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Articles 1 - 9 of 9
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Timing And Duration Of Folate Restriction Differentially Impacts Colon Carcinogenesis., Ali M. Fardous
Timing And Duration Of Folate Restriction Differentially Impacts Colon Carcinogenesis., Ali M. Fardous
Wayne State University Dissertations
Colorectal cancer (CRC) constitutes a major burden on the healthcare system as the second most commonly diagnosed cancer in the developed world. Dietary folate is considered an important modulator of colorectal cancer. Folate restriction has been implicated in increasing CRC incidence by disrupting nucleotide synthesis, Impacting DNA methylation and inducing genetic instability. Our research shows that the timing and duration of dietary folate restriction can differentially impact Colorectal cancer initiation. Acclimating mice to folate restriction for 8 weeks results in a reduced number of preneoplastic lesions compared to mice placed of folate restriction for 1 week prior to initiating the …
Computational Analysis Of Oxidative Stress In Endothelial Dysfunction: Insights On The Role Of Tetrahydrobiopterin, Ascorbate And Glutathione, Sheetal Kedar Panday
Computational Analysis Of Oxidative Stress In Endothelial Dysfunction: Insights On The Role Of Tetrahydrobiopterin, Ascorbate And Glutathione, Sheetal Kedar Panday
Wayne State University Dissertations
Oxidative stress and endothelial dysfunction are reported in the cardiovascular and neurovascular diseases. Oxidative stress is caused due to an increase in the generation of reactive oxygen (ROS) and nitrogen species (RNS) and incapacity of antioxidant systems to eliminate ROS and RNS. Endothelial dysfunction is characterized by a reduction in nitric oxide (NO) bioavailability. NO is constitutively produced by enzyme endothelial nitric oxide synthase (eNOS). A reduction in tetrahydrobiopterin (BH4), which is an essential cofactor of eNOS, can lead to eNOS uncoupling. There is complex interplay between the ROS/RNS and antioxidant system underlying pathophysiologies of vascular diseases, however our quantitative …
Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia
Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia
Wayne State University Dissertations
Rat1 is a 5′→3′ exoribonuclease in budding yeast belonging to the XRN-family of nucleases. It is a highly conserved protein with homologs being present in fission yeast, flies, worms, mice and humans. Rat1 and its homolog in metazoan have been shown to function in multiple facets of RNA metabolism. In this study, we report a novel role of Rat1 in splicing of pre-mRNA in budding yeast. In the absence of the functional Rat1 in the nucleus, an increase in the level of unspliced transcripts was observed in yeast cells. Strand-specific TRO analysis revealed that the accumulation of unspliced transcripts upon …
Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog
Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog
Wayne State University Dissertations
The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …
Novel Insights Into The Critical Role Of Cardiolipin In Cellular Metabolism And Mitochondrial Physiology, Jiajia Ji
Wayne State University Dissertations
Cardiolipin (CL) is the signature phospholipid of mitochondria. CL and its remodeling exert critical roles in biological processes both inside and outside of mitochondria. CL abnormalities have been associated with various mitochondrial disorders and aging. Understanding the role of CL in mitochondrial physiology and cellular metabolism could provide valuable insights into cell biology and human health. Several metabolic alterations have been reported in CL-deficient cells, including accumulated lactate, decreased PDH activity, and decreased TCA cycle function. This dissertation connected these findings by showing abnormal NAD+ metabolism in various models lacking CL. Importantly, it shows that NAD+ supplementation improves mitochondrial function …
Development And Application Of Chemical Tools To Identify Kinase-Substrate Interactions, Aparni Kithulgoda Gamage
Development And Application Of Chemical Tools To Identify Kinase-Substrate Interactions, Aparni Kithulgoda Gamage
Wayne State University Dissertations
Post translational modifications regulate a variety of biological processes inside the cell.Protein phosphorylation is one such PTM modification catalyzed by protein kinases, which aid to transfer a signal from one place to another inside the cell. However, irregularities in kinase-mediated signaling are often implicated in many diseases, making kinases effective drug targets. To understand kinase-related disease formation and to discover drugs to treat these diseases, it is crucial to have a clear understanding on kinase-mediated cell signaling networks. A current gap in the kinase biology field is a lack of tools to identify which kinase phosphorylates which protein substrate inside …
Single-Lipid Sorting And Dynamics At Nanoscale Membrane Curvatures: The Effects Of Fluorescence Labeling, Composition, Phase, And Temperature, Xinxin Woodward
Single-Lipid Sorting And Dynamics At Nanoscale Membrane Curvatures: The Effects Of Fluorescence Labeling, Composition, Phase, And Temperature, Xinxin Woodward
Wayne State University Dissertations
Nanoscale membrane curvature on cell plasma membrane assists in the spatial organization and domain formation that are critical for life of eukaryotic cells. Lipids and proteins can sense, be sorted by, and generate both functional domains and membrane curvature. Reveal the relationship between membrane curvature, phase separation, and single-molecule behavior is a key to understanding fundamental processes, such as phagocytosis initiation, cell signaling, and membrane budding. Single lipid dynamic and sorting on engineered membrane curvature is studied to understand the effects of fluorescence labeling, composition, phase separation, and temperature. Single particle tracking was used to find radial averaged diffusion at …
Variations On A Theme: Intricacies Of Unanchored Poly-Ubiquitin Signaling And Toxicity, Jessica Renee Blount-Pacheco
Variations On A Theme: Intricacies Of Unanchored Poly-Ubiquitin Signaling And Toxicity, Jessica Renee Blount-Pacheco
Wayne State University Dissertations
Ubiquitin is an 8.5 kDa post-translational modifier involved in essentially all eukaryotic cellular processes. Through a process called ubiquitination, ubiquitinating enzymes chemically attach ubiquitin to substrate proteins to control their fates, resulting in anything from their recruitment into signaling pathways to their proteasomal degradation, with a plethora of possibilities in between. Ubiquitin molecules can also be attached to one another, resulting in poly-ubiquitin chains with various effects depending on the number of ubiquitin molecules and the specific amino acid residues used to link them together. While most poly-ubiquitin in the cell exists as conjugated species, there are also untethered poly-ubiquitin …
Germinal Center B Cell Expression Of Aire Regulates Antibody Diversification And Autoimmunity, Jordan Zheng Zhou
Germinal Center B Cell Expression Of Aire Regulates Antibody Diversification And Autoimmunity, Jordan Zheng Zhou
Wayne State University Dissertations
B cells are a unique subset of immune cells that, in response to antigen, diversify their antibody repertoire to generate progressively higher affinity antibodies of different isotypes through the processes of affinity maturation/somatic hypermutation (SHM) and class switch recombination (CSR). One of the major sites in which this diversification occurs is in T cell dependent microanatomical structures known as germinal centers (GC). Here, we find that GC B cells express the protein, autoimmune regulator (Aire) in a CD40 dependent manner. In these cells, Aire interacts with activation induced cytidine deaminase (AID), the protein responsible for initiating the processes of diversification …