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The selection of 5��� splice sites in pre-mRNA transcripts containing multiple splice sites is poorly understood. RNA flexibility and how it affects splice site selection has not currently been investigated on a molecular level. However, secondary structures in proximity to the splice site and RNA-protein/small molecule binding events has been shown to shift splicing using ensemble fluorescence methods. Evidence suggests that using small molecules which target cancerous mutations caused by incorrectly spliced genes such as induced myeloid leukaemia cell differentiation and ��-cell lymphoma proteins may have therapeutic application. Single molecule experiments are not limited by ensemble averaging and so can be used to study the conformational flexibility of individual RNA molecules in functional splicing conditions.Single molecule fluorescence resonance energy transfer was used in this thesis to monitor the conformational flexibility of different nucleic acids including DNA (Holliday junction and molecular beacon) and RNA (adenovirus and ��-cell lymphoma sequences) structures. The experiments were performed under different conditions using various methods of surface passivation and surface tethering (direct tethering and encapsulation in lipid vesicles). The experiments outlined here indicate two main things: firstly, that monitoring nucleic acids which are freely diffusing in lipid vesicles (100 nm) is more representative of physiological conditions. Single molecules in lipid vesicles demonstrated more homogeneous conformational dynamics than those samples which had been tethered directly to the imaging surface. Secondly, we have shown that the G-quadruplex putative to the Xs splice site in the ��-cell lymphoma gene forms and is stabilised by ellipticine derivative, GQC-05 in HeLa cell nuclear extract. This suggests that the stabilisation of the quadruplex and alteration to mRNA flexibility upon binding likely underlies its ability to shift splicing of ��-cell lymphoma, from an anti- to a pro-apoptotic isoform. The single molecule results presented here complement previous literature and combined suggest that GQC-05 is a candidate pro-drug molecule for the therapeutic relief of tumours.

This paper reports the findings of a scoping review designed to identify research which has explored the relationship between cognitive impairment and homelessness. A systematic search of databases for articles published between 2007 and 2017 was conducted using keywords relating to cognitive impairments and homelessness. Sources were expanded using manual searches of citations and grey literature. Forty studies represented in 45 papers were selected for review using predefined inclusion criteria. Sources were subject to quality appraisal and data were extracted in line with review questions. Prevalence studies were over‐represented in the review, while qualitative data were lacking. Aetiology of impairments was delineated by acquired and developmental causes. A variety of measures were employed by studies which were not validated in homeless populations. Studies did not give sufficient consideration to co‐occurring disorders and overlapping symptoms between aetiologies. Because of these factors, it was difficult to conclude that all studies had accurately measured what they set out to; however, the evidence suggested that cognitive impairment was disproportionately over‐represented in homeless populations. Cognitive impairment was found to be both a risk factor to and perpetuator of homelessness. Risk factors for homelessness were similar to those of the general population, though exaggerated by sequelae of certain cognitive impairments. The results of this review suggest that more attention needs to be paid to the underlying socioeconomic disadvantages, persons with cognitive impairments face which may lead to homelessness. Further research should prioritise the voice of homeless persons with cognitive impairments, to better understand both causes of homelessness and effective methods of rehabilitation.