Browsing by Subject "Fumonisin"
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Item Development of a Biomarker and Clay Based Remediation Strategy for Populations at Risk for Fumonisin Toxicosis(2012-07-16) Robinson, AbrahamFumonisin B1 is the most prevalent congener of the fumonisin mycotoxins produced by Fusarium verticilliodies and is considered by many to be the most toxic. Fumonisin B1 has been classified by IARC as a class 2B carcinogen. This is primarily due to evidence suggesting increased exposure to FB1 through contaminated foodstuffs is responsible for increased incidence of esophageal cancer in regions of China and South Africa. Fumonisin B1 exposure has also been implicated in the increased incidence of neural tube defects along the Texas/Mexico border. Therefore the principal goals of this research were to 1) Identify sorbent materials that would be compatible with the chemical characteristics of fumonisin B1 and evaluate their ability to sequester the toxin using established in vitro techniques; 2) evaluate urinary FB1 as a biomarker of exposure from a fumonisin contaminated diet; 3) utilize urinary FB1 as a diagnostic tool to evaluate the efficacy of NS in reducing biomarkers of FB1 bioavailability in a Ghanaian population suspected to be co-exposed to aflatoxins and fumonisins. Isothermal analysis and an alternative animal model were examined and compared to previously published results to determine the sorbent toxin interaction activity in vitro as a predictor of in vivo efficacy. An HPLC method for detection and quantitation of urinary FB1 was developed based on methods previously adapted for primary amine and biomarker analysis. Urinary FB1 was evaluated as an HPLC detectable biomarker using a rodent model. Calcium and sodium montmorillonite clays were selected to interact with the positive charge on FB1 at low pH and sorb the molecule. Ferrihydrite was selected to interact with the negative charge on the FB1 molecule at neutral to high pH. While both polarities of sorbent were effective, montmorillonite clays demonstrated a higher capacity for sorption of FB1 than ferrihydrite. These in vitro results were confirmed in a rodent model where urinary FB1 was reduced 27% in NovaSil treated rats vs. controls. Finally, in a Ghanaian population co-exposed to aflatoxins and fumonisins, urinary FB1 was significantly reduced at 2 time points when the NovaSil treatment was compared to placebo.Item Human Exposure to Foodborne Toxins in Ghana: Intervention Strategy for Reduction of Aflatoxin and Fumonisin Bioavailability(2013-08-30) Mitchell, Nicole JeanInternational health has typically focused on remediation of infectious diseases in developing countries. However, recent reports from the International Agency for Research on Cancer (IARC) have highlighted the importance of cancer incidence/ mortality in the developing world. Foodborne mycotoxins produced by fungi, called aflatoxin (AF) and fumonisin (FB), have been associated with hepatocellular and esophageal carcinomas among other deleterious effects, such as growth faltering and immune dysfunction. Exposure to these toxins in Ghana is particularly high due to food insecurity, climate, and lack of regulatory infrastructures. Work to alleviate AF and FB contamination in Africa has focused on instituting good agricultural and storage practices however, exposures remain inextricable in many communities. Utilization of a calcium montmorillonite clay, UPSN, shows promise of tightly binding both AF and FB in the gastrointestinal tract, thereby reducing their bioavailability. The objectives of this research were to determine exposure susceptibility in Ghana and to assess efficacy and safety of UPSN treatment within vulnerable populations. Cross-sectional data from six different regions of Ghana indicated that AF exposure is associated with maize consumption and region of residence. However, food preparation practices were not correlated to AF levels in the present study. Therefore, future intervention strategies were focused on the end point of the food consumption chain by reducing AF exposure from maize immediately prior to ingestion (i.e. UPSN treatment). In a three-month trial an encapsulated montmorillonite clay was efficacious in reducing AF exposure. However, concern for sustainability and its applicability for children led to an effort to alter the dose dissemination form. Inclusion of UPSN in common Ghanaian foods retained the efficacy of the clay, reducing a short-term biomarker (AFM_(1)) by 55%, and was determined to be safe in children (ages 3-9). Importantly, daily assessment of AFM_(1) levels was successful in providing statistical significance of intervention effects within only five days of treatment. Initial results indicate that UPSN could efficiently to bind both AF and FB in the gastrointestinal tract, reducing biomarkers for both toxins in animal models. Thus, UPSN could positively impact health in developing communities at risk for AF and FB exposure.Item Molecular characterization of genes regulating fumonisin biosynthesis and development in maize pathogen fusarium verticilliodes(2009-05-15) Sagaram, Uma ShankarFusarium verticillioides (Sacc.) Nirenberg (teleomorph Gibberella moniliformis Wineland) is a fungal pathogen of maize that causes ear rots and stalk rots worldwide. In addition, it produces a group of mycotoxins called fumonisins when the fungus colonizes maize and maize-based products. Fumonisin B1 (FB1), the predominant form occurring in nature, can cause detrimental health effects in animals and humans. Several efforts were made to study the host and pathogen factors that contribute to the production of fumonisins. Using the available genomic resources, three genes with a potential role in FB1 regulation and development were identified. The genes are GBP1, GBB1 and GAP1. This research describes molecular characterization of these genes with respect to regulation of FB1 and development in F. verticillioides. GBP1 is a monomeric GTP binding protein with similarity to DRG and Obg sub-classes of G-proteins. GBB1 encodes heterotrimeric GTP binding protein ? subunit. GAP1 is a GPI (Glycophosphotidylinositol) anchored protein, which belongs to a family of cell wall proteins. Targeted deletion and complementation studies indicated that GBP1 is negatively associated with FB1 biosynthesis but had no effect on conidiation in F. verticillioides. GBB1 plays an important role in regulation of FB1 biosynthesis, conidiation and hyphal growth, but not virulence. GAP1 is associated with growth, development and conidiation but not in positive regulation of FB1 or pathogenicity. The outcome of this study revealed new molecular genetic components that will help scientists better understand signal transduction pathways that regulate FB1 biosynthesis and conidiation in F. verticillioides.Item Molecular Characterization of MADS-BOX Transcription Factors and Analysis of Field Population Diversity in the Maize Pathogen Fusarium verticillioides(2013-04-10) Ortiz, Carlos SFusarium verticillioides (Teleomorph Giberella moniliformis) is an ascomycete fungus responsible for ear and stalk rots of maize. Most importantly, it produces a group of mycotoxins called fumonisins upon colonization of maize kernels. Fumonisin B1 (FB1), the most prevalent fumonisin in nature, was first identified in 1988 and has been found to be toxic to human and animals. The gene cluster for FB1 biosynthesis and some environmental conditions responsible for the toxin production are known, but gaps in our understanding of the signaling pathways leading to FB1 biosynthesis still remain. MADS-box transcription factors (TF) are known to regulate diverse cellular functions in all eukaryotes, and in silico analyses revealed two genes, MADS1 and MAD2, in F. verticillioides. Reverse genetics studies indicated that MADS1 and MADS2 positively regulate sexual mating and FB1 biosynthesis but not pathogenicity in F. verticillioides. Furthermore, MADS1 was found to act as a broad regulator of polyketide-derived secondary metabolism. Additionally, population diversity studies were conducted in 164 F. verticillioides cultures isolated from 65 maize-producing counties in Texas. The result showed a fluid population with no particular niches formed. F. verticillioides strains were also isolated from counties that have previously tested negative for FB1 contamination in maize. The presence of the pathogen represents a risk for future FB1 contamination events if suitable conditions were to arise. My research revealed new genetic components involved in F. verticillioides secondary metabolite biosynthesis and provided a better understanding of the pathogen population fluidity in Texas.