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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

Metagenomic Sequencing of an In Vitro-Simulated Microbial Community

Description: Background: Microbial life dominates the earth, but many species are difficult or even impossible to study under laboratory conditions. Sequencing DNA directly from the environment, a technique commonly referred to as metagenomics, is an important tool for cataloging microbial life. This culture-independent approach involves collecting samples that include microbes in them, extracting DNA from the samples, and sequencing the DNA. A sample may contain many different microorganisms, macroorganisms, and even free-floating environmental DNA. A fundamental challenge in metagenomics has been estimating the abundance of organisms in a sample based on the frequency with which the organism's DNA was observed in reads generated via DNA sequencing. Methodology/Principal Findings: We created mixtures of ten microbial species for which genome sequences are known. Each mixture contained an equal number of cells of each species. We then extracted DNA from the mixtures, sequenced the DNA, and measured the frequency with which genomic regions from each organism was observed in the sequenced DNA. We found that the observed frequency of reads mapping to each organism did not reflect the equal numbers of cells that were known to be included in each mixture. The relative organism abundances varied significantly depending on the DNA extraction and sequencing protocol utilized. Conclusions/Significance: We describe a new data resource for measuring the accuracy of metagenomic binning methods, created by in vitro-simulation of a metagenomic community. Our in vitro simulation can be used to complement previous in silico benchmark studies. In constructing a synthetic community and sequencing its metagenome, we encountered several sources of observation bias that likely affect most metagenomic experiments to date and present challenges for comparative metagenomic studies. DNA preparation methods have a particularly profound effect in our study, implying that samples prepared with different protocols are not suitable for comparative metagenomics.
Date: December 1, 2009
Creator: Morgan, Jenna L.; Darling, Aaron E. & Eisen, Jonathan A.
Partner: UNT Libraries Government Documents Department

PREFERENTIAL INHIBITION OF THE GROWTH OF VIRUS-TRANSFORMED CELLS IN CULTURE BY RIFAZONE-82, A NEW RIFAMYCIN DERIVATIVE

Description: Rifazone-8{sub 2} (R-8{sub 2}), a new rifamycin derivative, is shown to preferentially inhibit the growth of virus-transformed chick cells in culture. Macromolecular synthesis and glucose uptake of transformed cells are also appreciably decreased in the presence of low concentrations of R-8{sub 2} where the normal cells appear unaffected. While R-8{sub 2} is shown to be a selective inhibitor of RNA-directed DNA polymerase in vitro, its action on the growth of transformed cells may involve some other mechanism.
Date: March 28, 1974
Creator: Bissell, Mina J.; Hatie, Carroll; Tischler, Allan N. & Calvin, Melvin.
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

S-Acyl Thioctic Acid Derivatives in Aerobacter Aerogenes andScenedesmus

Description: 1. Acetyl thioctic acid has been prepared chemically and i t s chromatographic and acetylating behavior i s described. 2. A C{sup 14} -containing substance has been found in Scenedesmus, photosynthesizing in the presence of a-C{sup 14}-pyruvate, which has properties suggesting that it i s acetyl thioctic acid. 3 . A C{sup 14}-containing substance has been found in Aerobacter aerogenes, metabolizing a-C{sup 14}-pyruvate, which shows the properties of a labile conjugate of thioctic acid with some relatively polar groups. 4. Acetyl thioctic acid i s formed in vitro when light acts on a solution of thioctic acid and pyruvate.
Date: March 30, 1955
Creator: Milhaud, Gerard; Benson, Andrew A.; Fuller, R. Clinton; Milhaud,Vera & Calvin, M.
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

The Nucleotide Sequences of a Mammalian Tyrosine Transfer RNA and a Cluster of Human Transfer RNA Genes

Description: Tyrosine tRNA was isolated from bovine liver and its nucleotide sequence was determined using in vitro 32p_ labeling techniques. Several important structural features of the tRNA are: the presence of gal-Q in the first position of the anticodon, acp3U at position 20, and a pair of adjacent N,N-dimethylguanosines (residues 26 and 27). A human DNA fragment harbored in a lambda phage clone was isolated, and restriction enzyme analysis revealed the presence of three tRNA genes in a 6.0-kb BamHI subfragment. Portions of the 6.0-kb DNA fragment containing the tRNA genes were sequenced by the method of Maxam and Gilbert and analyzed for transcriptional activity in vitro using homologous cytoplasmic extracts. A threonine tRNAUGU gene exhibited high transcriptional activity dependent on its 5'- flanking sequence. The enhanced transcription is not completely inhibited by alpha-amanitin. The value of studying tRNA structure in concert with the cognate tRNA. genes is discussed.
Date: August 1986
Creator: Johnson, Gary D. (Gary Dean), 1960-
Partner: UNT Libraries

Molecular analysis of a thylakoid K+ channel

Description: The work undertaken during the prior granting period sought to use a novel probe to identify and clone plant ion (K) channels. It was also proposed that in vitro biochemical studies of cation transport across purified preparations of thylakoid membrane be employed to characterize a putative K channel in this membrane system. Over the last several years (including those of the previous grant period), an enormous data base of partially-sequenced mRNAs and numerous genomes (including those of plants) has evolved and provides a powerful alternative to this brute-force approach to identify and clone cDNAs ending physiologically important membrane proteins such as channels. The utility of searching genetic databases for relevant sequences, in addition to the difficulty of working with membrane proteins, led to changes in research focus during the prior granting period, and has resulted in the identification of a new class of plant ion channels, which will be the focus of research during the proposed new granting period.
Date: May 1, 2000
Partner: UNT Libraries Government Documents Department

DETERMINATION OF IN-VITRO LUNG SOLUBILITY AND INTAKE-TO-DOSE CONVERSION FACTOR FOR TRITIATED LANTHANUM NICKEL ALUMINUM ALLOY

Description: A sample of tritiated lanthanum nickel aluminum alloy (LaNi4.25Al0.75 or LANA.75) similar to that used at the Savannah River Site Tritium Facilities was analyzed to estimate the particle size distribution of this metal tritide powder and the rate, at which this material dissolves in the human respiratory tract after it is inhaled. This information is used to calculate the committed effective dose received by a worker after inhaling the material. These doses, which were calculated using the same methodology given in the DOE Tritium Handbook, are presented as inhalation intake-to-dose conversion factors (DCF). The DCF for this metal tritide is less than the DCF for tritiated water and radiation worker bioassay programs designed for tritiated water are adequate to monitor for intakes of this material.
Date: November 11, 2011
Creator: Farfan, E.; Labone, T.; Staack, G.; Cheng, Y.; Zhou, Y. & Varallo, T.
Partner: UNT Libraries Government Documents Department

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Two-Generation Reproduction Study of Lewisite in Rats Final Report

Description: Occupational health standards have not been established for Lewisite [bis(2-chlorethyl)arsine], a potent toxic vesicant which reacts with the sulfhydryl groups of proteins through its arsenic group. The purposes of this study were to determine the reproductive consequences and dose~response of continuing Lewisite exposure of parental males and females and their offspring in a 42-week two-generation study. Solutions of Lewisite were prepared for administration by diluting the neat agent with sesame oil. Rats were administered Lewisite (0, 0.10, 0.25 or 0.60 mg/kg/day for 5 days a week) via intragastric intubation prior to mating, during mating and after mating until the birth of their offspring. The dams continued to receive Lewisite during lactation. At weaning, male and female offspring of each group were selected to continue on the study; rece1v1ng Lewisite during adolescence, mating and throughout gestation. Again, the dams continued to receive Lewisite until weaning of the offspring. Lewisite had no adverse effect on reproduction performance, fertility or reproductive organ weights of male or female rats through two consecutive generations. No adverse effect to offspring were attributed to Lewisite exposure. Minor changes in growth was the only maternal effect observed. Lewisite exposure of parental rats caused no gross or microscopic lesions in testes, epididymis, prostrate, seminal vesicles, ovaries, uterus or vagina. Severe inflammation of the lung was observed at necropsy in cases in which Lewisite gained access to the respiratory system from accidental dosing or reflux and aspiration; this usually caused early death of the animal. The NOEL for reproductive effects in this study was greater than 0.60 mg/kg/day.
Date: July 15, 1989
Creator: Sasser, L. B.; Cushing, J. A.; Kalkwarf, D. R.; Mellick, P. W. & Buschbom, R. L.
Partner: UNT Libraries Government Documents Department

Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

Description: Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.
Date: September 20, 2006
Creator: Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A. et al.
Partner: UNT Libraries Government Documents Department

THE COVALENT BINDING OF ENANTIOMERIC BENZO [A] PYRENE DIOL EPOXIDES TO DOUBLE STRANDED DNA IS STEREOSELECTIVE

Description: Reaction of optically pure (+) and (-) 7{beta},8{alpha}-dihydroxy-9{alpha},10{alpha}-epoxy-7,8,9.10-tetrahydrobenzo[a]pyrene with DNA in vitro yielded diastereomeric covalent adducts with the exocyclic amino groups of deoxyguanosine and deoxyadenosine. The ratio of two deoxyguanosine diastereomers derived by reacting the (+) and (-) hydrocarbons with native calf thymus and double stranded 0X174 DNA was 20:1 while reaction of the enantiomers with heat denatured calf thymus and single stranded 0X174 DNA resulted in a ratio near 1:1. In contrast, deoxyaadenosine diastereomer pairs were approximately 1:1 in all cases studied. The (+) and (-) enantiomers of the benzo[a]pyrene diol epoxide, therefore, interact asymmetrically with the guanine binding sites of double stranded but not single stranded polydeoxynucleotides. In contrast, reaction of the enantiomers with adenine is not stereoselective.
Date: July 1, 1978
Creator: Meehan, T. & Straub, K.
Partner: UNT Libraries Government Documents Department

APPLICATION OF THE THEORY OF INTERACTING CONTINUA TO BLOOD FLOW

Description: Micro-scale investigations of the flow and deformation of blood and its formed elements have been studied for many years. Early in vitro investigations in the rotational viscometers or small glass tubes revealed important rheological properties such as the reduced blood apparent viscosity, Fahraeus effect and Fahraeus-Lindqvist effect [1], exhibiting the nonhomogeneous property of blood in microcirculation. We have applied Mixture Theory, also known as Theory of Interacting Continua, to study and model this property of blood [2, 3]. This approach holds great promise for predicting the trafficking of RBCs in micro-scale flows (such as the depletion layer near the wall), and other unique hemorheological phenomena relevant to blood trauma. The blood is assumed to be composed of an RBC component modeled as a nonlinear fluid, suspended in plasma, modeled as a linearly viscous fluid.
Date: January 1, 2011
Creator: Massoudi, Mehrdad; Kim, Jeongho; Hund, Samuel J. & Antaki, James F.
Partner: UNT Libraries Government Documents Department

Decreased expression of RNA interference machinery, Dicer and Drosha, is associated with poor outcome in ovarian cancer patients

Description: The clinical and functional significance of RNA interference (RNAi) machinery, Dicer and Drosha, in ovarian cancer is not known and was examined. Dicer and Drosha expression was measured in ovarian cancer cell lines (n=8) and invasive epithelial ovarian cancer specimens (n=111) and correlated with clinical outcome. Validation was performed with previously published cohorts of ovarian, breast, and lung cancer patients. Anti-Galectin-3 siRNA and shRNA transfections were used for in vitro functional studies. Dicer and Drosha mRNA and protein levels were decreased in 37% to 63% of ovarian cancer cell lines and in 60% and 51% of human ovarian cancer specimens, respectively. Low Dicer was significantly associated with advanced tumor stage (p=0.007), and low Drosha with suboptimal surgical cytoreduction (p=0.02). Tumors with both high Dicer and Drosha were associated with increased median patient survival (>11 years vs. 2.66 years for other groups; p<0.001). In multivariate analysis, high Dicer (HR=0.48; p=0.02), high-grade histology (HR=2.46; p=0.03), and poor chemoresponse (HR=3.95; p<0.001) were identified as independent predictors of disease-specific survival. Findings of poor clinical outcome with low Dicer expression were validated in separate cohorts of cancer patients. Galectin-3 silencing with siRNA transfection was superior to shRNA in cell lines with low Dicer (78-95% vs. 4-8% compared to non-targeting sequences), and similar in cell lines with high Dicer. Our findings demonstrate the clinical and functional impact of RNAi machinery alterations in ovarian carcinoma and support the use of siRNA constructs that do not require endogenous Dicer and Drosha for therapeutic applications.
Date: May 6, 2008
Creator: Merritt, William M.; Lin, Yvonne G.; Han, Liz Y.; Kamat, Aparna A.; Spannuth, Whitney A.; Schmandt, Rosemarie et al.
Partner: UNT Libraries Government Documents Department