Browsing by Subject "biomarkers"
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Item Aeolian Delivery of Organic Matter to a Middle Permian Deepwater Ramp(2012-07-16) Artan, SinemWindblown dust is a significant source of sediment and organic matter for many basins, but its influence on ancient basins can be difficult to detect and quantify. We quantified the biomarker content, including n-alkanes, hopanes, and steranes of the Brushy Canyon Formation sandstones and siltstones to evaluate the significance of windblown dust in delivery of sediment and terrestrial organic matter to the Middle Permian Delaware Basin. Ramp siltstones of the basin have been interpreted as representing deposits of unconfined low-density turbidity currents or "aeolo-marine" sediments. We analyzed the organic contents of five samples of channel-confined turbiditic sandstones and siltstones and five samples of ramp siltstones outcropping in the Guadalupe Mountains National Park, West Texas, to estimate the relative proportions of terrestrial and marine organic matter in the two types of host rocks. The total organic carbon content of all samples varied from 0.07 percent - 2.04 percent. The abundance of high molecular weight n-alkanes (n-C27 and greater) suggests that terrestrial organic matter was present in nearly all samples. Terrestrial organic matter input to the basin was characterized using a crossplot of pristane/n-C17 versus phytane/n-C18. Ramp siltstones showed ~10-fold greater variation in terrestrial content than did turbiditic sandstones and siltstones. This observation is more consistent with the aeolo-marine interpretation of ramp siltstones, and suggests that terrestrial organic matter was delivered to the Delaware Basin by wind transport during deposition of the Brushy Canyon Formation.Item Biological and functional consequences of polymorphisms in the XPD gene(2006-10-23) Kevin James Wolfe; Sherif Z.Abdel-Rahman, Ph.D.; Thomas E. Albrecht, Ph.D.; Rodney S. Nairn, Ph.D.; Randa A. El-Zein, MD. Ph.D.; Mary Treinen-Moslen, Ph.D.; Jonathan B. Ward, Ph.D.Epidemiological studies have documented many associations between single nucleotide polymorphisms (SNPs) in the nucleotide excision repair gene XPD (ERCC2) and cancer risk. Little is known, however, about the underlying mechanisms for these associations. I used lymphocytes from healthy subjects to explore novel mechanisms which could explain the reported risk-modifying effects on disease susceptibility of three SNPs in the XPD gene, the synonymous C156A SNP in exon 6 and the nonsynonymous SNPs Asp312Asn in exon 10 and Lys751Gln in exon 23. Baseline and NNK-induced chromosomal aberrations (Ca) were assessed by cytogenetic analysis and then P values were calculated as estimates of sub-population differences for increased frequencies of CAs associated with the three XPD polymorphisms. I found significant elevation in baseline frequencies of CAs among smokers with the variant 312Asn polymorphism (P=0.028). Elevations in NNK-induced aberrations were found among younger subjects (age<39 years) with the 156A or the 751Gln polymorphism, (P=0.025 and P=0.037, respectively) and in females compared to males with a combination of the 312Asn and the 751Gln polymorphisms (P=0.045). Application of real time PCR showed that each SNP, alone and in combination, significantly decreased constitutive XPD mRNA levels (P<0.003) in lymphocytes. Decreases in XPD mRNA levels were significantly higher in older subjects and in smokers. Localized Mfold structure analysis of the mRNA sequence surrounding the studied SNPs were predicted to alter mRNA secondary structure, which indicated that these SNPs potentially affect local folding and mRNA stability. UVC treatment of cells with wild type XPD produced a significant increase (P=0.03) in XPD protein levels by 30 min, which surprisingly coincided with a decrease in XPD mRNA transcript copy number (P=0.0002). Fluorescent confocal microscopy demonstrated that this increase in XPD protein appeared largely due to an increase in nuclear localization of XPD, which was evident at 30 min and persistent at 6 hrs. New observations from this project provide possible mechanistic explanations for the association of polymorphisms in XPD with increased genetic damage (CAs) and cancer risk.Item Biomarkers of Exposure to Foodborne and Environmental Carcinogens: Enterosorbent Intervention in a High Risk Population(2011-10-21) Johnson, Natalie MalekThe need to assess human exposures to foodborne and environmental carcinogens, particularly in populations at high risk for cancer and disease, has led to the development of chemical-specific biomarkers. Sensitive biomarkers for aflatoxin and polycyclic aromatic hydrocarbons (PAHs) have been useful in providing information on population exposure and reducing associated public health impacts. Aflatoxins are fungal metabolites found in a variety of foods. Among these toxins, aflatoxin B1 (AFB1) is the most predominant and hepatocarcinogenic. Acutely, AFB1 can cause disease and death, necessitating safe and effective intervention strategies. Inclusion of NovaSil (NS) clay in the diet represents a practical, sustainable approach. NS has been shown to prevent aflatoxicosis in multiple animal species by binding aflatoxins in the gastrointestinal tract, reducing toxin bioavailability. Co-exposure to PAHs, hazardous environmental contaminants, has been shown to increase the risk for hepatocellular carcinoma (HCC). Therefore, objectives of this research were to utilize biomarkers to assess aflatoxin and PAH exposures in susceptible populations in Ghana and the U.S. and to evaluate the safety and efficacy of NS intervention in Ghana (a population at risk for aflatoxicosis). After 3-month intervention with 3.0g NS/day, median aflatoxin M1 (an AFB1 metabolite) was significantly reduced (up to 58 percent) compared to the placebo group. Furthermore, no significant differences were found in levels of nutrient minerals between NS and placebo groups at baseline and 3-months suggesting NS can be used to effectively sorb AFB1 without affecting serum concentrations of important minerals. PAH biomarker results showed participants in Ghana were significantly exposed to high levels of PAHs based on the presence of 1-hydroxypyrene (1-OHP) in the majority of urines (98.9 percent). NS treatment had no effect on 1-OHP levels, further confirming the preferential binding of aflatoxins by NS. U.S. population data from a Hispanic community in Texas with an elevated incidence of HCC demonstrated a lower percentage and level of aflatoxin and PAH biomarkers. Aflatoxin M1 excretion, however, was associated with increased consumption of certain foods prone to aflatoxin contamination; thus, some individuals may be more vulnerable to exposure and associated interactions that increase the risk for HCC (e.g., PAHs or hepatitis infection).Item Cave and cliff swallows as indicators of exposure and effects of environmental contaminants on birds from the Rio Grande, Texas(Texas A&M University, 2004-11-15) Musquiz, DanielCave (Petrochelidon fulva) and cliff swallows (Petrochelidon pyrrhonota) were collected along the Rio Grande and evaluated as potential indicators of environmental contamination. The Rio Grande receives toxic substances from agricultural, industrial, municipal, and non-point sources; consequently, high levels of contaminants have been detected in birds, mammals, fishes and sediments. Swallows were obtained from 8 sites between Brownsville and El Paso, as well as from a reference site in Burleson County, 320 miles north of the nearest site of the Rio Grande. Blood samples were analyzed by flow cytometry, a technique that allows the detection of DNA damage in blood and other tissues. Plasma samples were analyzed for thyroid hormones using a radioimmunoassay technique. Organochlorines and trace metal analysis was limited to a few samples. DDE and PCB levels were below levels known to cause reduced hatching, embryo mortality, and deformities, Hg, Pb, and As were below detection, and Se, Ni and Cr concentrations were lower than levels known to cause harm in birds. Neither species showed sex-related differences in chromosome damage. Cave swallows from the Del Rio area had the highest levels of DNA variation, which may be indicative of DNA damage, possibly from PAHs exposure. Previous studies indicate that sediment samples from tributaries near Del Rio have high levels of chromium compared to other sites along the Rio Grande. A significant increase in DNA variation between sampling years was detected in cave swallows from Llano Grande Lake. Wildlife samples collected from Llano Grande Lake have recorded high levels of DDE and PCBs; in addition, this urban/agricultural contaminant sink appears to be affected by PAH exposure. T3 levels were below the detection limit of the radioimmunoassay. There were no gender related differences in T4 levels in cave swallows. Cave swallows sampled from Laredo had significantly higher T4 levels than those from birds at other sites during 1999. It was not possible to determine thyroid hormone disruption in plasma samples. Thyroid hormone and flow cytometry data were useful in establishing baseline data. Areas of concern based on genotoxic data include Llano Grande Lake, Del Rio, and El Paso.Item Ecosystem health at the texas coastal bend: a spatial analysis of exposure and response(2009-05-15) Bissett, Wesley Thurlow, Jr.This dissertation investigated locational risks to ecosystem health associated with proximity to industrial complexes. The study was performed at the behest of ranchers and citizens living and working down-prevailing wind from the Formosa Plastics, Inc. and ALCOA facilities located in Calhoun County, Texas. Concerns expressed were for potential genotoxicity resulting from exposure to complex chemical mixtures released by the facilities. Exposure assessment of the marine environment was performed with sediments and oysters from Lavaca Bay being analyzed. Numerous chemicals were found to be present at concentrations considered likely to result in adverse responses in exposed populations. Bayesian geostatistical analysis was performed to determine if the concentrations were affected by a spatial process. Mercury and polycyclic aromatic hydrocarbons were the most notable of the chemicals found to be present at elevated concentrations and affected by a spatial process. Evaluation of maps generated from spatial modeling revealed that proximity to ALCOA resulted in elevated risks for exposure to harmful concentrations of pollutants. Genotoxicity was measured in two sentinel species. Oysters (Crassostrea virginica) were utilized for evaluation of the marine environment and cattle (Bos taurus and Bos taurus crossbred cattle) were chosen for evaluation of the terrestrial environment. Chromosomal aberration analysis was performed on oyster hematocytes. Analysis of the results failed to demonstrate the presence of an important generalized spatial process but some specific locations close to the ALCOA plant had elevations in this measure of genotoxicity. Stress as measured by the lysosomal destabilization assay was also performed on oyster hematocytes. These results were found to be affected by a significant spatial process with the highest degree of destabilization occurring in close proximity to ALCOA. Genotoxicity in cattle was evaluated with the single cell gel electrophoresis assay and chromosomal aberration analysis. Bayesian geostatistical analyis revealed the presence of important spatial processes. DNA-protein cross-linkage was the most notable with a strong indication of increased damage down-prevailing wind from the industrial complexes. Results indicated that proximity to industrial facilities increased the risk for harmful exposures, genotoxicity, and lysosomal destabilization.Item Evaluation of granulysin and perforin as candidate biomarkers for protection following vaccination with Mycobacterium bovis BCG or M. bovis DeltaRD1(2008-09-18) Charles Fernando Capinos Scherer; D. Mark Estes; Slobodan Paessler; Janice J. Endsley; Gregg N. Milligan; Bernardo Villarreal-Ramos; Alfredo G. TorresThe development of improved vaccines against tuberculosis (TB) is directly linked to the investigation of new and better correlates of protection after vaccination against TB. Cloning and characterization of bovine homologues of the antimicrobial protein granulysin (Bo-lysin) and perforin by our group could be used as potential biomarkers for TB vaccination efficacy. In the present study we examined the kinetics of granulysin, perforin, IFNgamma and Fas-L responses to Mycobacterium bovis purified protein derivative (PPD) stimulation by peripheral blood mononuclear cells from M. bovis DeltaRD1-, BCG- and non-vaccinated cattle. Gene expression profiles following PPD stimulation showed significant increases in transcripts for granulysin and IFNgamma in both CD4+ and CD8+ T cells in BCG-vaccinated as compared to non-vaccinated animals. Perforin and IFNgamma examined by flow cytometry, showed a difference of 1-2% more PPD-specific cells in BCG-vaccinated than non-vaccinated animals. In the vaccine trial, granulysin and perforin were significantly increased in both vaccine groups as compared to control after vaccination and challenge. IFNgamma expression was increased only after vaccination and secretion was higher in the control, as compared to both vaccine groups demonstrating no correlation with protection upon vaccination. In summary, results shown here provide evidence that granulysin and perforin are prospective candidates as biomarkers of protection after vaccination against TB.Item Historical Reconstruction of Terrestrial Organic Matter Inputs to Fiordland, NZ Over the Last ~500 Years(2012-10-19) Smith, RichardFjords contain a significant quantity of sediments deposited in coastal zones over the last ~100,000 years. Studies of Northern Hemisphere fjords have shown that a large part of the high concentration of sedimentary organic matter (OMsed) is terrestrial in origin (OMterr), composed of a modern detrital fraction and an old mineral-associated fraction (OMfossil). These results suggest that fjords are disproportionately responsible, on a per area basis, for the burial of organic matter in coastal zones. This study, after a rigorous examination of CuO and GDGT biomarker methods used to quantify terrestrial organic matter in coastal environments, demonstrated this hypothesis in a Southern Hemisphere fjord system, Fiordland, New Zealand. CuO analysis of Doubtful Sound surface sediments indicated a large contribution of vascular plant material to fjord sediments. The BIT Index correlated strongly with both delta13C and C/N values in Doubtful Sound surface sediments, indicated that it may accurately trace the relative proportions of marine and soil organic matter (OMsoil) in Fiordland. However, a detailed analysis of the conversion of the BIT Index to quantitative estimates of terrestrial (soil) organic matter revealed that these values are overestimates. Reconstructions of the BIT Index and tetraethers in cores from two locations on the Louisiana continental shelf demonstrated the influence of the crenarchaeol term on BIT Index-based terrestrial organic matter estimates. The differences in the applicability of the BIT Index to these two coastal environments was most likely due to large seasonal changes in productivity on the Louisiana Continental Shelf as well as higher marine relative to terrestrial inputs. Six cores were reconstructed for contributions from marine OM (OMmar), OMfossil, and OMterrestrial representing the last ~500 years of sedimentation. Spatial variations were larger than temporal variations, owing to negligible development and deforestation in the region. OMterr was the dominant fraction in all but one core, and OMfossil inputs were significant. Additionally, source reconstructions from a variety of biomarkers indicated that Landslides deliver large volumes of detrital organic matter to fjord sediments. These results confirm that fjords bury quantitatively significant volumes of organic carbon on a global scale.