Item'A Rich Man's Sickness': A Critical Hermeneutic Study on What It Is Like To Live with Diabetes in LiberiaBleah, Paulina; Nursing; Camargo-Plazas, PilarDiabetes is a growing public health concern in Liberia, where an estimated 2.1% of its population of 5.2 million people are living with the disease. The challenges with diabetes in Liberia are enormous. Diabetes places immense socioeconomic pressure on individuals and their families and burdens an already overstretched health care system, still recovering from the destructive effects of the 14-year Liberian civil war (1989 – 1996 and 1999 – 2003) and the West African Ebola virus epidemic (2014 – 2016). While efforts towards rebuilding the Liberian health care system are ongoing, people with diabetes experience significant challenges with access to social and health resources to manage their illness. As such, the aim of this critical hermeneutic study was to explore what it is like to live with diabetes in Liberia. I recruited 10 participants from a publicly funded hospital in Monrovia, Liberia, to partake in this study. Photovoice, a well-established participatory data collection approach, was used to gather images and stories that represented participants’ daily experiences of living with diabetes. The themes uncovered highlight the assets, needs, and opportunities related to diabetes management and care in Liberia; assets – participants shared support from family, their church community, and their religious beliefs helped them cope with and manage diabetes; needs – participants voiced challenges with accessing healthy foods, diabetes medications and supplies, and diabetes-related health services; and opportunities – participants advocated for local governments and policy makers to prioritize diabetes on national health agendas and support programs and initiatives (i.e., diabetes centres) to improve care and outcomes for people living with diabetes in Liberia. The findings from this study provide a clearer picture of the impact of diabetes on individuals, families, and communities in Liberia. The experiences of people living with diabetes in Liberia are under-researched. Therefore, this timely research provides an opportunity for local governments and international partners to enact key recommendations for the purposes of improving health outcomes and quality of life for people living with diabetes in Liberia. ItemMachine Learning-Driven Insights: Rare Disease Drug Discovery and Cancer Patient StratificationLi, Xinran; Chemical Engineering; Yang, LaurenceThe computational prowess of machine learning (ML), synergized with the establishment and refinement of diverse databases, emerges as a tool to revolutionize drug discovery and cancer treatment. In this thesis, a pipeline incorporating a novel deep-learning based ML method with traditional molecular docking was developed to accelerate drug screening for leishmaniasis. This thesis then concentrated its analytical lens on the categorization of triple negative breast cancer (TNBC) by applying unsupervised learning algorithms on gene expression data. The resultant subtypes, as delineated by each algorithm, underwent a comparative analysis. Furthermore, these clusters were enriched for gene ontology (GO) terms to unveil the distinct characteristics and prognosis implications of potential new clusters. ItemThe Universality of Intrinsic Flattening in Extragalactic Stellar DisksFavaro, Jeremy P.; Physics, Engineering Physics and Astronomy; Widrow, LawrenceHighly inclined (edge-on) galaxies provide the unique perspective necessary to constrain the intrinsic flattening, 𝑐/𝑎, of galactic disks. We use “dust-free” 3.6 𝜇m maps of 141 edge-on spiral galaxies from the Spitzer Survey of Stellar Structure in Galaxies (S4G) and its early-type galaxy extension to determine the intrinsic flattening of stellar disks. The proper assessment of the intrinsic flattening of galaxies requires careful consideration of galactic structure. To this end, we take inspiration from the findings of surface brightness profile decompositions to develop a robust method for the identification and analysis of isophotes that characterize the disk. Isophote axis ratios are averaged within two axial bins between 20% of the optical radius of the 25th magnitude isophote in the 𝐵-band, 𝑅25, and 80% of 𝑅25, which we demonstrate characterises the stellar disk’s 𝑐/𝑎. We then test for correlation between 𝑐/𝑎 and Hubble type. The relationships between 𝑐/𝑎 and other galactic physical parameters – total stellar mass, concentration index, total HI mass, mass of the central mass concentration (CMC), and circular velocity – are also investigated. We find that: (i) the intrinsic flattening of spiral galaxies is ⟨𝑐/𝑎⟩ = 0.130 ± 0.002 (stat) ± 0.034 (intrinsic/systematic); (ii) the intrinsic flattening of spiral galaxies is similar across morphological types; (iii) intrinsic flattening shows good positive correlation with measures of CMC size; and (iv) intrinsic flattening correlates well with the model-dependent ratio of scale height to scale length. ItemMetabolism of Glycosphingolipids and targeting GM2 synthesis pathway to develop substrate reduction approach in Tay-Sachs and Sandhoff disorders.Abidi, Iram; Biomedical and Molecular Sciences; Brockhausen , Inka; Walia, JagdeepGM2 gangliosidosis is a rare genetic lysosomal storage disorder (LSD) in children, with no effective therapies available presently. Tay-Sachs (TSD) and Sandhoff disorders (SD) are caused by a disruption of the catabolic pathway of gangliosides in lysosomes, accumulating GM2 and lyso-GM2, which damage cells and tissues. This leads to symptoms that often include neurological deterioration, such as cognitive decline, motor dysfunction, and seizures. For the purpose to develop substrate reduction therapy (SRT) for GM2 gangliosidosis in TSD and SD, we studied the enzyme beta1,4-N-acetylgalactosaminyltransferase 1, B4GALNT1, responsible for the synthesis of GM2. We attempted to predict its structural features by modelling the enzyme using Bioinformatics tools and characterized B4GALNT1 activity to establish its properties, stability, and inhibition. Additionally, we established an enzyme assay to produce Lyso-GM2 from GM2 using an in-vitro method, to utilise Lyso-GM2 as a possible biomarker for detection of TSD and SD. We used eukaryotic transient expression systems (HEK293 and Expi293cell lines) to express B4GALNT1 in vitro. Western blots demonstrated production of soluble protein in Expi293, which was successfully purified using Ni-NTA chromatography. The predicted 3D structure of B4GALNT1 established highly conserved residues, showing a potential catalytic DXD motif at position 356-358, close to residues Y501 and H483 which are likely to be important for donor binding. R505 is another significant amino acid reported to be mutated in a small number of patients with GM2 gangliosidosis. B4GALNT1 was strongly inhibited by bis-imidazolium salts that are selective inhibitors of glycosyltransferases. These inhibitors could decrease the synthesis of GM2 and other related glycosphingolipids in the biosynthetic pathway, and further avoid accumulation of GM2 and lyso-GM2 in patients with patients with lysosomal dysfunctionalities and neurodegeneration like TSD and SD. This work can lead to potential therapies for these disorders. ItemIdentifying Candidate Genes for Flowering Time and Floral Development in Genome and Transcriptome Assemblies of the Non-Model Plant Lythrum salicaria.Fuentes-Vergara, Mabel S.; Biology; Colautti, RobertClimate change is leading to environmental shifts, challenging the survival of many organisms. Some invasive species like Lythrum salicaria (purple loosestrife) can rapidly adapt to new conditions and thrive in human-altered habitats, offering a valuable model for studying the ecological and genetic factors that enable species survival under global change. While the ecological factors promoting the invasion and spread of L. salicaria are well-studied, the genetic basis for ecologically important traits is less understood. The aim of this thesis was to develop an annotated genome and transcriptome to investigate the genetic architecture of L. salicaria and the genetic basis of adaptive traits. A draft genome of a diploid ancestor from the native range was assembled using paired-end and mate-pair libraries sequenced on the Illumina HiSeq and MiSeq platforms. Ten transcriptomes were sequenced, representing four tetraploid individuals from the introduced range, and included different samples from the stem, floral meristem, flowers, and fruits of early and late-flowering phenotypes. Additionally, the genome assembly was annotated using the transcriptome as well as sequence-based predictions. The genome assembly was approximately 0.8 Gb in size across 648 scaffolds with 60,656 potential genes. A re-assembly of the transcriptome using the annotated genome resulted in 120,565 transcripts derived from 66,445 potential genes, including isoforms. An enrichment analysis identified 1,946 genes potentially involved in flowering processes, with 1,399 showing protein matches to 124 reviewed flowering-related proteins in the UniProtKB database. Additionally, matches were identified for genes related to stress response and defense metabolites. A key focus was the differential expression analysis of transcripts related to flowering time and floral tissues, providing insights into the genetic factors influencing these traits in L. salicaria. This research enhances the understanding of the genetic architecture of L. salicaria and identifies candidate genes for future investigations into plant genomics and adaptation strategies in changing environments.