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HSI2/VAL1 PHD-like domain promotes H3K27 trimethylation to repress the expression of seed maturation genes and complex transgenes in Arabidopsis seedlings

Description: This article studies the novel mutant allele hsi2-4, isolated in a genetic screen to identify Arabidopsis mutants with consitutively elevated expression of a glutathione S-transferase F8:luciferase reporter gene in Arabidopsis.
Date: November 1, 2014
Creator: Veerappan, Vijaykumar; Chen, Naichong; Reichert, Angelika & Allen, Randy D.
Partner: UNT College of Arts and Sciences

Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

Description: Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.
Date: July 23, 2007
Creator: Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda et al.
Partner: UNT Libraries Government Documents Department

The histone H3K9 methylation and RNAi pathways regulate normalnucleolar and repeated DNA organization by inhibiting formation ofextrachromosomal DNAs

Description: In order to identify regulators of nuclear organization, Drosophila mutants in the Su(var)3-9 histone H3K9 methyltransferase, RNAi pathway components, and other regulators of heterochromatin-mediated gene silencing were examined for altered nucleoli and positioning of repeated DNAs. Animals lacking components of the H3K9 methylation and RNAi pathways contained disorganized nucleoli, ribosomal DNA (rDNA) and satellite DNAs. The levels of H3K9 dimethylation (H3K9me2) in chromatin associated with repeated DNAs decreased dramatically in Su(var)3-9 and dcr-2 (dicer-2) mutant tissues compared to wild type. We also observed a substantial increase in extrachromosomal repeated DNAs in mutant tissues. The disorganized nucleolus phenotype depends on the presence of Ligase 4 (Lig4), and ecc DNA formation is not induced by removal of cohesin. We conclude that H3K9 methylation of rDNA and satellites, maintained by Su(var)3-9, HP1, and the RNAi pathway, is necessary for the structural stability of repeated DNAs, which is mediated through suppression of non-homologous end joining (NHEJ). These results suggest a mechanism for how local chromatin structure can regulate genome stability, and the organization of chromosomal elements and nuclear organelles.
Date: June 15, 2006
Creator: Peng, Jamy C. & Karpen, Gary H.
Partner: UNT Libraries Government Documents Department

Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

Description: Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.
Date: May 2, 2008
Creator: Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle et al.
Partner: UNT Libraries Government Documents Department

Multi-site genetic modulation of monolignol biosynthesis suggests new routes for formation of syringyl lignin and wall-bound ferulic acid in alfalfa (Medicago sativa L.)

Description: Article on multi-site genetic modulation of monolignol biosynthesis suggests new routes for formation of syringyl lignin and wall-bound ferulic acid in alfalfa (Medicago sativa L.).
Date: August 30, 2006
Creator: Chen, Fang; Reddy, M. S. Srinivasa; Temple, Stephen; Jackson, Lisa A.; Shadle, Gail L. & Dixon, R. A.
Partner: UNT College of Arts and Sciences

Mercury in Fish from a Sulfate-Amended Wetland Mesocosm

Description: This study used an experimental model of a constructed wetland to evaluate the risk of mercury methylation when the soil is amended with sulfate. The model was planted with Schoenoplectus californicus, and the sediments were varied during construction to provide a control and two levels of sulfate treatment.
Date: May 29, 2003
Creator: Harmon, S.M.
Partner: UNT Libraries Government Documents Department

Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization

Description: The timing and progression of DNA methylation changes during carcinogenesis are not completely understood. To develop a timeline of aberrant DNA methylation events during malignant transformation, we analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. The first barrier, stasis, is mediated by the retinoblastoma protein and can be overcome by loss of p16(INK4A) expression. HMEC that escape stasis and continue to proliferate become genomically unstable before encountering a second more stringent proliferation barrier, telomere dysfunction due to telomere attrition. Rare cells that acquire telomerase expression may escape this barrier, become immortal, and develop further malignant properties. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending on how stasis was overcome. A second step coincides with immortalization and results in hundreds of additional DNA methylation changes regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells. These results show that large-scale epigenetic remodeling occurs in the earliest steps of mammary carcinogenesis, temporally links DNA methylation changes and overcoming cellular proliferation barriers, and provides a bank of potential epigenetic biomarkers that mayprove useful in breast cancer risk assessment.
Date: April 20, 2009
Creator: Novak, Petr; Jensen, Taylor J.; Garbe, James C.; Stampfer, Martha R. & Futscher, Bernard W.
Partner: UNT Libraries Government Documents Department

Allele-specific deposition of macroH2A1 in Imprinting Control Regions

Description: In the current study, we analyzed the deposition patterns of macroH2A1 at a number of different genomic loci located in X chromosome and autosomes. MacroH2A1 is preferentially deposited at methylated CpG CpG-rich regions located close to promoters. The macroH2A1 deposition patterns at the methylated CpG islands of several imprinted domains, including the Imprinting Control Regions (ICRs) of Xist, Peg3, H19/Igf2 Igf2, Gtl2/Dlk1, and Gnas domains, show consistent allele-specificity towards inactive, methylated alleles. The macroH2A1 deposition levels at the ICRs and other Differentially Methylated Regions (DMRs) of these domains are also either higher or comparable to those observed at the inactive X chromosome of female mammals. Overall, our results indicate that besides DNA methylation macroH2A1 is another epigenetic component in the chromatin of ICRs displaying differential association with two parental alleles.
Date: January 13, 2006
Creator: Choo, J H; Kim, J D; Chung, J H; Stubbs, L & Kim, J
Partner: UNT Libraries Government Documents Department

Prediction of epigenetically regulated genes in breast cancer cell lines

Description: Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fxed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis. Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically signifcant negative correlation between methylation profles and gene expression in the panel of breast cancer cell lines. Subnetwork enrichment of these genes has identifed 35 common regulators with 6 or more predicted markers. In addition to identifying epigenetically regulated genes, we show evidence of differentially expressed ...
Date: May 4, 2010
Creator: Loss, Leandro A; Sadanandam, Anguraj; Durinck, Steffen; Nautiyal, Shivani; Flaucher, Diane; Carlton, Victoria EH et al.
Partner: UNT Libraries Government Documents Department

Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells

Description: BACKGROUND: The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood. METHODOLOGY/ PRINCIPAL FINDINGS: Epigenetic mechanisms participate in the control of miR-200c and miR-141 expression in both normal and cancer cells. A CpG island near the predicted mir-200c/mir-141 transcription start site shows a striking correlation between miR-200c and miR-141 expression and DNA methylation in both normal and cancer cells, as determined by MassARRAY technology. The CpG island is unmethylated in human miR-200/miR-141 expressing epithelial cells and in miR-200c/miR-141 positive tumor cells. The CpG island is heavily methylated in human miR-200c/miR-141 negative fibroblasts and miR-200c/miR-141 negative tumor cells. Mouse cells show a similar inverse correlation between DNA methylation and miR-200c expression. Enrichment of permissive histone modifications, H3 acetylation and H3K4 trimethylation, is seen in normal miR-200c/miR-141-positive epithelial cells, as determined by chromatin immunoprecipitation coupled to real-time PCR. In contrast, repressive H3K9 dimethylation marks are present in normal miR-200c/miR-141-negative fibroblasts and miR-200c/miR-141 negative cancer cells and the permissive histone modifications are absent. The epigenetic modifier drug, 5-aza-2'-deoxycytidine, reactivates miR-200c/miR-141 expression showing that epigenetic mechanisms play a functional role in their transcriptional control. CONCLUSIONS/ SIGNIFICANCE: We report that DNA methylation plays a role in the normal cell type-specific expression of miR-200c and miR-141 and this role appears evolutionarily conserved, since similar results were obtained in mouse. Aberrant DNA methylation of the miR-200c/141 CpG island is closely linked to their inappropriate silencing in cancer cells. Since the miR-200c cluster plays a significant role in EMT, our results suggest an important role for DNA methylation in the control of phenotypic ...
Date: December 23, 2009
Creator: Vrba, Lukas; Jensen, Taylor J.; Garbe, James C.; Heimark, Ronald L.; Cress, Anne E.; Dickinson, Sally et al.
Partner: UNT Libraries Government Documents Department

MERCURY RELEASE FROM DISTURBED ANOXIC SOILS

Description: The primary objectives of experiments conducted at the Energy & Environmental Research Center (EERC) were to provide information on the secondary release of mercury from contaminated anoxic sediments to an aqueous environment after disturbance/change of in situ physical conditions and to evaluate its migration and partitioning under controlled conditions, including implications of these processes for treatment of contaminated soils. Experimental work included (1) characterization of the mercury-contaminated sediment; (2) field bench-scale dredging simulation; (3) laboratory column study to evaluate a longer-term response to sediment disturbance; (4) mercury volatilization from sediment during controlled drying; (5) resaturation experiments to evaluate the potential for secondary release of residual mercury after disturbance, transport, drying, and resaturation, which simulate a typical scenario during soil excavation and transport to waste disposal facilities; and (6) mercury speciation and potential for methylation during column incubation experiments.
Date: July 16, 2001
Creator: Solc, Jaroslav & Bolles, Bethany A.
Partner: UNT Libraries Government Documents Department

LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast cancer

Description: Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We show here that LARG, from 11q23, has functional characteristics of a tumor suppressor. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, utilizing both loss of heterozygosity (LOH) analysis and microarray comparative genomic hybridization (CGH). LARG (also called ARHGEF12), identified from the analyzed region, was underexpressed in 34% of primary breast carcinomas and 80% of breast cancer cell lines including the MCF-7 line. Multiplex ligation-dependent probe amplification on 30 primary breast cancers and six breast cancer cell lines showed that LARG had the highest frequency of deletion compared to the BCSC-1 and TSLC1 genes, two known candidate tumor suppressor genes from 11q. In vitro analysis of breast cancer cell lines that underexpress LARG showed that LARG could be reactivated by trichostatin A, a histone deacetylase inhibitor, but not by 5-Aza-2{prime}-deoxycytidine, a demethylating agent. Bisulfite sequencing and quantitative high-throughput analysis of DNA methylation confirmed the lack of CpG island methylation in LARG in breast cancer. Restoration of LARG expression in MCF-7 cells by stable transfection resulted in reduced proliferation and colony formation, suggesting that LARG has functional characteristics of a tumor suppressor gene.
Date: May 6, 2008
Creator: Ong, Danny C.T.; Rudduck, Christina; Chin, Koei; Kuo, Wen-Lin; Lie, Daniel K.H.; Chua, Constance L.M. et al.
Partner: UNT Libraries Government Documents Department

Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation

Description: Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation, chromatin condensation and, in mammals, culminates in nuclear extrusion. To date, although mechanisms regulating avian erythroid chromatin condensation have been identified, little is known regarding this process during mammalian erythropoiesis. To elucidate the molecular basis for mammalian erythroblast chromatin condensation, we used Friend virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro. Chromatin isolated from early and late stage erythroblasts had similar levels of linker and core histones, only a slight difference in nucleosome repeats, and no significant accumulation of known developmentally-regulated architectural chromatin proteins. However, histone H3(K9) dimethylation markedly increased while histone H4(K12) acetylation dramatically decreased and became segregated from the histone methylation as chromatin condensed. One histone deacetylase, HDAC5, was significantly upregulated during the terminal stages of Friend virus-infected erythroblast differentiation. Treatment with histone deacetylase inhibitor, trichostatin A, blocked both chromatin condensation and nuclear extrusion. Based on our data, we propose a model for a unique mechanism in which extensive histone deacetylation at pericentromeric heterochromatin mediates heterochromatin condensation in vertebrate erythroblasts that would otherwise be mediated by developmentally-regulated architectural proteins in nucleated blood cells.
Date: August 21, 2008
Creator: Popova, Evgenya Y.; Krauss, Sharon Wald; Short, Sarah A.; Lee, Gloria; Villalobos, Jonathan; Etzell, Joan et al.
Partner: UNT Libraries Government Documents Department

X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

Description: The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.
Date: January 7, 2004
Creator: Game, John C.; Williamson, Marsha S. & Baccari, Clelia
Partner: UNT Libraries Government Documents Department

Reduction and Methyl Transfer Kinetics of the Alpha Subunit from Acetyl-Coenzyme A Synthase

Description: OAK-B135 Stopped-flow was used to evaluate the methylation and reduction kinetics of the isolated alpha subunit of acetyl-Coenzyme A synthase from Moorella thermoacetica. This catalytically active subunit contains a novel Ni-X-Fe4S4 cluster and a putative unidentified n =2 redox site called D. The D-site must be reduced for a methyl group to transfer from a corrinoid-iron-sulfur protein, a key step in the catalytic synthesis of acetyl-CoA. The Fe4S4 component of this cluster is also redox active, raising the possibility that it is the D-site or a portion thereof. Results presented demonstrate that the D-site reduces far faster than the Fe4S4 component, effectively eliminating this possibility. Rather, this component may alter catalytically important properties of the Ni center. The D-site is reduced through a pathway that probably does not involve the Fe4S4 component of this active-site cluster.
Date: January 15, 2003
Creator: Tan, Xiangshi; Sewell, Christopher; Yang, Qingwu & Lindahl, Paul A.
Partner: UNT Libraries Government Documents Department

Coal liquefaction process streams characterization and evaluation: The use of selective chemical reactions and carbon NMR spectroscopy in the speciation and quantification of oxygen functional groups in coal resids

Description: This study demonstrated the feasibility of using phase-transfer methylation reactions for the derivatization of hydroxyl functionalities and single-electron transfer reactions to cleave ether groups in distillation resid materials derived from direct coal liquefaction. {sup 13}C-NMR was used to analyze the reaction products. It was demonstrated that the techniques can be used to speciate and quantify about half of the oxygen in resids. The remaining half of the oxygen is presumed to be present as unreactive ethers, probably dibenzofurans. Hydroxyl concentrations were determined on five resid samples and ether cleavage reactions were conducted on three of those five. Further development of this general analytical strategy as a process development tool is justified based on these results.
Date: November 1, 1992
Creator: Stock, L. M. & Cheng, C.
Partner: UNT Libraries Government Documents Department

Catalytic reduction of carbon monoxide: Selective synthesis of C1 and higher oxygenates

Description: A-step synthesis of methyl formate, a C2 oxygenate, has been developed at BNL. The following features of the LLTMeOH technology and related studies are of interest: The BNL approach exemplifies a synergistic effect of two combined catalysts. The chosen reaction conditions favor methyl formate synthesis. The only identified by-product is methanol. The effect of stirring speed, temperature, solvent, catalyst loading, and syngas composition is noted.Of particular interest is a run with H{sub 2}CO = 37%/63% in which methyl formate selectivity approached 100%. Bases (K{sub 2}CO{sub 3}KHCO{sub 2}, KOCO{sub 2}Me) other than alkoxide have been used for methyl formate synthesis. A gas phase infrared mechanistic study of methanol carbonylation reaction, carried out with methoxide catalyst at 130{degree}C under 1/1 (H{sub 2}CO) syngas, showed that the fast alkyl formate anion formations was followed by an extremely slow protonation step. It appears that under these conditions, protonation step is rate determining (RDS). This approach results in enhancing carbon conversion of syngas derived from coal or other sources that produce CO-rich gas.
Date: May 1, 1993
Creator: Mahajan, D. & Gupta, N.
Partner: UNT Libraries Government Documents Department

Molecular Markers of Lung Cancer in MAYAK Workers

Description: The molecular mechanisms that result in the elevated risk for lung cancer associated with exposure to radiation have not been well characterized. Workers from the MAYAK nuclear enterprise are an ideal cohort in which to study the molecular epidemiology of cancer associated with radiation exposure and to identify the genes targeted for inactivation that in turn affect individual risk for radiation-induced lung cancer. Epidemiology studies of the MAYAK cohort indicate a significantly higher frequency for adenocarcinoma and squamous cell carcinoma (SCC) in workers than in a control population and a strong correlation between these tumor types and plutonium exposure. Two hypotheses will be evaluated through the proposed studies. First, radiation exposure targets specific genes for inactivation by promoter methylation. This hypothesis is supported by our recent studies with the MAYAK population that demonstrated the targeting of the p16 gene for inactivation by promoter methylation in adenocarcinomas from workers (1). Second, genes inactivated in tumors can serve as biomarkers for lung cancer risk in a cancer-free population of workers exposed to plutonium. Support for this hypothesis is based on exciting preliminary results of our nested, case-control study of persons from the Colorado cohort. In that study, a panel of methylation markers for predicting lung cancer risk is being evaluated in sputum samples from incident lung cancer cases and controls. The first hypothesis will be tested by determining the prevalence for promoter hypermethylation of a panel of genes shown to play a critical role in the development of either adenocarcinoma and/or SCC associated with tobacco. Our initial studies on adenocarcinoma in MAYAK workers will be extended to evaluate methylation of the PAX5 {alpha}, PAX5 {beta}, H-cadherin, GATA5, and bone morphogenesis 3B (BMP3B) genes in the original sample set described under Preliminary studies. In addition, studies will be initiated in SCC from workers ...
Date: February 15, 2007
Creator: Steven A. Belinsky, PhD
Partner: UNT Libraries Government Documents Department

TECHNOLOGY EVALUATION FOR WATERBORNE MERCURY REMOVAL AT THE Y12 NATIONAL SECURITY COMPLEX

Description: The Hg-contaminated processing water produced at Y-12 facility is discharged through the storm drain system, merged at Outfall 200, and then discharged to EFPC. Most of the baseflow mercury at Outfall 200 arises from a small number of short sections of storm drain. This report discusses the waterborne mercury treatment technologies to decrease mercury loading to the surface water of EFPC at Y-12 NSC. We reviewed current available waterborne Hg treatment technologies based on the specific conditions of Y-12 and identified two possible options: SnCl2 reduction coupled with air stripping (SnCl2/air stripping) and sorption. The ORNL 2008 and 2009 field studies suggested that SnCl2/air stripping has the capability to remove waterborne mercury with efficiency higher than 90% at Outfall 200. To achieve this goal, dechlorination (i.e., removing residual chlorine from water) using dechlorinating agents such as thiosulfate has to be performed before the reduction. It is unclear whether or not SnCl2/air stripping can reduce the mercury concentration from ~1000 ng/L to 51 ng/L at a full-scale operation. Therefore, a pilot test is a logical step before a full-scale design to answer questions such as Hg removal efficiency, selection of dechlorinating agents, and so on. The major advantages of the SnCl2/air stripping system are: (1) expected low cost at high flow (e.g., the flow at Outfall 200); and (2) production of minimum secondary waste. However, there are many environmental uncertainties associated with this technology by introducing tin to EFPC ecosystem, for example tin methylation causing abiotic Hg methylation, which should be addressed before a full-scale implementation. Mercury adsorption by granular activated carbon (GAC) is a proven technology for treating Hg at Y-12. The ONRL 2010 lab sorption studies suggest that thiol-based resins hold the promise to combine with GAC to form a more cost-effective treatment system. To achieve a treatment goal ...
Date: January 1, 2011
Creator: He, Feng; Liang, Liyuan & Miller, Carrie L
Partner: UNT Libraries Government Documents Department

INTERIM RESULTS FROM A STUDY OF THE IMPACTS OF TIN(II) BASED MERCURY TREATMENT IN A SMALL STREAM ECOSYSTEM: TIMS BRANCH, SAVANNAH RIVER SITE

Description: Mercury (Hg) has been identified as a 'persistent, bioaccumulative and toxic' pollutant with widespread impacts throughout North America and the world (EPA. 1997a, 1997b, 1998a, 1998b, 2000). Although most of the mercury in the environment is inorganic Hg, a small proportion of total Hg is transformed through the actions of aquatic microbes into methylmercury (MeHg). In contrast to virtually all other metals, MeHg biomagnifies or becomes increasingly concentrated as it is transferred through aquatic food chains so that the consumption of mercury contaminated fish is the primary route of this toxin to humans. For this reason, the ambient water quality criterion (AWQC) for mercury is based on a fish tissue endpoint rather than an aqueous Hg concentration, as the tissue concentration (e.g., < 0.3 {mu}g/g fillet) is considered to be a more consistent indicator of exposure and risk (EPA, 2001). Effective mercury remediation at point-source contaminated sites requires an understanding of the nature and magnitude of mercury inputs, and also knowledge of how these inputs must be controlled in order to achieve the desired reduction of mercury contamination in biota necessary for compliance with AWQC targets. One of the challenges to remediation is that mercury body burdens in fish are more closely linked to aqueous MeHg than to inorganic Hg concentrations (Sveinsdottir and Mason 2005), but MeHg production is not easily predicted or controlled. At point-source contaminated sites, mercury methylation is not only affected by the absolute mercury load, but also by the form of mercury loaded. In addition, once MeHg is formed, the hydrology, trophic structure, and water chemistry of a given system affect how it is transformed and transferred through the food chain to fish. Decreasing inorganic Hg concentrations and loading may often therefore be a more achievable remediation goal, but has led to mixed results in terms ...
Date: March 30, 2012
Creator: Looney, B.; Bryan, L. & Mathews, T.
Partner: UNT Libraries Government Documents Department

Engineering Plant One-Carbon Metabolism

Description: Primary and secondary metabolism intersect in the one-carbon (C1) area. Primary metabolism supplies most of the C1 units and competes with secondary metabolism for their use. This competition is potentially severe because secondary products such as lignin, alkaloids, and glycine betaine (GlyBet) require massive amounts of C1 units. Towards the goal of understanding how C1 metabolism is regulated at the metabolic and gene levels so as to successfully engineer C1 supply to match demand, we have: (1) cloned complete suites of C1 genes from maize and tobacco, and incorporated them into DNA arrays; (2) prepared antisense constructs and mutants engineered with alterations in C1 unit supply and demand; and (3) have quantified the impacts of these alterations on gene expression (using DNA arrays), and on metabolic fluxes (by combining isotope labeling, MS, NMR and computer modeling). Metabolic flux analysis and modeling in tobacco engineered for GlyBet synthesis by expressing choline oxidizing enzymes in either the chloroplast or cytosol, has shown that the choline biosynthesis network is rigid, and tends to resist large changes in C1 demand. A major constraint on engineering enhanced flux to GlyBet in tobacco is a low capacity of choline transport across the chloroplast envelope. Maize and sorghum mutants defective in GlyBet synthesis show greatly reduced flux of C1 units into choline in comparison to GlyBet-accumulating wildtypes, but this is not associated with altered expression of any of the C1 genes. Control of C1 flux to choline in tobacco, maize and sorghum appears to reside primarily at the level of N-methylation of phosphoethanolamine. A candidate signal for the control of this flux is the pool size of phosphocholine which down-regulates and feedback inhibits phosphoethanolamine N-methyltransferase. Methionine S-methyltransferase (MMT) catalyzes the synthesis of S-methylmethionine (SMM) from methionine (Met) and S-adenosylmethionine (AdoMet). SMM can be reconverted to Met by ...
Date: February 9, 2005
Creator: Rhodes, David
Partner: UNT Libraries Government Documents Department

BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

Description: A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. ...
Date: March 19, 2010
Creator: Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart et al.
Partner: UNT Libraries Government Documents Department