve as a forward looking strategy to address the 'historical inevitability of financial crises' in the unlikely event that the financial regulatory system fails.