Saudi Cultural Missions Theses & Dissertations

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    The role of Tet2 and Tet3 in the molecular programming of blood cell differentiation during zebrafish development
    (University of Nottingham, 2025) Alayed, Amal Saeed; Gering, Martin; Wilkinson, Rob
    DNA methylation is an epigenetic mark that regulates gene expression during cellular differentiation. Ten-eleven translocation (Tet) dioxygenase enzymes are involved in active demethylation and are required for hematopoietic stem cell (HSC) differentiation. HSCs arise from haemogenic endothelial cells (HECs) in arterial vessels, which depend on Notch signalling for their specification. Initially, the loss of HSC formation in tet2/tet3 double mutants was attributed to a failure in HEC formation caused by defective Notch signalling, despite normal vascular patterning and arterial specification. This study aimed to reinvestigate Notch signalling and HEC development in the ventral wall of the dorsal aorta (vDA) of tet2/tet3 double mutants to resolve these inconsistencies. Here, the Notch reporter transgene csl:mCherry was expressed in the endothelium of the vDA in the absence of Tet2 and Tet3. Confocal analysis of the gene trap line qmc551, which exhibits GFP expression in primitive red blood cells (prRBCs) and HECs of the vDA, demonstrated normal GFP expression in HECs of the vDA at 2 days post fertilisation (dpf). It also revealed a few GFP+ hematopoietic stem and progenitor cells (HSPCs) in the mesenchyme below the DA in tet2/tet3 double mutants. Whole-mount in situ hybridisation (WISH) experiments using the HEC marker growth factor independence 1aa (gfi1aa) revealed that, at 40 hours post fertilisation (hpf), gfi1aa expression persisted in the HECs of the vDA in tet2/tet3 double mutant embryos, contrasting with its typical downregulation in wild-type (WT) embryos at this stage. These findings suggest a defect in the endothelial- to-hematopoietic transition (EHT), likely resulting from disrupted epigenetic programming of HECs in the absence of the two Tet proteins. In tet2/tet3 double mutant embryos, circulation appeared normal without evident shunts; however, blood flow velocity was reduced. To investigate the molecular programming underlying these defects, single-cell transcriptome analysis was performed on a cell population enriched for qmc551:GFP and Gata1a:dsRed single and double- positive cells isolated from 2dpf WT and tet2/tet3 double mutant embryos. Transcriptomic analyses revealed significant downregulation of key endothelial genes, such as apelin, plvapb, casz1, and pecam1. These data suggest a critical role for Tet2 and Tet3 in endothelial programming and angiogenesis. The analysis also showed significant downregulation of erythroid genes in prRBCs. WISH experiments revealed increased gata1a expression in circulating prRBCs at 2 and 3dpf, indicating a late maturation defect in tet2/tet3 double mutant embryos. Additionally, reduced slc4a1a mRNA expression in mutants at 20hpf, prior to the onset of circulation, suggests delayed early differentiation of prRBCs. These findings indicate that the absence of both Tet2 and Tet3 leads to delayed erythroid development. In summary, this study elucidates the multifaceted roles of Tet2 and Tet3 proteins in regulating both primitive and definitive hematopoietic waves during zebrafish embryogenesis.
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    The Impact on Women’s Citizenship in the context of Saudi Arabia’s Vision 2030
    (University College London, 2024) AlOwain, Haifa; Walker, Julian
    The dissertation examins the concept of Inclusive Citizenship and develops an analytical framework based on it, reviews post-Vision 2030 changes in policies, and analyzes them through the lens of the framework to understand their impact of women’s citizenship practices as the case study, providing a lens through which to explore broader issues of citizenship and participation.
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    Essays on Sustainable Growth and Development in GCC Countries
    (Howard University, 2024-06-28) Alamri, Aisha; Kato, Mika
    This article analyzes the effects of natural resources and location determinants on foreign direct investment (FDI) in the Gulf Cooperation Countries (GCC) using panel data from 2000–2022. Using oil production, oil reserves, and oil production in relation to oil reserves as a means to measure natural resources, I determine fixed effect (FE) and random effect (RE) analyses based on the Hausman test. This study concluded that oil production, and oil production relative to oil reserves discouraged FDI in GCC countries. Furthermore, the study concludes that there is a positive relationship between oil prices, infrastructure, and FDI, while human capital has no influence on FDI.
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    Orofacial Development Changes in Children Following Cancer Treatment: A Comprehensive Review of Literature and Analysis of Current Data in Leeds Dental Institute.
    (University of Leeds, 2024) Alghamdi, Talal; Drummond, Bernadette
    Introduction: Childhood cancer survivors often experience various side effects after treatment, including dental and orofacial developmental conditions. According to the literature, the treatment for cancer in children can affect the development of teeth, the function of salivary glands, the development of facial structures, and the operation of the temporomandibular joint [TMJ]. Leeds Dental Institute [LDI] has accumulated a wealth of data while providing dental healthcare for cancer survivors. This extensive data has not been thoroughly explored or published. Thus, this study aims to investigate the long-term effects of cancer treatment on dental and orofacial structures from the literature and the available records in children at Leeds Dental Institute. Methods: This research is structured into two sections. The first is a comprehensive literature review of existing studies on the adverse effects of cancer treatments on oral and facial structures in children by searching six databases to establish a foundation for understanding the broader context of the issue. The second section is a retrospective data collection and analysis of paediatric patient data from the electronic records in LDI using a list of appointments attended by cancer patients in LDI. Results: Fifty-one articles were included in the comprehensive literature review following the database search and the inclusion criteria. Numerous studies concluded that chemotherapy and other anticancer treatments in children are linked to increased dental anomalies like microdontia and enamel defects, especially when treatment occurs at a young age. The findings have been summarised in tables. Of the 806 registered appointments identified, the clinical records of 85 childhood cancer survivors who met the inclusion criteria were included. The post-treatment identified conditions included microdontia, hypodontia and enamel hypoplasia. Demographics, cancer diagnosis and type of treatment, in addition to dental findings, were summarised in tables. The data were also categorised according to age at the cancer treatment time and type of treatment provided. Conclusions: The literature review and LDI patient data revealed that childhood cancer survivors commonly face serious long-term dental issues due to their treatments. These findings highlight the importance of a better understanding of cancer therapy's impact on orofacial development, requiring more attention and support from healthcare professionals, particularly dentists.
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    The role of Inversin in left-right patterning and cardiac development
    (Newcastle University, 2024-04-30) Alaradi, Mashael; Henderson, Deborah
    Vertebrate bodies have left-right (L-R) asymmetry, an arrangement set up early in development. L-R patterning is thought to be initiated by symmetry-breaking events at the embryonic node, which contains motile cilia that generate an asymmetric fluid flow to define the left-side of the embryo. This process results in normal organ positioning known as situs solitus (SS), where the gall bladder and most of the liver are on the right, whereas the spleen, stomach, pancreas and heart reside on the left. Disruption to L-R patterning can result in a spectrum of laterality defects, ranging from situs inversus totalis (SI, complete mirror imagery) or heterotaxy where organ positioning is randomised across the L-R axis of the body. In particular, the heart, a highly asymmetric organ, appears very sensitive to improper L-R patterning, with strong links between heterotaxy and Congenital Heart Defects (CHDs). In humans, laterality disturbances have been reported in several diseases which impact cilia structure and function such as Kartaganer syndrome and Primary Cilia Dyskinesia, whilst large scale mutagenesis screens in mice have supported a link between ciliopathies, heterotaxy and CHDs. The Inversin (Invs) mouse mutant, Inv, was initially identified due to complete penetrance of SI. Subsequently, Invs has been shown to localise to cilia and is also suggested to function as a molecular switch between different Wnt signalling pathways. There is also some evidence demonstrating that loss of Invs in mice results in CHDs. However, the direct link between laterality disturbances and CHDs in Inv mutants remains unknown, given the possibility that loss of Invs may alter Wnt signalling, which is required for normal heart development. Therefore, this project sought to establish whether Invs has a laterality-independent role in heart development, or if its role in LR patterning is responsible for CHDs. Firstly, I investigated the spatial and temporal distribution of Invs in the mouse heart, showing that the expression pattern of Invs is dynamic during cardiac development. I then examined Inv mouse mutants for laterality defects at embryonic and fetal stages. This analysis revealed that although SI was common, many Inv mutants did not have body axis inversion although they did have laterality disturbance including right isomerism, left isomerism and situs solitus; CHDs were observed in all Inv mutants examined. Analysis of the CHD observed suggested similarities with mouse mutants with improper addition of a migratory population of cardiac progenitor cells, known as the Second Heart Field (SHF). Accordingly, to examine a laterality independent role for Invs in the heart, I analysed the SHF in Inv mutant embryos and showed that abnormalities in this cell population could not be accounted for simply on the basis of a disruption in L-R patterning. Finally, as it has been proposed that Invs acts as a switch molecule between Wnt pathways, I investigated whether there could be a genetic interaction affecting L-R patterning and heart development between Invs and Vangl2, a non-canonical Wnt (PCP) component in. These data suggested a complex interaction between these two genes. Together, my work supports the idea that Invs could plays laterality-independent roles in heart development. However, significant further work is necessary in order to confirm this exciting finding.
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    The Impact of Saudi Vision 2030 on Human Resources Development in the Tourism Industry: A Case Study of The Red Sea Project
    (Saudi Digital Library, 2023-11-08) Aljumaey, Abdullah; Ladkin, Adele
    The research explores the impact of the Vision 2030 of Saudi Arabia (SA) in developing human resources. It further evaluates the Red Sea project that aims to develop the tourism industry in the country. Behavioural Theory Management (BMT) has been evaluated further that highlights the factors that influence the employee’s behaviour in completing the objectives of Vision 2030. The complete thesis discussed the effect of Vision 2030 introduced by Saudi for the development of human resources. The literature review chapter signifies the impact of the Red Sea Project on human development and the tourism sector. The vision also helps to clarify the aim and ways of proceeding with the development in Saudi from achieving different objectives. The tourism industry in SA is enhanced through efficient human resource development and by placing it at the centre of projects like the Red Sea in accomplishing Vision 2030 of the country. The Kingdom of Saudi Arabia vision represents a great structural shift in every economic sphere of the country. Moreover, with Vision 2030, it encourages building up a workforce in providing equal opportunity for everyone including the women in the country. the vision can help in fostering innovation and entrepreneurship and in the development of new tourism-related businesses. The significance of Saudi Vision 2030 is reshaping Saudi Arabia's economy through diversification and global prominence. It addresses challenges faced by the tourism industry in implementing the Vision's goals, including cultural preservation and infrastructure development. It also emphasizes the crucial part the Red Sea Project can have in achieving Vision 2030's goals, promoting economic diversification, environmental sustainability, and cross-cultural interaction to establish Saudi Arabia as a top travel destination.
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    Analysing the contribution of Wt1-expressing cells in the development of the vascular and visceral smooth muscle in mouse embryos and gastruloids
    (2023) Alghamdi, Suad Hassan S; Wilm, Bettina; Turner, David; Cross, Michael; Butts, Thomas
    During embryonic development, the epicardium, the mesothelium of the heart, contributes vascular smooth muscle cells (VSMCs) to the coronary vessels; however, the developmental origin of VSMCs in the embryo is not clearly defined. A previous study had reported that cells expressing the Wilms’ tumour protein (Wt1), a key marker of mesothelia, give rise to VSMCs in the intestine, mesentery, and coronary vessels, using genetic lineage tracing experiments (Wilm et al., 2005). Because Wt1 is expressed in the mesothelium of the body cavities, we concluded that Wt1-expressing mesothelial cells contributed to the VSMC compartment in the respective organs. Further studies analysing Wt1 lineage contribution led to the finding that Wt1 is switched on and remains expressed in the visceral mesothelium from around E9.5 onwards, while earlier transient expression of Wt1 in the nascent mesoderm specifies the future vascular and visceral smooth muscle of the intestine and mesentery (Wilm et al., 2021, Alghamdi et al., 2020). These results have revealed that the VSMC lineage is more complicated. In order to determine the contribution of Wt1-expressing cells to the VSMC lineage, this study used temporally controlled lineage-tracing experiments based on a Tamoxifen-inducible reporter system for different embryonic stages between 18.5 and 8.5 of embryonic development. Our lineage tracing of Wt1-expressing cells tagged at E8.5 and followed to different stages of embryonic development revealed their VSMC fate, with only a few visceral mesothelial cells found to be GFP-positive. Data of this thesis suggests that Wt1 expression before or during the initial phase of mesothelium formation in the intermediate and lateral plate mesoderm marks the cells that will become VSMCs. Furthermore, analysis of Wt1GFP/+ embryos at E8.5 was found to have some cells in the mesoderm and the primitive streak. This suggests a more intricate role for Wt1 in the lineage tracing of VSMCs that expressed Wt1. Further analysis of the Wt1-expressing mesoderm population was performed by using gastruloids generated from mouse embryonic stem cells (ESCs) as a valuable in vitro tool to study early embryonic development. We labelled gastruloid with different intermediate, lateral plate, and paraxial mesodermal markers to identify possible co-expression in the cells that expressed Wt1. Interestingly, gastruloids cultured for 72h and 96h showed co-expression of Wt1 and the mesodermal markers in the same region, while after 96h of culture, some of these cells appeared to have migrated to the anterior part of the gastruloid while other cells remained in the posterior part identified by expression of the early mesoderm marker Brachyury. This separation seemed to be completed in 120h gastruloids, which are thought to be equivalent to embryos at between E7.5 and E8.5, as the Wt1 expression only presented in the anterior side of the gastruloid. These findings led us to conclude that the origin of the Wt1-expressing cells that give rise to VSMSC in the intestine and the mesentery appears to be a posterior mesodermal-derived progenitor cell population. These progenitor cells then follow a specific journey during the next stages of embryonic development.
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    Saudi Women Role in Development of the Society
    (Saudi Digital Library, 2015) Alshahrani, Sabra Naji; Cviklova, Lucie
    In this research, we showed and clarified the role of Saudi women in development and to demonstrate the role played by Saudi women and the status of the effectiveness of society, although it was delayed for several different reasons, including social, cultural and economic. We explained the importance and prestige that Islam gave to women and statements in the Quran and in Sunnah agree on the importance of the work and effectiveness of women in society. Also the role of women in society is affected by the customs, traditions and interpretations of the values and traditions of society. Historically, in the beginning of the formation of the first and second Saudi states, the education of women did not play a large role except for primitive education in such matters as religion, reading and writing on a small level and due to reasons including the development of a growing, busy state. But in the Third Saudi State by King Abdulaziz bin Saud and later his sons, women's education was clear goal that set up infrastructures to make decisions in their right to education and learning. The golden age of women was in the reign of King Fahd bin Abdul Aziz and King Abdullah bin Abdulaziz. Their decisions in favor of women and opening foreign studies, has in a strong development on the academic level. In the last chapter, we did interviews with Saudi women through the Internet, we chose these women based on their struggles, the difficulties they have overcome and their service to their community in their respective fields.
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