Saudi Cultural Missions Theses & Dissertations
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Item Restricted Reward-based improvements of motor performance in health and disease(University of Birmingham, 2024-07-19) Alghamdi, Ahmad Ali; Galea, JoesphReward has been found to boost motor performance and improve learning in both healthy individuals and in clinical populations. The aim of this thesis was to gain a better understanding of how reward affects different specific aspects of motor performance and learning across various age and health status groups. This work provides an important step towards optimising the use of reward within clinical populations such as stroke patients. The introductory chapter (Chapter 1) provides a comprehensive review of relevant literature, setting the stage for the investigations that follow. As motor performance and reward responsiveness tend to decline with age, Chapter 2 investigated the age- related differences in reward-based improvement in motor performance. We observed that both young and older adults showed improved performance with rewards, but the young group exhibited significantly higher reward-based enhancement in motor performance. In chapter 3, we extended these results by examining how reward impacts motor performance in stroke patients. In this study, we also investigated the impact of rehabilitation on reward sensitivity. Our findings suggest that stroke patients' motor performance significantly improved with the presence of reward. We also found that patients' performance improved after rehabilitation, but there were no changes in reward sensitivity. Chapter 4 investigated the role of the primary motor cortex within the reward-based enhancement of motor performance using repetitive transcranial magnetic stimulation. No effects on performance were observed. In Chapter 5 of this thesis, we explored how reward affects sequential movements and how manipulating task difficulty can impact reward-based improvement in sequential movement fusion. Our findings suggest that sequential movement fusion is more effective when the task is easy, and this effect is further enhanced by the presence of a reward. The thesis concludes with Chapter 6, which synthesizes the findings, discusses their implications, and proposes directions for future research. This study not only advances our understanding of reward-based motor learning but also provides a foundation for optimizing reward utilization in clinical settings, offering hope for improved rehabilitation strategies.20 0Item Restricted Characterisation of novel Markers role in Senescence and targeting them to eliminate senescent cells(University of Leicester, 2024-04-22) Albati, Amal Abdulah; Macip, SalvadorAgeing is a deterioration of organ function that increases the susceptibility for diseases. This deterioration is due to an impairment of cellular homeostasis occurred in response to the nine hallmarks of senescence is considered one of these hallmarks, which was observed first by Leonard Hayflicks and Paul Moorhead which defined as a cell cycle arrest in response to genetic or environmental stresses such as UV radiation, oncogene stress, telomere attrition and DNA damage. Senescent cells are metabolically active cells characterized by an irreversible cell cycle arrest and resistance to apoptosis. Senescence has two opposite impacts on organisms, as it has a beneficial effect such as tissue repair, wound healing and tumor suppression. However, accumulation of senescent cells has a detrimental effect found to enhance ageing and age-related pathologies such as Alzheimer disease, diabetes, fibrosis and cancer. Therefore, clearance of senescent cells could ameliorate the symptoms of ageing and age-related diseases thus increasing the healthspan and lifespan of organisms. However, there is no yet specific marker used to detect and eliminate senescent cells. Consequently, it is important to find a marker or combination of markers that are specifically identify senescent cells and use them as therapeutic tool to target and eliminate the accumulation of senescent cells. Here, we illustrated that Ibrutinib, a clinically approved chemical inhibitor of BTK, decreased the accumulation of senescent cells in vivo, leading to extended lifespan and mitigating age related decline in physical fitness. Besides, Ibrutinib demonstrated a pivotal role in maintaining heart function with age by effectively reducing the accumulation of senescent cells. Additionally, we examined three potential markers of senescence identified by proteomic screening, evaluating their expression levels with age and after Ibrutinib treatment. Specifically, we sought to understand the impact of ibrutinib on these markers with age by comparing treated mice to untreated counterparts and young controls in mouse tissues. Moreover, we assessed the binding of RGD peptide to integrin αVβ3, a protein identified by proteomic screening as expressed more in senescent cells. The investigation aimed to determine the potential utility of the RGD peptide as a drug delivery tool for future applications.27 0Item Restricted Sex Differences in White Matter Hyperintensities in the Ageing Brain(Saudi Digital Library, 2023-11-22) Alqarni, Abdullah; Wei, Wen; Perminder, Sachdev; Jiyang, JiangCerebral white matter hyperintensities (WMH) appear in the brain magnetic resonance imaging scan at early age and become more prevalent at older age. Despite that old age is known as the main risk factor for WMH accumulation, the literature has shown that many vascular risk factors contribute significantly to the existence and progression of WMH. Women were shown to have higher WMH volume compared to men in the literature. However, the existing literature lacks comprehensive evidence to address why such pattern is noted. Therefore, this thesis aims to examine sex differences in WMH. Specifically, three studies were conducted: (1) investigating sex differences in the associations between vascular risk factors and WMH, (2) examining the contribution of the hormonal risk factors to WMH and their moderation effects on the associations between vascular risk factors and WMH, and (3) examining sex differences in longitudinal associations between vascular risk factors and WMH, and the effects of WMH progression on cognitive decline. Results showed that the pattern of higher WMH in women compared to men was identified across the studies, however, men had stronger contributions of vascular risk factors, especially obesity measures, to WMH. The second study showed that hypertensive postmenopausal women benefited significantly from using hormone replacement therapy, especially when taken early and for longer duration. Diabetic women and women with increased pulse wave velocity had increased deep WMH when post-menopausal duration was one standard deviation below the mean. In men, smokers with higher testosterone levels had significant increase in WMH. In the third study, significant sex differences were found in the association between WMH progression and cognition. Specifically, increases in periventricular WMH volume over time was associated with greater decline in visuospatial abilities in men, but not in women. In women, but not in men, higher average periventricular WMH volumes across time-points was associated with poorer executive function. The thesis comprehensively examined sex differences in vascular and hormonal risk factors associated with WMH, as well as in cognitive consequences of the progression of WMH. The findings highlight the importance of taking sex differences into consideration clinically and for future clinical research of WMH.25 0Item Restricted An Assessment of miRNA Manipulation on Senescence and Ageing Phenotypes in vitro and in vivo(2023-06-19) Manni, Emad Mohammed O; Harries, Lorna WAgeing has been widely described as a progressive functional deterioration of tissues that causes diminished organ function and increased mortality risk. It has been established that the proportion of senescent cells in tissues rises with age in many organs and in agerelated illnesses, suggesting that cellular senescence plays a significant role in the functional decline related to ageing. Correspondingly, it has previously been shown in animal models that eliminating senescent cells might mitigate the deleterious consequences of ageing. As a key regulator of several cellular mechanisms, there are microRNAs (miRNAs) known to be associated with senescence. However, miRNAs that may directly trigger or reverse senescence remain to be elucidated. Here, the first goal of thesis was to identify the miRNA profile of proliferating, senescent, and rescued senescent endothelial cells to determine miRNAs that may be causal or influential of cellular senescence. I found that miR-361-5p not only associated with senescence but also reduced the load of senescent cells in vitro in human endothelial cells upon induction in late passage cells. Secondly, C. elegans was used to examine the role of miR-361-5p targeted genes on ageing in vivo. I found that 56% of genes which were dysregulated in vitro adversely affected healthspan and/or lifespan in vivo. Finally, a previous finding from our lab (Holly et al., 2015) identified three miRNAs-associated with human ageing and senescence in human primary fibroblasts of which miR-15b-5p may reduce senescence markers and secretory phenotypes (SASP) in the human dermal fibroblast cells. This thesis presents new miRNAs (miR-361-5p and miR-15b-5p) which may be involved in the aetiology of senescence and may be used in future in ageing intervention.2 0