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In Vitro Modulation of Rat Liver Glyoxalase II Activity

Description: Glyoxylase II (Glo II, E.C. 3.1.2.6) catalyzes the hydrolysis of S-D-Lactoylglutathione (SLG) to D-Lactate and glutathione. This is the rate limiting step in the conversion of methylglyoxal to D-Lactate. The purpose of the present study was to determine whether or not a relationship exists between some naturally occuring metabolites and in vivo modulation of Glo II. We have observed a non-competitive inhibition (~ 45%) of Glo II in crude preparation of rat liver by GTP (0.3 mM). A factor (apparently protein),devoid of Glo II,when reconstituted with the purified Glo II, enhanced Glo II activity. This coordinate activation and inhibition of Glo II suggest a mechanism whereby SLG levels can be modulated in vivo.
Date: August 1988
Creator: Mbamalu, Godwin E.
Partner: UNT Libraries

Primate-Specific Evolution of an LDLR Enhancer

Description: Sequence changes in regulatory regions have often beeninvoked to explain phenotypic divergence among species, but molecularexamples of this have been difficult to obtain. In this study, weidentified an anthropoid primate specific sequence element thatcontributed to the regulatory evolution of the LDL receptor. Using acombination of close and distant species genomic sequence comparisonscoupled with in vivo and in vitro studies, we show that a functionalcholesterol-sensing sequence motif arose and was fixed within apre-existing enhancer in the common ancestor of anthropoid primates. Ourstudy demonstrates one molecular mechanism by which ancestral mammalianregulatory elements can evolve to perform new functions in the primatelineage leading to human.
Date: June 28, 2006
Creator: Wang, Qian-fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles et al.
Partner: UNT Libraries Government Documents Department

Cardiovascular function, compliance, and connective tissue remodeling in the turtle, Trachemys scripta, following thermal acclimation

Description: This article suggests that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow.
Date: April 13, 2016
Creator: Keen, Adam N.; Shiels, Holly A. & Crossley, Dane A., II
Partner: UNT College of Arts and Sciences

In Vivo Monitoring Program Manual, PNL-MA-574

Description: An overview of the administration for the In Vivo Monitoring Program (IVMP) for Hanford. This includes organizational structure and program responsibilities; coordination of in vivo measurements; scheduling measurements; performing measurements; reporting results; and quality assurance. Overall responsibility for the management of the IVMP rests with the Program Manager (PM). The PM is responsible for providing the required in vivo counting services for Hanford Site contractor employees in accordance with Department of Energy (DOE) requirements and the specific statements of work.
Date: July 1, 2010
Creator: Lynch, Timothy P.
Partner: UNT Libraries Government Documents Department

In Vivo Monitoring Program Manual, PNL-MA-574, Rev 5.1

Description: The following sections provide an overview of the administration for the In Vivo Monitoring Program (IVMP) for Hanford. This includes the organizational structure and program responsibilities; coordination of in vivo measurements; scheduling measurements; performing measurements; reporting results; and quality assurance.
Date: September 12, 2011
Creator: Lynch, Timothy P.
Partner: UNT Libraries Government Documents Department

Report on the Imaging Workshop for the Genomes to Life Program, April 16-18, 2002

Description: This report is a result of the Imaging Workshop for the Genomes to Life (GTL) program held April 16-19, 2002, in Charlotte, North Carolina. The meeting was sponsored by the Office of Biological and Environmental Research and the Office of Advanced Scientific Computing Research of the U.S. Department of Energy's (DOE) Office of Science. The purpose of the workshop was to project a broad vision for future needs and determine the value of imaging to GTL program research. The workshop included four technical sessions with plenary lectures on biology and technology perspectives and technical presentations on needs and approaches as they related to the following areas of the GTL program: (1) Molecular machines (protein complexes); (2) Intracellular and cellular structure, function, and processes; (3) Multicellular: Monoclonal and heterogeneous multicellular systems, cell-cell signaling, and model systems; and (4) Cells in situ and in vivo: Bacteria in the natural environment, microenvironment, and in vivo systems.
Date: August 4, 2003
Creator: Colson, STEVEN
Partner: UNT Libraries Government Documents Department

Potential Toxicity and Underlying Mechanisms Associated with Pulmonary Exposure to Iron Oxide Nanoparticles: Conflicting Literature and Unclear Risk

Description: This review article will focus on known risks following iron oxide nanoparticles (IONPs) exposure supported by human, animal, and cell culture-based studies, the potential challenges intrinsic to IONPs toxicity assessment, and how these may contribute to the poorly characterized IONPs toxicity profile.
Date: September 7, 2017
Creator: Kornberg, Tiffany G.; Stueckle, Todd A.; Antonini, James M.; Rojanasakul, Liying W.; Castranova, Vincent; Yang, Yong et al.
Partner: UNT College of Engineering

Primate-specific evolution of an LDLR enhancer

Description: Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.
Date: December 1, 2005
Creator: Wang, Qian-Fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles et al.
Partner: UNT Libraries Government Documents Department

Application Of The Climafor Baseline To Determine Leakage: TheCase Of Scolel Te.

Description: The acceptance of forestry-based project activities tomitigate greenhouse gases emissions has been subjected to a number ofmethodological questions to be answered, of which the most challengingare baseline establishment and identification of and measuring leakage.Here we pose hypotheses for and quantify leakage of the Scolel Te projectin Chiapas, Mexico. In this project small-scale farmers are implementingforestry, agroforestry, and forest conservation activities, with carbonsequestration as one of the goals. The main leakage monitoring domain isdefined as the area owned by the participating farmers or communitiesoutside the area where the specific project activities take place. Thenull-hypothesis (no leakage) is that non-project land owned by the farmeror community will experience the same carbon stock changes as predictedby the regional baseline, specifically developed for the project. Firstwe assessed the most likely causes and sources of leakage that may occurin the project. From this analysis, one type of leakage seems to beimportant, i.e., activity shifting. Second we estimated the leakage of asample of participating farmers and communities. Actual land use was thencompared with expected land use derived from the baseline. The Plan Vivoof each participant, complemented with readily available tools toidentify the main sources and drivers of leakage are used to developsimple leakage assessment procedures, as demonstrated in this paper.Negative leakage was estimated to be negligible in this study.Incorporating these procedures already in the project planning stage willreduce the uncertainties related to the actual carbon mitigationpotential of any forestry project.
Date: June 1, 2007
Creator: De Jong, B.H.J.; Bazan, E. Esquivel & Quechulpa Montalvo, S.
Partner: UNT Libraries Government Documents Department

In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences

Description: The identification of enhancers with predicted specificitiesin vertebrate genomes remains a significant challenge that is hampered bya lack of experimentally validated training sets. In this study, weleveraged extreme evolutionary sequence conservation as a filter toidentify putative gene regulatory elements and characterized the in vivoenhancer activity of human-fish conserved and ultraconserved1 noncodingelements on human chromosome 16 as well as such elements from elsewherein the genome. We initially tested 165 of these extremely conservedsequences in a transgenic mouse enhancer assay and observed that 48percent (79/165) functioned reproducibly as tissue-specific enhancers ofgene expression at embryonic day 11.5. While driving expression in abroad range of anatomical structures in the embryo, the majority of the79 enhancers drove expression in various regions of the developingnervous system. Studying a set of DNA elements that specifically droveforebrain expression, we identified DNA signatures specifically enrichedin these elements and used these parameters to rank all ~;3,400human-fugu conserved noncoding elements in the human genome. The testingof the top predictions in transgenic mice resulted in a three-foldenrichment for sequences with forebrain enhancer activity. These datadramatically expand the catalogue of in vivo-characterized human geneenhancers and illustrate the future utility of such training sets for avariety of iological applications including decoding the regulatoryvocabulary of the human genome.
Date: February 1, 2006
Creator: Pennacchio, Len A.; Ahituv, Nadav; Moses, Alan M.; Nobrega,Marcelo; Prabhakar, Shyam; Shoukry, Malak et al.
Partner: UNT Libraries Government Documents Department

The Influence of the Linker Geometry in Bis(3-hydroxy-N-methyl-pyridin-2-one) Ligands on Solution-Phase Uranyl Affinity

Description: Seven water-soluble, tetradentate bis(3-hydroxy-N-methyl-pyridin-2-one) (bis-Me-3,2-HOPO) ligands were synthesized that vary only in linker geometry and rigidity. Solution phase thermodynamic measurements were conducted between pH 1.6 and pH 9.0 to determine the effects of these variations on proton and uranyl cation affinity. Proton affinity decreases by introduction of the solubilizing triethylene glycol group as compared to un-substituted reference ligands. Uranyl affinity was found to follow no discernable trends with incremental geometric modification. The butyl-linked 4Li-Me-3,2-HOPO ligand exhibited the highest uranyl affinity, consistent with prior in vivo decorporation results. Of the rigidly-linked ligands, the o-phenylene linker imparted the best uranyl affinity to the bis-Me-3,2-HOPO ligand platform.
Date: August 12, 2010
Creator: Szigethy, Geza & Raymond, Kenneth
Partner: UNT Libraries Government Documents Department

AGONIST-INDUCED AFFINITY ALTERATIONS OF A CENTRAL NERVOUS SYSTEM NICOTINIC ACETYLCHOLINE RECEPTOR

Description: Pretreatment of {alpha}-bungarotoxin ({alpha}-Bgt) binding sites from rat brain with cholinergic agonists causes transformation of sites to a high-affinity form toward agonist over a time course of minutes, consistent with identity of those sites as central nicotinic acetylcholine receptors (nAChR). This agonist-induced alteration in receptor state may be correlated with physiological densensitization. Agonist inhibition of toxin binding to the high-affinity state is non-competitive, suggesting the existence of discrete toxin-binding and agonist-binding sites on the central nAChR. These results thus offer a possible explanation of observed impotency of {alpha}-Bgt toward blocking in vivo cholinergic responses in the central nervous system.
Date: May 1, 1978
Creator: Lukasiewicz, Ronald J. & Bennett, Edward L.
Partner: UNT Libraries Government Documents Department

Large-scale turnover of functional transcription factor bindingsites in Drosophila

Description: The gain and loss of functional transcription-factor bindingsites has been proposed as a major source of evolutionary change incis-regulatory DNA and gene expression. We have developed an evolutionarymodel to study binding site turnover that uses multiple sequencealignments to assess the evolutionary constraint on individual bindingsites, and to map gain and loss events along a phylogenetic tree. Weapply this model to study the evolutionary dynamics of binding sites ofthe Drosophila melanogaster transcription factor Zeste, using genome-widein vivo (ChIP-chip) binding data to identify functional Zeste bindingsites, and the genome sequences of D. melanogaster, D. simulans, D.erecta and D. yakuba to study their evolution. We estimate that more than5 percent of functional Zeste binding sites in D. melanogaster weregained along the D. melanogaster lineage or lost along one of the otherlineages. We find that Zeste bound regions have a reduced rate of bindingsite loss and an increased rate of binding site gain relative to flankingsequences. Finally, we show that binding site gains and losses areasymmetrically distributed with respect to D. melanogaster, consistentwith lineage-specific acquisition and loss of Zeste-responsive regulatoryelements.
Date: July 14, 2006
Creator: Moses, Alan M.; Pollard, Daniel A.; Nix, David A.; Iyer, VenkyN.; Li, Xiao-Yong; Biggin, Mark D. et al.
Partner: UNT Libraries Government Documents Department

Telomere dysfunction and cell survival: Roles for distinct TIN2-containing complexes

Description: Telomeres are maintained by three DNA binding proteins (TRF1, TRF2 and POT1), and several associated factors. One factor, TIN2, binds TRF1 and TRF2 directly and POT1 indirectly. Along with two other proteins, TPP1 and hRap1, these form a soluble complex that may be the core telomere maintenance complex. It is not clear whether sub-complexes also exist in vivo. We provide evidence for two TIN2 sub-complexes with distinct functions in human cells. We isolated these two TIN2 sub-complexes from nuclear lysates of unperturbed cells and cells expressing TIN2 mutants TIN2-13, TIN2-15C, which cannot bind TRF2 or TRF1, respectively. In cells with wild-type p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere uncapping and eventual growth arrest. In cells lacking p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere dysfunction and cell death. Our findings suggest that distinct TIN2 complexes exist, and that TIN2-15C-sensitive subcomplexes are particularly important for cell survival in the absence of functional p53.
Date: October 2, 2007
Creator: Kim, Sahn-ho; Davalos, Albert R.; Heo, Seok-Jin; Rodier, Francis; Zou, Ying; Beausejour, Christian et al.
Partner: UNT Libraries Government Documents Department

Quantitative Visualization of ChIP-chip Data by Using Linked Views

Description: Most analyses of ChIP-chip in vivo DNA binding have focused on qualitative descriptions of whether genomic regions are bound or not. There is increasing evidence, however, that factors bind in a highly overlapping manner to the same genomic regions and that it is quantitative differences in occupancy on these commonly bound regions that are the critical determinants of the different biological specificity of factors. As a result, it is critical to have a tool to facilitate the quantitative visualization of differences between transcription factors and the genomic regions they bind to understand each factor's unique roles in the network. We have developed a framework which combines several visualizations via brushing-and-linking to allow the user to interactively analyze and explore in vivo DNA binding data of multiple transcription factors. We describe these visualization types and also provide a discussion of biological examples in this paper.
Date: November 5, 2010
Creator: Huang, Min-Yu; Weber, Gunther; Li, Xiao-Yong; Biggin, Mark & Hamann, Bernd
Partner: UNT Libraries Government Documents Department

Involvement of extracellular matrix constituents in breast cancer

Description: It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary gland function, have only now begun to be dissected. The intricate variety of extracellular matrix-mediated events and the remarkable degree of plasticity of extracellular matrix structure and composition at virtually all times during ontogeny, make such studies difficult. Similarly, during carcinogenesis, the extracellular matrix undergoes gross alterations, the consequences of which are not yet precisely understood. Nevertheless, an increasing amount of data suggests that the extracellular matrix and extracellular matrix-receptors might participate in the control of most, if not all, of the successive stages of breast tumors, from appearance to progression and metastasis.
Date: June 1, 1995
Creator: Lochter, Andre & Bissell, Mina J
Partner: UNT Libraries Government Documents Department

Identification of clustered YY1 binding sites in Imprinting Control Regions

Description: Mammalian genomic imprinting is regulated by Imprinting Control Regions (ICRs) that are usually associated with tandem arrays of transcription factor binding sites. In the current study, the sequence features derived from a tandem array of YY1 binding sites of Peg3-DMR (differentially methylated region) led us to identify three additional clustered YY1 binding sites, which are also localized within the DMRs of Xist, Tsix, and Nespas. These regions have been shown to play a critical role as ICRs for the regulation of surrounding genes. These ICRs have maintained a tandem array of YY1 binding sites during mammalian evolution. The in vivo binding of YY1 to these regions is allele-specific and only to the unmethylated active alleles. Promoter/enhancer assays suggest that a tandem array of YY1 binding sites function as a potential orientation-dependent enhancer. Insulator assays revealed that the enhancer-blocking activity is detected only in the YY1 binding sites of Peg3-DMR but not in the YY1 binding sites of other DMRs. Overall, our identification of three additional clustered YY1 binding sites in imprinted domains suggests a significant role for YY1 in mammalian genomic imprinting.
Date: April 19, 2006
Creator: Kim, J D; Hinz, A; Bergmann, A; Huang, J; Ovcharenko, I; Stubbs, L et al.
Partner: UNT Libraries Government Documents Department

Detection of Weakly Conserved Ancestral Mammalian RegulatorySequences by Primate Comparisons

Description: Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detectcryptic functional elements, which are too weakly conserved among mammalsto distinguish from nonfunctional DNA. To address this problem, weexplored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.
Date: June 1, 2006
Creator: Wang, Qian-fei; Prabhakar, Shyam; Chanan, Sumita; Cheng,Jan-Fang; Rubin, Edward M. & Boffelli, Dario
Partner: UNT Libraries Government Documents Department

Accelerated Evolution of Conserved Noncoding Sequences in theHuman Genome

Description: Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detect"cryptic" functional elements, which are too weakly conserved amongmammals to distinguish from nonfunctional DNA. To address this problem,we explored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.
Date: July 6, 2006
Creator: Prambhakar, Shyam; Noonan, James P.; Paabo, Svante & Rubin, EdwardM.
Partner: UNT Libraries Government Documents Department

Killing of targets by effector CD8 T cells in the mouse spleen follows the law of mass action

Description: In contrast with antibody-based vaccines, it has been difficult to measure the efficacy of T cell-based vaccines and to correlate the efficacy of CD8 T cell responses with protection again viral infections. In part, this difficulty is due to poor understanding of the in vivo efficacy of CD8 T cells produced by vaccination. Using a: recently developed experimental method of in vivo cytotoxicity we have investigated quantitative aspects of killing of peptide-pulsed targets by effector and memory CD8 T cells, specific to three epitopes of lymphocytic choriomeningitis virus (LCMV), in the mouse spleen. By analyzing data on killing of targets with varying number of epitope-specific effector and memory CD8 T cells, we find that killing of targets by effectors follows the law of mass-action, that is the death rate of peptide-pulsed targets is proportional to the frequency of CTLs in the spleen. In contrast, killing of targets by memory CD8 T cells does not follow the mass action law because the death rate of targets saturates at high frequencies of memory CD8 T cells. For both effector and memory cells, we also find little support for the killing term that includes the decrease of the death rate of targets with target cell density. Interestingly, our analysis suggests that at low CD8 T cell frequencies, memory CD8 T cells on the per capita basis are more efficient at killing peptide-pulsed targets than effectors, but at high frequencies, effectors are more efficient killers than memory T cells. Comparison of the estimated killing efficacy of effector T cells with the value that is predicted from theoretical physics and based on motility of T cells in lymphoid tissues, suggests that limiting step in the killing of peptide-pulsed targets is delivering the lethal hit and not finding the target. Our results thus form a basis ...
Date: January 1, 2009
Creator: Ganusov, Vitaly V
Partner: UNT Libraries Government Documents Department

The photosynthetic response of the perennial ryegrass (Lolium perenne) in its fifth year of free-air CO(sub 2) enrichment (FACE) at Eschikon, Switzerland

Description: Stands of Ryegrass (Lolium perenne L. cv.Bastion) were grown in the field at ambient or elevated (600 {micro}mol mol{sup {minus}1}) [CO{sub 2}], high (560 kg Ha{sup {minus}1} y{sup {minus}1}) or low (140 kg Ha{sup {minus}1} y{sup {minus}1}) nitrogen addition and were harvested five times a year during the growing season. The plants were sown during 1992, additional plots being sown during 1995. These were in their fifth year and second year of growth respectively. Exposure to elevated [CO{sub 2}] was carried out with a Free-Air CO{sub 2} Enrichment (FACE) system which provides the most realistic system of fumigation currently available. Elevated [CO{sub 2}] increased diurnal CO{sub 2} uptake by between 40 to 83% while reducing stomatal conductance by between 1 and 38% in all of the 1992 grown plants measured at high [CO{sub 2}]. Analysis of the A/c{sub i} response of 1992 grown plants showed no acclimation of the photosynthetic apparatus in response to elevated [CO{sub 2}] - both V{sub c,max} (a measure of the maximum in vivo rate of carboxylation) and J{sub max} (a measure of the maximum capacity for the regeneration of RuBP) showed no significant change during any of the periods of regrowth. In contrast the leaves of 1995 grown plants, appeared to be experiencing an acclimatory change in their photosynthetic apparatus in response to elevated [CO{sub 2}]. However, this negative response seemed to be removed directly after a harvest when the source:sink balance had increased. The apparent lack of an acclimatory response after almost 5 years of growth at elevated [CO{sub 2}], suggests that L. perenne may be close to achieving the appropriate photosynthetic adjustments which would allow it to attain a significantly higher photosynthetic potential.
Date: 1999-01~
Creator: Anderson, J. P.; Long, S. P. & Williams, J.
Partner: UNT Libraries Government Documents Department