Saudi Cultural Missions Theses & Dissertations
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Item Restricted DESIGNING THROUGH THE BRAIN: An Interdisciplinary Exploration Between Architecture and Neuroscience(Politecnico di Milano, 2024) Alaithan, Ali; Croset, Pierre-AlainThroughout the course of architecture history, architects have consistently engaged with various disciplines to expand their understanding of how people interact with the surrounding milieu. Since the 20th century, some prominent architects have collaborated with psychologists to gain insights into how design influences behavior and actions, striving to create spaces that truly resonate with people. In modern times, we spend most of our time in indoor spaces, making it progressively evident that architecture affects our brain and body. Recently, there has been growing attention between architecture and neuroscience. This is a complex field, requiring insights from psychology and cognitive science to understand the indirect connections between brain processes and spatial experience. This conversation starts from a theoretical framework encompassing brain, mind and body. The brain is an engine for behavior and action within a space. Thus the primary objective here is to understand the human brain within the built environment. A deeper awareness of the brain’s intricate processes enhances our comprehension of how we interact with our surroundings. To fully grasp the complexity of this discussion, it is crucial to comprehend the underpinnings of understating the brain. Three essential theories —EvoDevoSocio, Darwin’s theory, and embodied perception— shapes our theoretical and scientific understanding of the brain. This ongoing conversation covers multiple themes, including: sensation and perception, learning and memory, decision making, emotions and affect, movement and more. This thesis explores the intricate theoretical and scientific connection between architecture and neuroscience, specifically focusing on aspects relevant to architects. Three central themes will be thoroughly studied — emotions, movement, learning and memory — covering both their theoretical foundations and recent scientific discoveries. These findings will be applied in an interdisciplinary design exploration of a community center. These scientific findings will act as “generators” that either evoke emotions, facilitate movement, or foster learning and memory. Thus, the objective of the research is not to develop a theoretical program for architecture, but to apply an interdisciplinary design methodology. Unlike traditional practices, which often rely on architects’ personal experience, this approach is rooted in a scientific understanding of the human brain, allowing architects to design spaces that meaningfully respond to human cognition and behavior.4 0Item Restricted AMIGO3 gene expression and function during oligodendrocyte differentiation in the central nervous system(University of Birmingham, 2024-04-21) Almutairi, Majed; Fulton, Daniel; Ahmed, ZubairDemyelination causes disruption to neuronal signalling and occurs in many neurodegenerative diseases or in response to brain injury. There are no cures available for demyelinating diseases, including multiple sclerosis (MS), the most common autoimmune inflammatory disease in the central nervous system (CNS). Current approaches to treat MS focus on anti-inflammatory drugs, which prevent demyelination progression and reduce clinical relapses, but do not allow repair or replacement myelin. A natural repair process called remyelination can occur following demyelination. Remyelination can help to repair demyelinating plaques and protect axons from degeneration, but endogenous remyelination is inefficient and fails with ageing and disease progression, Improving remyelination is therefore an important for the focus for the development of MS therapies. Studies of animal models have to led to the discovery of new therapeutic targets which can promote endogenous remyelination. An example is the leucine rich repeat protein (LRRP) leucine rich repeat and immunoglobulin-like domain containing protein 1 (LINGO1). Inhibition of LINGO1 promoted remyelination in several animal models of demyelination, but clinical inhabitation of LINGO1 showed unsuccessful results in clinical trials. We considered the idea that the LINGO1 clinical trials failed due to compensation from another LRRP, amphoterin-induced gene and open reading fram-3 (AMIGO3). AMIGO3 is upregulated more rapidly than LINGO1 after spinal cord injury (SCI) in animal models, and also increases in expression rapidly after axotomy in culture of dorsal root ganglion neurons and retinal ganglion cells. Importantly, AMIGO3 expression is rapidly increased in the CNS during postnatal development when myelinating oligodendrocyte (OL) are generated, and decreases again quickly after myelination begins. AMIGO3 may therefore act a regulator of OL differentiation, and its inhibition could be an alternative therapeutic target for demyelinating diseases. Considering the above, the first aim of this project was to study the function of AMIGO3 using in vitro models of OL differentiation. For this work, a primary mixed glial culture system was developed to study OL differentiation during early stage of CNS development. Using this system we found that AMIGO3 is downregulated in mixed glial cultures during OL differentiation. We also found that downregulation of AMIGO3 expression by siRNA resulted in the upregulation of OL maturation. On the other hand, increased AMIGO3 levels produced by treatment with recombinant AMIGO3 reduced OL maturation, and activated RhoA GTP activity, a molecule involved in AMIGO3 intracellular signalling. These findings suggest that AMIGO3 downregulates OL differentiation via RhoA GTP signalling. AMIGO3 is known to engage in homotypic interactions, thus expression on different glial cells could allow cell to cell signalling. Also, AMIGO3 is expressed in cells of the OL lineage and astrocytes, thus AMIGO3 expression in non-OL glia could provide a signal to regulate OL differentiation. Considering this idea, the second aim in this thesis was to compare the expression of AMIGO3 and LINGO1 in primary cultures of astrocytes and microglia. Using Western blot and immunocytochemistry we found strong expression of AMIGO3 proteins in astrocytes, but not in microglia. Surprisingly, we also found that astrocytes express LINGO1 proteins. This work shows that astrocytes, but not microglia, are an abundant source of both AMIGO3 and LINGO1, which together could influence OL differentiation and myelin formation and repair.107 0Item Restricted Comparative Analysis of Organofluorine Mass Balance and Per- and Polyfluoroalkyl Substances in Marine and Terrestrial Environments(Saudi Digital Library, 2023-11-23) Alzbedy, Amnah; Jörg Feldmann, Rainer; Ebe, Gareth NortonAbstract Per- and polyfluoroalkyl substances (PFAS) are a group of anthropogenic pollutants. Several PFAS are highly persistent and associated with various adverse health effects and environmental concerns. In response to these concerns, restrictions have been placed on some legacy compounds, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Consequently, new PFAS compounds have emerged; however, information on the risk of these compounds to human health and the environment is unknown. In this thesis, combustion ion chromatography (CIC) and high-resolution continuous source-graphite furnace molecular absorption spectrometry (HR-GFMAS) were employed to assess the level of all extractable organic fluorine (EOF) in various tissues of whales stranded in Scotland. A comparison between CIC and HR-GFMAS revealed that both methods give results within one order of magnitude, with CIC consistently slightly lower concentrations. The EOF was then related to the sum of all quantified PFAS, analysed by targeted HPLC-MS/MS analysis. A mass balance study was conducted in the blubber, brain, kidney, liver and muscle of pilot whales aged 1 to 35 years. The findings showed that the majority of the EOF was unidentified in all whale samples. For instance, target analytes were unable to explain more than 80% of the extractable organofluorine (EOF) in brain and blubber samples. Due to the detection of perfluoroalkyl substances (PFAS) in marine environments, further work was conducted to explore the impact of these compounds in other environments; in this case, plant uptake was explored. Plant systems are a potentially importatant route of human exposure to these compounds due to the human consumption of crop plants. As a result, the study of PFAS accumulation in crops provides valuable information, particularly in light of the introduction of new PFAS substitutes that have been promoted as safer alternatives. Research in this area is needed because previous concerns regarding GenX accumulation have been raised. A greenhouse experiment using wheat and rice under different growing conditions was conducted to gain insight into the conditions influencing GenX uptake in plants. Moreover, a mass balance analysis was performed on both sample media to estimate the fractions that could be analysed using targeted LC-MS/MS, thereby improving our understanding of PFAS behaviour in plants. The findings revealed that GenX had the ability to accumulate in both rice and wheat shoots, and under non-flooded rice accumulates higher concentrations of GenX compared growing under flooded conditions. It was found that GenX contributed between 78 to 97% of the extractable organic fluorine in flooded rice shoots. Despite the limitations of organofluorine mass balance analysis, it is vital to recognize and address potential health and environmental risks associated with unidentified organofluorine compounds. Considering the scarcity of naturally occurring organofluorine compounds, this analytical approach is crucial in estimating the overall exposure and impacts of per- and polyfluoroalkyl substances (PFAS).26 0Item Restricted The Relationship between Depression, Stress-Related Neurobiology, and Incident Heart Failure: Understanding the Neurobiological Mechanisms Underlying Exercise as a Preventive Measure(Saudi Digital Library, 2023-04) Alhamam, Abdulaziz Arif Abdulaziz; Tawakol, AhmedBackground: Depression is associated with risk of developing heart failure (HF). Also, higher stress-related neural activity (SNA) associates with subsequent risk of cardiovascular disease. We investigated whether depression predicts subsequent HF through heightened SNA. Methods: Individuals (N=102,028; median age 57 years; 42.6% male) enrolled in the Mass General Brigham Biobank were identified to study the association of depression and incident HF, subset of 1,227 who underwent clinically indicated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging were retrospectively identified. SNA was measured using validated methods, as amygdalar metabolic activity corrected for regulatory brain (i.e., medial prefrontal cortical) activity. Depression and subsequent development of HF was determined via medical record review using International Classification of Diseases 10 (ICD-10) codes. Survival analyses using Cox and Kaplan-Meier models were performed. Results: Over a median follow-up period of 3.5 (IQR 2.0-5.0) years, 2,631 (2.6%) individuals developed HF (717 Heart failure with reduced ejection fraction (HFrEF), 1,214 Heart failure with preserved ejection fraction (HFpEF)). Individuals with subsequent HF (versus no HF) had higher baseline SNA (mean Z-score 0.19 ± 1.07 versus -0.08 ± 0.99; p=0.005, adjusted for age and sex). SNA associated with subsequent HF when divided into tertiles (Figure 2B) and as a continuous measure (standardized HR [95% CI]: 1.40 [1.13-1.74], p=0.002, adjusted for age, sex, hypertension, hyperlipidemia, diabetes, and smoking). The association between depression and HF subtype was stronger for HFpEF (1.46 [1.28-1.65], p<0.001) than for HFrEF (1.09 [0.92 -1.3], p=0.32). Conclusion: In this retrospective study of individuals with depression have higher risk of incident HF through heightened SNA with a somewhat stronger association for HFpEF. Understanding the link between depression and subsequent HF may provide important insights into better HF prevention and management strategies.16 0Item Restricted Brain Imaging Biomarkers in Multiple Sclerosis(2023-05-10) Altokhis, Amjad; Evangelou , Nikos; Constantinescu, CrisBackground: Iron rim lesions (IRLs), white matter lesions (WMLs) accumulation and linear brain atrophy measurements have been suggested to be important imaging biomarkers in multiple sclerosis (MS). The extent to which these markers are related to MS diagnosis and predict disease prognosis remains unclear. Furthermore, research Magnetic Resonance Imaging (MRI) findings need validation in clinical settings before they can be incorporated into clinical practice. Methods: I conducted two reviews one was a mapping review on IRLs and the other was a meta-analysis on WMLs in MS. I then tested the diagnostic and prognostic usefulness of the IRL in two studies: (1) a large, cross-sectional, multi-centre study of patients with MS and mimicking disorders using 3T MRI, (2) a retrospective single-centre study of patients with first presentation of a clinically isolated syndrome (CIS) or at the early stage of the disease using 7T MRI. I also explored the utility of routine, non-standardised MRI scans measuring WMLs number, volume and linear measures of atrophy at the early stage of the disease and examined their role in predicting long-term disability. Results: The IRLs achieved high specificity (up to 99%) in diagnosing MS compared to MS-mimics but low sensitivity of 24%. All patients with IRLs showing a central vein sign (CVS) had MS or CIS, giving a diagnostic specificity of 100% but equally low sensitivity of 21%. Moreover, the presence of IRLs was also a predictor of long-term disability, especially in patients with ≥4 IRLs. IRLs had a greater impact on disability compared to the WMLs number and volume. Linear brain atrophy of Inter-Caudate Distance (ICD) and Third Ventricle Width (TVW) had a significant impact in predicting disability after 10 years. Conclusions: The perilesional IRLs may reduce diagnostic uncertainty in MS by being a highly specific imaging diagnostic biomarker, especially when used in conjunction with the CVS. Also, the presence and number of IRLs hold prognostic value for long-term physical disability in MS. Simple and reliable assessment of brain atrophy remains challenging in clinical practice.18 0