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Browsing by Author "Ramonell, Katrina"

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    Cadmium-Induced Nonalcoholic Fatty Liver Disease: Implications of the Heme Oxygenase 1/Biliverdin Reductase Enzymatic Pathway
    (University of Alabama Libraries, 2022) Nam, Younji; Jenny, Matthew; University of Alabama Tuscaloosa
    NAFLD is the most common form of chronic liver disease and is currently at epidemic levels in Western countries the disease and experiencing annual increased prevalence due to shifting to a westernized lifestyle. Epidemiological studies have identified a correlation between cadmium (Cd) body burden and the prevalence and severity of non-alcoholic fatty liver disease (NAFLD). Furthermore, recent studies have demonstrated that Cd exposure can produce NAFLD-related phenotypes in animal models. HMOX1 catalyzes the degradation of heme into free iron (Fe2+), carbon monoxide (CO) and biliverdin. While HMOX1 acts as an antioxidant through the metabolism of heme, biliverdin reductase (BLVR) utilizes cytosolic NADPH to reduce biliverdin to bilirubin, which has been shown to have antioxidant potential. Although the HMOX/BLVR enzymatic pathway plays an important protective role, studies have demonstrated that the aberrant hyperactivity of the HMOX1/BLVR enzymatic pathway has pleiotropic health effects that may contribute to the NAFLD-related pathologies. Studies have shown that HMOX1 is highly expressed in many different cancer types. Other studies have also demonstrated that overexpression of HMOX1 promotes tumorigenesis by increasing cancer cell survival. These contrasting roles for the pathway yield the potential for a threshold effect in which temporal activation of the pathway elicits a beneficial effect that protects against the development of NAFLD-related diseases, but persistent overexpression or hyperactivation that exceeds the threshold can become detrimental and promote the development of liver pathologies. In Chapter 2, we elucidate a mechanism of NRF2-mediated hyperactivation of HMOX1 in vitro using the HepG2 cell line. Differential gene expression profiles were generated using Custom PCR arrays screening 180 genes involved in stress response and toxicity as well as carcinogenesis. Additionally, the mechanism of the HMOX1 hyperactivation was elucidated by accessing NRF2 binding in the HMOX1 gene promoter using ChlP qPCR. To gain further insight into the mechanism by which chronic Cd exposure promotes NAFLD-related pathologies, in Chapter 3 we demonstrate the effect of sub-chronic and chronic Cd exposure on the development of NAFLD-related pathology in vivo using zebrafish as a model organism. In Chapter 4, we characterize the individual roles of transgenic over-expression of HMOX1, BLVRA, and BLVRB in the progression of NAFLD during normal, as well as altered sensitivity to acute Cd toxicity in HMOX1 overexpression. Finally, In Chapter 5, we discuss novel regulatory mechanisms in the HMOX1/BLVR enzymatic pathway to access the mode of hyperactivation of NRF2.
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    Genomics of Diploidization in Palms and Grasses
    (University of Alabama Libraries, 2024) Deb, Sontosh Kumar; McKain, Michael R.
    Polyploidy refers to a state in which organisms have more than two complete sets of chromosomes. Following polyploidy, short and long-term cytological and genomic changes lead polyploids to restore a diploid-like state--the process known as diploidization. The diploidization rate and mechanisms show lineage-specific differences, and there is insufficient evidence to define a clear paradigm of how different polyploid species respond to post-polyploidy changes. Here, I investigated the consequences of whole genome duplication (WGD) following an ancient event in palms and another recent event in grass species Zea mays. I generated a chromosome-level genome assembly of a mangrove palm species Nypa fruticans, characterized its variation in the structural features compared to other palm genomes, and investigated the retention of duplicated genes. I found that the N. fruticans genome differs in chromosomal rearrangements and in accumulation of transposable elements with other palm species following WGD. I also identified high retention of duplicated genes in N. fruticans. Functional enrichment analysis showed that the dosage balance hypothesis and selective pressures of adapting to a harsh intertidal environment could primarily explain the retention of the duplicated genes. Further exploration of salt-tolerant orthologous genes also supports the hypothesis. To study maize, I generated a chromosome-level monoploid genome assembly of a parental relative Vossia cuspidata and used phylogenomic approaches to detect signals of homoeologous exchange, exploring its impact on the evolutionary history of maize subgenomes following WGD. The study found that V. cuspidata is closely related to one of the maize diploid progenitors, with homoeologous exchanges potentially obscuring the ancestry of maize subgenomes. Further, through transcriptomic profiling of maize and its wild relatives, I investigated the functional differences in the flooding tolerance of these species. I identified evolutionarily conserved and species-specific genes in response to flooding stress. The findings suggest that extensive rewiring of the gene regulatory circuitry and the outcome of phenotypic plasticity resulting from the interaction with their environment might underlie the variation in flooding response in maize and its relatives. Altogether, my dissertation provides important insights into the dynamics and complexity of diploidization and suggests that understanding the lineage-specific differences requires further investigations.
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    Identification and Characterization of Arabidopsis Toxicos En Levadura 12: a Gene Involved in Chitin-Elicitor-Triggered Immunity and Salt Tolerance
    (University of Alabama Libraries, 2022) Kong, Feng; Ramonell, Katrina; University of Alabama Tuscaloosa
    Plants have evolved complex systems to respond to changes in environmental conditions. Understanding the underlying signal transduction events in the plant response is crucial for greater insight into plant-environment interactions and to establish transgenic strategies to improve stress tolerance in crops. The aim of this dissertation was to identify and characterize the Arabidopsis Toxicos en Levadura 12 (ATL12) gene and explore the role of ATL12 in defense against powdery mildew and in salt stress tolerance. ATL12 encodes a conserved C3HC4 RING-type protein that has E3 ubiquitin ligase activity. Subcellular co-localization assays indicate that ATL12 localizes to the plasma membrane. Compared to Columbia wild-type, mutants in atl12 are more susceptible to fungal infection, whereas overexpression of ATL12 increased resistance to the fungus. Mutants of atl12 display a decreased seed germination rate, a reduction in root length growth, and a higher survival rate under high salt conditions. QRT-PCR studies showed that ATL12 is highly induced by chitin at early time points and its expression is linked to the activation of the MAPK cascade, pointing to the possible role of ATL12 in the early hypersensitive response and the local plant response to fungal pathogens. Additionally, the expression of respiratory burst oxidase homolog protein D/F was also found to decrease in the atl12 mutant, while the expression of ATL12 was not affected in atrbohd and atrbohf mutants. Together these data suggest that chitin-induced ATL12 expression is also linked to NADPH oxidase AtRBOHD/F-driven ROS production. ATL12 is also salt-inducible, and its expression is up-regulated at late stages in response to NaCl stress. Over-expression of ATL12 increases the expression of the salt stress-associated genes SOS1 and SOS2, and the ABA-dependent genes RD29B and RAB18. Further the expression of ATL12 was up-regulated after treatment with salicylic acid and jasmonic acid, indicating a possible role for ATL12 in plant hormone-mediated defense responses. In summary, these results indicate that ATL12 is involved in crosstalk between the SA-, JA-, chitin-induced MAPK, and NADPH oxidase-mediated defense responses against fungal pathogens and that it modulates salt stress responses through an ABA-dependent pathway and intensifying the ROS response in Arabidopsis thaliana.
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    The Monomer-Dimer Equilibrium of M-Methylnitrosobenzene
    (University of Alabama Libraries, 2023) Tomasoa, Venskha Meldia; Blackstock, Silas C
    Nitrosobenzenes (NBs) are colored molecules that have a unique ability to self-assemble via reversible dynamic covalent bond formation into colorless dimeric structures - i.e, they are chemochromic. The degree of molecular association is dependent on their environment. This study involves the synthesis, purification, crystallization, and monomer/dimer partitioning of m-methylnitrosobenzene, m-MeNB, in the solid-crystal state and in a range of solvents at varying concentrations and temperatures. X-ray diffraction analysis on a single crystal of m-MeNB provides its dimeric molecular structure, and VT-NMR experiments in four different solvents, over a range of polarity, evaluate the monomer/dimer equilibrium for m-MeNB under different solvation conditions, allowing the dissection of the NB self-assembly process into enthalpic and entropic components as a function of its molecular environment. The solvents investigated include CDCl3, acetone-d6, methanol-d4, and D2O. Keq values for monomer/dimer compositions range from over 2 x 103 in these solvent environments.
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    Short-Chain Chitin Oligomers: Promoters of Plant Growth
    (MDPI, 2017) Winkler, Alexander J.; Alfonso Dominguez-Nunez, Jose; Aranaz, Inmaculada; Poza-Carrion, Cesar; Ramonell, Katrina; Somerville, Shauna; Berrocal-Lobo, Marta; Universidad Politecnica de Madrid; University of Hamburg; Complutense University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); University of Alabama Tuscaloosa; Carnegie Institution for Science; Instituto Nacional Investigacion Tecnologia Agraria Alimentaria (INIA)
    Chitin is the second most abundant biopolymer in nature after cellulose, and it forms an integral part of insect exoskeletons, crustacean shells, krill and the cell walls of fungal spores, where it is present as a high-molecular-weight molecule. In this study, we showed that a chitin oligosaccharide of lower molecular weight (tetramer) induced genes in Arabidopsis that are principally related to vegetative growth, development and carbon and nitrogen metabolism. Based on plant responses to this chitin tetramer, a low-molecular-weight chitin mix (CHL) enriched to 92% with dimers (2mer), trimers (3mer) and tetramers (4mer) was produced for potential use in biotechnological processes. Compared with untreated plants, CHL-treated plants had increased in vitro fresh weight (10%), radicle length (25%) and total carbon and nitrogen content (6% and 8%, respectively). Our data show that low-molecular-weight forms of chitin might play a role in nature as bio-stimulators of plant growth, and they are also a known direct source of carbon and nitrogen for soil biomass. The biochemical properties of the CHL mix might make it useful as a non-contaminating bio-stimulant of plant growth and a soil restorer for greenhouses and fields.