SACM - United Kingdom
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Item Restricted Defining The Role of PRPF8 in Congenital Heart Diseases(The University of Manchester, 2025) Althali, Nouf; Ray O’Keefe, Kathryn Hentges andCongenital heart disease (CHD) is the most common birth abnormality, impacting over 1% of live births worldwide and representing a major cause of infant mortality and morbidity. Despite advances in genetic studies identifying several causal variants, the molecular mechanisms behind many congenital heart defects (CHDs) remain insufficiently elucidated. We have discovered a mutant mouse line with laterality and cilia defects accompanied by cardiac abnormalities caused by a missense mutation in the spliceosome gene Prpf8. The role of PRPF8 in congenital heart defects has not been investigated prior to this thesis research. In this project four PRPF8 missense variants: V250M, P372L, T589M and M1730T, that have been found in CHD patients, were studied to determine if PRPF8 function is altered by these variants. These PRPF8 variants were predicted that may cause aberrant splicing and/or altered biochemical interactions between PRPF8 and the other spliceosomal proteins, leading to developmental heart malformations likely due to aberrant splicing or expression of cardiac genes. PRPF8 variants were investigated using multiple bioinformatics prediction tools to predict the impact of PRPF8 variants found in human CHD patients on protein function. Moreover, PRPF8 variant protein-protein interactions and protein stability were assessed. We also generated the analogous missense variants in yeast Prp8 to study their effect during splicing. Moreover, a Prpf8 mouse model was used to evaluate the expression of Prpf8 in cardiac and neural crest cell markers. Our bioinformatics analysis revealed some of these variants were predicted to be damaging and affect protein functions while others were not. Significantly, although the most highly predicted damaging variant, PRPF8 T589M, did not interfere with PRPF8 interactions with its binding partners, EFTUD2 and PPIL2, it, and other PRPF8 variants, adversely impacted PRPF8 protein stability. This suggests a specific mechanism in which decreased protein stability, rather than a loss of physical interactions, accounts for the impact of these mutations. Our splicing reporter assay findings indicate that all examined mutations impair PRP8's splicing efficiency, causing remarkable gene expression alteration and splicing defects. The Prpf8 mutant mouse displays reduced neural crest marker expression, suggesting a vital role for PRPF8 in cardiac development via the regulation of neural crest cell development. Novel insights gained from this work may aid our ability to understand the role of PRPF8 in CHD and its links with cardiac defects, informing diagnostic and therapeutic strategies.10 0Item Restricted Fostering Intercultural Empathy Through Participatory Storytelling: A Study of Narrative, Cultural, and Reflective Practices in Global Gatherings(University Of Arts London, 2025) Alsulamani, Duaa; NoemiCreative Connection is a collaborative storytelling project that fosters empathy and connection across cultural backgrounds. Inspired by the shared experience of Al-Hajj, this research explores how storytelling can break invisible barriers and create meaningful intercultural connections. Through participatory methods and visual storytelling workshops, the project highlights the distinction between verbal and visual communication, enabling participants to share experiences and engage in deeper dialogue. The impact of storytelling in community and multicultural gatherings demonstrated its power to dissolve barriers and strengthen a sense of belonging.4 0Item Restricted THE ALIGNMENT OF SAUDI VISION 2030 BANKRUPTCY LAW WITH UNCITRAL MODEL LAW ON CROSS-BORDER INSOLVENCY (1997) AND ITS IMPLICATIONS FOR FOREIGN DIRECT INVESTMENT(University of Essex, 2025) Alharbi, Anas; Amajuoyi, Dr UgochiSaudi Arabia’s Vision 2030 seeks to diversify the nation’s economy by minimizing dependence on oil and enhancing its Foreign Direct Investment (FDI). However, for Saudi Arabia to achieve this objective its legal regime must align with international guidelines to promote investor confidence. Specifically, the Saudi Arabia’s new 2018 Bankruptcy Law should align with the UNCTRAL Model Law on Cross-Border Insolvency (MLCBI). This study seeks to examine the extent to which the legal reforms provided by Saudi Arabia’s new 2018 Bankruptcy Law aligns with UNCITRAL MLBI to foster predictability, transparency and stability for international investors. This dissertation utilizes legal doctrinal methods to provide an in-depth analysis of the two provisions and comparative legal research methods to compare them. The study reveals that although Saudi’s Bankruptcy Law incorporates some MLCBI principles like recognition and relief, some areas still need improvement such as the judicial capacity and creditors rights. As a recommendation, the study proposes improvement regarding clarity of ambiguous provisions, capacity building of legal professionals and continuous updates of the bankruptcy legal regime in the country to enhance the country’s competitiveness for FDI.6 0Item Restricted Host specific phenotypes of Campylobacter jejuni in the farmyard(University of Reading, 2024-03-07) Almuqrin, Abdulmajeed Mohammed A; MacIntyre, SheilaCampylobacter jejuni stands as the predominant etiological agent responsible for bacterial gastroenteritis worldwide. Notably, isolates of this pathogen exhibit considerable genetic variability, thereby giving rise to discernible differences in both physiological and virulence properties. Historically, the predominant emphasis of scientific and clinical research has been directed towards C. jejuni strains procured from human clinical specimens, the agricultural milieu and the food production industry. However, it is important to acknowledge that such isolates may not unequivocally serve as true representatives of the natural populations of C. jejuni. Recent observations revealing significant diversity within Campylobacter populations colonizing wild animals have sparked increased interest among microbiologists focused on understanding mechanisms of C. jejuni host adaptation, colonization and pathogenesis. An earlier comparative genomics analysis of newly isolated C. jejuni strains from farm associated Norway rats revealed that ~20% of isolates belonged to a clearly distinct and previously unrecorded clonal complex, termed RG-1. This suggested that Norway rats harbor an unexplored C. jejuni diversity. This study established continued association of RG-1 strains with farm rats, with no evidence of recovery of related strains from other sources. By also addressing the genetic diversity and physiological properties of these strains this study has aimed to identify factors that may contribute to the apparently specialized niche association of the RG-1 clade of C. jejuni. The continued prevalence of C. jejuni RG-1 strains and the diversity of rat-associated C. jejuni were investigated by isolation from faecal samples of Norway rats inhabiting two local farms. Of the forty-four isolates identified as C. jejuni, thirty-three were found to be glc positive C. jejuni while four strains (Dg434a, Dg456, Dg471 and Dg475) were identified as RG-1 isolates. Strains were identified as RG-1 using a targeted PCR screen, developed using a comparative genomics approach that shortlisted a set of 13 potential marker genes for RG-1. Further, in-silico analyses and PCR trials further narrowed this down to 3 target genes which along with hipO could be used in an extensive rapid screen to directly assess prevalence of RG-1 strains in a wider range of geographic and animal sources. Hybrid genome sequencing followed by phylogenetic analyses confirmed assignment of the newly isolated RG-1 strains. All four clustered in a distinct clade with thirty previously isolated RG-1 strains, when compared to the diverse range of all previously sequenced rat-associated Campylobacter isolates. Notably, phylogenetic analysis within the RG-1 group highlighted divergence between farms and clustering of isolates from the same farm, regardless of the farmed animal. MLST analyses identified that three of the four RG-1 strains (Dg456, Dg471, and Dg475) are closely related to Dg147, sharing the same allelic profile for the aspA, glnA, gltA, glyA, tkt, and uncA loci but differing in the pgm locus. However, the fourth strain, Dg434a, exhibited differences in alleles for aspA, pgm, and tkt7, indicating its phylogenetic distance from most other RG-1 strains. The phylogenetic distinctions between RG-1 strains and other C. jejuni clinical and chicken isolates suggested a potentially unique ecological niche for these strains and hinted at variations in crucial metabolic and physiological traits. Functional annotations of genome sequences of RG-1 strains highlighted possession of key genes related to specific carbon source metabolism, amino acid catabolism, motility, oxidative stress response, and heat shock resistance. Comparative genomics revealed 28 unique genes in RG-1 strains absent in other C. jejuni strains and potentially relevant to niche survival and host colonization. Growth of RG-1 strains exhibited the classic microaerophilic profile of C. jejuni but generally exhibited poorer growth and lower motility than NCTC 11168 and some other rat isolates. A notable distinguishing feature of RG-1 isolates was the exceptionally poor survival at 42oC. This narrow range of growth temperature for RG-1 could be one of the reasons for successful colonisation of rats and apparently not chickens. Adaptability to different growth temperatures may be an important property in defining the habitat or host niche of more diverse C. jejuni strains. Similarly, the mucosal contents might play an important role in providing protection to RG-1 strains and suitable environment for growth and colonisation of the host gut as caecal mucus preparations from rats and chicken both provided protection to RG-1 strains. This project confirms continued association of the highly diverged clade of C. jejuni RG-1 strains with farm associated rats and identifies several factors that may contribute to niche survival and specific host colonization. This provides a solid foundation for further analysis of geographic and host prevalence of these strains together with elucidation of mechanisms involved in niche preference. Ultimately, this clade of strains may prove to be a useful example of C. jejuni with high host specificity with possibilities for development of protection against infection in the agriculture industry.26 0Item Restricted Macromolecules For Protein Binding Using Dendrimer and Graphene Oxide(The University of Sheffield, 2024) Alageel, Amal; Twyman, LanceThis research explored non-covalently functionalized dendrimers and graphene oxide as macromolecular ligands for protein binding. Their structures were functionalized with amino acids to modulate protein recognition and binding. Developing macro-ligands to target large protein binding surfaces is an effective strategy for inhibiting protein-protein interactions. While covalently functionalized macromolecules have shown potential, their synthesis and control over the positioning of binding groups can be challenging. Therefore, in the first area of research, dendrimers that had been functionalized using non-covalent methods were examined. This involved synthesizing neutral PAMAM dendrimers that could not bind to the surface of α-chymotrypsin (Chy) and a series of linear chains that could bind the protein. These chains were originally synthesised using a simple Boc protection strategy that involved a considerable amount of aqueous workup. However, the use of water resulted in very low yields and poor purity. This thesis describes a new CBz protection method that avoids the use of aqueous workup and was able to generate the required chains in excellent yield and high purity. Linear chains with either tyrosine or valine were prepared and up to 6 of these could be encapsulated within the G3.5 OH ended dendrimer, with a further 4 or 5 remaining dissolved in the bulk water. The resulting complexes were tested for their ability to bind the protein cytochrome-c. To facilitate a quantitative analysis, the quencher zinc tetra(4-hydroxyphenyl) porphyrin (Zn-THPP) was also encapsulated. Using a fluorescence titration technique a dissociation constant (Kd) of 33 nM was measured for the G3.5 dendrimer encapsulated with the tyrosine chains. In contrast, no binding could be detected using the dendrimer alone, or the dendrimer encapsulated with the valine chains. The next part of this project examined a similar “dynamic” approach to protein binding, using graphene oxides (GO) functionalized through both covalent and non-covalent approaches. This involved synthesising a series of anthracenes modified with various amino acids. These could be added to GO covalently, via a Diels-Alder reaction. In this case the functional groups were fixed in specific positions on the GO surface, and any biding would involve the protein moving around, which would limit the binding efficiency. The same anthracenes could also be added to the GO surface using non-covalent π-π interactions (by simply mixing the GO and functionalized anthracenes together in water). In this case the functional groups were free to move around the surface of the GO, allowing for maximum binding efficiency. As expected, the non-covalently functionalized anthracenes demonstrated enhanced binding to chymotrypsin through a series of inhibitory experiments. The research was extended to the study of GO systems functionalized with a mixture of functional groups (using covalent and non-covalent methods). Subsequent binding studies indicated that these mixed systems were more effective than corresponding systems functionalised with a single functional group, highlighting the benefits of combining amino acids for better binding affinity. Overall, the work described presents a proof of principle that addresses the difficulties in controlling functional group placement in precise 3D locations on the surface of protein binding ligands.17 0Item Restricted The Impact of Business Analysis on the Analysis of Investment Portfolios (UK and US Stock Market)(University of Aberdeen, 2025) Alqadhibi, Sulaiman; Lee, SeunghoBusiness is dynamic work aimed at achieving the objective of generating profits. In order to achieve this goal, a company must initially gather a range of resources and utilise them for financial gain, guided by managerial choices. When considered in a broader context, managerial decisions encompass various domains: the allocation of resources, the utilisation of these resources to operate the business, and the appropriate combination of finance . Business involves a wide range of sectors, including manufacturing, mining, trading, and financial services, among others. The underlying issue that unites all of these categories is the management and allocation of resources. These two characteristics are the primary influences on the overall structure of company. Financial management plays a crucial role in the overall structure of the organisation. In the creation of our investment portfolio, we prioritised two objectives: diversification and companies that present substantial growth. We selected companies that we believe will drive the future in a variety of sectors, including renewable energy, healthcare, technology, and artificial intelligence. The objective of our diversification strategy is to mitigate and spread risks.24 0Item Restricted Defining The Role of PRPF8 in Congenital Heart Diseases(The University of Manchester, 2025) Althali ,Nouf; Ray O’Keefe, Kathryn Hentges andCongenital heart disease (CHD) is the most common birth abnormality, impacting over 1% of live births worldwide and representing a major cause of infant mortality and morbidity. Despite advances in genetic studies identifying several causal variants, the molecular mechanisms behind many congenital heart defects (CHDs) remain insufficiently elucidated. We have discovered a mutant mouse line with laterality and cilia defects accompanied by cardiac abnormalities caused by a missense mutation in the spliceosome gene Prpf8. The role of PRPF8 in congenital heart defects has not been investigated prior to this thesis research. In this project four PRPF8 missense variants: V250M, P372L, T589M and M1730T, that have been found in CHD patients, were studied to determine if PRPF8 function is altered by these variants. These PRPF8 variants were predicted that may cause aberrant splicing and/or altered biochemical interactions between PRPF8 and the other spliceosomal proteins, leading to developmental heart malformations likely due to aberrant splicing or expression of cardiac genes. PRPF8 variants were investigated using multiple bioinformatics prediction tools to predict the impact of PRPF8 variants found in human CHD patients on protein function. Moreover, PRPF8 variant protein-protein interactions and protein stability were assessed. We also generated the analogous missense variants in yeast Prp8 to study their effect during splicing. Moreover, a Prpf8 mouse model was used to evaluate the expression of Prpf8 in cardiac and neural crest cell markers. Our bioinformatics analysis revealed some of these variants were predicted to be damaging and affect protein functions while others were not. Significantly, although the most highly predicted damaging variant, PRPF8 T589M, did not interfere with PRPF8 interactions with its binding partners, EFTUD2 and PPIL2, it, and other PRPF8 variants, adversely impacted PRPF8 protein stability. This suggests a specific mechanism in which decreased protein stability, rather than a loss of physical interactions, accounts for the impact of these mutations. Our splicing reporter assay findings indicate that all examined mutations impair PRP8's splicing efficiency, causing remarkable gene expression alteration and splicing defects. The Prpf8 mutant mouse displays reduced neural crest marker expression, suggesting a vital role for PRPF8 in cardiac development via the regulation of neural crest cell development. Novel insights gained from this work may aid our ability to understand the role of PRPF8 in CHD and its links with cardiac defects, informing diagnostic and therapeutic strategies.17 0Item Restricted Sustainable water management: Practices, challenges and benefits: A case study of hospitality sector in Alula, Saudi Arabia.(University of Gloucestershire, 2025) Aljohani, Manar; Abd Razak, AzleySustainable management is becoming increasingly relevant globally, with resource management as a key element. Businesses faces critical issues related to water, making effective management essential for businesses like hospitality. This study examines sustainable water management (SWM) in Alula's hospitality sector, a new case that has not yet been thoroughly investigated. It combines three elements: 1- Practices applied in Alula's hospitality sector – Which practices are most used, and are they primarily low-cost and simple? 2- Challenges and barriers – Are costs, lack of awareness, resource limitations, technical difficulties, expert shortages, and guest behaviours the biggest barriers affecting practice choice? 3- Sustainable practises benefits and look if they have benefit in reduce operational cost and water consumption. It applied three assumptions. The study applied three assumptions and used a mixed-methods approach, combining quantitative data from questionnaires with qualitative insights from interviews with industry professionals. The findings conclude that while basic SWM practices are, like low flow showerhead, adopted in Alula's hospitality sector, significant barriers hinder the implementation of more advanced measures. Addressing these challenges through enhanced stakeholder engagement, increased awareness, and improved access to resources and expertise is crucial. This research contributes to a deeper understanding of SWM in emerging tourist destinations and provides sight for policymakers and industry stakeholders to promote SWM42 0Item Restricted Perceptions And Reported Practices of Teacher Leadership by Saudi Teachers, Principals and Supervisors in Saudi Arabia(The University of Nottingham, 2024) Alhumaid, Musaad; Bush, Tony; Taylor, PhilThis research investigates teacher leadership in selected public schools within Riyadh's Educational Directorate, Saudi Arabia. It explores the perceptions of key stakeholders: principals, supervisors, and teachers, concerning teacher leadership, the factors that empower or inhibit teachers to lead, and the professional development and nurturing of teacher leadership. The study is framed by Grant’s teacher leadership model and three related theories, communities of practice, distributed leadership, and professional learning communities. A nested case study approach was adopted to select two contrasting schools, assessed through their annual evaluations. The qualitative research design combined interviews, observations, focus groups, and reflective essays, involving participants with at least two years of teaching experience. The findings show very different understandings of teacher leadership across the two schools. Gold school appears to adopt a broad view of teacher leadership, within and beyond classrooms, while Silver school has a narrow perspective, limited to classroom leadership. Supervisors, principals, and teachers have different perceptions about teacher leaders. These differences are influenced by culture as well as the school system. The targeted professional development and school environment promoting empowerment and collaboration is closely related to the effective promotion of teacher leadership. The identified obstacles to fostering teacher leadership include limited autonomy, unclear roles, and a lack of consistent support mechanisms. The study findings indicate the need to structure programmes and policies so that teachers can enact leadership and play more meaningful roles in school improvement.4 0Item Restricted The role of the adhesion protein tensin-3 (TNS3) in controlling basement membrane remodelling during breast cancer progression in mammalian models(University of sheffield, 2025-01-24) Alomaim, Haya; Rainero, ElenaBreast cancer is one of the most common cancers in women, often beginning as ductal carcinoma in situ (DCIS), where mammary epithelial cells proliferate within ducts due to the presence of the basement membrane (BM). In 30% of patients, cancer cells progress to invasive ductal carcinoma (IDC) and metastasis. The mechanisms underlying this progression remain poorly understood. Tensin 3 (TNS3), a member of the TNS family that includes TNS1, TNS2, and TNS4, interacts with β1 integrin to promote cell-ECM adhesion during this transition. We found that TNS3 is upregulated in DCIS and IDC tumours compared to normal mammary glands in a mouse model of breast cancer. Interestingly, TNS3 downregulation in MCF10DCIS and MCF10CA1 cells suppressed invasive protrusions and reduced spheroid growth. Additionally, MCF10DCIS and MCF10CA1 cell growth on Matrigel was impaired under glutamine deprivation. Mechanistically, downregulating β1 integrin and TNS3 significantly reduced laminin-332 expression in 3D cultured MCF10DCIS cells and impaired filopodia formation. Moreover, silencing TNS3 lowered α3 and α6 integrin levels. Blocking α3 and α6 integrin function further decreased laminin-332 expression and filopodia formation, suggesting that TNS3 modulates BM dynamics through α3 and α6 integrins. Consistently, TNS3 knockdown reduced laminin-332, α3 integrin expression, and filopodia formation in MCF10CA1 cells. Reports suggest that TNS3 acts as a tumour promoter in cancer cells but as a tumour suppressor in non-transformed epithelial cells. Our results indicate that silencing TNS3 promotes proliferation and invasion of MCF10A cells while increasing α3 integrin, laminin-332, and filopodia formation. Overexpression of TNS3 in a Drosophila cancer model strongly impaired tumour growth and metastasis. Overall, these findings highlight TNS3’s critical role in regulating the basement membrane and filopodia formation, acting as both a tumour promoter in cancer cells and a tumour suppressor in normal mammary epithelial cells.7 0